Dose Ranging Study of BMS-945429 in Subjects With Moderate to Severe Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety, efficacy and dose response of BMS-945429 in subjects with moderate to severe Crohn's disease and who have had an insufficient response to conventional therapy or have failed Anti-Tumor Necrosis Factor (anti-TNF) therapy.

Official Title
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A Phase IIb, Double-Blind, Randomized, Placebo-Controlled, Double-Dummy, Dose-Ranging Study to Evaluate the Clinical Efficacy and Safety of Induction and Maintenance Therapy With BMS-945429 in Subjects With Moderate to Severe Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: Placebo matching with BMS-945429
* Biological: Placebo matching with BMS-945429
* Biological: Placebo matching with BMS-945429
* Biological: Placebo matching with BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed Crohn's Disease diagnosis via radiology, endoscopy or histology within prior 12 months. Diagnosed for at least 3 months Active Disease with Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 Failed conventional therapy or steroid dependent Exclusion Criteria: Diagnosed/clinical findings of Ulcerative Colitis (UC), indeterminate colitis, non colonic/ileal disease Stricture/stenosis, Stoma, proctocolectomy, subtotal colectomy, ileorectal anastomosis History of diverticulitis, or evidence of Gastrointestinal (GI) perforations

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: Induction Cohort: Placebo matching with BMS-945429 (Clazakizumab)<br> | Biological: Placebo matching with BMS-945429<br>* Injection, Intravenous (IV), 0 mg, Day One Only, One Day<br>Biological: Placebo matching with BMS-945429<br>* Injection, Subcutaneous (SC), 0 mg, Every 4 weeks, 8 weeks<br>|
| Experimental: Induction Cohort: BMS-945429 (Clazakizumab)(600 IV/200 SC mg)<br> | Biological: Placebo matching with BMS-945429<br>* Injection, Subcutaneous (SC), 0 mg, Week 4 Only, One Day<br>Biological: BMS-945429<br>* Injection, Intravenous (IV), 600 mg, Day One Only, One Day<br>* Other names: Clazakizumab;Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 200 mg, Week 8 only, One Day<br>* Other names: Clazakizumab;|
| Experimental: Induction Cohort: BMS-945429 (Clazakizumab)(300 IV/100 SC mg)<br> | Biological: Placebo matching with BMS-945429<br>* Injection, Subcutaneous (SC), 0 mg, Week 4 Only, One Day<br>Biological: BMS-945429<br>* Injection, Intravenous (IV), 300 mg, Day One Only, One Day<br>* Other names: Clazakizumab;Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 100 mg, Week 8 Only, One Day<br>* Other names: Clazakizumab;|
| Experimental: Induction Cohort: BMS-945429 (Clazakizumab)(150 IV/100 SC mg)<br> | Biological: Placebo matching with BMS-945429<br>* Injection, Subcutaneous (SC), 0 mg, Week 4 Only, One Day<br>Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 100 mg, Week 8 Only, One Day<br>* Other names: Clazakizumab;Biological: BMS-945429<br>* Injection, Intravenous (IV), 150 mg, Day One Only, One Day<br>* Other names: Clazakizumab;|
| Experimental: Induction Cohort: BMS-945429 (Clazakizumab)(400 SC/200 SC mg)<br> | Biological: Placebo matching with BMS-945429<br>* Injection, Intravenous (IV), 0 mg, Day One Only, One Day<br>Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 200 mg, Week 8 only, One Day<br>* Other names: Clazakizumab;Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 400 mg, Day One and Week 4, 4 weeks<br>* Other names: Clazakizumab;|
| Experimental: Maintenance Cohort: Placebo matching with BMS-945429 (Clazakizumab)<br> | Biological: Placebo matching with BMS-945429<br>* Injection, Subcutaneous (SC), 0 mg, Every 4 weeks, Up to 48 weeks<br>|
| Experimental: Maintenance Cohort: BMS-945429 (Clazakizumab)(100 SC mg)<br> | Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 100 mg, Every 4 weeks, Up to 48 weeks<br>* Other names: Clazakizumab;|
| Experimental: Maintenance Cohort: BMS-945429 (Clazakizumab)(200 SC mg)<br> | Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 200 mg, Every 4 weeks, Up to 48 weeks<br>* Other names: Clazakizumab;|
| Experimental: Open Label Cohort: BMS-945429 (Clazakizumab)(200 SC mg)<br> | Biological: BMS-945429<br>* Injection, Subcutaneous (SC), 200 mg, Every 4 weeks, Up to 96 weeks, depending on when subject enters this period<br>* Other names: Clazakizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI) | CDAI scores range from 0 to 600. A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. A decrease in greater than 100 points indicates a clinically significant improvement in disease activity | At 8 weeks during the Induction Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI | CDAI scores range from 0 to 600. A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. A decrease in greater than 100 points indicates a clinically significant improvement in disease activity | At 8 weeks during the Induction Period | 
| Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | IBDQ consists of 32 questions divided into four dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items) and social function (5 items). Every question has graded responses from 1 (worst situation) to 7 (best situation), and thus the total score is ranging from 32 to 224 with higher scores representing better quality of life. | Week 8 and Week 12 | 
| Number of Participants During the Induction Period With Anti-clazakizumab Antibodies |  | Up to Week 12 | 
| Steady-state Trough Concentration (Cmin) of Clazakizumab During the Induction Period |  | Week 4, Week 8 | 
| Observed Maximum Concentration (Cmax) of Clazakizumab During the Induction Period |  | Week 0 and Week 4 | 
| Area Under the Plasma Concentration-time Curve in One Dosing Interval [AUC(TAU)] of Clazakizumab During the Induction Period |  | Week 0, Week 4, Week 8 |