Induction and Maintenance Study of BMS-936557 Patients 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 determine whether BMS-936557 is effective in the treatment of moderate to severely active ulcerative colitis in patients who have had insufficient response and/or intolerance to other medical therapy for ulcerative colitis

Official Title
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A Phase IIb Randomized, Placebo-Controlled Study to Evaluate the Clinical Efficacy and Safety of Induction and Maintenance Therapy With BMS-936557 in Subjects With Active Ulcerative Colitis (UC)

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Placebo
* Drug: Placebo
* Drug: Anti-IP-10 Antibody
* Drug: Anti-IP-10 Antibody
* Drug: Anti-IP-10 Antibody
* Drug: Anti-IP-10 Antibody
* Drug: Anti-IP-10 Antibody
* Drug: Anti-IP-10 Antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of moderate to severe UC confirmed by endoscopic and histologic evidence Mayo score ≥6 with an endoscopic subscore of ≥2 Inadequate response and/or intolerance to one or more conventional therapy (i.e. oral aminosalicylates, immunosuppressants, corticosteroids, and/or TNF antagonist) Exclusion Criteria: Diagnosis of Crohn's Disease or Indeterminate Colitis Diagnosis of UC that is limited to the rectum Evidence of fulminant colitis, toxic megacolon, or bowel perforation Current need for a colostomy or ileostomy Previous total or subtotal colectomy

Ages Eligible for Study
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Minimum Age: 18 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: Cohort 1: Induction<br>Placebo or Anti-IP-10 Antibody | Drug: Placebo<br>* Normal Saline, Intravenous, 0mg, Once a week for the first two weeks and every other week thereafter, 7 Weeks<br>Drug: Anti-IP-10 Antibody<br>* Solution for IV administration, Intravenous, 15 mg/kg, Once a week for the first two weeks and every other week thereafter, 7 weeks<br>|
| Experimental: Cohort 2: Induction<br>Placebo or Anti-IP-10 Antibody | Drug: Placebo<br>* Normal Saline, Intravenous, 0mg, Once a week for the first two weeks and every other week thereafter, 7 Weeks<br>Drug: Anti-IP-10 Antibody<br>* Solution for IV administration, Intravenous, 25 mg/kg, Once a week for the first two weeks and every other week thereafter, 7 weeks<br>|
| Experimental: Cohort 3: Induction<br>Placebo or Anti-IP-10 Antibody | Drug: Placebo<br>* Normal Saline, Intravenous, 0mg, Once a week for the first two weeks and every other week thereafter, 7 Weeks<br>Drug: Anti-IP-10 Antibody<br>* Solution for IV administration, Intravenous, 15 mg/kg, Once a week for the first two weeks and every other week thereafter, 7 weeks<br>Drug: Anti-IP-10 Antibody<br>* Solution for IV administration, Intravenous, 25 mg/kg, Once a week for the first two weeks and every other week thereafter, 7 weeks<br>|
| Experimental: Maintenance<br>Placebo or Anti-IP-10 Antibody | Drug: Placebo<br>* Normal Saline, Intravenous, 0 mg, Every other week, Up to 757 days<br>Drug: Anti-IP-10 Antibody<br>* Solution for IV administration, Intravenous, 5 mg/kg, Every other week, Up to 757 days<br>Drug: Anti-IP-10 Antibody<br>* Intravenous, Solution for IV administration, 10 mg/kg, Every other week, Up to 757 days<br>Drug: Anti-IP-10 Antibody<br>* Intravenous, Solution for IV administration, 20 mg/kg, Every other week, Up to 757 days<br>|
| Other: Open Label<br> | Drug: Anti-IP-10 Antibody<br>* Intravenous, Solution for IV administration, 15 mg/kg or optimal dose, Every other week. Open<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of the subjects with clinical remission (defined as Mayo score ≤ 2 points with no individual subscore > 1 point) of BMS-936557 with that of the placebo |  | End of Induction [Week 11, Induction Period-78 (IP-78)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of the subjects with clinical response of BMS-936557 with that of the placebo | Defined as a reduction from baseline in Mayo score ≥3 points and ≥30% and decrease from baseline in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1 point | IP-78 (Week 11) | 
| Proportion of subjects with mucosal healing (defined as endoscopy subscore of ≤1 point) of BMS-936557 with that of the placebo |  | IP-78 (Week 11) | 
| Proportion of subjects reporting Adverse event (AE), Serious adverse events (SAEs), AEs leading to discontinuation, and markedly abnormal laboratory values |  | IP-78 (Week 11) | 
| Mean change from baseline at Inflammatory Bowel Disease Questionnaire (IBDQ) of subjects treated with BMS-936557 and placebo |  | Baseline (IP-1, Week 1) and IP-78 (Week 11) |