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

• ClinicalTrials.gov Identifier: NCT03104413
• Recruitment Status: Active, not recruiting
• First Posted: April 7, 2017
• Last Update Posted: February 26, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: April 4, 2017
• First Posted Date: April 7, 2017
• Last Update Posted Date: February 26, 2021
• Actual Study Start Date: December 18, 2017
• Actual Primary Completion Date: November 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 25, 2020)

• Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission [ Time Frame: Week 12 ]
  The CDAI is used to evaluate disease activity in patients with Crohn's disease.
• Percentage of Participants With Endoscopic Response [ Time Frame: Week 12 ]
  Endoscopic response defined as decrease from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD).

Original Primary Outcome Measures (submitted: April 4, 2017)

• Percentage of participants with clinical remission per average daily stool frequency (SF) and average daily abdominal pain (AP) score at Week 12 [ Time Frame: Week 12 ]
  Clinical remission per average daily SF and average daily AP score.
• Percentage of participants with endoscopic response at Week 12 [ Time Frame: Week 12 ]
  Endoscopic response defined as decrease from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD).

Current Secondary Outcome Measures (submitted: September 25, 2020)

• Percentage of Participants With Clinical Remission [ Time Frame: Up to Week 12 ]
  Clinical remission per average daily SF and average daily AP score.
• Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response [ Time Frame: Up to Week 12 ]
  The CDAI is used to evaluate disease activity in patients with Crohn's disease.
• Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue [ Time Frame: Week 12 ]
  The FACIT-Fatigue is a validated tool that measures an individual's level of fatigue during their usual daily activities.
• Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission [ Time Frame: Week 4 ]
  The CDAI is used to evaluate disease activity in patients with Crohn's disease.
• Percentage of Participants With CDAI Clinical Response and Endoscopic Response [ Time Frame: Week 12 ]
  The CDAI is used to evaluate disease activity in patients with Crohn's disease. Endoscopic response defined as decrease from Baseline in SES-CD.
• Percentage of Participants With Stool Frequency (SF) Remission [ Time Frame: Week 12 ]
  SF remission is defined using the average daily SF, and not worse than baseline.
• Percentage of Participants With Abdominal Pain (AP) Remission [ Time Frame: Week 12 ]
  AP remission is defined using the average daily AP score, and not worse than baseline.
• Percentage of Participants With Endoscopic Remission [ Time Frame: Week 12 ]
  Endoscopic remission is defined as decrease in SES-CD as compared to baseline
• Percentage of Participants With Enhanced Clinical Response [ Time Frame: Up to Week 12 ]
  Enhanced clinical response defined as decrease in average daily SF and/or decrease in average daily AP score, and/or clinical remission per average daily SF and average daily AP score.
• Percentage of Participants With Ulcer-Free Endoscopy [ Time Frame: Week 12 ]
  Endoscopic healing was assessed using SES-CD.
• Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs), in Participants With EIMs at Baseline [ Time Frame: Week 12 ]
  Manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver.
• Percentage of Participants With CD-Related Hospitalization [ Time Frame: Up to Week 12 ]
  Participants with an event that results in admission to the hospital.
• Percentage of Participants Without Draining Fistulas in Participants With Draining Fistulas at Baseline [ Time Frame: Week 12 ]
  Participants without draining fistulas at Week 12 in participants who had draining fistulas at baseline.

Original Secondary Outcome Measures (submitted: April 4, 2017)

• Percentage of participants with enhanced clinical response at Week 4 [ Time Frame: Week 4 ]
  Enhanced clinical response defined as decrease in average daily SF and/or decrease in average daily AP score, and/or clinical remission per average daily SF and average daily AP score.
• Percentage of participants with clinical remission per Crohn's Disease Activity Index (CDAI) at Week 12 [ Time Frame: Week 12 ]
  The CDAI is used to evaluate disease activity in patients with Crohn's disease.
• Percentage of participants with enhanced clinical response at Week 12 [ Time Frame: Week 12 ]
  Enhanced clinical response defined as decrease in average daily SF and/or decrease in average daily AP score, and/or clinical remission per average daily SF and average daily AP score.
• Percentage of participants with clinical remission per average daily stool frequency (SF) and average daily abdominal pain (AP) score at Week 4 [ Time Frame: Week 4 ]
  Clinical remission per average daily SF and average daily AP score.
• Percentage of participants with enhanced clinical response and endoscopic response at Week 12 [ Time Frame: Week 12 ]
  Enhanced clinical response defined as decrease in average daily SF and/or decrease in average daily AP score, and/or clinical remission per average daily SF and average daily AP score. Endoscopic response defined as decrease from Baseline in SES-CD.
• Percentage of participants with endoscopic healing at Week 12 [ Time Frame: Week 12 ]
  Endoscopic healing was assessed using SES-CD.
• Crohn's Symptom Severity (CSS): Change from Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
  The CSS is a patient questionnaire to assess severity of Crohn's symptoms.
• Percentage of participants with resolution of Extra-Intestinal Manifestations (EIMs) at Week 12, in participants with EIMs at Baseline [ Time Frame: Week 12 ]
  Manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver.
• Percentage of participants with hospitalization through Week 12 [ Time Frame: Week 12 ]
  Participants with an event that results in admission to the hospital.
• Percentage of participants with draining fistulas at Week 12 in participants with draining fistulas at Baseline [ Time Frame: Week 12 ]
  Participants with draining fistulas at Week 12 in subjects who had draining fistulas at baseline.
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue): Change from Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
  The FACIT-Fatigue is a validated tool that measures an individual's level of fatigue during their usual daily activities over the past week.
• 36-Item Short Form Health Survey (SF-36): Change from Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
  The SF-36 is an indicator of overall health status.
• Percentage of participants with Crohn's Disease-related surgeries through Week 12 [ Time Frame: 12 weeks ]
  Participants who underwent surgery related to CD.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: placebo for risankizumab IV
  placebo for risankizumab administered as intravenous (IV) infusion.
• Drug: risankizumab SC
  risankizumab administered by subcutaneous (SC) injection
  Other Names:

  • ABBV-066 BI 655066
  • SKYRIZI
• Drug: risankizumab IV
  risankizumab administered as intravenous (IV) infusion.
  Other Names:

  • ABBV-066 BI 655066
  • SKYRIZI

Study Arms

• Experimental: Risankizumab Dose 1 (Induction Period 1)
  Participants randomized to receive risankizumab dose 1 in Induction Period 1.
  Intervention: Drug: risankizumab IV
• Experimental: Risankizumab Dose 2 (Induction Period 1)
  Participants randomized to receive risankizumab dose 2 in Induction Period 1.
  Intervention: Drug: risankizumab IV
• Placebo Comparator: Placebo (Induction Period 1)
  Participants randomized to receive placebo for risankizumab in Induction Period 1.
  Intervention: Drug: placebo for risankizumab IV
• Experimental: 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.
  Intervention: Drug: risankizumab IV
• Experimental: 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.
  Intervention: Drug: risankizumab SC
• Experimental: 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.
  Intervention: Drug: risankizumab SC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 24, 2021): 618
• Original Estimated Enrollment (submitted: April 4, 2017): 579
• Estimated Study Completion Date: May 26, 2021
• Actual Primary Completion Date: November 30, 2020 (Final data collection date for primary outcome measure)

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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Egypt, Estonia, France, Germany, Greece, Ireland, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Ukraine, United Kingdom, United States
• Removed Location Countries: American Samoa, Brazil, Hungary, Turkey

Administrative Information

• NCT Number: NCT03104413
• Other Study ID Numbers: M15-991; 2016-003190-17 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Responsible Party: AbbVie
• Study Sponsor: AbbVie
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: February 2021