Search Results
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VOICE-Early Response to Vedolizumab and IL-23 Antagonists in Participants With Crohn's Disease: A Prospective Observational Study (VOICE)
clinicaltrials@northshore.org
ALL
18 years and over
NCT06249555
Inclusion Criteria:
• Participant is an adult 18 years of age or older with confirmed CD, as per standard clinical criteria which may include symptoms, endoscopy, histopathology, and imaging.
• Participant has active CD and has been prescribed as standard of care (SOC) and is planned to start VDZ or IL-23 antagonist therapy (UST, RISA, or GUS or MIR \[if approved for the treatment of CD during the recruitment period for this study\]) for the first time in accordance with the product label, as determined by the treating physician.
• Participant has a baseline PROMIS Pain Interference-SF score ≥ 15 (corresponding T-score ≥ 55) (PROMIS Pain Interference-SF 8a \[V1.1\]). a. Score is calculated by adding score (1 to 5) for each of the 8 subcomponents.
• Participant has completed all SOC biologic work-up assessments (this may include assessment of tuberculosis, chronic infections, Clostridioides difficile infection and vaccination status per local practice).
• Ability of participant to participate fully in all aspects of this observational study. Full comprehension of consent language and informed consent must be obtained from the participant and documented.
Exclusion Criteria:
• Participant has CD-related surgery planned or anticipated during the study.
• Participant has prior exposure to an advanced therapy for the treatment of CD (biologic or small molecule) other than an anti-TNF (i.e., anti-integrin, anti-IL, Janus kinase inhibitors, or sphingosine-1-phosphate receptor 1). Prior failure or intolerance to 2 or more anti-TNF (i.e., infliximab, adalimumab, or certolizumab pegol) therapies in the past 3 years is also cause for exclusion.
• Participant has an active infection at baseline requiring intravenous systemic antibiotics. Note: The treating physician must have completed all appropriate baseline screening tests as per the product label.
• Participant has evidence of C. difficile toxin or is prescribed treatment for C. difficile infection, or other intestinal bacterial pathogen, ≤ 2 weeks prior to Screening.
• Participant has chronic non-inflammatory bowel disease pain.
DRUG: Vedolizumab (VDZ), DRUG: Ustekinumab (UST), DRUG: Risankizumab (RISA)
Crohn',s Disease
Vedolizumab, Ustekinumab, Patient reported outcome, IL-23 antagonists, Risankizumab
Oral N-acetylcysteine for Retinitis Pigmentosa (NAC Attack)
clinicaltrials@northshore.org
ALL
18 years to 65 years old
PHASE3
NCT05537220
Inclusion Criteria:
General
* Ability and willingness to provide informed consent
* Age ≥ 18 and ≤65 years at time of signing Informed Consent Form
* Ability and willingness to comply with the study protocol and to participate in all study visits and assessments in the investigator's judgement
* For candidates of childbearing potential: willingness to use a method of contraception
* Agreement not to take supplements other than vitamin A
Ocular Inclusion Criteria
* Both eyes must exhibit the RP phenotype with evidence of loss of night vision, gradual constriction of visual fields, and maintenance of visual acuity;
* In addition, an eye must meet the following criteria to be included in the study:
* Gradable EZ on a horizontal SD-OCT scan through the fovea center with width ≤ 8000 µm and ≥1500 µm and with well-defined truncation at both the nasal and temporal sides;
* BCVA ≥ ETDRS letter score of 61 (20/60 Snellen equivalent);
* Sufficiently clear ocular media and adequate pupillary dilation to allow good quality images sufficient for analysis and grading by central reading center.
Exclusion Criteria:
General Exclusion Criteria
* Active cancer within the past 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score ≤ 6 and stable prostate specific antigen for \> 12 months
* Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis during the study
* Liver disease, cystic fibrosis, asthma, or chronic obstructive pulmonary disease (COPD), history of thrombocytopenia not due to a reversible cause or other blood dyscrasia
* Uncontrolled blood pressure (defined as systolic \> 180 and/or diastolic \> 100 mmHg while at rest) at screening. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient's blood pressure must be controlled by antihypertensive medication, the patient may become eligible if medication is taken continuously for at least 30 days.
* History of other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion that oral NAC may be contraindicated or that follow up may be jeopardized
* Cerebrovascular accident or myocardial infarction within 6 months of screening
* Participation in an investigational study that involves treatment with any drug or device within 6 months of screening
* Three relatives already enrolled in study
* Pregnant, breast feeding, or intending to become pregnant during the study treatment period. Women of childbearing potential who have not had tubal ligation must have a urine pregnancy test at screening.
* Known history of allergy to NAC
* Having taken NAC in any form in the past 4 months
* Phenylketonuria
* Fructose intolerance
* Glucose-galactose malabsorption
* Sucrase-isomaltase insufficiency
* Abnormal laboratory value including the value of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin being greater than 1.5 x the upper limit of normal
* Any major abnormal findings on blood chemistry, hematology, and renal function lab tests that in the opinion of the Site Investigator and/or the Study Chair makes the candidate not suitable to participate in the trial
* HIV or hepatitis B infection
Ocular Exclusion Criteria
* Evidence of cone-rod dystrophy or pattern dystrophy including focal areas of atrophy or pigmentary changes in the central macula
* Cystoid spaces involving the fovea substantially reducing vision
* Glaucoma or other optic nerve disease causing visual field loss or reduced visual acuity
* Intra ocular pressure \>27 mm Hg from two measurements. If a patient's initial measurement exceeds 27 mm Hg, a second reading must be taken.
* Any retinal disease other than RP causing reduction in visual field or visual acuity
* Any prior macular laser photocoagulation
* Intraocular surgery within 3 months prior to screening
* High myopia with spherical equivalent refractive error \> 8 diopters. If an eye has had cataract surgery or refractive surgery, a pre-operative refractive error spherical equivalent \> 8 diopters is an exclusion
* Any concurrent ocular condition that might affect interpretation of results
* History of uveitis in either eye DRUG: N-acetylcysteine, DRUG: Placebo
Retinitis Pigmentosa
N-acetylcysteine, Ellipsoid zone, Macular sensitivity, Best corrected visual acuity, Ellipsoid zone width, Ellipsoid zone area, Oxidative damage, Usher Syndrome, Antioxidants
A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB (ACTION3)
clinicaltrials@northshore.org
ALL
12 years to 80 years old
PHASE3
NCT05183646
DOUBLE BLIND PERIOD
• Patients must be 12 to 80 years old
• A diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause. Confirmed by kidney biopsy within 7 years of screening
• Must be either receiving an ARB at the maximal tolerated dose or willing to transition
• If taking corticosteroids, the dosage must be stable for ≥4 weeks prior to Screening and during Stabilization
• If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or endothelin receptor antagonists (ERAs, including dual antagonists), the dose and regimen must be stable for ≥12 weeks prior to Screening and during Stabilization
• Urine PCR \>1.5 g/g (\>169.5 mg/mmol) or 24-hour total protein \>1.5 g/day based on 24-hour urine collection during Screening.
• Estimated eGFR ≥25 and ≤120 mL/min/1.73 m2 at Screening for adults \& eGFR ≥25mL/min/1.73 m2 for adolescent patients (\<18 years)
• Seated blood pressure ≤160/100 mm Hg (mean of 3 values) (patients ≥18 years of age) or between the 5th and 95th percentile for age, sex, and height (patients \<18 years of age) at Screening
• Body weight ≥35 kg (all patients) AND a body mass index (BMI) ≤40 kg/m2 (patients ≥18 years of age) or between the 5th and 98th percentile for age and sex (patients \<18 years of age) at Screening.
• A female patient is eligible to participate if she is not pregnant or planning to become pregnant during the study, not breastfeeding, and at least one of the following conditions applies:
• Is not of childbearing potential
• If of childbearing potential and beginning at menarche, agrees to use a highly effective method of contraception consistently during the treatment period.
• A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception
• A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent.
• Has FSGS secondary to another condition.
• Patients with nephrotic syndrome (\>3.5 g/day proteinuria and serum albumin \<30 g/L) who have not previously been treated with standard of care FSGS-directed therapies (including steroids).
• History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin \[HbA1c\] \>8% at Screening)
• History of lymphoma, leukemia, or any active malignancy within the past 2 years (except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected and with no evidence of metastatic disease).
• Active clinically significant hepatobiliary disease.
• Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening.
• Has a physical, medical, or psychological condition, that in the opinion of the Investigator, may interfere with the evaluation the study.
• The patient has a history of alcohol or illicit drug use disorder within 1 year prior to Screening.
• Had a prior organ transplant or stem cell transplant, with the exception of corneal transplant.
• Positive screening assessment for viral hepatitis B surface antigen, or anti-hepatitis C virus (HCV) antibody AND positive HCV RNA, or human immunodeficiency virus 1 and 2.
• Serum potassium levels \>5.5 mmol/L at Screening.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2 × upper limit of normal (ULN) at Screening.
• Treatment with non-steroid immunosuppressant agents including biological drugs (e.g. rituximab), calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 12 weeks prior to Screening.
• History of serious side effects or allergic response to an angiotensin II antagonist or has a known sensitivity to any components in the IP.
• Unable to swallow oral medication.
• Prior participation in any Dimerix-sponsored DMX-200 clinical study.
• Participation in a clinical study with an investigational product (IP) within 28 days or 5 half-lives (whichever is longer) prior to Screening or plans to participate in another study during the course of this study.
• Are study site personnel directly affiliated with this study and their immediate families OLE PERIOD
• A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent.
• Patients who have completed participation in the double-blind period, including the Week 104 visit, and who may derive benefit from (continued) treatment with DMX-200, and/or continued follow-up
• The patient received blinded Investigational Product throughout the duration of the double-blind period up to the Week 104 visit
• The patient continues to meet the contraceptive requirements
• The patient has met the criteria for permanent IP discontinuation or study discontinuation
• Any safety concerns identified during the double-blind period which, in the Investigator's opinion, may interfere with the patient's continued participation during the OLE period.
Inclusion Criteria:
• Patients must be 12 to 80 years old
• A diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause. Confirmed by kidney biopsy within 7 years of screening
• Must be either receiving an ARB at the maximal tolerated dose or willing to transition
• If taking corticosteroids, the dosage must be stable for ≥4 weeks prior to Screening and during Stabilization
• If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or endothelin receptor antagonists (ERAs, including dual antagonists), the dose and regimen must be stable for ≥12 weeks prior to Screening and during Stabilization
• Urine PCR \>1.5 g/g (\>169.5 mg/mmol) or 24-hour total protein \>1.5 g/day based on 24-hour urine collection during Screening.
• Estimated eGFR ≥25 and ≤120 mL/min/1.73 m2 at Screening for adults \& eGFR ≥25mL/min/1.73 m2 for adolescent patients (\<18 years)
• Seated blood pressure ≤160/100 mm Hg (mean of 3 values) (patients ≥18 years of age) or between the 5th and 95th percentile for age, sex, and height (patients \<18 years of age) at Screening
• Body weight ≥35 kg (all patients) AND a body mass index (BMI) ≤40 kg/m2 (patients ≥18 years of age) or between the 5th and 98th percentile for age and sex (patients \<18 years of age) at Screening.
• A female patient is eligible to participate if she is not pregnant or planning to become pregnant during the study, not breastfeeding, and at least one of the following conditions applies:
• Is not of childbearing potential
• If of childbearing potential and beginning at menarche, agrees to use a highly effective method of contraception consistently during the treatment period.
• A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception
• A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent.
Exclusion Criteria:
• Has FSGS secondary to another condition.
• Patients with nephrotic syndrome (\>3.5 g/day proteinuria and serum albumin \<30 g/L) who have not previously been treated with standard of care FSGS-directed therapies (including steroids).
• History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin \[HbA1c\] \>8% at Screening)
• History of lymphoma, leukemia, or any active malignancy within the past 2 years (except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected and with no evidence of metastatic disease).
• Active clinically significant hepatobiliary disease.
• Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening.
• Has a physical, medical, or psychological condition, that in the opinion of the Investigator, may interfere with the evaluation the study.
• The patient has a history of alcohol or illicit drug use disorder within 1 year prior to Screening.
• Had a prior organ transplant or stem cell transplant, with the exception of corneal transplant.
• Positive screening assessment for viral hepatitis B surface antigen, or anti-hepatitis C virus (HCV) antibody AND positive HCV RNA, or human immunodeficiency virus 1 and 2.
• Serum potassium levels \>5.5 mmol/L at Screening.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2 × upper limit of normal (ULN) at Screening.
• Treatment with non-steroid immunosuppressant agents including biological drugs (e.g. rituximab), calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 12 weeks prior to Screening.
• History of serious side effects or allergic response to an angiotensin II antagonist or has a known sensitivity to any components in the IP.
• Unable to swallow oral medication.
• Prior participation in any Dimerix-sponsored DMX-200 clinical study.
• Participation in a clinical study with an investigational product (IP) within 28 days or 5 half-lives (whichever is longer) prior to Screening or plans to participate in another study during the course of this study.
• Are study site personnel directly affiliated with this study and their immediate families OLE PERIOD
Inclusion Criteria:
• A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent.
• Patients who have completed participation in the double-blind period, including the Week 104 visit, and who may derive benefit from (continued) treatment with DMX-200, and/or continued follow-up
• The patient received blinded Investigational Product throughout the duration of the double-blind period up to the Week 104 visit
• The patient continues to meet the contraceptive requirements
Exclusion Criteria:
• The patient has met the criteria for permanent IP discontinuation or study discontinuation
• Any safety concerns identified during the double-blind period which, in the Investigator's opinion, may interfere with the patient's continued participation during the OLE period.
DRUG: DMX-200, DRUG: Placebo
FSGS
fsgs, focal segmental glomerulosclerosis, kidney disease
A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
clinicaltrials@northshore.org
ALL
12 years and over
PHASE3
NCT07220083
Inclusion criteria:
• Male or female participants ≥12 years old on the day of signing informed consent/assent (Visit 1)
• Weight of ≥40 kg at the screening visit (Visit 1)
• Body mass index (BMI) of ≤40 kg/m² at the screening visit (Visit 1)
• Participants with a diagnosis prior to the screening visit (Visit 1) of either: * Biopsy-confirmed primary focal segmental glomerulosclerosis (pFSGS) (based on Investigator's judgement) OR * Genetic focal segmental glomerulosclerosis (FSGS) resulting from a gain-of-function mutation in the transient receptor potential cation subfamily C member 6 (TRPC6) gene (based on historical genetic test)
• Urine protein-creatinine ratio (UPCR) ≥1500 mg/g based on the mean of the spot urine sample and first morning void (FMV) urine sample (both assessed by central laboratory) at the screening visit (Visit 1)
• Estimated glomerular filtration rate (eGFR) * For adult participants (≥18 years): ≥25 mL/min/1.73 m² (chronic kidney disease epidemiology collaboration (CKD-EPI) formula based on serum cystatin C) at the screening visit (Visit 1) * For adolescent participants (12 to \<18 years): ≥25 mL/min/1.73 m² based on chronic kidney disease under 25 years (CKiD U25) formula using serum cystatin C at the screening visit (Visit 1) Further inclusion criteria apply. Exclusion criteria:
• Known monogenic or syndromic causes of FSGS (with the exception of TRPC6 gain-of-function gene mutations)
• Clinical or histologic evidence of secondary adaptive or toxic forms of FSGS (based on Investigator's judgement)
• FSGS of undetermined cause (FSGS-UC) with a diagnosis prior to the screening visit (Visit 1) (based on Investigator's judgement)
• A history of organ transplantation or planned organ transplantation during the course of the trial
• Use of intravenous immunosuppressive agents (e.g. cyclophosphamide, rituximab, obinutuzumab) in the last 6 months prior to screening (Visit 1) Further exclusion criteria apply.
• Male or female participants ≥12 years old on the day of signing informed consent/assent (Visit 1)
• Weight of ≥40 kg at the screening visit (Visit 1)
• Body mass index (BMI) of ≤40 kg/m² at the screening visit (Visit 1)
• Participants with a diagnosis prior to the screening visit (Visit 1) of either: * Biopsy-confirmed primary focal segmental glomerulosclerosis (pFSGS) (based on Investigator's judgement) OR * Genetic focal segmental glomerulosclerosis (FSGS) resulting from a gain-of-function mutation in the transient receptor potential cation subfamily C member 6 (TRPC6) gene (based on historical genetic test)
• Urine protein-creatinine ratio (UPCR) ≥1500 mg/g based on the mean of the spot urine sample and first morning void (FMV) urine sample (both assessed by central laboratory) at the screening visit (Visit 1)
• Estimated glomerular filtration rate (eGFR) * For adult participants (≥18 years): ≥25 mL/min/1.73 m² (chronic kidney disease epidemiology collaboration (CKD-EPI) formula based on serum cystatin C) at the screening visit (Visit 1) * For adolescent participants (12 to \<18 years): ≥25 mL/min/1.73 m² based on chronic kidney disease under 25 years (CKiD U25) formula using serum cystatin C at the screening visit (Visit 1) Further inclusion criteria apply. Exclusion criteria:
• Known monogenic or syndromic causes of FSGS (with the exception of TRPC6 gain-of-function gene mutations)
• Clinical or histologic evidence of secondary adaptive or toxic forms of FSGS (based on Investigator's judgement)
• FSGS of undetermined cause (FSGS-UC) with a diagnosis prior to the screening visit (Visit 1) (based on Investigator's judgement)
• A history of organ transplantation or planned organ transplantation during the course of the trial
• Use of intravenous immunosuppressive agents (e.g. cyclophosphamide, rituximab, obinutuzumab) in the last 6 months prior to screening (Visit 1) Further exclusion criteria apply.
DRUG: BI 764198, DRUG: Placebo
Focal Segmental Glomerulosclerosis
A Study to Investigate Efficacy, Safety and Tolerability of Barzolvolimab Versus Placebo in Adults With Cold Induced Urticaria and Symptomatic Dermographism Inadequately Controlled by H1-antihistamines (EMBARQ - ColdU and SD) (EMBARQ)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT07266402
Key
• Males and females, \>/= 18 years of age.
• Diagnosis of cold induced urticaria or symptomatic dermographism \>/= 3 months.
• Diagnosis of cold induced urticaria or symptomatic dermographism despite the use of a stable regimen of second generation non-sedating H1-antihistamine as defined by:
• The presence of hives for \>/= 6 weeks at any time prior to Visit 1 despite the use of H1-antihistamines.
• Must be on a stable regimen of second generation non-sedating H1-antihistamine for \>/= 4 weeks prior to study treatment.
• Cold induced urticaria: A Critical Threshold Temperature (CTT) of ≥ 15 °C and \< 37 °C using the TempTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.
• Symptomatic dermographism: A Critical Friction Threshold (CFT) of ≥ 3 using the FricTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.
• Cold induced urticaria: Positive ice-cube test resulting in hives at the provocation site during Screening
• Normal blood counts and liver function tests.
• Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for ≥ 150 days after treatment.
• Willing and able to complete a daily symptom electronic diary and comply with study visits.
• Participants with and without prior biologic experience are eligible. Key
• Women who are pregnant or nursing.
• Clearly defined cause for chronic urticaria.
• Active, pruritic skin condition in addition to cold induced urticaria or symptomatic dermographism.
• Medical condition that would cause additional risk or interfere with study procedures.
• Known HIV, hepatitis B or hepatitis C infection.
• Vaccination with a live vaccine within 30 days prior to screening (subjects must agree to avoid vaccination with a live vaccine during the study). Inactivated vaccines are allowed such as seasonal influenza injection or COVID-19 vaccine.
• History of anaphylaxis, unless due to cold exposure over a large part of the body (such as swimming in cold water).
• Prior treatment with barzolvolimab There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.
Inclusion Criteria:
• Males and females, \>/= 18 years of age.
• Diagnosis of cold induced urticaria or symptomatic dermographism \>/= 3 months.
• Diagnosis of cold induced urticaria or symptomatic dermographism despite the use of a stable regimen of second generation non-sedating H1-antihistamine as defined by:
• The presence of hives for \>/= 6 weeks at any time prior to Visit 1 despite the use of H1-antihistamines.
• Must be on a stable regimen of second generation non-sedating H1-antihistamine for \>/= 4 weeks prior to study treatment.
• Cold induced urticaria: A Critical Threshold Temperature (CTT) of ≥ 15 °C and \< 37 °C using the TempTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.
• Symptomatic dermographism: A Critical Friction Threshold (CFT) of ≥ 3 using the FricTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.
• Cold induced urticaria: Positive ice-cube test resulting in hives at the provocation site during Screening
• Normal blood counts and liver function tests.
• Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for ≥ 150 days after treatment.
• Willing and able to complete a daily symptom electronic diary and comply with study visits.
• Participants with and without prior biologic experience are eligible. Key
Exclusion Criteria:
• Women who are pregnant or nursing.
• Clearly defined cause for chronic urticaria.
• Active, pruritic skin condition in addition to cold induced urticaria or symptomatic dermographism.
• Medical condition that would cause additional risk or interfere with study procedures.
• Known HIV, hepatitis B or hepatitis C infection.
• Vaccination with a live vaccine within 30 days prior to screening (subjects must agree to avoid vaccination with a live vaccine during the study). Inactivated vaccines are allowed such as seasonal influenza injection or COVID-19 vaccine.
• History of anaphylaxis, unless due to cold exposure over a large part of the body (such as swimming in cold water).
• Prior treatment with barzolvolimab There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.
DRUG: Barzolvolimab, DRUG: Matching Placebo
Chronic Inducible Urticaria, Cold Urticaria, Cold-Induced Urticaria, Symptomatic Dermographism
Chronic Inducible urticaria, cold urticaria, cold-induced urticaria, ColdU, symptomatic dermographism,, SD, barzolvolimab, CDX0159, CDX-0159
Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV)
clinicaltrials@northshore.org
ALL
45 years to 99 years old
PHASE3
NCT07037433
Inclusion Criteria
* Age ≥ 45 years at screening.
* BMI of ≥ 27.0 kg/m\^2 at screening.
* History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:
* Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).
* Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).
* Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) \< 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.
Exclusion Criteria
* History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).
* New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.
* Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.
* For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):
* HbA1c \> 10.0% (86 mmol/mol) at screening.
* History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.
* One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.
* History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.
* Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the trial.
* History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.
* Family (first-degree relative\[s\]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).
* Calcitonin ≥ 50 ng/L (pg/mL) at screening.
* Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) \> 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) \> 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).
* History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).
* Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.
DRUG: Maridebart Cafraglutide, DRUG: Placebo
Atherosclerotic Cardiovascular Disease, Overweight, Obesity
Atherosclerotic Cardiovascular Disease, Overweight, Obesity, Maridebart cafraglutide, AMG 133, MariTide
Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01) (DO-01)
clinicaltrials@northshore.org
FEMALE
18 years and over
PHASE3
NCT06819007
Key
• Sign and date the tissue prescreening ICF, prior to HER2 central testing. Sign and date the Main ICF, prior to the start of any trial- specific qualification procedures. Consent to optional PGx prior to any PGx procedures. \*For participants in the safety run-in phase, a safety run-in ICF needs to be signed and dated prior to the start of any trial-specific qualification procedures.
• Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old.
• Has histologically confirmed diagnosis of epithelial high-grade ovarian, fallopian tube or primary peritoneal carcinoma per local assessment (including but not limiting to serous, endometrioid, clear cell, carcinosarcoma, mucinous).
• Is newly diagnosed FIGO Stage III or IV.
• Has HER2 expression per 2016 ASCO-CAP gastric cancer IHC scoring (3+/2+/1+) guidelines1 by prospective central testing. \*For participants in the safety run-in phase, HER2 expression assessed by either local (require using ASCO-CAP gastric cancer IHC scoring \[IHC 3+/2+/1+\] guidelines) or central assessment (if available) is acceptable. Submission of the pathology report is required for participants enrolled based on local HER2 IHC results.
• Has adequate tumor tissue sample available for assessment of HER2 by central laboratory. Tumor tissue block or sufficient tissue slides are required for HER2 testing and retrospective HRD status determination. \*Participants in the safety run-in phase who are enrolled based on local HER2 IHC results are recommended to provide tumor tissue sample from the same specimen for central assessment.
• Has a local HRD or BRCA test result available. Participants with BRCA-wildtype will have a local HRD test results, as applicable.
• Has received up to 6 cycles of standard of care bevacizumab in combination with frontline platinum- based chemotherapy as per approved indication and clinical guidelines and is eligible to continue single agent bevacizumab maintenance per standard of care and investigator discretion. Key
• Has ovarian, fallopian tube, or peritoneal cancer of non-epithelial origin.
• Has a known or suspected deleterious BRCA alteration as per local test that makes the patient eligible for PARP inhibitor.
• Participant to receive PARP inhibitor as maintenance per standard of care and investigator discretion. Reasons for which the participant is not eligible for PARP inhibitor will be recorded in the eCRF as follows: * HRD negative * HRD positive with SD as best response after platinum * HRD positive non-serous histology Note: For participants enrolled from the Republic of Korea * HRD tested, but inconclusive * HRD positive but safety concern (safety concern to be specified).
• Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products and other monoclonal antibodies.
• Previous Cerebral-Vascular Accident, Transient Ischemic Attack or Sub- Arachnoids Hemorrhage within 6 months prior to randomization. \*Note: For participants enrolled from the Republic of Korea,
• Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation therapy).
• Has a history of hemorrhagic disorders, abdominal fistula, gastrointestinal perforation, or active gastrointestinal bleeding within 6 months before randomization.
• Evidence of active or ongoing bowel obstruction.
• Has a medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal at Screening (as defined by the manufacturer), and without any myocardial infarction related symptoms should have a cardiologic consultation during the Screening Period to rule out myocardial infarction.
• Has a corrected QT interval prolongation to \>480 msec based on average of the Screening triplicate 12-lead ECG.
• Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
Inclusion Criteria:
• Sign and date the tissue prescreening ICF, prior to HER2 central testing. Sign and date the Main ICF, prior to the start of any trial- specific qualification procedures. Consent to optional PGx prior to any PGx procedures. \*For participants in the safety run-in phase, a safety run-in ICF needs to be signed and dated prior to the start of any trial-specific qualification procedures.
• Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old.
• Has histologically confirmed diagnosis of epithelial high-grade ovarian, fallopian tube or primary peritoneal carcinoma per local assessment (including but not limiting to serous, endometrioid, clear cell, carcinosarcoma, mucinous).
• Is newly diagnosed FIGO Stage III or IV.
• Has HER2 expression per 2016 ASCO-CAP gastric cancer IHC scoring (3+/2+/1+) guidelines1 by prospective central testing. \*For participants in the safety run-in phase, HER2 expression assessed by either local (require using ASCO-CAP gastric cancer IHC scoring \[IHC 3+/2+/1+\] guidelines) or central assessment (if available) is acceptable. Submission of the pathology report is required for participants enrolled based on local HER2 IHC results.
• Has adequate tumor tissue sample available for assessment of HER2 by central laboratory. Tumor tissue block or sufficient tissue slides are required for HER2 testing and retrospective HRD status determination. \*Participants in the safety run-in phase who are enrolled based on local HER2 IHC results are recommended to provide tumor tissue sample from the same specimen for central assessment.
• Has a local HRD or BRCA test result available. Participants with BRCA-wildtype will have a local HRD test results, as applicable.
• Has received up to 6 cycles of standard of care bevacizumab in combination with frontline platinum- based chemotherapy as per approved indication and clinical guidelines and is eligible to continue single agent bevacizumab maintenance per standard of care and investigator discretion. Key
Exclusion Criteria:
• Has ovarian, fallopian tube, or peritoneal cancer of non-epithelial origin.
• Has a known or suspected deleterious BRCA alteration as per local test that makes the patient eligible for PARP inhibitor.
• Participant to receive PARP inhibitor as maintenance per standard of care and investigator discretion. Reasons for which the participant is not eligible for PARP inhibitor will be recorded in the eCRF as follows: * HRD negative * HRD positive with SD as best response after platinum * HRD positive non-serous histology Note: For participants enrolled from the Republic of Korea * HRD tested, but inconclusive * HRD positive but safety concern (safety concern to be specified).
• Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products and other monoclonal antibodies.
• Previous Cerebral-Vascular Accident, Transient Ischemic Attack or Sub- Arachnoids Hemorrhage within 6 months prior to randomization. \*Note: For participants enrolled from the Republic of Korea,
• Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation therapy).
• Has a history of hemorrhagic disorders, abdominal fistula, gastrointestinal perforation, or active gastrointestinal bleeding within 6 months before randomization.
• Evidence of active or ongoing bowel obstruction.
• Has a medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal at Screening (as defined by the manufacturer), and without any myocardial infarction related symptoms should have a cardiologic consultation during the Screening Period to rule out myocardial infarction.
• Has a corrected QT interval prolongation to \>480 msec based on average of the Screening triplicate 12-lead ECG.
• Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
DRUG: Trastuzumab Deruxtecan, DRUG: Bevacizumab
Ovarian Cancer
Ovarian cancer, epithelial ovarian cancer, HER2, Trastuzumab Deruxtecan, Bevacizumab
Extension Trial to Evaluate the Long-term Efficacy, Safety, and Tolerability of Maridebart Cafraglutide (MARITIME-1-EXTENSION)
clinicaltrials@northshore.org
ALL
18 years to 99 years old
PHASE3
NCT07684235
Inclusion Criteria:
* Signed informed consent form (ICF) which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
* Completed the parent trial (2010181)
* Completed week 72 visit in parent trial
* Did not permanently discontinue trial intervention in parent trial
* Randomized within 7 Days of week 72 visit in the parent trial
* Participants must use protocol-specified contraception during treatment, and for an additional 16 weeks after the last dose of trial intervention
Exclusion Criteria:
* Planned (during the trial) surgical, endoscopic, or device-based treatment for obesity
* Body mass index ≤ 18.5 kilograms per meter square (kg/m\^2)
* Participant has known sensitivity to any of the products or components to be administered during dosing
* History of ischemic optic neuropathy
* Any malignancy diagnosed during parent trial (20210181) except for the following treated with curative intent: nonmelanoma skin cancers, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ.
* Newly identified (i.e., identified during 20210181) multiple endocrine neoplasia syndrome type 2 or family (first-degree relative\[s\]) history of medullary thyroid cancer.
* Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at week 72 visit from parent trial before randomization
* Any suicidal ideation of category 4 or 5 OR any suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) Since Last Visit version at week 72 visit from parent trial before randomization.
* Participant unlikely to be able to complete all protocol-required procedures, restrictions and requirements, in the judgment of the individual and investigator.
* History or evidence of any other clinically significant disorder, condition, or disease (including, but not limited to known drug or alcohol abuse, eating disorders, and conditions identified during the parent trial) that, in the opinion of the investigator, would pose a risk to participant safety.
* Currently pregnant (confirmed with positive pregnancy test) or breastfeeding or
* Planning to become pregnant or breastfeed while on trial until an additional 16 weeks after the last dose of trial intervention.
* Major surgical procedures planned during the trial.
* Participants with minor surgical procedures (not requiring general anesthesia or deep sedation) planned during the trial may be eligible at the discretion of the investigator.
* Investigative site personnel directly affiliated with the trial and/or their immediate family (ie, spouse, parent, child, or sibling, whether biological or legally adopted). DRUG: Maridebart cafraglutide, DRUG: Placebo
Obesity, Overweight
Overweight, BMI, Obesity, Maridebart cafraglutide, Chronic weight management, MariTide, Extension, Long-Term
An Outpatient Study of the Efficacy of ARS-2 in Patients With Chronic Spontaneous Urticaria
clinicaltrials@northshore.org
ALL
18 years to 65 years old
PHASE2
NCT06927999
Inclusion Criteria:
* Is a male or female between the ages of 18 and 65 years, inclusive.
* Has been clinically diagnosed with CSU and experiences an acute flare of moderate to severe urticaria symptoms (itch and hive severity UAS score ≥ 2) approximately 1-2 times a month or every other month consistently during the past year while on a chronic treatment.
* Has been on a daily chronic treatment for ≥ 6 weeks.
* Is willing to use a smartphone study application to record study assessments and AEs.
* Has body weight more than 15 kilogram (kg).
* Has no medical history of clinically significant hypertension and cardiovascular disease in the last 10 years
* If female, is not pregnant or breastfeeding based on a negative urine pregnancy test at baseline.
* Is able to communicate clearly with the Investigator and staff; able to read, complete questionnaires, and perform study procedures on the smartphone study application.
* Is willing and able to provide written informed consent prior to participating in the study.
* Controlled hypertension without beta blocker confirmed by the Investigator is acceptable.
* At screening, has stable vital signs in the following ranges (after 5 minutes of rest):
* Systolic blood pressure (SBP) ≥90 and ≤140 milliliters of mercury (mmHg)
* Diastolic blood pressure (DBP) ≥50 and ≤90 mmHg
* Heart rate (HR) ≥45 and ≤100 beats per minute (bpm)
Exclusion Criteria:
* Has a history of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
* Has any clinically significant medical condition or PE finding as deemed inappropriate by the Investigator.
* Has abnormal cardiovascular exam at screening including any prior history of myocardial infarction or clinically significant abnormal electrocardiogram (ECG)
* Has had significant traumatic injury or major surgery within 30 days prior to study screening.
* Known hypersensitivity to any compound in the test product, or any other closely related compound (e.g., dihydropyridine-derived molecules).
* Has participated in a clinical trial within 30 days prior to the first dose of study drug.
* Has an immediate family member of the Investigator, or an employee of the study center, with direct involvement in the proposed study, or other studies under the direction of the Investigator or study center or is in a dependent relationship with a study center employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling), or may consent under duress. DRUG: Placebo, DRUG: 0.5 mg epinephrine, DRUG: 1 mg epinephrine
Urticaria Chronic
A Study to Evaluate the Safety and Efficacy of Ruxolitinib Cream in Pediatric Participants With Nonsegmental Vitiligo (TRuE-VIP1)
clinicaltrials@northshore.org
ALL
2 years to 11 years old
PHASE3
NCT06548360
Inclusion Criteria:
* Clinical diagnosis of nonsegmental vitiligo with depigmented area including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 2% BSA on nonfacial areas, ≥ 2 T-VASI.
* Total body vitiligo area does not exceed 10% BSA.
* Pigmented hair within some of the areas of vitiligo on the face.
* Must agree to discontinue all agents used to treat vitiligo from screening through the final safety follow-up visit.
* For sexually active participants (except participants who are prepubescent) willingness to avoid pregnancy or fathering a child from screening through 30 days after the last application of study cream.
Exclusion Criteria:
* Diagnosis of other forms of vitiligo (eg, segmental).
* Other differential diagnosis of vitiligo or other skin depigmentation disorders (eg, piebaldism, pityriasis alba, leprosy, postinflammatory hypopigmentation, progressive macule hypomelanosis, nevus anemicus, chemical leukoderma, and tinea versicolor).
* Any other skin disease that, in the opinion of the investigator, would interfere with the study drug application or study assessments.
* Prior or current use of depigmentation treatments (eg, monobenzone).
* Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including application of study cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* Use of protocol-defined treatments within the indicated washout period before baseline.
* History of treatment failure with any systemic or topical JAK inhibitor (eg, ruxolitinib, tofacitinib, baricitinib, abrocitinib, and upadacitinib) for vitiligo or any other inflammatory condition.
* Protocol-defined clinically significant abnormal laboratory values at screening.
* Pregnant or lactating participants or those considering pregnancy during the period of their study participation.
* In the opinion of the investigator, unable or unlikely to comply with the application schedule and study evaluations.
* Living with anyone participating in any current Incyte-sponsored ruxolitinib cream study.
* Employees of the sponsor or investigator or are otherwise dependents of them.
* Known allergy or reaction to any component of the study cream formulation.
Other protocol-defined Inclusion/Exclusion Criteria may apply. DRUG: Ruxolitinib Cream, DRUG: Vehicle Cream
NonSegmental Vitiligo
NonSegmental Vitiligo, pediatric
A Study to Test Whether Nerandomilast Helps People With Lungfibrosis Related to Rheumatic Diseases
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06806592
Inclusion Criteria:
* Participant has systemic autoimmune rheumatic diseases associated interstitial lung diseases (SARD-ILD), defined as
* Diagnosis by a rheumatologist (or equally qualified medical physician) with at least 1 of the following SARDs: Rheumatoid arthritis (RA), systemic sclerosis (SSc) (participants must be anticentromere auto-antibody negative), idiopathic inflammatory myopathy (IIM), Sjögren's disease, or mixed connective tissue disease (MCTD) (participants must be anti-U1-ribonucleoprotein particle (RNP) auto-antibody positive)
* Presence of fibrotic interstitial lung disease (ILD) on high-resolution computed tomography (HRCT), defined as presence of reticular abnormality with traction bronchiectasis with or without honeycombing (HC), with disease extent \>10% on HRCT performed within 12 months of Visit 1 or, if historical scan is not available, on baseline HRCT taken prior to Visit 2, as confirmed by central review
* No lung function improvement and no clinically significant ILD improvement as a treatment response to immunosuppressant (IS) therapy according to both criteria:
* No improvement in absolute forced vital capacity (FVC) % predicted \>5% within the 15 months prior to Visit 1, as measured by 2 spirometry assessments that must be ≥3 months apart. (Note: 1: In the case of multiple PFTs over the 15 months prior to screening, exceptional values of absolute change in FVC % predicted \>5% are acceptable if the overall trend of FVC % predicted is declining or stable; note 2: Visit 1 spirometry may be used to fulfill the inclusion criterion if there is only 1 spirometry reading in the 15 months prior to Visit 1)
* No clinically significant improvement in ILD based on clinician's judgement (including symptoms, imaging/HRCT, or other assessments as considered relevant and documented by the Investigator)
* FVC ≥45% of predicted normal at Visit 1
* Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥25% of predicted normal corrected for haemoglobin (Hb) within 3 months prior to or at Visit 1
* Participants must be on stable treatment with any IS agent for ≥6 months (or ≥3 months for participants with IIM-ILD) prior to visit 2, with the following specifications:
* If using prednisone, participants must be on stable dose for ≥4 weeks prior to Visit 2
* If using rituximab, participants must have completed their first cycle \>6 months prior to Visit 2
* If using nintedanib, participants must be on a stable dose for ≥12 weeks prior to Visit 2
* In the opinion of the Investigator, no change in background standard of care (SoC) treatment with immunosuppressant (IS), immunomodulator (IM), or nintedanib is planned
* Further inclusion criteria apply
Exclusion Criteria:
* Organising pneumonia as predominant pattern in the HRCT
* Prebronchodilator forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) \<0.7 at Visit 1
* Acute ILD exacerbation within 3 months prior to Visit 1 and/or during the screening period, based on Investigator judgement
* Active vasculitis, unstable or uncontrolled within 8 weeks prior to Visit 1 or during the screening period
* Any suicidal behaviour in the past 2 years
* Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the past 3 months or at Visit 1, and/or at Visit 2
* Use of any of the following medications: cyclophosphamide within 6 months of Visit 1, pirfenidone within 8 weeks of Visit 1
* Further exclusion criteria apply DRUG: Nerandomilast, DRUG: Placebo matching nerandomilast
Interstitial Lung Diseases, Systemic Autoimmune Rheumatic Diseases Associated Interstitial Lung Diseases
Evaluation of the Efficacy and Safety of Magnetic Resonance Angiography (MRA) Using Gadopiclenol Compared to Gadoterate Meglumine in the Assessment of Steno-occlusive Disease in Adult Patients With Suspected Vascular Disease
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT07348640
Inclusion Criteria:
• Male or female patients 18 years of age or older willing to participate in the trial and follow all study procedures specified in the protocol.
• Patient having read the information in the ICF and having provided his/her consent to participate in writing by dating and signing the ICF prior to any trial related procedure being conducted.
• Patient with suspected steno-occlusive disease in supra-aortic (carotid/vertebrobasilar) (a), peripheral (b) or abdominal/renal (c) arteries based on:
• clinical signs and symptoms including but not limited to prior stroke, transient ischemic attack (TIA), amaurosis fugax (transient monocular blindness) and/or previous diagnostic tests (CTA, IA-DSA, or ultrasound) or
• symptoms of lower-extremity arterial disease (stages II-IV according to the Leriche-Fontaine classification, or 1 to 6 according to Rutherford classification 113 and/or confirmed by previous imaging (Doppler ultrasound, CTA, MRA, IADSA) or
• suspected renovascular hypertension based on one or more of the following criteria: i. hypertension refractory to standard therapy ii. acute worsening of pre-existing hypertension iii. abrupt onset of sustained, moderate to severe hypertension at age \<35 years suggestive of fibromuscular dysplasia (FMD) iv. progressive renal insufficiency (creatinine \> 2 mg/dL; no other apparent cause of progressive renal failure based on routine medical history, physical examination, 24-h urine collection and urinary protein excretion) v. abnormal/inconclusive renal doppler ultrasound. vi. other criteria (to be specified)
• Are scheduled for or had undergone CTA and/or IA-DSA according to imaging standards to cover the supra-aortic (carotid/vertebrobasilar) and/or peripheral and/or abdominal/renal territory described in this protocol.
Exclusion Criteria:
• Is a pregnant or lactating female. Exclude the possibility of pregnancy for women of childbearing potential: * by testing on site at the institution (serum βHCG or urine) * by surgical history (e.g., tubal ligation or hysterectomy) * post-menopausal with a minimum 1 year without menses.
• Has any known allergy to one or more of the ingredients in the investigational products or has a history of hypersensitivity to other GBCAs.
• Has severe renal impairment defined as an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2 calculated using the Modification of Diet in Renal Disease (MDRD) formula.
• Has known or suspected acute kidney injury (AKI) based on: a. Increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 hours or b. Increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within prior 7 days or c. Urine volume \< 0.5 mL/kg/h for 6 hours
• Has received any contrast agent (for MRI, CT, DSA) prior to the first IMP administration or is scheduled to receive any contrast agent between the two MRA or after the second IMP administration.
• Has received or is scheduled for therapeutic intervention (e.g., endovascular therapy, vascular surgery, etc.) of any kind for vascular disease in the arterial territory of interest performed between the 2 MRA procedures or between the study MRAs and the CTA/IADSA procedures when applicable.
• Has any contraindications to MRI.
• Is suffering from severe claustrophobia.
• Has received an investigational drug or medical device before admission into this study or scheduled to receive any investigational treatment in the course of the trial.
• Was previously included in this trial.
• Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post-dose follow-up examinations.
DRUG: gadopiclenol, DRUG: Gadoterate meglumine (Dotarem)
Steno-occlusive Disease
steno-occlusive disease, gadopiclenol, Magnetic Resonnance Angiography
RECOVER-SLEEP: Platform Protocol
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06404086
Inclusion Criteria:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• ≥ 18 years of age at the time of enrollment
• Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization: Suspected\* case of SARS-CoV-2 infection - Three options, A through C: A. Met the clinical OR epidemiological criteria:
• Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia;
• Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presented with acute respiratory infection with a history of fever or measured fever of ≥ 38°C and cough, with onset within the last 10 days, and required hospitalization; or C. Presented with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test. Probable\* case of SARS-CoV-2 infection, defined as having met the clinical criteria above AND was a contact of a probable or confirmed case or is linked to a COVID-19 cluster; or Confirmed case of SARS-CoV-2 infection - Two options, A through B: A. Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Met clinical criteria AND/OR epidemiological criteria (See suspected case A), with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test. \* Suspected and probable cases will only be allowed if they occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required.
• New/worse sleep problems following a SARS-CoV-2 infection that have persisted for at least 12 weeks and are still present at the time of consent
• PROMIS 8a SRI or 8b SD T Score ≥ 55\*\* \*\* Screening with both the PROMIS 8a SRI and 8b SD will occur for the phenotype assessment portion of the protocol.
• Willing and able to provide informed consent, complete the surveys and clinical assessments, and return for all of the necessary follow-up visits
• Adequate method of birth control for participants of child-bearing potential
Exclusion Criteria:
An individual who meets any of the following criteria will be excluded from participation in this study:
• Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
• Known pregnancy, breastfeeding, or contemplating pregnancy during the study period
• Untreated sleep apnea (AHI ≥ 15 or severe sleep-related hypoxemia)
• Current night or rotating shift work
• Known history of narcolepsy prior to SARS-CoV-2 infection
• Any non-marijuana illicit drug use within 30 days of informed consent
• Known history of severe mental disorder, such as psychotic disorders and bipolar disorder
• Current or recent use (within the last 14 days) of study intervention or similar intervention to treat the underlying condition, unless a washout period is permitted per appendix\*
• Known allergy/sensitivity or any hypersensitivity to components of the study intervention or control\*
• Known contraindication(s) to study intervention including prohibited concomitant medications and without the ability to safely hold prohibited concomitant medications (see appendices)\*
• Currently receiving/using intervention from another clinical trial that could impact or mask treatment effect; refer to MOP for details
• Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study (\*)If only one study intervention appendix is open at the time of enrollment. If multiple study intervention appendices are open, a participant may be excluded from any study intervention appendix based on contraindications listed in the study intervention appendix, current use of study intervention, or known allergy/sensitivity/hypersensitivity yet remain eligible for the remaining study intervention appendices.
DRUG: Modafinil, DRUG: Modafinil Placebo, DRUG: Solriamfetol, DRUG: Solriamfetol Placebo, DRUG: Melatonin, DRUG: Melantonin Placebo, DEVICE: Tailored lighting (TL) Active, DEVICE: Tailored lighting (TL) Placebo
Long COVID, Long COVID-19, Hypersomnia, Sleep Disturbance
PASC
Long-term Safety and Efficacy of ESK-001 in Moderate to Severe Plaque Psoriasis (ONWARD3)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06846541
Inclusion Criteria:
• Males or females, age ≥18 years
• Completed either of the two previous (parent) studies of ESK-001 (ESK-001-016 or ESK-001-017)
• ESK-001 safety and tolerability were acceptable in the parent study
• Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must agree to adhere to highly effective methods of contraception for the entirety of the study
Exclusion Criteria:
• Pregnant, lactating, or planning to get pregnant during the study period
• Any acute or chronic illness/condition or evidence of an unstable clinical condition that in the Investigator's judgment will substantially increase the risk to the patient if they continue to receive ESK-001 treatment in this extension study
• Deemed by the Investigator to be inappropriate for the study or unable to comply with the protocol
DRUG: Open-Label ESK-001, DRUG: Blinded ESK-001, DRUG: Placebo
Plaque Psoriasis, Psoriasis (PsO), Psoriasis, Moderate Psoriasis, Severe Psoriasis
Psoriasis, PASI, Safety, ESK-001
A Study to Assess Efficacy and Safety of JNJ-77242113 Compared to Placebo and Ustekinumab in Participants With Moderate to Severe Plaque Psoriasis (ICONIC-ASCEND)
clinicaltrials@northshore.org
ALL
12 years and over
PHASE3
NCT06934226
Inclusion Criteria:
* Diagnosis of plaque psoriasis, with or without psoriatic arthritis (PsA), prior to the first administration of study intervention
* Total body surface area (BSA) greater than or equal to (\>=)10 percent (%) at screening and baseline
* Total psoriasis area and severity index (PASI) \>=12 at screening and baseline
* Total investigator global assessment (IGA) \>=3 at screening and baseline
* Candidate for phototherapy or systemic treatment for plaque psoriasis
Exclusion Criteria:
* Nonplaque form of psoriasis (for example \[e.g.\], erythrodermic, guttate, or pustular)
* Current drug-induced psoriasis (e.g., a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium)
* Known allergies, hypersensitivity, or intolerance to JNJ-77242113, ustekinumab, or its excipients
* Major surgical procedure within 8 weeks before screening, or will not have fully recovered from surgical procedure, or has a surgical procedure planned during the time the participant is expected to participate in the study
* Transplanted organ (with exception of a corneal transplant greater than \[\>\] 12 weeks before the first administration of study intervention) DRUG: JNJ-77242113, DRUG: Matching Placebo to JNJ-77242113, DRUG: Ustekinumab, DRUG: Matching Placebo to Ustekinumab
Plaque Psoriasis
A Study of 2 Doses of Ritlecitinib in People 12 Years of Age and Older With Alopecia Areata (ALLEGRO-100)
clinicaltrials@northshore.org
ALL
12 years and over
PHASE3
NCT06873945
Inclusion Criteria:
Age:
• 18 years of age or older at screening. Adolescents (12 to \<18 years of age at screening) are also eligible for this study, but only if permitted by the local IRB/EC and local regulatory health authority (if applicable). Where these approvals have not been granted, only participants 18 years of age and older at screening will be enrolled. In Part 2 of the study, only adolescents (12 to \<18 years of age at both Screening and Day 1) who did not participate in Part 1 will be enrolled. Disease Characteristics:
• Must meet the following alopecia areata criteria at both Screening and Baseline:
• Have a clinical diagnosis of alopecia areata with no other etiology of hair loss.
• ≥50% hair loss of the scalp, as measured by SALT, without evidence of terminal hair regrowth within the previous 6 months.
• Current episode of hair loss ≤10 years.
Exclusion Criteria:
Medical Conditions:
• Diseases or conditions other than alopecia areata which affect hair loss, including other types of alopecia, other scalp disease that may impact the alopecia areata assessment, or active systemic diseases that may cause hair loss.
• History of severe allergic or anaphylactoid reaction to any kinase inhibitor or a known allergy/hypersensitivity to any component (including excipients) of the study intervention.
• Any psychiatric condition including recent or active suicidal ideation or behavior that meets protocol-defined criteria.
• General Infection History: * Have a history of systemic infection requiring hospitalization or parenteral therapy (antimicrobial, antiviral, antiparasitic, antiprotozoal, or antifungal), or as otherwise judged clinically significant by the investigator, within 3 months prior to Day 1. * Have active acute or chronic infection requiring treatment with oral antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 1. NOTE: participants may be rescreened after the infection resolves. * Evidence or history of untreated, currently treated or inadequately treated active or latent infection with Mycobacterium tuberculosis.
• Specific Viral Infection History: * History (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster. * Infected with hepatitis B or hepatitis C viruses: all participants will undergo screening for hepatitis B and C for eligibility.
• Other Medical Conditions: * Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere's disease, labyrinthitis, or other auditory condition that is considered acute, fluctuating or progressive. * Abnormal findings on the screening chest imaging (eg, chest x-ray) including, but not limited to, presence of active TB or other infections, cardiomyopathy, or malignancy. Chest imaging may be performed up to 12 weeks prior to Screening. * Have any malignancies or have a history of malignancies with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. * Have a history of any lymphoproliferative disorder such as EBV-related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs and symptoms suggestive of current lymphatic or lymphoid disease. * Significant trauma or major surgery within 1 month of the first dose of study drug or considered in imminent need for surgery.
• Adolescent participants 12 to \<18 years of age without one of the following: * Documented evidence from a health professional of having received varicella vaccination (2 doses); or * Evidence of prior exposure to varicella zoster virus (VZV) based on serological testing (ie, a positive VZV IgG Ab result) at Screening.
• Any medical or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Prior/Concomitant Therapy:
• Current or prior use of any prohibited medication(s), vaccine(s), or treatment(s) within the protocol-defined timelines. Prior/Concurrent Clinical Study Experience:
• Previous administration with an investigational drug or vaccine within 8 weeks (or longer as determined by the local requirement) or 5 half-lives (whichever is longer) before the first dose of study intervention in this study. Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study. Receipt of study intervention in Study B7981094 or other studies of ritlecitinib. Diagnostic Assessments:
• Any exclusionary abnormalities in laboratory values at Screening, as assessed by the study-specific laboratory and, if deemed necessary, confirmed by a single repeat.
• Screening standard 12-lead ECG that demonstrates clinically relevant abnormalities. Other
Exclusion Criteria:
• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
DRUG: Ritlecitinib 100 mg, DRUG: Ritlecitinib 50 mg, DRUG: Placebo - 100 mg, DRUG: Placebo - 50 mg
Alopecia Areata
alopecia universalis, alopecia totalis, alopecia, patchy hair loss, diffuse hair loss, ophiasis, hair disease, Ritlecitinib, Litfulo, hair loss, adolescents, adults
Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT05174169
Inclusion Criteria:
The patient must have an ECOG performance status of 0 or 1.
Patients must have histologically/pathologically confirmed Stage IIB, IIC, or Stage III colon adenocarcinoma with R0 resection according to AJCC 8th edition criteria.
No radiographic evidence of overt metastatic disease within 45 days prior to Step 1/Study entry (CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and pelvis).
The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge on colonoscopy or above the peritoneal reflection as documented during surgery or on pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation).
The patient must have had an en bloc complete gross resection of tumor (curative resection). Patients who have had a two-stage surgical procedure, to first provide a decompressive colostomy and then in a later procedure to have the definitive surgical resection, are eligible.
The resected tumor specimen and a blood specimen from patients with Stage IIB, IIC, or Stage III colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera (after Step 1/Study entry and before Step2/Randomization). Patient must have sufficient tissue to meet protocol requirements. This blood specimen for the Signatera assay must be collected after surgery (and recommended at least 14 days post surgery).
Tumor must be documented as microsatellite stable or have intact mismatch repair proteins through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are excluded.
The treating investigator must deem the patient a candidate for all potential agents used in this trial (5FU, LV, oxaliplatin and irinotecan).
The interval between surgery (post-operative Day 7) and Step 1/Study entry must be no more than 60 days. NOTE: Step 1/Study Entry may occur as early as post operative Day 7, but it cannot occur beyond 60 days from the actual date of the patient's surgery.
Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.
Adequate hematologic function within 28 days before Step 1/Study entry defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
* BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
* Platelet count must be greater than or equal to 100,000/mm3; and
* Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before Step 1/Study entry defined as follows:
* total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
* alkaline phosphatase must be less than 2.5 x ULN for the lab; and
* AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before Step 1/Study entry defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL) NOTE: Adjusted body weight (AdjBW) should be used for patients that have BMI greater than or equal to 28 (less than or equal to 30% above IBW).
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Pregnancy test (urine or serum according to institutional standard) done within 14 days before Step 1/Study entry must be negative (for women of childbearing potential only).
Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine.
Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Patient must have developed a ctDNA +ve assay during serial monitoring.
Patient's willingness to be re-randomized affirmed.
The patient must continue to have an ECOG performance status of 0 or 1.
No radiographic evidence of overt metastatic disease.
Pregnancy test (urine or serum according to institutional standard) done within 14 days before second randomization must be negative (for women of childbearing potential only).
Adequate hematologic function within 28 days before second randomization defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
* BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
* Platelet count must be greater than or equal to 100,000/mm3; and
* Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before second randomization defined as follows:
* total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
* alkaline phosphatase must be less than 2.5 x ULN for the lab; and
* AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before second randomization defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL)
Exclusion Criteria:
Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.).
Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.
Tumor-related bowel perforation.
History of prior invasive colon malignancy, regardless of disease-free interval.
History of bone marrow or solid organ transplantation (regardless of current immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and organ/tissue donation are not exclusionary.
Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not permitted). EXCEPTION: one cycle of chemotherapy (regimen per treating physicians' discretion - 5-FU or capecitabine with or without oxaliplatin) is allowed but not required after consent. The optional cycle of chemotherapy should be started greater than or equal to 4 weeks from surgery and while awaiting Step 2 randomization.
Other invasive malignancy within 5 years before Step 1/Study entry. Exceptions are colonic polyps, non-melanoma skin cancer or any carcinoma-in-situ.
Synchronous primary rectal and/ or colon cancers.
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
Sensory or motor neuropathy greater than or equal to grade 2, according to CTCAE v5.0.
Blood transfusion within two weeks before collection of blood for central ctDNA testing.
Active seizure disorder uncontrolled by medication.
Active or chronic infection requiring systemic therapy.
Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.
Patients known to have Gilbert's Syndrome or homozygosity for UGT1A1\*28 polymorphism.
Pregnancy or lactation at the time of Step 1/Study entry.
Co-morbid illnesses or other concurrent disease that would make the patient inappropriate for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up).
Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Pregnancy or lactation at the time of randomization.
No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the opinion of the treating investigator. DEVICE: Signatera test, DRUG: mFOLFOX6 3-6 month, DRUG: CAPOX 3 month, DRUG: mFOLFIRINOX, DRUG: mFOLFOX6 6 month, DRUG: CAPOX 6 month
Stage III Colon Cancer
ctDNA positive, ctDNA negative, Adjuvant Chemotherapy, Natera, Signatera, mFOLFOX6, Stage III, CAPOX, mFOLFIRINOX, Oxaliplatin, 5-Fluorouracil (5-FU), Capecitabine, Leucovorin, Irinotecan, Stage II
A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Idiopathic Pulmonary Fibrosis
clinicaltrials@northshore.org
ALL
40 years and over
PHASE3
NCT06003426
Inclusion Criteria
* Subjects with IPF aged ≥ 40 years at the time of signing the informed consent.
* Diagnosis of IPF within 7 years prior to screening that is supported by centrally read chest high-resolution computed tomography (HRCT) obtained at screening and verification of usual interstitial pneumonia.
* If on pirfenidone or nintedanib, participants must have been on a stable dose for at least 90 days prior to screening.
* If not currently on pirfenidone or nintedanib, participants must not have received either of these medications within 28 days prior to screening.
* Women who are of childbearing potential must have a highly effective form of contraception and must provide a negative urine/serum pregnancy test.
* Men who are sexually active with women of childbearing potential agree to use male barrier contraception.
Exclusion Criteria
* History of stroke or transient ischemic attack within 3 months prior to screening.
* Participants who exhibit symptoms of heart failure at rest.
* Participants who have a current malignancy or a previous malignancy in the past 5 years prior to screening, except for those who have a documented history of cured nonmetastatic squamous cell skin carcinoma, basal cell skin carcinoma, or cervical carcinoma in situ.
* Other protocol-defined Inclusion/Exclusion criteria apply.
DRUG: BMS-986278, DRUG: BMS-986278 Placebo
Idiopathic Pulmonary Fibrosis
BMS-986278, LPA1 antagonist, IPF, Pulmonary fibrosis
A Study to Evaluate the Efficacy and Safety Study of Povorcitinib in Participants With Inadequately Controlled Moderate to Severe Asthma
clinicaltrials@northshore.org
ALL
18 years to 65 years old
PHASE2
NCT05851443
Inclusion Criteria:
* Physician-diagnosed asthma requiring treatment with medium- to high-dose ICS-LABA for at least 12 months prior to screening.
* Pre-BD FEV1 \< 80% predicted according to central over read value at Visit 2.
* Documented historical post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL in FEV1.
* At least 2 documented asthma exacerbations (requiring treatment with systemic CS, hospitalization, or emergency department visit) within 12 months prior to screening but not within the past 4 weeks prior to screening
* ACQ-6 ≥ 1.5 at screening.
Exclusion Criteria:
* Maintenance use of asthma controllers other than ICS-LABA.
* Have undergone bronchial thermoplasty.
* Current smokers or participants with a smoking history of ≥ 10 pack-years and participants using vaping products, including electronic cigarettes.
* Women who are pregnant (or who are considering pregnancy) or breastfeeding.
* Current conditions or history of other diseases, as follows:
* Clinically important pulmonary disease other than asthma ,Thrombocytopenia, coagulopathy, or platelet dysfunction.
* Venous and arterial thrombosis, deep vein thrombosis, pulmonary embolism, moderate to severe heart failure (NYHA Class III or IV), cerebrovascular accident, myocardial infarction, coronary stenting, or CABG surgery.
* Diagnosis of other significant cardiovascular diseases, including but not limited to angina, peripheral arterial disease, or uncontrolled arrhythmias such as atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and forms of carditis.
* Recipient of an organ transplant that requires continued immunosuppression.
* Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome).
* Any malignancies or history of malignancies.
* Chronic or recurrent infectious disease.
* Receipt of any biologic drugs used for asthma \< 12 weeks or 5 half-lives (if known), whichever is longer, prior to screening DRUG: povorcitinib, OTHER: placebo, DRUG: ICS-LABA
Moderate to Severe Asthma
Asthma, Moderate to Severe, INCB54707, Povorcitinib, ICS-LABA
Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression (MAESTRA 2)
clinicaltrials@northshore.org
FEMALE
18 years and over
PHASE3
NCT07214779
Inclusion Criteria:
* Histological diagnosis of high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Have platinum-resistant disease.
* Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum containing regimen.
* Participants who have received 2 to 4 lines of platinum-based therapy must have progressed on or within 6 months after the last dose of platinum.
* Archival FFPE tumor tissue block or slides from a specimen no older than 5 years must be available. If not available, participant must be willing to undergo a pretreatment tumor biopsy.
* Received at least 1 and no more than 4 prior lines of systemic therapy following the initial diagnosis, after which single-agent chemotherapy is considered an appropriate next therapeutic option.
* Should have received prior treatment with bevacizumab unless there was a contraindication for its use.
* Should have received prior treatment with mirvetuximab soravtansine if the tumor is positive for FRα, unless there is an exception for its use on medical grounds.
* Measurable disease per RECIST v1.1.
Exclusion Criteria:
* Have endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of these histologies, or low-grade/borderline ovarian cancer.
* Have primary platinum-refractory disease, defined as progression on or within 3 months after the last dose of first line platinum-containing therapy.
* Clinically significant or uncontrolled cardiac disease within 6 months before the first dose of study treatment.
* Known active CNS metastases and/or carcinomatous meningitis.
* Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years before the first dose of study treatment.
* Clinically significant gastrointestinal abnormalities.
Other protocol-defined Inclusion/Exclusion Criteria may apply. DRUG: INCB123667, DRUG: Investigator's choice of chemotherapy
Ovarian Cancer
INCB123667
Zinc Supplementation With Botulinum Toxin for Overactive Bladder
clinicaltrials@northshore.org
FEMALE
21 years to 100 years old
PHASE2
NCT07405554
Inclusion Criteria:
* Non-pregnant adult female at least 21 years old, with no plans to become pregnant during the course of the trial) and if of child-bearing potential, with a negative pregnancy test, and if sexually active, must be using medically acceptable contraception.
* ≥ 6 urgency urinary incontinence episodes on a 3-day baseline bladder diary, with these urge incontinence episodes representing greater than 50% of the total incontinent episodes recorded.
* Willing and able to complete all study related items and interviews.
* Refractory urgency urinary incontinence: defined as persistent symptoms despite at least one or more conservative treatments (e.g. supervised behavioral therapy, supervised physical therapy)
* Persistent symptoms despite the use of a minimum of two anticholinergics, or unable to tolerate medication due to side effects, or has a contraindication to taking anticholinergic/Beta 3 agonist medication.
* Currently not on an anticholinergic or antimuscarinic/Beta 3 agonist medication (e.g. oxybutynin, tolterodine, darifenacin, trospium chloride, solifenacin-succinate, fesoterodine and/or mirabegron) or be willing to stop medication for 3 weeks prior to completing baseline bladder diary and expected to remain off medications through duration of study.
* Demonstrates ability (or have caregiver demonstrate ability) to perform clean intermittent self-catheterization.
* Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function.
Exclusion Criteria:
* Neurologic diseases such as multiple sclerosis, Parkinson Disease, CVA within 6 months prior to enrollment, myasthenia gravis, Charcot-Marie-Tooth disease, clinically significant peripheral neuropathy, and complete spinal cord injury.
* Untreated urinary tract infection (UTI).
* Any prior use of either study therapy for treatment of urinary urge incontinence (Botox A® or Interstim®).
* PVR \>150 ml on 2 occasions within 6 months prior to enrollment (If the PVR value was obtained by ultrasound and was ≥150 ml, the PVR will be confirmed by catheterization which will be the gold standard).
* Current or prior bladder malignancy.
* Surgically altered detrusor muscle, such as augmentation cystoplasty.
* Subjects taking aminoglycosides.
* Currently pregnant or lactating.
* Allergy to lidocaine or bupivacaine.
* Prior pelvic radiation.
* Uninvestigated hematuria. DRUG: Zinc Citrate Oral Capsule, DRUG: Placebo
Overactive Bladder (OAB)
overactive bladder, botulinum toxin, zinc
Effects of TNF Blockade on Human BPH/LUTS
Malgorzata Antoniak, Ph.D. - MAntoniak@northshore.org
MALE
45 years to 80 years old
PHASE2
NCT06062875
Inclusion Criteria:
* Male sex
* Age 45-80 years
* Diagnosed by physician with BPH
* Prostate volume ≥ 60mL
* IPSS ≥ 8
* Able and willing to complete questionnaires
* Able and willing to provide informed consent
* Able to read, write, and speak in English
* No prior treatment with TNF inhibitor (adalimumab, etanercept, infliximab, certolizumab, golimumab)
* No plans to move from study area in the next 6 months
Deferral Criteria:
* Microscopic hematuria without appropriate workup per AUA/Society of Urodynamics, Female Pelvic Medicine \& Urogenital Reconstruction (SUFU) Guidelines
* Positive urine culture
Exclusion Criteria:
* Female sex or intersex
* Age \< 45 or \> 80 years
* Being a prisoner or detainee
* Urinary retention with need for catheterization
* Gross hematuria
* Contraindication to treatment with adalimumab (e.g., presence of sepsis or active infection, active tuberculosis, Hepatitis B infection, invasive fungal infection, lymphoma, leukemia or other active malignancy, congestive heart failure, significant hematologic abnormality, allergy to adalimumab or its components, anti-drug antibodies, congestive heart failure)
* Diagnosis of autoimmune disease (rheumatoid arthritis, plaque psoriasis, ulcerative colitis, Crohn's disease, hidradenitis suppurativa, spondyloarthritis)
* Interstitial cystitis
* Pelvic or endoscopic genitourinary surgery within the preceding 6 months (not including diagnostic cystoscopy)
* History of lower urinary tract or pelvic malignancy including prostate cancer; history of pelvic radiation therapy
* Ongoing symptomatic urethral stricture
* Current chemotherapy or other cancer therapy
* Severe neurological or psychiatric disorder that would prevent study participation (e.g., bipolar disorder, psychotic disorder, Alzheimer's Disease)
* Current moderate or severe substance use disorder DRUG: Adalimumab
Benign Prostatic Hyperplasia (BPH)
A Study of EP0031 in Patients With Advanced RET-altered Malignancies
clinicaltrials@northshore.org
ALL
18 years and over
PHASE1
NCT05443126
Inclusion Criteria:
Applicable to all patients:
• Must be ≥18 years of age, with documented RET-altered cancers
• Patients should be well informed and consented about alternative treatment options including approved RET-targeted therapies
• ECOG performance status of 0 or 1 and life expectancy \>3 months at screening
• Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures
• Additional cohort specific criteria apply
Exclusion Criteria:
Patients with any of the following will not be included in the study:
• Any known major driver gene alterations other than RET.
• Spinal cord compression or brain metastases. Patients with stable brain metastases can be enrolled.
• Active infection requiring systemic antibiotic, antifungal, or antiviral medication
• Severe or uncontrolled medical condition or psychiatric condition
• Chronic glomerulonephritis or renal transplant
• Patients with active hepatitis B infection or active hepatitis C
• Patients with active HIV infection. Patients living with HIV may be eligible if they have adequate CD4+ T-cell count and no history of AIDS-defining opportunistic infections in the past 12 months
• Receipt of any strong inhibitor or inducer of CYP3A4
• Impaired hepatic or renal function, inadequate bone marrow reserve or organ function
• Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG or any factor that increases the risk of QTc prolongation or of arrhythmic events , or congestive heart failure Grade II-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months
• Uncontrolled hypertension
• Corneal ulceration at screening
DRUG: EP0031
Advanced Solid Tumor
selective RET-inhibitor
Letrozole in Uterine Leiomyosarcoma
clinicaltrials@northshore.org
FEMALE
18 years and over
PHASE2
NCT05649956
Inclusion Criteria:
• Patient or a legally authorized representative must have signed an approved informed consent and authorization permitting the release of personal health information.
• Patient must have histologically confirmed newly diagnosed uterine leiomyosarcoma with disease limited to the uterus (FIGO 2009 Stage I). Submission of pathology report documenting uterine leiomyosarcoma histology is required in the IRT Source Document Portal following randomization.
• Patient tumors must express ER positivity by immunohistochemistry (ER expression greater than 10% by immunohistochemistry). ER status test results must be provided at enrollment. Sites are required to report results of ER status testing in the IRT Source Document Portal.
• Patient must have completed hysterectomy and bilateral salpingo-oopherectomy no more than 12 weeks from enrollment.
• All patients must have NO measurable disease as defined by RECIST 1.1 within 6 weeks of enrollment. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI.
• Patients must have an ECOG performance status of 0, 1, or 2.
• Patients must have adequate organ and marrow function as defined below: NOTE: Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower limit of normal = LLN Bone marrow function: * Absolute neutrophil count (ANC) greater than or equal to 1500 cells/mcl * Platelet count greater than or equal to 100,000 cells/mcl * Hemoglobin greater than or equal to 9.0 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the Investigator. Initial treatment must not begin earlier than the day after erythrocyte transfusion). Renal function: • Serum creatinine less than or equal to 1.5 x ULN Hepatic function: * AST (aspartate aminotransferase) and ALT (alanine aminotransferase) less than or equal to 3.0 x ULN * Serum albumin greater than or equal to 2.5 g/dL
• Patient must be at least 18 years of age.
• Patient must be able to swallow oral medication.
Exclusion Criteria:
Exclusion Criteria 1. Patients who do not have pure uterine sarcomas (i.e., no mixed malignant mullerian tumors are permitted).
2\. Patients with any other severe concurrent disease, which would make the patient inappropriate for entry into this study, including significant hepatic, renal, or gastrointestinal diseases.
3\. Patients with concomitant invasive malignancy or a history of prior malignancy except non-melanoma skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least three years. Patients are also excluded if their previous cancer treatment contraindicates this protocol.
4\. Patients who have a history of taking any aromatase inhibitor within the past 5 years.
5\. Patients with active or uncontrolled systemic infection. 6. Patients with history of uncontrolled cardiac disease, i.e., uncontrolled hypertension (defined as systolic greater than 150 mm Hg or diastolic greater than 90 mm HR despite antihypertensive medications), unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure (NYHA Class II or greater), clinically significant cardiac arrhythmias, and cardiomyopathy with an ejection fraction under 40%.
7\. Patients currently receiving chemotherapy or radiation therapy. 8. Patients with severe hepatic impairment and/or cirrhosis. 9. Patients with duodenal stent or other GI disorder/defect that would interfere with absorption of oral medication.
10\. Patients deemed otherwise clinically unfit for clinical trial per investigators discretion.
11\. Patients with known hypersensitivity to any of the excipients of letrozole. 12. Patients who are pregnant or breast-feeding. 13. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 30 days of prior to enrollment.
14\. Patients currently using systemic estrogens, including herbals and supplements with estrogenic properties. The use of vaginal estrogen is permitted if symptoms are refractory to moisturizers and lubricants. DRUG: Letrozole
Uterine Leiomyosarcoma
Pharmacokinetics, Safety, and Efficacy of Povorcitinib in Adolescent Participants With Moderate to Severe Hidradenitis Suppurativa
clinicaltrials@northshore.org
ALL
12 years to 17 years old
PHASE2
NCT07213973
Inclusion Criteria:
* Aged ≥ 12 to \< 18 years at the time of informed consent/assent signing.
* Body weight ≥ 30 kg at both screening and baseline visits.
* Diagnosis of moderate to severe HS for at least 3 months prior to the screening visit.
* Total abscess and inflammatory nodule count of at least 5 at both the screening and baseline visits.
* HS lesions corresponding to refined Hurley Stage IB, IC, IIB, IIC, or III at both the screening and baseline visits.
* Documented history of inadequate response to at least a 3-month course of at least 1 conventional systemic therapy (oral antibiotic or biologic drug) for HS (or demonstrated intolerance to, or have a contraindication to, a conventional systemic therapy for treatment of their HS).
* Agreement to use contraception.
* Willing and able to comply with the study protocol and procedures.
* Further inclusion criteria apply.
Exclusion Criteria:
* Presence of \> 20 draining tunnels (fistulas) at either the screening or baseline visit.
* Women who are pregnant (or who are considering pregnancy) or breastfeeding.
* Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q-wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator.
* Laboratory values outside of the protocol-defined ranges.
* Further exclusion criteria apply. DRUG: Povorcitinib
Hidradenitis Suppurativa (HS)
Hidradenitis Suppurativa, HS, INCB054707, Povorcitinib, Acne inversa, Hidradenitis
A Trial to Evaluate Ovarian Suppression Following Subcutaneous ZOLADEX 10.8 mg in Premenopausal Women With Early-stage and Advanced HR+ Breast Cancer
clinicaltrials@northshore.org
FEMALE
18 years to 55 years old
PHASE1
NCT07310420
Inclusion Criteria:
• Age and gender: Female participants aged 18 to 55 years, inclusive.
• Hormone receptor positive (HR+): Either estrogen receptor positive (ER+) or progesterone receptor positive (PR+) breast cancer, defined as 1% to 100% of tumor nuclei are positive for ER or PR via immunohistochemistry.
• Participants must be of premenopausal status.
• Recent radiotherapy:
• Prior radiotherapy is allowed.
• All radiotherapy-related toxicities (except alopecia) must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) v6.0 Grade ≤1 before trial enrollment.
• Concurrent medications:
• Cyclin-dependent kinase 4 (CDK4/6) inhibitors are permitted.
• PIK3CA/AKT inhibitors are permitted.
• Concomitant use of bisphosphonates is permitted.
• Concomitant use of endocrine therapy (eg, aromatase inhibitor, fulvestrant, or other FDA-approved selective estrogen receptor degrader \[SERDs\]) is permitted.
• Concurrent standard-of-care human epidermal growth factor receptor 2 (HER2)- targeted therapy (including but not limited to trastuzumab, pertuzumab, trastuzumab deruxtecan, or T-DM1) is permitted.
• Informed consent: Able to understand and willing to provide informed consent and able to comply with the trial procedures and restrictions.
• Abstinence and contraception: Female participants may be enrolled if they are:
• Practicing true abstinence for at least 28 days prior to investigational product (IP) administration until 12 weeks after the last IP administration and having a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day -1, OR
• Using 2 forms of highly effective nonhormonal contraception, including 1 physical barrier (condom or diaphragm) plus another nonhormonal method (eg, intrauterine device, spermicidals) from Screening or at least 2 weeks prior to IP administration (whichever is earlier) until 12 weeks after the last IP administration and having a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day -1.
• Performance status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Inclusion Criteria specific to the advanced breast cancer cohort:
• Advanced breast cancer diagnosis: Histological confirmation of breast cancer with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent per investigator's assessment.
• Chemotherapy History:
• A participant may have received chemotherapy provided the criteria for premenopausal status, as defined in Inclusion Criterion #3, are met at trial screening.
• All chemotherapy-related toxicities must have recovered to CTCAE v6.0 ≤Grade 1 before trial participation, except for alopecia, peripheral neuropathy, or paresthesia (≤Grade 2).
• Prior treatment:
• Participants may have received prior radiotherapy.
• Participants may have received or be receiving a cyclin-dependent kinase (CDK) 4/6 inhibitor, a PIK3CA-AKT inhibitor, or bisphosphonates.
• Gonadotropin-releasing hormone (GnRH) treatment-naïve participants will have no history of GnRH agonist or other endocrine therapy in the advanced/metastatic setting.
• GnRH treatment-exposed participants may have received a GnRH agonist or other endocrine therapy in the advanced/metastatic setting, provided they had established premenopausal status (Inclusion Criterion #3) prior to initiating GnRH agonist therapy, within 6 months prior to trial enrollment.
• Participants may have received HER2-targeted therapy (including but not limited to trastuzumab, pertuzumab, trastuzumab deruxtecan, or T-DM1). Inclusion Criteria specific to the early-stage breast cancer cohort:
• Early-stage breast cancer diagnosis:
• Histologically confirmed unilateral or bilateral invasive adenocarcinoma of the breast.
• Pathologically staged as Stage I, II, or III (specifically T1-T4, N0-N3, M0) at the time of definitive surgery, according to the current American Joint Committee on Cancer (AJCC) Staging Manual.
• Chemotherapy history:
• A participant may have received adjuvant or neoadjuvant chemotherapy provided the criteria for premenopausal status, as defined in Inclusion Criterion #3, are met at trial Screening.
• All chemotherapy-related toxicities must have recovered to CTCAE v6.0 ≤Grade 1 before trial participation except for alopecia, peripheral neuropathy, or paresthesia (≤Grade 2).
• Prior treatment:
• Participants may have received prior radiotherapy.
• Participants may have received or be receiving a CDK 4/6 inhibitor, a PIK3CA-AKT inhibitor, or bisphosphonates.
• GnRH treatment-naïve participants will have no history of GnRH agonist or other endocrine therapy.
• GnRH treatment-exposed participants may have received a GnRH agonist or other endocrine therapy provided they had established premenopausal status (Inclusion Criterion #6) prior to initiating GnRH agonist therapy, within 6 months prior to trial enrollment.
• Participants may have received HER2-targeted therapy (including but not limited to trastuzumab, pertuzumab, trastuzumab deruxtecan, or T-DM1).
Exclusion Criteria:
• Postmenopausal: Naturally or surgically postmenopausal (regardless of age).
• Body mass index (BMI): \<18 kg/m\^2 or \>35.0 kg/m\^2.
• Prior surgical or radiation procedures: History of bilateral oophorectomy or prior radiotherapy to the ovaries.
• Selective estrogen receptor modulator (SERM) use during trial: Participants may not receive tamoxifen or other SERMs during the trial and must discontinue any SERMs prior to enrollment, other endocrine therapies (eg, aromatase inhibitor, fulvestrant, or other FDA-approved SERDs) are allowed.
• Hypersensitivity: Known hypersensitivity, idiosyncratic, or allergic reactions to goserelin, GnRH, GnRH agonists/analogs, or any trial drug components.
• Expected survival: Estimated life expectancy \<6 months from the start of trial therapy, based on the principal investigator's (PI) clinical judgment.
• Performance status: ECOG performance status ≥3.
• Life-threatening disease or metastasis: Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, symptomatic pulmonary lymphangitic spread, symptomatic pleural disease, or any symptomatic brain/leptomeningeal metastases (proven or suspected). Participants with asymptomatic or stable/treated brain metastases are eligible to enroll if neurologically stable and are receiving a stable or decreasing corticosteroid dose at the time of enrollment. Participants with discrete pulmonary parenchymal metastases are eligible if respiratory function is not compromised.
• Hepatic function:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2×upper limit of normal (ULN) if no liver metastases, or \>5×ULN with liver metastases.
• Total bilirubin ≥1.5×ULN (≥2.5×ULN for Gilbert's syndrome).
• Renal function: Creatinine clearance (CrCl) ≤30 mL/min as calculated by the Cockcroft-Gault formula.
• Hematologic parameters:
• Hemoglobin (Hgb) \<8.0 g/dL.
• White blood cell (WBC) count \<3000/mm\^3.
• Platelets \<100,000/mm\^3.
• Eligibility for participants taking CDK4/6 inhibitors should be based on D-1 labs.
• An absolute neutrophil count (ANC) \<1500/mm3 on D-1 is exclusionary.
• Other malignancies: Active malignancy within the past 3 years, except for adequately treated basal or squamous cell skin cancer or in situ cervical carcinoma.
• Concurrent medical conditions: Presence of any severe, uncontrolled, or serious illness, medical condition (including psychiatric/addictive disorders), or clinical finding that could compromise trial adherence, as assessed by the investigator.
• Investigational drug exposure: Exposure to any investigational drug or device within 30 days prior to trial enrollment.
• Pregnancy: Participant has childbearing potential with a positive serum pregnancy test or positive urine pregnancy test at Screening or Day 1.
• Breastfeeding: Participant is currently breastfeeding.
• Contraceptive use: Sexually active with a male partner and not willing to use nonhormonal contraceptive methods throughout the trial. Exceptions: male partner is vasectomized (provided he is her sole sexual partner, and he has received medical assessment of the surgical success), participant has had bilateral salpingectomy or tubal occlusion hysterectomy.
• Cardiac conditions:
• Corrected QT interval (QTc) using Fridericia's correction (QTcF) \>450 ms at Screening.
• Uncontrolled or symptomatic heart disease, including: i. New York Heart Association (NYHA) Class III or IV heart failure. ii. Myocardial infarction within the past 6 months. iii. Unstable angina or significant arrhythmias requiring intervention. c. Documented congenital QT syndrome.
• Clinically relevant abnormal medical history or abnormal findings on physical examination, vital signs, echocardiogram (ECG), or laboratory tests at Screening that the investigator judges as likely to interfere with the objectives of the trial or the safety of the participant.
• History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
• History of alcohol abuse or drug addiction (including soft drugs like cannabis products) within the last 1 year prior to IP administration.
• Major surgery within 30 days prior to IP dosing or a major surgical procedure planned during the trial.
• Any other condition that precludes adequate understanding, cooperation, and compliance with trial procedures or any condition that could pose a risk to the participant's safety, as per the investigator's judgment.
DRUG: ZOLADEX
Advanced Breast Cancer, Early Breast Cancer
Ovarian Suppression, ZOLADEX, HR+, Breast Cancer, Goserelin Implant
An Extension Study to Assess Safety and Efficacy of Remibrutinib in Participants With Moderate to Severe HS
clinicaltrials@northshore.org
ALL
18 years to 100 years old
PHASE3
NCT07665437
Key
Inclusion Criteria:
* Signed informed consent must be obtained before any assessment is performed.
* Participant has completed the full study treatment period according to the protocol (68 weeks) in the core studies (CLOU064J12301 or CLOU064J12302).
* Participant does not meet any treatment discontinuation criteria of the core study at Week 68.
Key Exclusion Criteria:
* Ongoing or planned use of prohibited HS or non-HS treatments.
* Participants not expected to benefit from participation in the extension study or participants expected to be exposed to an undue safety risk if participating in the extension study, as assessed by the Investigator.
* Current severe progressive or uncontrolled disease, which in the judgment of the Investigator renders the participant unsuitable for the study.
Other protocol-defined inclusion/exclusion criteria may apply. DRUG: Remibrutinib
Hidradenitis Suppurativa
BTK inhibitor, hidradenitis suppurativa, HiSCR, remibrutinib, Phase 3, extension study
PODOMOUNT-Basket, a Study to Test Whether BI 764198 Helps Adults and Adolescents With Different Types of Kidney Disease
clinicaltrials@northshore.org
ALL
12 years and over
PHASE2
NCT07355296
Inclusion Criteria:
* Male or female participants ≥18 years of age (≥12 years of age for Treatment resistant primary Minimal Change Disease (TR-pMCD)) on the day of signing informed consent/assent (Visit 1)
* Body Mass Index (BMI) of ≤40 kg/m2 at screening visit (Visit 1)
* Weight of ≥40 kg at screening
* Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 (chronic kidney disease (CKD) EPI formula based on serum cystatin C) at screening visit
* For adult participants (≥18); ≥25 mL/min/1.73 m2 (CKD-EPI formula based on serum cystatin C) at the screening visit
* For adolescent participants (\<18); ≥25 mL/min/1.73 m2 (chronic kidey disease under 25 years (CKiD U25) formula using height and serum cystatin C) at the screening visit
* Seated blood pressure (mean of 3 values) systolic blood pressure (SBP) ≤160 mmHg (adult participants ≥18) or SBP ≤140 mmHg (participants \<18) at the screening visit (Visit 1). A participant with a documented history of white coat hypertension may be included as long as the participant is considered medically stable by the investigator and "true" blood pressure can be considered to be ≤160 mmHg (adult participants ≥18) or ≤140 mmHg (adolescent participants \<18)
* Participants should be treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), at a stable optimised dose for at least 8 weeks prior to the screening visit (Visit 1), with no plan to change the dose until the end of the randomised treatment period (i.e. end of trial (EoT), Week 20) unless not tolerated or indicated as per the discretion of the investigator
* If treated with (non-steroidal) mineralocorticoid receptor antagonist (MRA), endothelin receptor antagonists (ERA), glucagon-like peptide-1 (GLP-1) or Sodium-glucose co-transporter-2 (SGLT2) inhibitors (SGLT2i), participants must be on a stable dose for at least 8 weeks prior to the screening visit (Visit 1), preferably with no plan to change the dose until the end of the randomised double-blind treatment period (i.e. EoT, Week 20)
* Participants treated with oral immunosuppressive therapy except glucocorticoids (e.g. Calcineurin inhibitor(s) (CNI), mycophenolate mofetil/-sodium, cyclophosphamide) must be on a stable dose for at least 12 weeks prior to the screening visit (Visit 1) with no plans to change their dose during the trial treatment period
* Patients treated/to be treated with oral glucocorticoids have to be at a dose ≤10 mg/d prednisolone or equivalent for ≥4 weeks prior to screening with no plan to increase the dose during the treatment period.
Further inclusion criteria apply.
Exclusion Criteria:
* A history of organ transplantation or planned transplantation during the course of the study
* Use of intravenous immunosuppressive agents (e.g. cyclophosphamide, rituximab, obinutuzumab) in the past 6 months prior to screening visit (Visit 1)
* Participants in whom initiation of oral or IV immunosuppression is anticipated during the course of the trial
* Treatment with metformin or dofetilide (multidrug and toxin extrusion protein 1 (MATE1) substrates) within one week prior to randomisation visit (Visit 2) through 5 days after the EoT visit
* Treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (CYP3A4/5) within one week or 5 half-lives (whichever is longer) prior to randomisation visit (Visit 2)
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \>3X the upper limit of normal (ULN) at screening visit (Visit 1)
* Clinically significant laboratory abnormalities or medical conditions which pose a safety risk for the participant or may interfere with the trial objectives in the investigator's opinion (except for renal function tests or deviation of clinical laboratory values that are related to the podocytopathy in question) at screening visit
* QTc intervals (QTcF) greater than 450 ms in males or greater than 470 ms in females, or any other clinically relevant ECG findings (at the investigator's discretion) at screening visit (Visit 1) Further exclusion criteria apply. DRUG: BI 764198, DRUG: Placebo matching BI 764198
Proteinuric Kidney Diseases
LUNAR-2: TTFields With Pembrolizumab + Platinum-based Chemotherapy for Metastatic NSCLC (LUNAR-2)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06216301
Inclusion Criteria
* ≥22 years of age in the USA
≥18 years of age outside of the USA.
* Histologically or cytologically diagnosis of stage 4 (according to Version 8 of the American Joint Committee on Cancer \[AJCC\] criteria) non-squamous or squamous NSCLC.
* Evaluable (measurable or non-measurable) disease in the thorax per RECIST v1.1.
* Have not received prior systemic treatment for their metastatic NSCLC. Subjects who received adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease are eligible if the therapy was completed at least 12 months prior to the development of metastatic disease.
* ECOG Performance Status (PS) of 0-1.
* Adequate hematologic and end-organ function
o For subjects not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN (unless participant is receiving anticoagulant therapy as long as INR or aPTT is within therapeutic range of intended use of anticoagulants).
* A female participant is eligible to participate if she is not pregnant, not breastfeeding
* If male subject with a female partner(s) of child-bearing potential, must agree to use an effective contraception
* All subjects must sign written informed consent.
Exclusion Criteria:
All individuals meeting any of the following exclusion criteria will be excluded from study participation:
* Mixed small cell and NSCLC histology.
* EGFR sensitizing mutation and/or ALK translocation, and/or ROS1 and/or RET targetable gene rearrangement, and/or METex14 skipping mutation, and/or NTRK1/2 gene fusion and/or BRAF V600 mutations directed therapy is indicated or planned for other targeted therapy, where such testing and therapy is locally approved and available.
* Has received systemic therapy for metastatic disease.
* Had major surgery \<3 weeks prior to randomization
* Received radiation therapy to the lung that is \> 30 Gy within 6 months of randomization.
* Has received prior radiotherapy within 2 weeks of randomization. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Is expected to require any other form of antineoplastic therapy while on study.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
* Has symptomatic Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Subjects with asymptomatic CNS metastases or with previously treated brain metastases may participate provided they were treated before randomization (if applicable) and are neurologically stable and without requirement of steroid treatment for at least 7 days prior to randomization.
* Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior randomization. Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
* Had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms in the 12 months prior to randomization.
* Participation in another clinical study with an investigational agent or device during the 4 weeks prior to randomization.
* Concurrent treatment with other experimental treatments for NSCLC while in the study.
* Has a known sensitivity to any component of the planned systemic therapies (pembrolizumab, cisplatin/carboplatin, pemetrexed/paclitaxel/nab-paclitaxel) .
* Pregnant or breastfeeding
* Admitted to an institution by administrative or court order. DEVICE: NovoTTF-200T, DRUG: Pembrolizumab, DRUG: Platinum based chemotherapy
Metastatic Non-small Cell Lung Cancer
NSCLC, Metastatic
Efficacy and Safety of Oral Rifaximin in Patients With Active Microscopic Colitis
Daniel Amusin, BS - damusin@northshore.org
All
18 years and over
Phase 2
NCT04043897
Inclusion Criteria:
• Collagenous colitis (CC) or lymphocytic colitis (LC) diagnosed on colon biopsies reviewed by 2 separate pathologists
• CC will be defined histologically to be the following: thickness of the collagenous subepithelial table >10 micrometer using an ocular micrometer, inflammation in the lamina propria consisting of mainly lymphocytes and plasma cells, lack of crypt architectural distortion, and regenerative-appearing changes in the surface and/or crypt epithelium
• LC will be defined histologically to be the following: intraepithelial lymphocytes >20 per 100 epithelial cells in the subjective area of highest lymphocyte density, inflammation in the lamina propria consisting of mainly lymphocytes and plasma cells, and regenerative-appearing changes in the surface and/or crypt epithelium
• Subjects in active flare, defined as >3 watery/loose stools per day on >4 / 7 days over >4 weeks in the past 3 months.
Exclusion Criteria:
-
Drug: Rifaximin 550mg
Microscopic Colitis
Microscopic Colitis