A Study to Assess Adverse Events and Change in Disease Activity of Risankizumab Subcutaneous Induction Treatment for Moderately to Severely Active Crohn's Disease.

Study Overview
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Brief Summary
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Crohn's disease (CD) is a long-lasting disease that causes severe inflammation (redness, swelling), in the digestive tract, most often affecting the bowels. It can cause many different symptoms including abdominal pain, diarrhea, tiredness, and weight loss. This study will assess how safe and effective risankizumab subcutaneous (SC) induction treatment is in treating moderately to severely active CD in adult participants. Risankizumab is an approved drug for adults with CD. This study comprises of a Period A and a Period B. In Period A, participants are placed in 1 of 2 groups to receive either risankizumab SC or Placebo. In Period B, based on response, participants will receive risankizumab SC Dose B or Placebo. Participants who do not have improvement in CD symptoms at Week 12 will receive risankizumab SC Dose C and participants with worsening CD symptoms in period B will receive risankizumab SC. Approximately 276 adult participants with a diagnosis of moderately to severely active CD will be enrolled in approximately 250 sites globally. Participants will receive SC induction treatment of risankizumab or matching placebo for up to 24 weeks in Period A and B. The duration of the study will be approximately 49 weeks.

Official Title
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A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy and Safety of Risankizumab Subcutaneous Induction Treatment in Subjects With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Risankizumab SC
* Drug: Placebo for risankizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-confirmed diagnosis of CD for at least 3 months prior to Baseline. Participant meets the following disease activity criteria: Moderate to severe CD as assessed by COAi Endoscopic evidence of mucosal inflammation as documented by a SES-CD Participant has demonstrated intolerance, loss of response or inadequate response to conventional or advanced therapies for CD. Exclusion Criteria: Participants with a current diagnosis of ulcerative colitis or indeterminate colitis. Participants with unstable doses of concomitant Crohn's disease therapy. Participants with prior exposure to p19 inhibitors. Participants with complications of Crohn's disease. Participants having an ostomy or ileoanal pouch.

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: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period A: Risankizumab Dose A<br>Participants randomized to receive risankizumab Dose A administered by subcutaneous (SC) injection for up to 12 weeks during Period A. | Drug: Risankizumab SC<br>* subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Placebo Comparator: Period A: Placebo<br>Participants randomized to receive placebo risankizumab administered by Subcutaneous (SC) injection for up to 12 weeks during Period A. | Drug: Placebo for risankizumab<br>* subcutaneous (SC) injection<br>|
| Experimental: Period B: Risankizumab Dose B<br>Participants randomized to receive risankizumab Dose A in Period A that achieved adequate response to receive risankizumab Dose B administered by subcutaneous (SC) injection for up to 20 weeks. | Drug: Risankizumab SC<br>* subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Placebo Comparator: Period B: Placebo<br>Participants randomized to receive placebo risankizumab in Period A that achieved adequate response to continue to receive placebo risankizumab administered by Subcutaneous (SC) injection for up to 20 weeks in Period B. | Drug: Placebo for risankizumab<br>* subcutaneous (SC) injection<br>|
| Experimental: Period B: Risankizumab Dose C<br>Participants with inadequate response in Period A to receive Dose C administered by Subcutaneous (SC) injection for up to 20 weeks during Period B | Drug: Risankizumab SC<br>* subcutaneous (SC) injection<br>* Other names: SKYRIZI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission (CDAI < 150) | 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 | Week 12 | 
| Percentage of Participants With Endoscopic Response | The Simple Endoscopic Score for Crohn's Disease (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) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Remission | 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. | Week 12 | 
| Percentage of Participants With Endoscopic Remission | Endoscopic remission: SES-CD ≤ 4 and at least a 2 point reduction versus baseline and no subscore greater than 1 in any individual variable | Week 12 | 
| Percentage of Participants With Ulcer-Free Endoscopy | Ulcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in participants with SES-CD ulcerated surface subscore ≥ 1 at Baseline | Week 12 | 
| Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue | The FACIT-Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a 5-point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement. | Week 12 | 
| Percentage of Participants with a CR-100 Clinical Response | CR-100 defined as at least a 100-point reduction from Baseline in CDAI | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Risankizumab, Skyrizi, Crohn's Disease, ABBV-066