A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study to Assess the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Crohn's Disease Who Failed Prior Biologic Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 618
- 试验地点
- 403
- 主要终点
- US Specific: Percentage of Participants With Endoscopic Response
研究概览
简要总结
The objective of Study M15-991 is to evaluate the efficacy and safety of risankizumab versus placebo during induction therapy in participants with moderately to severely active CD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged >=18 to <= 80 years, or minimum age of adult consent according to local regulations, at the Baseline Visit. Where locally permissible, participants 16 to < 18 years of age who meet the definition of Tanner stage 5 for development at the Baseline Visit.
- •Confirmed diagnosis of CD for at least 3 months prior to Baseline.
- •Crohn's disease activity index (CDAI) score 220 - 450 at Baseline.
- •Confirmed diagnosis of moderate to severe CD as assessed by stool frequency (SF), abdominal pain (AP) score, and Simple Endoscopic Score for Crohn's Disease (SES-CD).
- •Demonstrated intolerance or inadequate response to biologic therapy for CD.
- •If female, participant must meet the contraception recommendations.
排除标准
- •Participant with a current diagnosis of ulcerative colitis or indeterminate colitis.
- •Participants with unstable doses of concomitant Crohn's disease therapy.
- •Receipt of Crohn's disease approved biologic agents (infliximab, adalimumab, certolizumab, vedolizumab, natalizumab within 8 weeks prior to Baseline or ustekinumab within 12 weeks prior to Baseline), or any investigational biologic or other agent or procedure within minimally 35 days or 5 half-lives prior to Baseline, whichever is longer.
- •Prior exposure to p19 inhibitors (e.g., risankizumab).
- •Complications of Crohn's disease.
- •Having an ostomy or ileoanal pouch.
- •Known active Coronavirus Disease 2019 (COVID-19) infection.
研究组 & 干预措施
Risankizumab Dose 2 (Induction Period 1)
Participants randomized to receive risankizumab dose 2 in Induction Period 1.
干预措施: risankizumab IV (Drug)
Risankizumab Dose 1 (Induction Period 1)
Participants randomized to receive risankizumab dose 1 in Induction Period 1.
干预措施: risankizumab IV (Drug)
Placebo (Induction Period 1)
Participants randomized to receive placebo for risankizumab in Induction Period 1.
干预措施: placebo for risankizumab IV (Drug)
Risankizumab Dose 1 (Induction Period 2)
Participants who received placebo in Period 1 and participants with inadequate response at Week 12 in Period 1 randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion in Period 2.
干预措施: risankizumab IV (Drug)
Risankizumab Dose 2 (Induction Period 2)
Participants with inadequate response at Week 12 in Period 1 randomized to receive risankizumab dose 2 administered by subcutaneous (SC) injection in Period 2.
干预措施: risankizumab SC (Drug)
Risankizumab Dose 3 (Induction period 2)
Participants with inadequate response at Week 12 in Period 1 randomized to receive risankizumab dose 3 administered by subcutaneous (SC) injection in Period 2.
干预措施: risankizumab SC (Drug)
结局指标
主要结局
US Specific: Percentage of Participants With Endoscopic Response
时间窗: Week 12
The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline).
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission
时间窗: Week 12
The CDAI consists of 8 components; 7 are based on participant diary entries, participant interviews, physical examinations, measurement of body weight and height and 1 is based on laboratory analysis. CDAI clinical remission of Crohn's disease is defined as CDAI \< 150.
Global Outside of US: Percentage of Participants With Clinical Remission
时间窗: Week 12
Clinical remission is defined as using the average daily Stool Frequency (SF) ≤ 2.8 and not worse than Baseline AND average daily Abdominal Pain (AP) score ≤ 1 and not worse than Baseline.
Global Outside of US: Percentage of Participants With Endoscopic Response
时间窗: Week 12
The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline).
次要结局
- US Specific: Percentage of Participants With Ulcer-Free Endoscopy(Week 12)
- US Specific: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at Baseline Baseline(Week 12)
- US Specific: Percentage of Participants With CD-Related Hospitalization(Up to Week 12)
- Global Outside of US: Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue(Week 12)
- US Specific: Percentage of Participants With Clinical Remission(Week 12)
- US Specific: Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue(Week 12)
- US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission(Week 4)
- US Specific: Percentage of Participants With CDAI Clinical Response and Endoscopic Response(Week 12)
- US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response(Week 12)
- US Specific: Percentage of Participants With Abdominal Pain (AP) Remission(Week 12)
- US Specific: Percentage of Participants With Stool Frequency (SF) Remission(Week 12)
- US Specific: Percentage of Participants With Endoscopic Remission(Week 12)
- US Specific: Percentage of Participants With Enhanced Clinical Response(Week 12)
- US Specific: Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline(Week 12)
- Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission(Week 12)
- Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response(Week 12)
- Global Outside of US: Percentage of Participants With Clinical Remission(Week 4)
- Global Outside of US: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score(Week 12)
- Global Outside of US: Percentage of Participants With Enhanced Clinical Response and Endoscopic Response(Week 12)
- Global Outside of US:: Percentage of Participants With Endoscopic Remission(Week 12)
- Global Outside of US: Percentage of Participants With Enhanced Clinical Response(Week 12)
- Global Outside of US: Percentage of Participants With Ulcer-Free Endoscopy(Week 12)
- Global Outside of US: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at Baseline Baseline(Week 12)
- Global Outside of US: Percentage of Participants With CD-Related Hospitalization(Week 12)
- Global Outside of US: Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline(Week 12)
- Global Outside of US: Change From Baseline in Work Productivity and Impairment Questionnaire - Crohn's Disease (WPAI-CD) Overall Work Impairment(Week 12)
- Global Outside of US: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) Score(Week 12)