Safety and Efficacy of Deucravacitinib in Participants With Moderate to Severe Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of oral deucravacitinib in participants with moderate to severe ulcerative colitis (UC).

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of BMS-986165 in Subjects With Moderate to Severe Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: BMS-986165
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Must have active ulcerative colitis (UC) extending ≥ 15 cm from the anal verge and confirmed by a screening/baseline colonoscopy/sigmoidoscopy prior to the randomization visit Must have documented diagnosis of UC of at least 3 months' duration prior to screening Must have active moderate to severe UC, as defined by a modified Mayo score of 5 to 9 points, inclusive, which includes a stool frequency (SF) subscore of ≥ 2, and a rectal bleeding (RB) subscore ≥ 1, and a screening endoscopic (ES) subscore of ≥ 2 Exclusion Criteria: Previous/current documented diagnosis of CD, indeterminate colitis, ischemic colitis, or pseudomembranous colitis (other than associated with Clostridium difficile [C. difficile]) Stool positive for C. difficile toxin at screening visit Current or recent (within 12 weeks prior to the randomization visit) evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: BMS-986165<br> | Drug: BMS-986165<br>* Specified Dose on Specified Days<br>* Other names: Deucravacitinib;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Specified Dose on Specified Days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission Response Rate at Week 12 | Clinical remission response rate is the percentage of participants achieving clinical remission, defined as absolute total Mayo Score and absolute Mayo endoscopy, stool frequency, rectal bleeding. Will be calculated using a modified Mayo score with the following: Stool Frequency (SF) subscore ≤ 1, with ≥ 1 point decrease from baseline, and Rectal Bleeding (RB) subscore = 0, and Endoscopic (ES) subscoreb ≤ 1 (modified, excludes friability) The modified Mayo score (0 to 9 points) is the sum of 3 components: the SF, RB, and ES subscores Modified Mayo Score: The modified Mayo score is a 9-point scale; a score of 5 to 9 points (inclusive), which is required for randomization, denotes moderate to severe disease (by protocol definition). considered in clinical remission if a Mayo Score of less than or equal to 2 with no individual subscore greater than 1 | From first dose to 12 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate at 12 Weeks | Clinical response is defined as percentage of participants with a reduction in total Mayo Score and reduction in rectal bleeding subscore Will be defined as the following: A decrease from baseline in the modified Mayo score of ≥ 2 points, and A decrease from baseline in the modified Mayo score ≥ 30%, and A decrease in rectal bleeding(RB) subscore of ≥ 1 point or absolute RB subscore ≤ 1 | From first dose to 12 weeks | 
| Endoscopic Response at Week 12 | Endoscopic response will be defined as percentage of participants with a reduction in the total Ulcerative Colitis Endoscopic Index of Severity score. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scale: Vascular Pattern: Normal (score 0) patchy obliteration (score 1) Obliterated (score 2) Bleeding None (score 0) Mucosal (score 1) Luminal mild (score 2) Luminal Moderate or severe (score 3) Erosions and Ulcers None (score 0) Erosions ( score 1) Superficial Ulcer (2) Deep Ulcer (score 3) A total score represents the following: remission (0-1); mild (2-4); moderate (5-6); and severe (7-8). | up to 12 Weeks | 
| Histological Improvement Response Rate at 12 Weeks | Histologic improvement is defined as percentage of participants with a Geboes score of ≤ 3.1 Neutrophils <5% of crypts, with no crypt destruction, erosions, ulcerations, and granulation tissue. Achieving the following scores for the corresponding grades of the Geboes score: Score of 0 or 1 for Grade 3 (neutrophils in the epithelium: none or < 5% crypts involved), and Score of 0 for Grade 4 (crypt destruction: none), and Score of 0 Grade 5 (erosion or ulceration: no erosions, ulcerations, or granulation tissue) grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease | up to 12 Weeks |