A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study of the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Crohn's Disease
Overview
- Phase
- Phase 3
- Intervention
- risankizumab IV
- Conditions
- Crohn's Disease
- Sponsor
- AbbVie
- Enrollment
- 931
- Locations
- 475
- Primary Endpoint
- US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of risankizumab versus placebo during induction therapy in participants with moderately to severely active Crohn's disease (CD).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Diagnosis of CD for at least 3 months prior to 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 conventional or to biologic therapy for CD.
- •If female, participant must meet the contraception recommendations.
Exclusion Criteria
- •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 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.
Arms & Interventions
Risankizumab Dose 1 (Period 1)
Participants randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion.
Intervention: risankizumab IV
Risankizumab Dose 2 (Period 1)
Participants randomized to receive risankizumab dose 2 administered by intravenous (IV) infusion.
Intervention: risankizumab IV
Placebo (Period 1)
Participants randomized to receive placebo for risankizumab administered by intravenous (IV) infusion.
Intervention: placebo for risankizumab
Risankizumab Dose 1 (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.
Intervention: risankizumab IV
Risankizumab Dose 2 (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.
Intervention: risankizumab SC
Risankizumab Dose 3 (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.
Intervention: risankizumab SC
Outcomes
Primary Outcomes
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission
Time Frame: 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
Time Frame: 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
Time Frame: 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 Endoscopic Response
Time Frame: 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).
Secondary Outcomes
- US Specific: Percentage of Participants With Clinical Remission(Week 12)
- US Specific: Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline(Week 12)
- US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission(Week 4)
- US Specific: Percentage of Participants With Stool Frequency (SF) Remission(Week 12)
- Global Outside of US: Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue(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: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission(Week 12)
- US Specific: Percentage of Participants With Endoscopic Remission(Week 12)
- US Specific: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at(Week 12)
- US Specific: Percentage of Participants With CD-Related Hospitalization(Week 12)
- US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response(Week 12)
- US Specific: Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue(Week 12)
- US Specific: Percentage of Participants With CDAI Clinical Response and Endoscopic Response(Week 12)
- US Specific: Percentage of Participants With Abdominal Pain (AP) Remission(Week 12)
- US Specific: Percentage of Participants With Enhanced Clinical Response(Week 12)
- Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response(Week 12)
- US Specific: Percentage of Participants With Ulcer-Free Endoscopy(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(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(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: 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 CD-Related Hospitalization(Week 12)
- Global Outside of US: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) Score(Week 12)