Search Results
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A Study to Assess Change in Disease Activity and Adverse Events of Oral Upadacitinib in Adult and Adolescent Participants With Moderate to Severe Hidradenitis Suppurativa Who Have Failed Anti-TNF Therapy (Step-Up HS)
clinicaltrials@northshore.org
ALL
12 years and over
PHASE3
NCT05889182
Inclusion Criteria:
* Diagnosis of hidradenitis suppurativa (HS) for at least 6 months prior to Baseline, as determined by the investigator (i.e., through medical history and interview of participant).
* Documented history of previous use of \>= 1 tumor necrosis factor (TNF) inhibitor for HS for at least 12 weeks and/or 1 approved non-anti-TNF biologic therapy for HS for at least 16 weeks characterized by inadequate response or for any duration characterized by intolerance as determined by the investigator.
* Participant must have a total abscess and inflammatory nodule (AN) count of \>= 5 at Baseline.
* HS lesions must be present in at least 2 distinct anatomic areas at Baseline.
* At least 1 anatomic area of HS involvement characterized as Hurley Stage II or higher at Baseline.
* Draining fistula count of \<= 20 at Baseline.
Exclusion Criteria:
* History of active skin disease other than HS that could interfere with the assessment of HS, including skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline visit.
* Treatment with any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug or be currently enrolled in another interventional clinical study. Investigational drugs are also prohibited during the study.
* Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 (e.g., rituximab) within 12 months prior to Baseline or until B cell count returns to normal level or pre-treatment level.
* Use of prescription topical therapies (including topical antibiotics) that can also be used to treat HS within 14 days prior to the Baseline visit.
* Received any systemic (including oral) antibiotic treatment for HS or any other chronic inflammatory disorder within 14 days prior to the Baseline visit. DRUG: Upadacitinib, DRUG: Placebo
Hidradenitis Suppurativa
Hidradenitis Suppurativa, Upadacitinib, ABT-494, Rinvoq, STEP-UP HS
24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up
clinicaltrials@northshore.org
ALL
12 years to 17 years old
PHASE3
NCT05677451
Key
Inclusion Criteria:
* Male and female adolescent participants aged \>= 12 to \< 18 years of age at the time of signing the informed consent
* CSU duration for \>= 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation)
* Diagnosis of CSU inadequately controlled by second-generation H1-AH at the time of randomization defined as:
* The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the use of second-generation H1-AH during this time period according to local treatment guidelines
* UAS7 score (range 0 - 42) \>= 16, ISS7 score (range 0 - 21) \>= 6 and HSS7 score (range 0 - 21) \>= 6 during the 7 days prior to randomization (Day 1)
* Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants' medical history)
Key Exclusion criteria:
* Previous use of remibrutinib or other BTK inhibitors
* Significant bleeding risk or coagulation disorders
* History of gastrointestinal bleeding
* Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited
* History or current hepatic disease
* Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant
* History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
* Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
* Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary angioedema, or drug-induced urticaria
* Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
Other protocol-defined inclusion/exclusion criteria may apply. DRUG: LOU064 (blinded), DRUG: placebo
Chronic Spontaneous Urticaria
BTK inhibitor, Chronic spontaneous urticaria, Urticaria activity score, Hives severity score, Itch severity score
Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET)
clinicaltrials@northshore.org
FEMALE
18 years to 60 years old
PHASE3
NCT05879926
Inclusion Criteria:
* A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
* The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health information.
* Female patients must be greater than or equal to 18 years of age.
* Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
* Age 50 years or under with spontaneous menses within 12 months; or
* Age greater than 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
* Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
* Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
* The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%).
* Patients may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
* Patients may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
* Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
* For patients who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS (ductal carcinoma in situ) with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. (Patients with margins positive for LCIS (lobular carcinoma in situ) are eligible without additional resection.)
* For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible if post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
* Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
* The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
* By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or higher.)
* By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a, pN1b, pN1c).
* Patients with positive isolated tumor cells (ITCs) in axillary nodes will be considered N0 for eligibility purposes.
* Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
* Oncotype DX RS (recurrence score) requirements\*:
* If node-negative:
* Oncotype DX RS must be RS 21-25, or
* Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as: low histologic grade with primary tumor size greater than 3 cm, intermediate histologic grade with primary tumor size greater than 2 cm, or high histologic grade with primary tumor size greater than 1 cm.
* If 1-3 nodes involved:
* Oncotype DX RS must be less than 26.
\* Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes the activity of certain genes in early-stage breast cancer) result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1). Blocks or unstained slides must be sent to the Genomic Health centralized laboratory for testing at no cost to these patients. If MammaPrint High Risk or MP2, these patients are not eligible.
* The tumor must be ER and/or PgR-positive (progesterone receptor) by current ASCO/CAP guidelines based on local testing results. Patients with greater than or equal to 1% ER and/or PgR staining by IHC will be classified as positive.
* The tumor must be HER2-negative by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines based on local testing results.
* The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry must be no more than 16 weeks.
* Short course of endocrine therapy of less than 6 weeks duration before pre-entry is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must be performed on core biopsy specimen obtained prior to initiation of neoadjuvant endocrine therapy if received.
* Patients with a prior or concurrent non-breast malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. This would include prior cancers treated with curative intent.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Radiation therapy should be used according to standard guidelines; the intended radiation therapy should be declared prior to pre-entry.
Exclusion Criteria:
* • Definitive clinical or radiologic evidence of metastatic disease.
* pT4 (pathological state) tumors, including inflammatory breast cancer.
* History of ipsilateral or contralateral invasive breast cancer. (Patients with synchronous and/or previous DCIS or LCIS are eligible.)
* If prior ipsilateral DCIS was treated with lumpectomy and XRT (ionizing radiation therapy), a mastectomy must have been performed for the current cancer.
* Life expectancy of less than 10 years due to co-morbid conditions in the opinion of the investigator.
Known results from most recent lab studies obtained as part of routine care prior to study entry showing ANY of the following values:
* ANC (absolute neutrophil count) less than 1200/mm3;
* Platelet count less than 100,000/mm3;
* Hemoglobin less than 10 g/dL;
* Total bilirubin greater than ULN (upper limit of normal) for the lab or greater than 1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin;
* AST(aspartate aminotransferase)(SGOT)/ALT (alanine transminase)(SGPT): greater than 3 × institutional ULN;
* Renal function of GFR (glomular filtration rate) less than 30 mL/min/1.73m2.
* 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.
* Non-epithelial breast malignancies such as sarcoma or lymphoma.
* Any treatment with radiation therapy, chemotherapy, or biotherapy administered for the currently diagnosed breast cancer prior to pre-entry. (Patients with prior ET of more than 6 weeks duration for treatment of this cancer are not eligible.) Prior tamoxifen given for breast cancer prevention is allowed. Prior AI or GnRH for fertility preservation is allowed.
* Hormonally based contraceptive measures must be discontinued prior to pre-entry (including progestin/progesterone IUDs).
* Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible unless the HBV viral load is undetectable on suppressive therapy. Patients with a history of hepatitis C virus (HCV) infection are ineligible unless they have been treated and cured or have an undetectable HCV viral load if still on active therapy.
* Pregnancy or lactation at the time of pre-entry. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to pre-entry.)
* Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results. DRUG: Ovarian Function Suppression + Aromatase Inhibitor, DRUG: Adjuvant Chemotherapy + Ovarian Function Suppression
Breast Cancer
A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT04928846
Inclusion Criteria:
* Projected life expectancy of at least 12 weeks.
* Participants must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory using the VENTANA MET (SP44) RxDx assay.
* Archival or fresh tumor material must be submitted for assessment of c-Met protein expression levels during the Pre-Screening period. Tumor material from the primary tumor site and/or metastatic sites are allowed.
* If a participant was prescreened for Study M14-239 but did not enroll, tumor material previously submitted for Study M14-239 may be used for Study M18-868 Pre-Screening upon confirmation from AbbVie that sufficient evaluable tumor material is available (Except China).
* A histologically or cytologically documented non-squamous cell NSCLC that is locally advanced or metastatic.
* A known epidermal growth factor receptor (EGFR) activating mutation status.
\-- Participants with actionable EGFR activating mutations are not eligible
* Actionable alterations in genes other than EGFR are eligible.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
* Have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting.
* Neoadjuvant and adjuvant systemic cytotoxic chemotherapy will count as a prior line for eligibility purposes if progression occurred within 6 months of the end of therapy.
* Have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC:
* Participants WITHOUT an actionable gene alteration: must have progressed on (or be considered ineligible for) platinum-based chemotherapy and immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).
* Participants WITH an actionable gene alteration for which immune checkpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase \[ALK\] translocation): must have progressed on (or be considered ineligible for) anti-cancer therapy targeting driver gene alterations and platinum-based chemotherapy.
* Participants with actionable gene alterations for which immune checkpoint inhibitor is standard of care must have also progressed on (or be considered ineligible for) immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).
* Must be considered appropriate for docetaxel therapy based on the assessment of the treating physician.
* Participants with metastases to the central nervous system (CNS) are eligible only after adequate treatment (such as surgery, radiotherapy, or drug therapy) is provided and:
* They are asymptomatic and off or on a stable or reducing dose of systemic steroids (on no more than 10 mg per day \[QD\] prednisone or equivalent) and/or anticonvulsants for at least 2 weeks prior to randomization.
Exclusion Criteria:
* Evidence of new, untreated CNS metastases or progressing CNS metastases after treatment.
* Evidence of leptomeningeal disease.
* Participants with adenosquamous or neuroendocrine histology, nor sarcomatoid features.
* Epidermal growth factor receptor (EGFR) activating mutations.
* Participants who have received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E..
* Participants who have received prior docetaxel therapy.
* A history of other malignancies except:
* Malignancy treated with curative intent and with no known active disease present for \>=2 years before the first dose of study drug and felt to be at low risk for recurrence by investigator. Additionally, participants must not be receiving any ongoing anti-cancer therapy, including maintenance therapy, prior to randomization..
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without current evidence of disease.
* A history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. A history of prior radiation pneumonitis in the radiation field (fibrosis) is not permitted.
* Unresolved or neuroendocrine histology, nor sarcomatoid features adverse event (AE) \>= Grade 2 from prior anticancer therapy, except for alopecia or anemia. Participants with hormone deficiencies caused by prior anticancer therapy who are asymptomatic and on a stable dose of replacement hormone are eligible for study.
* Major surgery within 21 days prior to randomization.
* Clinically significant condition(s) as listed in the protocol. BIOLOGICAL: Telisotuzumab Vedotin, DRUG: Docetaxel
Non Small Cell Lung Cancer
c-Met Overexpressing Non-Small Cell Lung Cancer, c-Met NSCLC, Telisotuzumab Vedotin, ABBV-399, Docetaxel, Cancer, Non Small Cell Lung Cancer, NSCLC, TeliMET NSCLC-01, Teliso-V
A Master Protocol Study (LY900038) of Multiple Intervention-Specific-Appendices (ISAs) in Adult Participants With Obesity or Overweight
clinicaltrials@northshore.org
ALL
18 years to 75 years old
PHASE2
NCT06143956
Inclusion Criteria:
* Have a body mass index (BMI)
* ≥30 kilogram/square meter (kg/m²), or
* ≥27 kg/m² and \<30 kg/m², or with at least 1 weight-related comorbidity
* Have had a stable body weight for the 3 months prior to randomization (\<5%) body weight gain and/or loss.
Exclusion Criteria:
* Have a prior or planned surgical treatment for obesity, except prior liposuction or abdominoplasty, if performed \>1 year prior to screening.
* Have type 1 diabetes mellitus, latent autoimmune diabetes in adults, or history of ketoacidosis or hyperosmolar coma.
* Have poorly controlled hypertension.
* Have signs and symptoms of any liver disease other than nonalcoholic fatty liver disease.
* Have any of the following cardiovascular conditions within 3 months prior to screening:
* acute myocardial infarction
* cerebrovascular accident (stroke)
* unstable angina, or
* hospitalization due to congestive heart failure.
* Have a history of symptomatic gallbladder disease within the past 2 years.
* Have a lifetime history of suicide attempts. DRUG: LY3305677, DRUG: LY3841136, DRUG: Tirzepatide, DRUG: Placebo, DRUG: LY3549492
Obesity, Overweight
Patient Quality of Recovery After TAVR With Different Sedation Regimens
clinicaltrials@northshore.org
ALL
18 years to 90 years old
PHASE4
NCT07556523
Inclusion Criteria:
* 18-90 years old, inclusive
* Undergoing transfemoral TAVR under Monitored Anesthesia Care (MAC)
* Speaks English or Spanish
* Consents to participate
Exclusion Criteria:
* Preoperative heart rate \< 50 bpm or arrhythmias (e.g., AFib with RVR)
* Conduction abnormalities (e.g., 2nd/3rd degree AV block without pacer)
* Allergy or contraindication to study drugs
* Pulmonary artery pressure \> 70mmHg
* Morbid obesity BMI \> 50
* Pregnancy
* Unable to consent in English or Spanish DRUG: Propofol, DRUG: Dexmedetomidine, DRUG: Midazolam, DRUG: Fentanyl
Transcatheter Aortic Valve Replacement (TAVR), Aortic Valve Stenosis
Transcatheter aortic valve replacement, TAVR, Sedation strategy, Anesthesia
A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung15)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06417814
Inclusion Criteria:
* Histologically or cytologically confirmed non-squamous NSCLC.
* Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor \[EGFR\] tyrosine kinase inhibitor \[TKis\] sensitivity \[Ex19del, L858R, G719X, S768I, or L861Q\], either alone or in combination with other EGFR mutations, which may include T790M).
* Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
* Less than or equal to (\<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
* At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
* World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate bone marrow reserve and organ function within 7 days before randomization.
Exclusion Criteria:
* Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
* Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
* Has significant third-space fluid retention (example \[eg.\], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
* History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
* Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
* Unstable spinal cord compression and/or unstable brain metastases.
* Participants with symptomatic brain metastases (including leptomeningeal involvement).
* Clinically significant corneal disease.
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections.
* Has known human immunodeficiency virus (HIV) infection that is not well controlled. DRUG: Dato-DXd, DRUG: Osimertinib, DRUG: Pemetrexed, DRUG: Carboplatin, DRUG: Cisplatin
Metastatic Non-small Cell Lung Cancer
Epidermal growth factor receptor gene mutation, Standard of Care, Locally, advanced carcinoma, Metastatic carcinoma, Non-small cell lung cancer, Dato-dxd, Datopotamab deruxtecan, Osimertinib, Tagrisso, Pemetrexed, Carboplatin, Cisplatin
A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer (RAMP 301)
clinicaltrials@northshore.org
FEMALE
18 years and over
PHASE3
NCT06072781
Inclusion Criteria:
Patients may be eligible for inclusion in the study if they meet the following criteria:
• Histologically proven LGSOC (ovarian, fallopian, peritoneal)
• Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test.
• Suitable for treatment with at least one of the Investigator's Choice of Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole.
• Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
• Measurable disease according to RECIST v1.1.
• An Eastern Cooperative Group (ECOG) performance status ≤ 1.
• Adequate organ function.
• Adequate recovery from toxicities related to prior treatments.
• For patients with reproductive potential, a negative pregnancy test must be confirmed and agreement to use highly effective method of contraceptive.
• Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria:
Patients will be excluded from the study if they meet any of the following criteria:
• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
• Co-existing high-grade serous ovarian cancer or mixed histology.
• Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
• History of prior malignancy with recurrence \<3 years from the time of enrollment.
• Major surgery within 4 weeks, minor surgery within 1 week, or palliative radiotherapy within 1 week of the first dose of study intervention.
• Symptomatic brain metastases requiring steroids or other interventions, known leptomeningeal metastases, or spinal cord compression.
• An active skin disorder that has required systemic therapy within one year of the first dose of study intervention.
• History of medically significant rhabdomyolysis.
• For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to the MEK inhibitor.
• Symptomatic bowel obstruction within 3 months of the first dose of study intervention
• Concurrent ocular disorders.
• Concurrent heart disease or severe obstructive pulmonary disease.
• Active or past medical history of interstitial lung disease/pneumonitis, including drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS).
• Subjects with the inability to swallow oral medications.
• History of hypersensitivity to any of the active agents or ingredients of study intervention: peanut, soya, polyoxyl castor oil, etcetc.). Prior hypersensitivity to anthracyclines or anthracenediones if the use of pegylated liposomal doxorubicin (PLD) is planned.
• Pregnant or breastfeeding.
• Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.
DRUG: avutometinib, DRUG: Defactinib, DRUG: Pegylated liposomal doxorubicin, DRUG: Paclitaxel, DRUG: Letrozole, DRUG: Anastrozole
Low Grade Serous Ovarian Cancer
Low Grade Serous Ovarian Cancer, KRAS, KRAS wt, KRAS mt
Docetaxel to Androgen Receptor Pathway Inhibitors in Patients With Metastatic Castration Sensitive Prostate Cancer and Suboptimal PSA Response (TRIPLE-SWITCH)
clinicaltrials@northshore.org
MALE
18 years and over
PHASE3
NCT06592924
Inclusion Criteria:
* Histologically/cytologically confirmed adenocarcinoma of the prostate
* Metastatic disease by conventional imaging
* PSA of ≥5.0 ng/ml (5.0 ug/L) prior to commencement of ADT
* Receipt of ADT for mCSPC for at least 6 months and no greater than 12 months at time of enrollment.
* Receipt of ARPI (e.g. abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for at least 4 months at time of enrollment
* Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
* Serum testosterone \<1.7 nmol/L or 50 ng/dL.
* PSA ≥ 0.2 ng/ml (0.2 ug/L) within 14 days of enrollment. If there is any rise in PSA since starting ADT and achieving castrate-level testosterone, PSA must be repeated and must not fulfill ineligibility criteria 4.2.1.
* Candidate for docetaxel chemotherapy
* ECOG Performance Status (PS) 0 to 2.
* Adequate organ and marrow function measured within 14 days prior to enrollment.
* Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrollment in the trial to document their willingness to participate.
* Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* In accordance with CCTG policy, protocol treatment is to begin within 5 working days of participant enrollment.
* If the participant and the participant's partner are of childbearing potential, they must agree to use medically accepted methods of contraception
* HIV-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Participant access to all protocol therapies must be confirmed prior to enrollment
Exclusion Criteria:
* Two consecutive rises in PSA since achieving castration on ADT at least 2 weeks apart with at least one PSA ≥5% above the PSA nadir and with at least one PSA having an absolute increase of ≥0.5 ng/ml above the PSA nadir.
* Evidence of radiographic progression or clinical progression since start of ADT.
* Docetaxel criteria:
* Prior treatment with taxane chemotherapy
* Grade 2 or worse peripheral neuropathy
* Severe hypersensitivity to drugs formulated with polysorbate 80
* 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 II or better.
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous.
* Patients with a prior or concurrent malignancy whose natural history of treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Concurrent treatment with other anti-cancer systemic therapy other than ADT and ARPI.
* Live attenuated vaccination administered within 30 days prior to enrollment/randomization.
* For participants with a history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* High-grade neuroendocrine prostate cancer or small cell features. DRUG: Abiraterone, DRUG: Enzalutamide, DRUG: Apalutamide, DRUG: Darolutamide (BAY 1841788), DRUG: Docetaxel, DRUG: ADT
Prostate Cancer (Adenocarcinoma)
PR26, Castration sensitive
A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06136650
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
* Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening
* Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography (CT)/magnetic resonance imaging (MRI)
* Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) (metastatic hormone-sensitive prostate cancer \[mHSPC\] or non-metastatic hormone-sensitive prostate cancer \[nmHSPC\]), or castration-resistant prostate cancer (CRPC) (metastatic castration-resistant prostate cancer \[mCRPC\] or non-metastatic castration-resistant prostate cancer \[nmCRPC\]), for at least 8 weeks of NHA treatment (at least 14 weeks of NHA treatment for participants with bone progression). Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel
* Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
* Has ongoing androgen deprivation therapy (ADT) with serum testosterone \<50 ng/dL (\<1.7 nM)
* Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 10 days before randomization
* Has adequate organ function
* Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
* Participants who have adverse event (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy (HRT) or participants who have ≤Grade 2 neuropathy or ≤Grade 2 osteopenia/osteoporosis are eligible
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has presence of gastrointestinal condition
* Is unable to swallow capsules/tablets
* Has history of pituitary dysfunction
* Has poorly controlled diabetes mellitus
* Has clinically significant abnormal serum potassium or sodium level
* Has any of the following at screening visit: Hypotension: systolic blood pressure (BP) \<110 mmHg, or uncontrolled hypertension: systolic BP ≥160mmHg or diastolic blood BP ≥90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive therapy
* Has a history of active or unstable cardio/cerebrovascular disease, including thromboembolic events
* History or family history of long QTc syndrome
* Has a history of seizure(s) within 6 months before providing documented informed consent (IC) or has any condition that may predispose to seizure within 12 months prior to the date of enrollment
* Has a history of clinically significant ventricular arrhythmias or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place
* Has received a taxane-based chemotherapy for metastatic castration-resistant prostate cancer (mCRPC)
* Has not adequately recovered from major surgery or have ongoing surgical complications
* Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures
* Participants on an unstable dose of thyroid hormone therapy, as judged by the investigator, within 6 months before the start of the study intervention
* Receives prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids
* Receives prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
* Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein (P-gp) inhibitors within 2 weeks before the first dose of study intervention
* Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or opevesostat
* Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* 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 the first dose of study medication
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention
* Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is allowed
* Active infection requiring systemic therapy
* Has concurrent active Hepatitis B virus and Hepatitis C virus infection DRUG: Opevesostat, DRUG: Dexamethasone, DRUG: Fludrocortisone acetate, DRUG: Hydrocortisone, DRUG: Abiraterone acetate, DRUG: Prednisone acetate, DRUG: Enzalutamide
Metastatic Castration-resistant Prostate Cancer (mCRPC), Prostatic Neoplasms
Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations (OBERON)
clinicaltrials@northshore.org
ALL
40 years to 130 years old
PHASE3
NCT05166889
Inclusion Criteria:
• Participant must be ≥ 40 years of age and capable of giving signed informed consent.
• Documented diagnosis of COPD for at least one year prior to enrolment.
• Post BD FEV1/FVC \< 0.70 and post-BD FEV1 \>20% of predicted normal value.
• Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment.
• Documented optimized inhaled dual or triple therapy at a stable dose for at least 3 months prior to enrolment.
• Smoking history of ≥ 10 pack-years.
• CAT total score ≥10, with each of the phlegm (sputum) and cough items with a score ≥ 2.
Exclusion Criteria:
• Clinically important pulmonary disease other than COPD.
• Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant's respiratory symptoms.
• Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18.
• Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that could affect safety, study findings or participants ability to complete the study.
• COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.
• Active significant infection within the 4 weeks prior to randomization, pneumonia within 6 weeks prior to randomization, or medical condition that predisposes the participant to infection.
• Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
• Significant COVID-19 illness within the 6 months prior to enrolment.
• Unstable cardiovascular disorder.
• Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
• History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2.
• History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C)
• Evidence of active liver disease, including jaundice during screening.
• Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms.
• Participants who have evidence of active TB.
• Participants that have previously received tozorakimab.
• Any clinically significant abnormal findings in physical examination, vital signs, ECG, or laboratory testing during the screening period, which in the opinion of the investigator may put the participant at risk because of their participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study.
• Active vaping of any products or using smoked marijuana within the 6 months prior to randomization and during the study.
DRUG: Tozorakimab, DRUG: Tozorakimab, DRUG: Placebo
Chronic Obstructive Pulmonary Disease (COPD)
Chronic Obstructive Pulmonary Disease, COPD, tozorakimab, exacerbations, ICS, LABA/LAMA
Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis (FREXALT)
clinicaltrials@northshore.org
ALL
18 years to 55 years old
PHASE3
NCT06141473
Inclusion Criteria:
* The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria.
* The participant has an EDSS score ≤5.5 at the first visit (Screening Visit)
* The participant must have at least 1 of the following prior to screening:
* ≥1 documented relapse within the previous year OR
* ≥2 documented relapses within the previous 2 years, OR
* ≥1 documented Gd enhancing lesion on an MRI scan within the previous year.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion Criteria:
* The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria
* The participant has a history of infection or may be at risk for infection:
* The presence of psychiatric disturbance or substance abuse.
* History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment.
* Current hypogammaglobulinemia defined by Ig levels below the LLN at Screening or a history of primary hypogammaglobulinemia.
* A history or presence of disease that can mimic MS symptoms, such as, but not limited to neuromyelitis optica spectrum disorder, systemic lupus erythematosus, Sjogren's syndrome, acute disseminated encephalomyelitis, and myasthenia gravis.
* The participant has had a relapse in the 30 days prior to randomization.
* The participant has contraindication for MRI, ie, presence of pacemaker, metallic implants in high risk areas (ie, artificial heart valves, aneurysm/vessel clips), presence of metallic material (eg, shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol scheduled MRI scans.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. DRUG: Frexalimab, DRUG: Teriflunomide, DRUG: Placebo infusion, DRUG: Placebo tablet, DRUG: MRI contrast-enhancing agents, DRUG: Cholestyramine, DRUG: Activated charcoal
Multiple Sclerosis
A Master Protocol Study (LY900028) of Multiple Intervention-Specific-Appendices (ISAs) in Participants With Chronic Pain (CPMP)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT05986292
Inclusion Criteria:
* have a visual analog scale (VAS) pain value \>40 and \<95 at screening and prerandomization screening.
* have a history of daily pain for at least 12 weeks based on participant report or medical history
* have a value of ≤30 on the pain catastrophizing scale
* have a body mass index \<40 kilogram/square meter (kg/m²) (inclusive)
* are willing to maintain a consistent regimen of any ongoing nonpharmacologic pain-relieving therapies (for example, physical therapy) and will not start any new nonpharmacologic pain-relieving therapies during study participation.
* are willing to discontinue all medications taken for chronic pain conditions, except rescue medication for the duration of the study
Exclusion Criteria:
* have second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia
* have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest (for example, ablation techniques)
* have surgery planned during the study for any reason, related or not to the disease state under evaluation.
* have, in the judgment of the investigator, an acute, serious, or unstable medical condition or a history or presence of any other medical illness that would preclude study participation.
* have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision.
* have fibromyalgia
* have substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association)
* have any clinically important abnormality at screening, as determined by investigator, in physical or neurological examination, vital signs, electrocardiogram (ECG), or clinical laboratory test results that could be detrimental to the participant or could compromise the study.
* have a positive human immunodeficiency virus (HIV) test result at screening
* have a history of alcohol, illicit drug, analgesic or narcotic use disorder within 2 years prior to screening. DRUG: LY3016859 ISA, DRUG: LY3556050 ISA, DRUG: LY3526318 ISA, DRUG: LY3857210 ISA, DRUG: Placebo Oral, DRUG: Placebo
Osteoarthritis, Knee, Diabetic Neuropathic Pain, Chronic Low-back Pain
A Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Moderate to Severe Plaque Psoriasis (ONWARD1)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06586112
Inclusion Criteria:
• Males or females, age ≥18 years
• Diagnosis of plaque psoriasis for ≥6 months
• Plaques covering ≥10% of BSA
• PASI ≥12
• sPGA ≥3
• Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must agree to adhere to highly effective methods of contraception
Exclusion Criteria:
• Nonplaque psoriasis or other inflammatory skin conditions
• immune-mediated conditions commonly associated with psoriasis (eg inflammatory bowel disease). Participants with psoriatic arthritis may participate
• Pregnant, lactating, or planning to get pregnant during the study
• Use of drugs prior to Study Day 1 that treat or may affect psoriasis: * Topical within 2 weeks * Phototherapy or any systemic treatments within 4 weeks * Any biologic agent targeted to IL-12 or IL-23 within 6 months, oral IL-12 or IL-23 or TNFα inhibitor within 2 months, or IL-17 within 4 months * Systemic immunosuppressants or immunomodulatory drugs within 4 weeks * Modulators of B cells within 6 months, or T cells within 3 months * JAK inhibitors or TYK2 inhibitors within 4 weeks * PDE4 inhibitor within 2 months * Any investigational agent, within 30 days or 5 half-lives or is currently enrolled in an investigational study
• Lack of clinical response to a TYK2, IL-12, or IL-23 targeted psoriasis treatment
• Participants with QTcF \>450 msec (males) or \>470 msec (females) at Screening
• Unstable cardiovascular disease, defined as a recent clinical deterioration or a cardiac hospitalization within the last 3 months
• Evidence of recent or recurrent herpes zoster or herpes simplex viral infection
• Evidence of active infection or positive test result for hepatitis B, hepatitis C, HIV or TB
• History of serious bacterial, fungal, or viral infections that led to hospitalization, or any recent serious infection requiring antibiotic treatment
• Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the participant's immune status
• Lab abnormalities indicating significant renal, hepatic or bone marrow dysfunction
• History of any immune-mediated or inflammatory medical condition for which participants requires current systemic corticosteroids \* Stable doses of inhaled corticosteroids for treatment of asthma are allowed
• Known current malignancy or current evaluation for a potential malignancy or history of malignancy within the past 5 years prior to screening, except for adequately treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix
• Live vaccines within 4 weeks prior to Study Day 1
• Participant has planned surgery during the study period
• Any acute or chronic illness/condition or evidence of an unstable clinical condition that, in the opinion of the Investigator, will substantially increase the risk to the participant if he or she participates in the study
• History of mental illness within the last 5 years, unless receiving a fixed regimen of psychiatric medications for at least 6 months before screening or has not required or been prescribed any psychiatric medication within 12 months before screening
• Evidence of severe depressive symptoms or active suicidal ideation or behavior
DRUG: ESK-001, DRUG: Apremilast, DRUG: Placebo
Plaque Psoriasis
Methadone and Quality of Postoperative Recovery
clinicaltrials@northshore.org
All
18 years to 90 years old
Phase 4
NCT03168958
Inclusion Criteria:
• All patients presenting for elective cardiac surgery with CPB will be eligible for enrollment
Exclusion Criteria:
• Preoperative renal failure requiring dialysis or severe renal dysfunction (serum creatinine > 2.0 mg/dL)
• Significant hepatic dysfunction (liver function tests > 2 times upper normal limit)
• Pulmonary disease necessitating home oxygen therapy
• Preoperative requirement for inotropic agents or intraaortic balloon pump to maintain hemodynamic stability
• Allergy to methadone or fentanyl
• Significant preoperative pain requiring treatment with opioids or recent history of opioid abuse
• Inability to speak or read the English language or neurologic conditions that may impair the ability to complete the QoR 40 questionnaire.
Drug: Methadone, Drug: Saline
Quality of Recovery Scores
Effect of Methadone and Hydromorphone on the QT Interval After Anesthesia and Surgery
Lucyna W Klatzco - lklatzco@northshore.org
All
18 years to 80 years old
Phase 4
NCT03893734
Inclusion Criteria:
• All patients presenting for elective surgical cases requiring general anesthesia and associated with moderate-to-severe postoperative pain will be eligible for enrollment.
Exclusion Criteria:
• History of arrhythmias, pacemaker, or defibrillator
• Allergy to methadone or hydromorphone
• Preoperative altered mental status
• Abnormal serum electrolyte values
• Existence of significant valvular disease or cardiac rhythm other than sinus
• Significant preoperative pain requiring treatment with opioids or recent history of opioid abuse
Drug: methadone, Drug: Hydromorphone
EKG-QT Prolongation
A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack- LIBREXIA-STROKE (LIBREXIA-STROK)
clinicaltrials@northshore.org
ALL
40 years and over
PHASE3
NCT05702034
Inclusion Criteria:
* Ischemic Stroke: a neurological deficit attributable to an acute brain infarction and national institute of health stroke score scale (NIHSS) score less than or equal to (\<=) 7 and at least 1 of the following: persistent signs or symptoms of the ischemic event at the time of randomization, or acute, ischemic brain lesion determined by standard-of-care neuroimaging, or participant underwent thrombolysis or thrombectomy, or transient ischemic attack (TIA): acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete symptom resolution of the deficit and no brain infarction on neuroimaging (example, computed tomography (CT) scan or magnetic resonance imaging (MRI), performed as part of standard medical practice), and ABCD2 Score greater than or equal to (\>=) 6
* Participants will be randomized as soon as possible after determining eligibility and within 48 hours of onset of event.
* Current or planned antiplatelet treatment per international and/or local guidelines. If acetyl salicylic acid (ASA) is used, it will be limited to low dose (75 to 100 milligrams (mg)/day). Loading dose of antiplatelet agents (including ASA) are allowed per standard-of-care
* A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant until 4 days (5 half lives) after the last dose of study intervention
* Willing and able to adhere to the lifestyle restrictions specified in this protocol
Exclusion Criteria:
* Prior history of intracranial hemorrhage except subarachnoid hemorrhage greater than (\>) 1 year prior with adequate treatment
* The index stroke or TIA is considered to have a cardio-embolic etiology based on local standard-of-care investigations and for which guidelines recommend anticoagulation
* The index stroke or TIA considered to have another known cause, not related to athero-thrombotic sources (treatment of acute stroke trial \[TOAST\] Other Determined Etiology), based on local standard-of-care investigations
* Increased risk of bleeding, including clinically significant bleeding within the previous 3 months or known bleeding diathesis or known activated partial thromboplastin time (aPTT) prolongation or spinal cord hemorrhage or retinal hemorrhage
* Current active liver disease, eg, acute hepatitis, known cirrhosis, including participants receiving antiviral treatment for hepatitis
* Known allergies, hypersensitivity, or intolerance to milvexian or its excipients DRUG: Milvexian, DRUG: Placebo
Ischemic Stroke, Ischemic Attack, Transient
A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy (ALMOND)
clinicaltrials@northshore.org
ALL
18 years to 75 years old
PHASE2
NCT05707377
Inclusion Criteria:
* Biopsy-confirmed PMN within 5 years before the initial screening (ie, the day the informed consent is signed)
* UPCR (based on 24-hour urine collection) \> 3.5 at initial screening and at confirmation assessment
* Treatment with a maximally tolerated or allowed dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for ≥ 24 weeks before randomization (12 weeks before initiation of study drug for Part 1) and with adequate blood pressure control (blood pressure \< 130/80 mmHg, measured on ≥ 2 occasions \[not on the same day\] within 4 weeks before the assignment of study treatment)
* Anti-PLA2R antibody \> 50 RU/mL at confirmation assessment (Part 1 only)
Exclusion Criteria:
* Participants with a secondary cause of membranous nephropathy
* Type 1 or 2 diabetes mellitus with hemoglobin A1c (HbA1c) ≥ 7% at screening
* Severe renal disease as determined by rapid decline in eGFR (defined as \> 15 mL/min/1.73m\^2 within 24 weeks prior to randomization, not otherwise explained)
* A known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infections
* Patients at risk for tuberculosis at screening
* Known infection with serologic status reflecting active or chronic hepatitis B virus infection, or presence of hepatitis C virus antibody
* Severe hepatic insufficiency (Child-Pugh C)
* Clinically significant cardio-cerebrovascular diseases
Note: Other protocol defined Inclusion/Exclusion criteria may apply. DRUG: Zanubrutinib, DRUG: Tacrolimus
Primary Membranous Nephropathy
BGB-3111, Zanubrutinib, BTKi
A Study of Baricitinib (LY3009104) in Children From 6 Years to Less Than 18 Years of Age With Alopecia Areata (BRAVE-AA-PEDS)
clinicaltrials@northshore.org
ALL
6 years to 17 years old
PHASE3
NCT05723198
Inclusion Criteria:
* Enrollment will be fully sequential by age group, with adolescents (12 to less than 18 years old) enrolling before children (6 to less than 12 years old).
* Have severe areata alopecia (AA) for at least 1 year
* Diagnosis for at least 1 year
* Current AA episode of at least 6 months' duration
* SALT score ≥50% at screening and baseline
* History of trial and failure with at least 1 available treatment (topical or other) for AA
* History of psychological counseling related to AA
* Current episode of severe AA of less than 8 years.
* Note: Participants who have severe AA for ≥8 years may be enrolled if episodes of regrowth, spontaneous or under treatment, have been observed on the affected areas over the past 8 years.
Exclusion Criteria:
* Primarily "diffuse" type of AA (characterized by diffuse hair shedding).
* Are currently experiencing other forms of alopecia including, but not limited to trichotillomania, telogen effluvium, chemotherapy-induced hair loss, or any other concomitant conditions (for example, tinea capitis, psoriasis, lupus erythematosus, or secondary syphilis) that would interfere with evaluations of the effect of study medication on AA.
* Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden
* Have uncontrolled arterial hypertension
* Have had major surgery within 8 weeks prior to screening or will require major surgery during the study
* Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking IP or interfere with the interpretation of data.
* Have a positive test for hepatitis B virus (HBV) infection
* Have hepatitis C virus (HCV) infection (positive for anti hepatitis C antibody with confirmed presence of HCV ribonucleic acid \[RNA\]).
* Have evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies. DRUG: Baricitinib, DRUG: Placebo
Areata Alopecia, Alopecia, Hypotrichosis, Hair Diseases, Skin Diseases, Pathological Conditions, Anatomical
A Study to Evaluate the Efficacy and Safety Study of Povorcitinib in Participants With Prurigo Nodularis (STOP-PN1) (STOP-PN1)
clinicaltrials@northshore.org
ALL
18 years to 75 years old
PHASE3
NCT06516952
Inclusion Criteria:
* Male and female participants 18 to 75 years of age.
* Clinical diagnosis of PN for at least 3 months prior to Screening visit.
* Pruritus, defined as an average Itch NRS score ≥ 7 during the 7 days prior to Day 1/Baseline.
* Total of ≥ 20 pruriginous lesions on ≥ 2 different body regions (both legs, and/or both arms, and/or trunk) at Screening and Day 1/Baseline.
* Documented history of treatment failure, demonstrated intolerance, or contraindication to a previous PN treatment.
* Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
* Chronic pruritus due to a condition other than PN or neuropathic and psychogenic pruritus.
* Diagnosis of PN secondary to medications.
* Active AD lesions (signs and symptoms other than dry skin) within 3 months prior to Screening visit.
* Women who are pregnant (or are considering pregnancy) or breastfeeding.
* Medical history including thrombocytopenia, coagulopathy or platelet dysfunction; venous and arterial thrombosis, deep vein thrombosis, pulmonary embolism, stroke, moderate to severe heart failure, cerebrovascular accident, myocardial infarction, or other significant cardiovascular diseases; Q-wave interval abnormalities; disseminated herpes zoster or dermatomal herpes zoster; disseminated herpes simplex; chronic/recurrent infections; malignancies.
* Evidence of infection with TB, HBV, HCV or HIV.
* History of failure to any topical or systemic JAK or TYK2 inhibitor as treatment of PN or any inflammatory disease.
* Laboratory values outside of the protocol-defined ranges.
Other protocol-defined Inclusion/Exclusion Criteria apply. DRUG: Povorcitinib, DRUG: Placebo
Prurigo Nodularis
Prurigo nodularis, PN, INCB054707, chronic pruritus
Anticoagulation in ICH Survivors for Stroke Prevention and Recovery (ASPIRE)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT03907046
Inclusion Criteria:
* Age at least 18 years
* Intracerebral hemorrhage (ICH) (including primary intraventricular hemorrhage) confirmed by brain CT or MRI
* Can be randomized within 14-180 days after ICH onset
* Non-valvular AF (defined as atrial fibrillation or atrial flutter), documented by electrocardiography or a physician-confirmed history of prior AF
* Provision of signed and dated informed consent form by patient or legally authorized representative
* For females of reproductive potential: use of highly effective contraception
Exclusion Criteria:
* Index event is hemorrhagic transformation of a brain infarction or hemorrhage into a tumor
* History of earlier ICH within 12 months preceding index event
* Active infective endocarditis
* Clear indication for anticoagulant drugs (e.g., requires anticoagulation for deep vein thrombosis or pulmonary embolism) or antiplatelet drugs (e.g., requires aspirin or clopidogrel for recent coronary stent).
* Previous or planned left atrial appendage closure
* Clinically significant bleeding diathesis
* Serum creatinine ≥2.5 mg/dL
* Active hepatitis or hepatic insufficiency with Child-Pugh score B or C
* Anemia (hemoglobin \<8 g/dL) or thrombocytopenia (\<100 x 10\^9/L) that is chronic in the judgment of the investigator
* Pregnant or breastfeeding
* Known allergy to aspirin or apixaban
* Concomitant participation in a competing trial
* Considered by the investigator to have a condition that precludes safe or active participation in the trial
* Persistent, uncontrolled systolic blood pressure (≥180 mm Hg)
* ICH caused by an arteriovenous malformation (AVM) that has not yet been secured DRUG: Apixaban, DRUG: Aspirin
Intracerebral Hemorrhage, Atrial Fibrillation
ARTEMIS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With a Heart Attack (ARTEMIS)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06118281
Key inclusion:
* Age 18 years or above at the time of signing the informed consent.
* Hospitalisation for acute myocardial infarction with evidence of type 1 myocardial infarction (MI) by invasive angiography performed at site with percutaneous coronary intervention (PCI) capabilities.
* ST-segment elevation myocardial infarction (STEMI) with all the following: a) Relevant onset of symptoms suggestive of cardiac ischaemia within 12 hours before hospitalisation, at the investigator's discretion.
b) Electrocardiogram (ECG)-changes (in the absence of left ventricular hypertrophy or left bundle branch block): ST-segment elevation at the J point in at least two contiguous leads greater than or equal 0.25 (millivolt) mV in men less than 40 years, greater than or equal 0.2 mV in men greater than or equal 40 years, or greater than or equal 0.15 mV in women in leads V2-V3; and/or greater than or equal 0.1 mV in all other leads.
OR
* Non-ST-segment myocardial infarction with all the following: a) Relevant onset of symptoms suggestive of cardiac ischaemia within 24 hours before hospitalisation, at the investigator's discretion. b) Rise and/or fall in car-diac troponin I or T with at least one value above the 99th percentile upper reference limit.
* Possibility for both randomisation and administration of the loading dose of study intervention as early as possible after invasive procedure, and latest within 36 hours of hospitalisation (time 0) for STEMI, and latest within 72 hours of hospitalisation (time 0) for NSTEMI.
* Presence of at least one of the following criteria confirmed based on the participant's medical records and/or medical history interview: a) Any prior MI. b) Prior coronary revascularisation. c) Diabetes mellitus treated with ongoing glucose-lowering agent(s). d)Known chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) greater than or equal to 15 and less than 60 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2). e) Prior ischaemic stroke. f) Known carotid disease or peripheral artery disease in the lower extremities. g) Multivessel coronary artery disease (current/prior). h) For STEMI patients only: anterior MI at index acute myocardial infarction (AMI)
Key exclusion:
* Use of fibrinolytic therapy for treatment of the current AMI.
* Chronic heart failure classified as being in New York Heart Association (NYHA) Class IV.
* Ongoing haemodynamic instability defined as any of the following: a) Killip Class III or IV. b) Sustained and/or symptomatic hypotension (systolic blood pressure less than 90 millimeters of mercury (mmHg)).
* Severe kidney impairment defined as any of the following: a) eGFR less than 15 mililitre per minute per 1.73 m\^2. b) Chronic haemodialysis or peritoneal dialysis.
* Known alanine aminotransferase (ALT) greater than 8 x upper limit of normal (reference range) (ULN).
* Severe hepatic disease defined as at least one of the following: a) Previously known or current hepatic encephalopathy (clinical evaluation). b) Previously known or current ascites (clinical eval-uation). c) Jaundice (clinical evaluation). d) Previous oesophageal/gastric variceal bleeding. c) Known hepatic cirrhosis.
* Major cardiac surgical (including but not restricted to coronary artery bypass graft surgery (CABG)), non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days or any major surgical procedure planned at the time of randomisation or as treatment for the current AMI (CABG). Deferred (staged)percutaneous coronary intervention for a non-culprit vessel identified during the current AMI is allowed.
* Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
* Known (acute or chronic) hepatitis B or hepatitis C.
* History or evidence of untreated latent tuberculosis (TB) such as (but not limited to): a) History of a positive TB test or chest X-ray compatible with latent TB; and TB treatment initiated less than 28 days prior to randomisation. b) Participants with TB risk factors but unwilling to undergo TB treatment if confirmed positive for latent TB based on central laboratory test at baseline (visit 2).
DRUG: Ziltivekimab, DRUG: Placebo
Cardiovascular Risk, Acute Myocardial Infarction (AMI)
A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata (Up-AA)
clinicaltrials@northshore.org
ALL
12 years to 63 years old
PHASE3
NCT06012240
Inclusion Criteria:
* Adult individuals must be \< 64 years old at Baseline Visit. Where permitted outside United States (US)/European Union (EU), adolescent individuals who are at least 12 years old at Screening may participate in Study 1 and Study 2. Adolescent individuals in the US who are at least 12 years old at Screening may participate in Study 4.
* Diagnosis of severe alopecia areata (AA) with Severity of Alopecia Tool (SALT) score \>= 50 scalp hair loss at Screening and Baseline.
* Severe AA with no spontaneous scalp hair regrowth over the past 6 months.
* Current episode of AA of less than 8 years.
Exclusion Criteria:
* Current diagnosis of primarily diffuse type of AA.
* Current diagnosis of other types of alopecia that would interfere with evaluation of AA, including but not limited to female pattern hair loss, male pattern hair loss (androgenetic alopecia) Stage III or greater based on Hamilton-Norwood classification, traction alopecia, lichen planopilaris (LPP), discoid lupus, frontal fibrosing alopecia (FFA), central centrifugal cicatricial alopecia (CCCA), folliculitis decalvans, trichotillomania, and telogen effluvium.
* Diagnosis of other types of inflammatory scalp, eyebrow, or eyelash disorders that would interfere with evaluation of AA as determined by the investigator, including but not limited to seborrheic dermatitis, scalp psoriasis, atopic dermatitis (AD), and tinea capitis. DRUG: Upadacitinib, DRUG: Placebo
Alopecia Areata
Alopecia Areata, Upadacitinib, Rinvoq, ABT-494
A Study of Eltrekibart (LY3041658) in Adult Participants With Moderate to Severe Hidradenitis Suppurativa
clinicaltrials@northshore.org
ALL
18 years to 75 years old
PHASE2
NCT06046729
Inclusion Criteria:
* Have a diagnosis of HS for at least 12 months.
* Have HS lesions in at least 2 distinct anatomical regions. At least 1 of the lesions must be at least Hurley Stage II or III.
* Have an (abscess plus inflammatory nodule) count of at least 5.
* Agree to use topical antiseptics daily.
* Had an inadequate response or intolerance to a 28-day course of oral antibiotics.
Exclusion Criteria:
* Have more than 20 draining fistulae.
* Have had surgical treatment for HS in the last 4 weeks before randomization.
* Have an active skin disease or condition, that could interfere with the assessment of HS.
* Have a current or recent acute, active infection.
* Are immunocompromised.
* Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug abuse within 1 year before screening. DRUG: Eltrekibart, DRUG: Placebo
Hidradenitis Suppurativa
A Study to Evaluate Effectiveness and Safety of Deucravacitinib in Participants With Non-Pustular Palmoplantar and Genital Psoriasis
clinicaltrials@northshore.org
ALL
18 years and over
PHASE4
NCT06042920
Key
Inclusion Criteria:
Inclusion Criteria for Non-Pustular Palmoplantar Psoriasis
* Men and women diagnosed with stable plaque psoriasis with involvement of the palm(s)and/or sole(s) for at least 6 months or more. Stable psoriasis is defined as no morphology changes or significant flares of disease activity in the opinion of the investigator.
* Moderate-to-severe plaque psoriasis defined as s-PGA score of ≥ 3 on a 5-point scale at both screening visit and Day 1.
* Moderate-to-severe non-pustular PP psoriasis, defined as pp-PGA score of ≥ 3 on a 5-pointscale and pp-PASI ≥ 8 at both screening visit and Day 1.
* A total maximum of 5 sterile pustules across both palms and soles limited only to psoriatic plaques will be allowed.
* Evidence of typical plaque psoriasis outside palms and soles at both screening visit and Day 1.
* Deemed by the investigator to be a candidate for phototherapy or systemic therapy.
* Failed to respond to, or intolerant of ≥ 1 topical therapy.
Inclusion Criteria for Genital Psoriasis
* Men and women diagnosed with stable plaque psoriasis with involvement of the genital area for at least 6 months or more. Stable psoriasis is defined as no morphology changes or significant flares of disease activity in the opinion of the investigator.
* Moderate-to-severe plaque psoriasis defined as s-PGA score of ≥ 3 on a 5-point scale at both screening visit and Day 1.
* Moderate-to-severe GenPs, defined as static Physician's Global Assessment of Genitalia (s-PGA-G) score of ≥ 3 on a 6-point scale at both screening visit and Day 1.
* Evidence of typical plaque psoriasis in a non-genital area at both screening visit and Day 1.
* Deemed by the investigator to be a candidate for phototherapy or systemic therapy.
* Failed to respond to, or intolerant of ≥ 1 topical therapy.
Key Exclusion Criteria:
Target Disease Exceptions
* Has non-plaque psoriasis (for PP pustulosis, PP pustular psoriasis, isolated pustules on palms or soles with or without erythema outside psoriatic plaques, guttate, pustular, erythrodermic, and drug-induced psoriasis) at screening or Day 1.
Other protocol-defined inclusion/exclusion criteria apply. DRUG: Deucravacitinib, DRUG: Placebo
Palmoplantar Psoriasis, Genital Psoriasis
Deucravacitinib, BMS-986165, SOTYKTU, Plaque psoriasis
A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Heart Failure and Inflammation (HERMES)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT05636176
Inclusion Criteria:
* Serum high-sensitivity C-reactive protein (hs-CRP) greater than equal to 2 milligrams per liter (mg/L) at screening (visit 1) Disease specific - cardiovascular
* At least one of the following:
• N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than equal to 300 picograms per milliliter (pg/mL) at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP must be greater than equal to 600 pg/mL. Note that the screening electrocardiogram (ECG) must be obtained the same day as sampling for NT-proBNP.
• Hospitalisation or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to screening (visit 1) in combination with NT-proBNP greater than equal to 200 pg/mL at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NT-proBNP must be greater than equal to 600 pg/mL. * Diagnosis of heart failure (New York Heart Association \[classification\] \[NYHA\] Class II-IV). * Left ventricular ejection fraction (LVEF) greater than 40 percentage (%) documented by echocardiography within 12 months prior to or at screening (visit 1). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (e.g., myocardial infarction \[MI\] or heart failure \[HF\] hospitalisation). * Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing at least one of the following: * Left atrial (LA) volume index greater than 34 milliliter per meter square (mL/m\^2). * LA diameter greater than equal to 3.8 centimeter (cm). * LA length greater than equal to 5.0 cm. * LA area greater than equal to 20 cm square. * LA volume greater than equal to 55 milliters (mL). * Intraventricular septal thickness greater than equal to 1.1 cm. * Posterior wall thickness greater than equal to 1.1 cm. * Left ventricular (LV) mass index greater than equal to 115 grams per meter square (g⁄m\^2 ) in men or greater than equal to 95 g⁄m\^2 in women. * E/e' (mean septal and lateral) greater than equal to 10. * e' (mean septal and lateral) less than 9 centimeter per second (cm/s). * No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and randomisation (visit 2).
Exclusion Criteria:
Medical conditions - cardiovascular
* Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation, within 30 days prior to screening (visit 1).
* Systolic blood pressure greater than equal to 180 millimeters of mercury (mmHg) at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patient should be receiving greater than equal to 3 antihypertensive drugs. (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Heart rate above 110 or below 40 beats per minute as evaluated on the electrocardiogram (ECG) performed at screening (visit 1) (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1). (Note: Planned coronary angiogram is not exclusionary).
* Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1).
* Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2).
* Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease.
* Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
* Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).
Medical conditions - infections/immunosuppression
\- Clinical evidence of, or suspicion of, active infection at the discretion of the investigator. DRUG: Ziltivekimab, DRUG: Placebo
Heart Failure
Study of Remibrutinib (LOU064) Efficacy and Safety and Exploration of Its Mechanism of Action in Participants With Chronic Urticaria
clinicaltrials@northshore.org
ALL
18 years to 100 years old
PHASE2
NCT06865651
Inclusion Criteria:
• Signed informed consent must be obtained prior to participation in the study.
• Male and female participants ≥ 18 years of age at the time of signing of the informed consent forms.
• CINDU patients: Confirmed diagnosis of CINDU with a duration of ≥ 4 months (defined as onset of CINDU with supporting documentation (e.g. medical record, clinical history, photographs) and inadequate control with H1-AH at local label approved doses at the time of randomization. The response to the provocation test for each CINDU subtype is required before randomization (either during screening or prior to randomization on Day 1):
• CINDU patients: Patients should be symptomatic for their most bothersome symptom as assessed with the USDD during baseline with a NRS score of 3 or more
• CSU patients: Diagnosis of CSU (acc. to Zuberbier et al 2022c) not adequately controlled with H1-AH at approved doses alone for at least 4 weeks prior to randomization, as defined by all of the following: * UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during 7 days prior to randomization * CSU for ≥ 6 months
• Participants must be willing and able to attend the protocol defined test procedure throughout the study.
Exclusion Criteria:
• Participants who have a familial/hereditary form (e.g. familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study.
• Diseases, other than CSU or CINDU, with urticaria or angioedema symptoms including but not limited to: * urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), * food allergies yielding urticaria symptoms when the allergen is not avoided by the dietary habits of the participant * hereditary or acquired angioedema.
• CINDU patients only: To prevent any confounding effect of CSU symptoms, the CINDU study population will consist of participants with predominant CINDU and should not have a significant share of CSU symptoms (that might make the assessment of CINDU symptoms difficult) as per the investigator's judgement.
• CSU patients only: Patients should have no relevant inducible urticaria trigger
• Any other skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism
• Known or suspected ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis) and/or known positivity for Human Immunodeficiency Virus (HIV) infection.
• Evidence of an ongoing Hepatitis C infection (defined by the detection at screening of Hepatitis C virus antibodies (anti-HCVAb) and hepatitis C ribonucleic acid (HCV-RNA) in participants who are positive for anti-HCVAb) and/or an ongoing Hepatitis B infection (defined by the detection of Hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus (HBV)-DNA at screening; participants who are positive for anti-hepatitis B core (HBc) antibodies but who are negative for antibodies against HBsAg and HBV-DNA can be included into the study if they agree to monitoring for HBsAg and HBV-DNA reactivation).
• Major surgery within 8 weeks prior to screening or planned surgery for the duration of the study.
• Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Screening), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant.
• Uncontrolled disease states, such as asthma, or inflammatory bowel disease, or any other disease where flares are commonly treated with oral or parenteral corticosteroids.
• History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
• History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN values, or abnormal urinary constituents (e.g. proteinuria, hematuria) * Evidence of urinary obstruction, or difficulty in voiding at screening * Evidence of congenital renal abnormalities with known effect on renal function * Calculated eGFR \< 60 mL/min
• Hematology parameters at screening: * Hemoglobin: \< 10 g/dL * Platelets: \< 100,000/mm3 * Leucocytes: \< 3,000/mm3 * Neutrophils:\< 1,500/mm3
• History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening
• Use of other investigational drugs s within 5 half-lives or within 30 days (for small molecules) prior to Screening or until the expected pharmacodynamic (PD) effect has returned to baseline (for biologics), whichever is longer; or longer if required by local regulations
• Contraindications to or hypersensitivity to remibrutinib (or its excipients or to drugs of similar chemical classes) or other substances provided to the subjects as rescue medication to control symptoms, such as antihistamines.
• Participants taking prohibited therapies as listed in Section 6.6.2. In particular patients with pretreatment with remibrutinib or another BTK-inhibitor within 4 months prior to randomization.
• History of live or live attenuated vaccine within 6 weeks prior to randomization or requirement to receive these vaccinations at any time during the study drug treatment.
• Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d which are allowed. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
• Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC)).
• History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion)
• Significant bleeding risk or coagulation disorders.
• Known history or evidence of ongoing alcohol or drug abuse within the last 6 months before randomization as per source records.
• Pregnant or nursing (breast feeding) women.
• Women of child-bearing potential, defined as fertile, following menarche and until becoming post-menopausal unless they are permanent sterile or they are using highly effective methods of contraception during dosing for 7 days after stopping study treatment. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Bilateral oophorectomy with or without hysterectomy, total hysterectomy or bilateral salpingectomy at least six weeks prior to the first dose of study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered to be not of child-bearing potential. * Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks prior to the first dose of study treatment) * Male partner sterilization (vasectomy) of male partner(s) of the female participant at least six months prior to screening). The vasectomized male partner should be sole partner for that participant and received medical assessment of the surgical success. * Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception. The decision on the contraceptive method should be reviewed at least every 3 months to evaluate the individual need and compatibility of the method chosen. In case of use of hormonal contraception, women should have been stable on the same method for a minimum of 3 months before taking study treatment. Women are considered post-menopausal if they have no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Women are considered not of child-bearing potential if they are post-menopausal or permanently sterileor have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks prior to first dose of study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child-bearing potential. If local regulations are more stringent than the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.
DRUG: Remibrutinib, DRUG: Placebo
Chronic Urticaria (CU): Chronic Inducible Urticaria (CINDU) and Chronic Spontaneous Urticaria (CSU)
Remibrutinib, LOU064, Chronic urticaria, CINDU, CSU, Symptomatic dermographism, Cold urticaria, Cholinergic urticaria, Heat urticaria, Solar urticaria, Delayed pressure urticaria, Aquagenic urticaria, Contact urticaria
Ataciguat for Slowing the Progression of Moderate Calcific Aortic Valve Stenosis: A Randomized, Placebo Controlled Study (KATALYST-AV)
clinicaltrials@northshore.org
ALL
50 years and over
PHASE2
NCT07001800
Key
• Adult male or female at least 50 years of age
• Has moderate CAVS as defined by:
• An AVA of ≥1.0 cm2 to ≤1.50 cm2
• An AVC score between ≥600 to 1200 Agatston units (AU) for women and between ≥600 to 2000 AU for men
• Has a left ventricular ejection fraction (EF) of ≥45% at the time of Screening as determined by the echocardiography Imaging Core Laboratory
• For participants on beta blockade, the dose must be stable for at least 90 days prior to the Screening Visit with no anticipated changes during the study Key
• For participants in the CPET sub-study in Part A and all participants in Part B: Has any medical or physical condition that, in the Investigator's opinion, could lead to an inability to complete Protocol-required CPET procedures (eg, pulmonary disease, joint, leg, hip, back conditions that limit physical activity, or other absolute contraindications for CPET)
• Anticipated or planned prior aortic valve replacement, repair, surgery, or intervention in the next 6 months
• Has moderate, moderate-to-severe, or severe (Grade 2 or higher) mitral stenosis, mitral regurgitation, and/or aortic regurgitation
• Has suspected or known congenital aortic valve disease including bicuspid aortic valve
• New York Heart Association (NYHA) Class III or Class IV
• Has a primary etiology for heart failure other than aortic valve disease
• Has coronary artery disease or anticipating coronary stenting surgery
• Abnormal electrocardiogram (ECG) results or long-standing persistent or permanent atrial fibrillation
Inclusion Criteria:
• Adult male or female at least 50 years of age
• Has moderate CAVS as defined by:
• An AVA of ≥1.0 cm2 to ≤1.50 cm2
• An AVC score between ≥600 to 1200 Agatston units (AU) for women and between ≥600 to 2000 AU for men
• Has a left ventricular ejection fraction (EF) of ≥45% at the time of Screening as determined by the echocardiography Imaging Core Laboratory
• For participants on beta blockade, the dose must be stable for at least 90 days prior to the Screening Visit with no anticipated changes during the study Key
Exclusion Criteria:
• For participants in the CPET sub-study in Part A and all participants in Part B: Has any medical or physical condition that, in the Investigator's opinion, could lead to an inability to complete Protocol-required CPET procedures (eg, pulmonary disease, joint, leg, hip, back conditions that limit physical activity, or other absolute contraindications for CPET)
• Anticipated or planned prior aortic valve replacement, repair, surgery, or intervention in the next 6 months
• Has moderate, moderate-to-severe, or severe (Grade 2 or higher) mitral stenosis, mitral regurgitation, and/or aortic regurgitation
• Has suspected or known congenital aortic valve disease including bicuspid aortic valve
• New York Heart Association (NYHA) Class III or Class IV
• Has a primary etiology for heart failure other than aortic valve disease
• Has coronary artery disease or anticipating coronary stenting surgery
• Abnormal electrocardiogram (ECG) results or long-standing persistent or permanent atrial fibrillation
DRUG: Ataciguat, DRUG: Placebo
Moderate Aortic Valve Stenosis
Ataciguat, sGC activator, sGC stimulator, Aortic valve stenosis, Moderate aortic valve stenosis, Calcific aortic valve stenosis, CAVS, Moderate Calcific Aortic Valve Stenosis, Aortic Stenosis (AS)
Long-Term Safety Study of Deucravacitinib Versus Ustekinumab in Participants With Psoriasis (PRAGMATYK)
clinicaltrials@northshore.org
ALL
40 years and over
PHASE3
NCT07116967
Inclusion Criteria:
* Participants with moderate-to-severe plaque psoriasis:
• Deemed by the Investigator to be a candidate for phototherapy or systemic treatment for psoriasis, including ustekinumab;
• Have at least 1 of the following cardiovascular risk factors: * Current cigarette smoker * Diagnosis of hypertension * Diagnosis of hyperlipidemia * Diabetes mellitus type 1 or 2 * History of one or more of the following cardiovascular events: Coronary intervention (PCI) or coronary artery bypass grafting (CABG), myocardial infarction (heart attack), cardiac arrest, hospitalization for unstable angina, acute coronary syndrome, stroke, or transient ischemic attack * Obesity * Family history of premature coronary heart disease or sudden death in a first-degree male relative younger than 55 years of age or in a first-degree female relative younger than 65 years of age.
Exclusion Criteria:
* Participants must not have recent history of 1 of the following cardiovascular events: MI, stroke, or coronary revascularization, or VTE within 90 days prior to Day 1.
* Participants must not have unstable CVD, defined as a recent clinical cardiovascular event (eg, unstable angina, rapid atrial fibrillation), or a cardiac hospitalization (eg, pacemaker implantation, HF) within 90 days prior to Day 1.
* Participants must not have evidence of active cancer or history of cancer (solid organ or hematologic malignancy including myelodysplastic syndrome) or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma, or carcinoma of cervix in situ that has been treated with no evidence of recurrence).
* Other protocol define inclusion/exclusion criteria apply. DRUG: Deucravacitinib, DRUG: Ustekinumab
Plaque Psoriasis
Deucravacitinib, Plaque psoriasis, Cardiovascular risk, PRAGMATYK
A Study of Eloralintide (LY3841136) in Participants With Obesity or Overweight, and Type 2 Diabetes (ENLIGHTEN-2)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT07282600
Inclusion Criteria:
* Have type 2 diabetes
* Are on stable treatment for type 2 diabetes for at least 90 days prior to screening
* Have a BMI ≥ 27 kg/m2
* Have a stable body weight (\<5% body weight change) for 90 days prior to screening
Exclusion Criteria:
* Have a prior or planned surgical treatment for obesity (liposuction, cryolipolysis, or abdominoplasty allowed if performed \>1 year before screening)
* Have a prior or planned endoscopic procedure and/or device-based therapy for obesity (prior device-based therapy acceptable if device removal was more than 6 months prior to screening)
* Have type 1 diabetes
* Have taken any of the following antihyperglycemic medications within 90 days before screening:
* amylin analogs
* glucagon-like peptide-1 (GLP-1) receptor agonists
* glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP) receptor agonists, or
* insulin
* Have had within 90 days prior to screening:
* heart attack
* stroke
* coronary artery revascularization
* unstable angina, or
* hospitalization due to congestive heart failure
* Have a history or diagnosis of New York Heart Association Functional Classification Class IV congestive heart failure
* Have taken medications or alternative remedies intended for weight loss within 90 days of screening DRUG: Eloralintide, DRUG: Placebo
Overweight, Obesity
Type 2 Diabetes