E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 |
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. |
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E.2.2 | Secondary objectives of the trial |
1) Compare the efficacy of BMS-936557 vs. placebo for induction of clinical response (defined as 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) at Week 11 (IP-78).
2) Compare the efficacy or BMS-936557 vs. placebo for induction of mucosal healing (defined as endoscopy subscore of ≤1 point) at Week 11 (IP-78).
3) Assess health-related quality of life outcome (IBDQ) of BMS-936557 and placebo in the induction period.
4) Assess the safety of BMS-936557 in the induction period |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Exploratory Objectives for Induction Period (see section 1.3.3.1 of the protocol):
- Assess the efficacy of BMS-936557 and placebo for induction of histologic remission (Geboes index score < 2.0) at Week 11 (IP-78)
- Assess the pharmacodynamics of BMS-936557 and placebo in whole blood and colon biopsies, including total and free IP-10 levels, and correlate with drug exposure and response to treatment
Exploratory Objectives for Maintenance Period (see section 1.3.3.1 of the protocol):
- Assess the efficacy of BMS-936557 vs placebo for maintenance of histologic remission (Geboes index score < 2.0) at Week 24 and Week 48 (MP-169 and MP-337)
- Assess the pharmacodynamics of BMS-936557 vs placebo in whole blood and colon biopsies, including total and free IP-10 levels, and correlate with drug exposure and response to treatment |
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E.3 | Principal inclusion criteria |
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) |
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E.4 | Principal exclusion criteria |
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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Compare the efficacy of BMS-936557 vs placebo for induction of clinical remission (defined as Mayo score ≤ 2 points with no individual subscore > 1 point) at Week 11 [Induction Period-78 (IP-78)] |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of Induction (Week 11, IP-78) |
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E.5.2 | Secondary end point(s) |
1) Compare the efficacy of BMS-936557 vs. placebo for induction of clinical response (defined as 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) at Week 11 (IP-78).
2) Compare the efficacy or BMS-936557 vs. placebo for induction of mucosal healing (defined as endoscopy subscore of ≤1 point) at Week 11 (IP-78).
3) Assess health-related quality of life outcome (IBDQ) of BMS-936557 and placebo in the induction period.
4) Assess the safety of BMS-936557 in the induction period |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
Brazil |
Canada |
France |
Germany |
Hungary |
Italy |
Mexico |
Netherlands |
Poland |
South Africa |
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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The end of the study is the last visit of the last subject in Open Label. Open Label is planned to continue until 12 months after approval of the study drug by the responsible health authority or until the drug becomes commercially available within the country whichever comes first. In case the study would be earlier terminated due to safety concerns, the drug would not continue to be provided to ongoing subjects even if they are benefiting from the treatment. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |