A Phase 2, Double-blind, placebo-controlled study of BMS-986166 or Branebrutinib in Patients with Moderate to Severe Atopic Dermatitis.
- Conditions
- Moderate to Severe Atopic Dermatitis.MedDRA version: 21.1Level: LLTClassification code 10003639Term: Atopic dermatitisSystem Organ Class: 100000004858Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2020-004767-77-ES
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 240
•Females or males 18 (or local age of majority)-65 years inclusive
•Dx of AD of at least 24 months duration
•Screening EASI = 12 and = 16 at baseline
•vIGA = 3 at screening and baseline
•documented history of inadequate control of AD by a stable regimen (= 4 weeks) of topical corticosteroids, calcineurin inhibitors or biologics, within 6 months of randomization or inappropriateness of tx dur to side effects or safety risks.
•Documentation of positive VZV Ig antibody status or complete VZV vaccination within 90 days of first dosing.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 230
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
•Any major illness, condition, infection, cancer or hx of cancer or lymphoproliferative disease, including prelymphoma
•Pregnancy, lactation, or plans for either
•Clinically relevant cardiovascular or pulmonary conditions (including severe sleep apnea)
•History of significant ocular disease
•History of diabetes mellitus Type 1 or uncontrolled diabetes mellitus Type 2 with hemoglobin ALC > 8% or diabetic patients with significant comorbidities like retinopathy or nephropathy
• History of testicular disease or epididymal disease/disorder except uncomplicated epididymitis successfully treated with antibiotics
•Serum creatinine and total bilirubin > 2mg/dL
•eGFR < 60mL/min/1.73 m2
•ALT/AST > 1.5x ULN
•Hemoglobin < 10 g/dL
•Abnormal OCT test suggestive of macular or choroidal pathology
•Surgery within the past 30 days before first dose or planned surgery during the study
•History of TB
•Positive result for Hepatitis B, Hepatitis C, HIV infection
•History of congenital or acquired immunodeficiency
•Presence of COVID-19 symptoms, COVID (suspected or confirmed) within 12 weeks of screening, at screening, or on Day 1, known or suspected sequelae of any sort following a prior episode of COVID, COVID vaccination within 14 days of screening (or plans to receive COVID vaccine during the study)
•High likelihood (based on subject history) of requiring rescue therapy in < 4 weeks of randomization
•Evidence of acute AD flare between screening and baseline/randomization
•Treatment with anticoagulant or antiplatelet therapies (including aspirin for cardioprotection within 2 weeks prior to randomization
•AD-related prescription or OTC skin barrier treatments within 2 weeks of randomization
•Use of strong or moderate inhibitors or inducers of CYP2C8 or 3A4 within 5 half-lives or 14 days prior to randomization (inhibitors) or within 3 weeks prior to randomization (inducers)
•Use of systemic immunosuppressive drugs or oral herbal immunomodulatory medications within 8 weeks of randomization
•IV immunoglobulin within 8 weeks of randomization or during the study
•Use of biologics within 8 weeks to 6 months (depending on type) prior to randomization
•Prior exposure to BTK inhibitors or S1PR modulators
•Use of any immunomodulator or investigational drug within the longer of 5 PK half-lives or 5 PD half-lives or within 6 months prior to randomization
•WBC < 3000/µL or > 14,000/µL
•ANC < the lower of either LLN or 1500/µL
•ALC < 1000/µL
•Platelet count < 100,000/µL
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): 1. Mean percentage change from baseline in Eczema Area and Severity Index (EASI) score;Timepoint(s) of evaluation of this end point: 1. At Week 16;Main Objective: - To evaluate the efficacy of BMS-986166 and of branebrutinib, each versus placebo at Week 16 in<br>patients with moderate-to-severe Atopic Dermatitis.;Secondary Objective: - To further evaluate the efficacy of BMS-986166 and of branebrutinib, each versus placebo at Week 16 in<br>patients with moderate-to-severe Atopic Dermatitis.<br>- To assess the safety and tolerability of BMS-986166 and of branebrutinib in patients with moderate-to-severe<br>Atopic Dermatitis.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 2. Proportion of participants exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (cleared) or 1 (almost cleared) AND a = 2 point reduction from baseline<br>3. Proportions of participants exhibiting a = 50% (EASI-50) reduction from baseline in EASI score <br>4. Proportion of participants exhibiting a = 4-point improvement from baseline in Pruritus NRS at Week<br>16.<br>5. Mean percentage change from baseline in Pruritus Numerical Rating Scale (NRS) score<br>6. Mean change from baseline in percentage of affected Body Surface Area (BSA) <br>7. Incidence and severity of all AE, and SAE<br>8. Incidence and severity of clinically significant changes in vital signs, ECG, OCT, PFT, and/or safety<br>laboratory tests;Timepoint(s) of evaluation of this end point: 2-8: At Week 16