E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis. |
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E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis is a chronic condition characterized by red, itchy, dry, bumpy patches of skin. Lesions are typically found in the hands, neck, upper chest, inner elbows, and backs of the knees. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate the efficacy of BMS-986166 and of branebrutinib, each versus placebo at Week 16 in patients with moderate-to-severe Atopic Dermatitis. |
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E.2.2 | Secondary objectives of the trial |
- To further evaluate the efficacy of BMS-986166 and of branebrutinib, each versus placebo at Week 16 in patients with moderate-to-severe Atopic Dermatitis. - To assess the safety and tolerability of BMS-986166 and of branebrutinib in patients with moderate-to-severe Atopic Dermatitis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•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.
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E.4 | Principal exclusion criteria |
•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), vaccination with live attenuated vaccines 90 days prior to treatment, during the study, and for 60 days after end of treatment •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
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Mean percentage change from baseline in Eczema Area and Severity Index (EASI) score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 3. Proportions of participants exhibiting a ≥ 50% (EASI-50) reduction from baseline in EASI score 4. Proportion of participants exhibiting a ≥ 4-point improvement from baseline in Pruritus NRS at Week 16. 5. Mean percentage change from baseline in Pruritus Numerical Rating Scale (NRS) score 6. Mean change from baseline in percentage of affected Body Surface Area (BSA) 7. Incidence and severity of all AE, and SAE 8. Incidence and severity of clinically significant changes in vital signs, ECG, OCT, PFT, and/or safety laboratory tests |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Canada |
Germany |
Poland |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as the last contact with the last participant (either last visit at which the last endpoint data is collected or last contact which could be a phone call). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 15 |