A Study to Assess the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Crohn's Disease Who Failed Prior Biologic Treatment

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: placebo for risankizumab IV
* Drug: risankizumab SC
* Drug: risankizumab IV


Participation Criteria
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Eligibility Criteria
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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. 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. 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 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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risankizumab Dose 1 (Induction Period 1)<br>Participants randomized to receive risankizumab dose 1 in Induction Period 1. | Drug: risankizumab IV<br>* risankizumab administered as intravenous (IV) infusion.<br>* Other names: SKYRIZI;|
| Experimental: Risankizumab Dose 2 (Induction Period 1)<br>Participants randomized to receive risankizumab dose 2 in Induction Period 1. | Drug: risankizumab IV<br>* risankizumab administered as intravenous (IV) infusion.<br>* Other names: SKYRIZI;|
| Placebo Comparator: Placebo (Induction Period 1)<br>Participants randomized to receive placebo for risankizumab in Induction Period 1. | Drug: placebo for risankizumab IV<br>* placebo for risankizumab administered as intravenous (IV) infusion.<br>|
| Experimental: Risankizumab Dose 1 (Induction Period 2)<br>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. | Drug: risankizumab IV<br>* risankizumab administered as intravenous (IV) infusion.<br>* Other names: SKYRIZI;|
| Experimental: Risankizumab Dose 2 (Induction Period 2)<br>Participants with inadequate response at Week 12 in Period 1 randomized to receive risankizumab dose 2 administered by subcutaneous (SC) injection in Period 2. | Drug: risankizumab SC<br>* risankizumab administered by subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Experimental: Risankizumab Dose 3 (Induction period 2)<br>Participants with inadequate response at Week 12 in Period 1 randomized to receive risankizumab dose 3 administered by subcutaneous (SC) injection in Period 2. | Drug: risankizumab SC<br>* risankizumab administered by 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 |
| --- | --- | --- |
| US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission | 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 | 
| US Specific: Percentage of Participants With Endoscopic Response | 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). | Week 12 | 
| Global Outside of US: 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 | 
| Global Outside of US: Percentage of Participants With Endoscopic Response | 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). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| US Specific: 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 | 
| US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response | Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline. | Week 4 | 
| US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response | Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline. | Week 12 | 
| US Specific: 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 four 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 | 
| US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission | Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical remission of Crohn's disease is defined as CDAI < 150. | Week 4 | 
| US Specific: Percentage of Participants With CDAI Clinical Response and Endoscopic Response | Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline. Endoscopic response was a decrease in Simplified Endoscopic Score for Crohn's Disease (SES-CD) > 50% from Baseline (or for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2 point reduction from Baseline). | Week 12 | 
| US Specific: Percentage of Participants With Stool Frequency (SF) Remission | Stool Frequency (SF) remission is defined as an average daily SF <= 2.8 and not worse than baseline. | Week 12 | 
| US Specific: Percentage of Participants With Abdominal Pain (AP) Remission | The Abdominal Pain rating is an assessment that is graded from 0 to 3: 0= None, 1= Mild, 2= Moderate and 3= Severe. AP remission is defined as average daily AP score <= 1 and not worse than baseline. | Week 12 | 
| US Specific: 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 | 
| US Specific: Percentage of Participants With Enhanced Clinical Response | Enhanced clinical response: ≥ 60% decrease in average daily SF and/or ≥ 35% decrease in average daily AP score and both not worse than Baseline, and/or clinical remission | Week 4 | 
| US Specific: Percentage of Participants With Ulcer-Free Endoscopy | Ulcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore ≥ 1 at Baseline | Week 12 | 
| US Specific: Percentage of Participants With Enhanced Clinical Response | Enhanced clinical response: ≥ 60% decrease in average daily SF and/or ≥ 35% decrease in average daily AP score and both not worse than Baseline, and/or clinical remission | Week 12 | 
| US Specific: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at Baseline Baseline | Manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver. | Week 12 | 
| US Specific: Percentage of Participants With CD-Related Hospitalization | Participants with at least one admission to the hospital due to Crohn's Disease. | Up to Week 12 | 
| US Specific: Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline | Participants without draining fistulas at Week 12 in participants who had draining fistulas at baseline. | Week 12 | 
| Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission | The CDAI consists of 8 components; 6 are based on participant diary entries, participant interviews, and physical examinations, and 2 are based on laboratory analysis, and measurement of body weight and height. CDAI clinical remission of Crohn's disease is defined as CDAI < 150. | Week 12 | 
| Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response | Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline. | Week 4 | 
| Global Outside of US: 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 4 | 
| Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response | Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline. | Week 12 | 
| Global Outside of US: 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 four 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 | 
| Global Outside of US: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score | The IBDQ is a 32-item (ranges 1 - 7) self-report questionnaire for patients with IBD to evaluate the patient reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). The IBDQ total Score ranges from 32 to 224 with a higher score indicating better outcome. | Week 12 | 
| Global Outside of US: Percentage of Participants With Enhanced Clinical Response and Endoscopic Response | Enhanced clinical response was defined as ≥ 60% decrease in average daily Stool Frequency and/or ≥ 35% decrease in average daily Abdominal Pain score and both not worse than baseline, and/or clinical remission. Endoscopic Response was defined as a decrease in Simplified Endoscopic Score for Crohn's Disease (SES-CD) > 50% from Baseline (or for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2 point reduction from Baseline). | Week 12 | 
| Global Outside of US:: 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 | 
| Global Outside of US: Percentage of Participants With Enhanced Clinical Response | Enhanced clinical response: ≥ 60% decrease in average daily SF and/or ≥ 35% decrease in average daily AP score and both not worse than Baseline, and/or clinical remission | Week 4 | 
| Global Outside of US: Percentage of Participants With Ulcer-Free Endoscopy | Ulcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore ≥ 1 at Baseline | Week 12 | 
| Global Outside of US: Percentage of Participants With Enhanced Clinical Response | Enhanced clinical response: ≥ 60% decrease in average daily SF and/or ≥ 35% decrease in average daily AP score and both not worse than Baseline, and/or clinical remission | Week 12 | 
| Global Outside of US: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at Baseline Baseline | Manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver. | Week 12 | 
| Global Outside of US: Percentage of Participants With CD-Related Hospitalization | Participants with at least one admission to the hospital due to Crohn's Disease. | Week 12 | 
| Global Outside of US: Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline | Participants without draining fistulas at Week 12 in participants who had 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 | WPAI: CD is a questionnaire used to evaluate lost productivity due to CD ; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity. Total work productivity impairment takes into account both hours missed due to CD symptoms and the patient's assessment of the degree to which CD affected their productivity while working (overall work impairment [OWI]). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. | Week 12 | 
| Global Outside of US: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) Score | The Short Form-36 Health Survey determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36. Scores on each item were summed and averaged (range = 0-100); a positive change from Baseline indicates improvement. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABBV-066, BI 655066