A Study of BMS-986166 or Branebrutinib for the Treatment of Participants With Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, and tolerability of BMS-986166 and of branebrutinib, each versus placebo, for the treatment of participants with moderate to severe atopic dermatitis.

Official Title
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A Phase 2, Randomized, Double-blinded, Placebo-controlled, 5 Parallel-group Study of BMS-986166 or Branebrutinib for the Treatment of Patients With Moderate to Severe Atopic Dermatitis

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: BMS-986166
* Drug: Branebrutinib
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic atopic dermatitis (AD) diagnosed according to the Eichenfield modification of Hanifin's and Rajka's (E-HR) criteria at Screening Disease duration of at least 24 months since diagnosis by any criteria 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 therapy due to side effects or safety risks leading to prior discontinuation Application of fixed doses of an additive-free, basic bland emollient twice-daily for ≥ 7 days before baseline visit and for the duration of the study Exclusion Criteria: Any major illness/condition or evidence of an unstable clinical condition or local active infection/infectious illness that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study or interfere with the interpretation of study results Clinically relevant cardiovascular conditions or pulmonary conditions High likelihood - based on participant history, and investigator judgement - of requiring rescue therapy in < 4 weeks prior to randomization Evidence of acute flare between the Screening and Baseline/ Randomization Skin lesion(s) and/or pruritus due to conditions other than AD that would interfere with the study specified assessments Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Specified dose on specified days<br>|
| Experimental: Treatment BMS-986166 Dose 1<br> | Drug: BMS-986166<br>* Specified dose on specified days<br>|
| Experimental: Treatment BMS-986166 Dose 2<br> | Drug: BMS-986166<br>* Specified dose on specified days<br>|
| Experimental: Treatment BMS-986166 Dose 3<br> | Drug: BMS-986166<br>* Specified dose on specified days<br>|
| Experimental: Treatment Branebrutinib<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change From Baseline in EASI Score at Week 16 | The Eczema Area and Severity Index (EASI) is a validated, composite scoring system assessed by the investigator based on the extent of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD and the intensity of each of 4 key signs of AD (erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (absent), 1 (mild), 2 (moderate), and 3 (severe). For each of the 4 body regions, the mean intensity of inflamed lesions for each of the 4 signs is recorded. Xerosis, scaling, urticaria, or post-inflammatory pigmentation changes are not included. The total EASI score ranges from 0 to 72. The lower the score the better. | From baseline and 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage 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 at Week 16 | The vIGA-AD is a static 5-point assessment intended to assess the global severities of key acute clinical signs of AD, including erythema, induration/papulation, and oozing/crusting (lichenification excluded). The rating of cleared (0), almost cleared (1), mild (2), moderate (3), and severe (4) will be assessed. | From baseline and 16 weeks | 
| Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16 | The Eczema Area and Severity Index (EASI) is a validated, composite scoring system assessed by the investigator based on the extent of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD and the intensity of each of 4 key signs of AD (erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (absent), 1 (mild), 2 (moderate), and 3 (severe). For each of the 4 body regions, the mean intensity of inflamed lesions for each of the 4 signs is recorded. Xerosis, scaling, urticaria, or post-inflammatory pigmentation changes are not included. The total EASI score ranges from 0 to 72. The lower the score the better. | From baseline and 16 weeks | 
| Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16 | Participants will complete a daily diary recording the intensity of their pruritus they experienced during the preceding 24 hours. The intensity of pruritus will be assessed using a validated 11-point NRS, ranging from 0 (no itching) to 10 (the worst itching imaginable). The lower the score the better. | From baseline and 16 weeks | 
| Mean Percentage Change From Baseline in Pruritus NRS Score at Week 16 | Participants will complete a daily diary recording the intensity of their pruritus and the average quality of sleep they experienced during the preceding 24 hours. The intensity of pruritus will be assessed using a validated 11-point NRS, ranging from 0 (no itching) to 10 (the worst itching imaginable). The quality of sleep will be assessed using a validated 11-point NRS ranging from 0 (the best possible sleep) to 10 (the worst possible sleep). The lower the score the better. | From baseline and 16 weeks | 
| Mean Change From Baseline in Percentage of Affected BSA at Week 16 | A widely used method of measuring Body Surface Area (BSA) involvement by AD, is the rule of nines in which for each section of the body (the possible highest score for each region is: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], genitals [1%]) and will be reported as a percentage of all major body sections combined. | From baseline and 16 weeks | 
| Number of Participants With Mild Moderate or Severe AEs | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities. Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not be confused with an SAE. Severe is a category utilized for rating the intensity of an event, and both AEs and SAEs can be assessed as severe. | From initial treatment to 30 days post discontinuation, approximately 29 weeks | 
| Number of Participants With Mild Moderate or Severe SAEs | A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death is life threatening Requires inpatient hospitalization or causes prolongation of existing hospitalization Results in persistent or significant disability Is a congenital anomaly/birth defect. Is an important medical event | From initial treatment to 30 days post discontinuation, approximately 29 weeks | 
| Number of Participants With Clinically Relevant ECG Abnormalities | 12 Lead Electrocardiogram (ECG). The participant will remain supine for 5 to 10 minutes prior to the ECG and must have lab work done after the tracing so that the ECG results remain as accurate as possible. | Week 24 after initial treatment | 
| Number of Participants With Clinically Relevant OCT Abnormalities | Optical coherence tomography (OCT) is a non-invasive imaging test. It uses light waves to take cross-section pictures of your retina. Diagnosis is made by an ophthalmologist. | Week 24 after initial treatment | 
| Number of Participants With Clinically Relevant PFT Abnormalities | Pulmonary function tests (PFT) include: forced expiratory volume (FEV1), percent predicted FEV1, forced vital capacity (FVC), percent predicted FVC, and Diffusion capacity of carbon monoxide (DLCO). | Week 24 after initial treatment | 
| Number of Participants With Clinically Meaningful Changes in Vital Signs | The following vital signs will be assessed: systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and body temperature. | Week 24 after initial treatment | 
| Number of Participants With Clinically Relevant Changes in LFTs | Liver Function Tests (LFTs) will include the following measurements: ALT OR AST > 3 X ULN ALT OR AST > 5 X ULN ALT OR AST > 8 X ULN TOTAL BILIRUBIN > 2 X ULN ALT OR AST > 3 X ULN AND (TOTAL BILIRUBIN > 2 X ULN OR INR >1.5) AST = aspartate aminotransferase ALT = alanine aminotransferase ULN = Upper limit number INR = International Normalized Ratio | Week 24 after initial treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, BMS-986166, BMS-986195, Branebrutinib