A Study of the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Crohn's Disease

Phase 3

Completed

Conditions: Crohn's Disease

Interventions: Drug: risankizumab IV
Drug: risankizumab SC
Drug: placebo for risankizumab

Registration Number: NCT03105128

Lead Sponsor: AbbVie

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 931

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Risankizumab Dose 2 (Period 1)	risankizumab IV	Participants randomized to receive risankizumab dose 2 administered by intravenous (IV) infusion.
Risankizumab Dose 2 (Period 2)	risankizumab SC	Participants with inadequate response at Week 12 in Period 1 randomized to receive risankizumab dose 2 administered by subcutaneous (SC) injection in Period 2.
Risankizumab Dose 1 (Period 1)	risankizumab IV	Participants randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion.
Risankizumab Dose 3 (Period 2)	risankizumab SC	Participants with inadequate response at Week 12 in Period 1 randomized to receive risankizumab dose 3 administered by subcutaneous (SC) injection in Period 2.
Placebo (Period 1)	placebo for risankizumab	Participants randomized to receive placebo for risankizumab administered by intravenous (IV) infusion.
Risankizumab Dose 1 (Period 2)	risankizumab IV	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.

Primary Outcome Measures

Name	Time	Method
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission	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	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	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	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 Outcome Measures

Name	Time	Method
US Specific: Percentage of Participants With Clinical Remission	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.
US Specific: Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline	Week 12	Participants without draining fistulas at Week 12 in participants who had draining fistulas at baseline.
Global Outside of US: Change From Baseline in Work Productivity and Impairment Questionnaire - Crohn's Disease (WPAI-CD) Overall Work Impairment	Week 12	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.
Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission	Week 12	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.
US Specific: Percentage of Participants With Endoscopic Remission	Week 12	Endoscopic remission: SES-CD ≤ 4 and at least a 2 point reduction versus baseline and no subscore greater than 1 in any individual variable
US Specific: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at	Week 12	Manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver.
US Specific: Percentage of Participants With CD-Related Hospitalization	Week 12	Participants with at least one admission to the hospital due to Crohn's Disease.
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response	Week 12	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.
US Specific: Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue	Week 12	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.
US Specific: Percentage of Participants With CDAI Clinical Response and Endoscopic Response	Week 12	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).
US Specific: Percentage of Participants With Abdominal Pain (AP) Remission	Week 12	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.
US Specific: Percentage of Participants With Enhanced Clinical Response	Week 12	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
Global Outside of US: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response	Week 12	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.
US Specific: Percentage of Participants With Ulcer-Free Endoscopy	Week 12	Ulcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore ≥ 1 at Baseline
Global Outside of US: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score	Week 12	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.
Global Outside of US: Percentage of Participants With Enhanced Clinical Response	Week 12	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
Global Outside of US: Percentage of Participants With Ulcer-Free Endoscopy	Week 12	Ulcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore ≥ 1 at Baseline
Global Outside of US: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at Baseline	Week 12	Manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver.
Global Outside of US: Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline	Week 12	Participants without draining fistulas at Week 12 in participants who had draining fistulas at baseline.
Global Outside of US: Percentage of Participants With Clinical Remission	Week 4	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 Enhanced Clinical Response and Endoscopic Response	Week 12	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).
Global Outside of US: Percentage of Participants With Endoscopic Remission	Week 12	Endoscopic remission: SES-CD ≤ 4 and at least a 2 point reduction versus baseline and no subscore greater than 1 in any individual variable
Global Outside of US: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) Score	Week 12	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.
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission	Week 4	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.
US Specific: Percentage of Participants With Stool Frequency (SF) Remission	Week 12	Stool Frequency (SF) remission is defined as an average daily SF \<= 2.8 and not worse than baseline.
Global Outside of US: Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue	Week 12	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.
Global Outside of US: Percentage of Participants With CD-Related Hospitalization	Week 12	Participants with at least one admission to the hospital due to Crohn's Disease.

Trial Locations

Locations (475): Phoenix VA Health Care System /ID# 162267
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Phoenix, Arizona, United States
HonorHealth Research Institute - Shea /ID# 161783
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Scottsdale, Arizona, United States
Digestive Disease Consultants, A Division of Arizona Digestive Health, P.C /ID# 211883
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Tempe, Arizona, United States
University of Arizona /ID# 158469
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Tucson, Arizona, United States
Atria Clinical Research /ID# 164740
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Little Rock, Arkansas, United States
Newport Huntington Medica /ID# 213033
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Huntington Beach, California, United States
United Medical Doctors /ID# 207040
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Los Alamitos, California, United States
TLC Clinical Research Inc /ID# 212503
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Los Angeles, California, United States
Gastrointestinal Biosciences Clinical Trials, LLC /ID# 162656
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Los Angeles, California, United States
United Medical Doctors - Murrieta /ID# 158424
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Murrieta, California, United States
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Phoenix VA Health Care System /ID# 162267
🇺🇸Phoenix, Arizona, United States