A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy

• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: November 15, 2017
• First Posted Date: November 17, 2017
• Last Update Posted Date: June 4, 2019
• Actual Study Start Date: November 29, 2017
• Estimated Primary Completion Date: January 9, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2017)

• Proportion of participants with clinical remission [ Time Frame: Week 12 ]
  Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
• Proportion of participants with endoscopic response [ Time Frame: Week 12 ]
  Endoscopic response is defined as decrease in SES-CD from Baseline.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03345836 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: September 14, 2018)

• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: From Week 0 to Week 12 ]
  The FACIT-F questionnaire was developed to assess fatigue.
• Proportion of participants with enhanced clinical response [ Time Frame: Week 2 ]
  Enhanced Clinical Response defined as decrease in average daily SF and/or decrease in average daily AP score.
• Proportion of participants achieving response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom domain [ Time Frame: At Week 12 ]
  IBDQ bowel symptom domain response is defined as the increase of IBDQ bowel symptom domain score >= 8
• Proportion of participants with hospitalizations due to CD [ Time Frame: Week 12 ]
  This is assessed during 12 week double-blind induction period by reviewing participant's hospitalization data.
• Proportion of participants with clinical remission [ Time Frame: Week 4 ]
  Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
• Proportion of participants with clinical remission per Crohn's Disease Activity Index (CDAI) remission in participants with a Baseline CDAI of 220 to 450 [ Time Frame: Week 12 ]
  CDAI remission is defined as CDAI < 150.
• Proportion of participants with endoscopic remission [ Time Frame: Week 12 ]
  Endoscopic remission is defined per SES-CD.
• Proportion of participants with >= 50% reduction in draining fistulas [ Time Frame: Week 12 ]
  This is assessed in participants with draining fistulas at Baseline.
• Change from Baseline in Crohn's Symptoms Severity Questionnaire (CSS) [ Time Frame: From Week 0 to Week 12 ]
  The CSS is a self-administered questionnaire that consists of questions about how the participants felt in regards to their Crohn's disease.
• Proportion of participants who discontinue corticosteroid use for Crohn's disease (CD) and achieve clinical remission [ Time Frame: Week 12 ]
  This is assessed in participants taking corticosteroids at Baseline.

Original Secondary Outcome Measures (submitted: November 15, 2017)

• Proportion of participants with clinical remission per Crohn's Disease Activity Index (CDAI) remission in participants with a Baseline CDAI of 220 to 450 [ Time Frame: Week 12 ]
  CDAI remission is defined as CDAI < 150.
• Proportion of participants with clinical remission [ Time Frame: Week 4 ]
  Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
• Proportion of participants with enhanced clinical response [ Time Frame: Week 2 ]
  Enhanced Clinical Response defined as decrease in average daily SF and/or decrease in average daily AP score.
• Proportion of participants with endoscopic remission [ Time Frame: Week 12 ]
  Endoscopic remission is defined per SES-CD.
• Proportion of participants who discontinue corticosteroid use for Crohn's disease (CD) and achieve clinical remission [ Time Frame: Week 12 ]
  This is assessed in participants taking corticosteroids at Baseline.
• Proportion of participants with >= 50% reduction in draining fistulas [ Time Frame: Week 12 ]
  This is assessed in participants with draining fistulas at Baseline.
• Change from Baseline in Crohn's Symptoms Severity Questionnaire (CSS) [ Time Frame: From Week 0 to Week 12 ]
  The CSS is a self-administered questionnaire that consists of questions about how the participants felt in regards to their Crohn's disease.
• Proportion of participants with hospitalizations due to CD [ Time Frame: Week 12 ]
  This is assessed during 12 week double-blind induction period by reviewing participant's hospitalization data.
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: From Week 0 to Week 12 ]
  The FACIT-F questionnaire was developed to assess fatigue.
• Change from Baseline in Short Form 36 (SF-36) [ Time Frame: From Week 0 to Week 12 ]
  The SF-36 questionnaire is a self-administered multi-domain scale with 36 items.

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

Descriptive Information

• Brief Title: A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy
• Brief Summary: The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in subjects with moderately and severely active Crohn's disease (CD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Other: Matching placebo for upadacitinib
  Tablet
• Drug: upadacitinib
  Tablet
  Other Name: ABT-494

Study Arms

• Experimental: Arm B
  Participants will receive placebo for 12 weeks.
  Intervention: Other: Matching placebo for upadacitinib
• Arm C
  Participants will receive open-label upadacitinib dose A for 12 weeks.
  Intervention: Drug: upadacitinib
• Experimental: Arm A
  Participants will receive upadacitinib dose A for 12 weeks.
  Intervention: Drug: upadacitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 25, 2019): 645
• Original Estimated Enrollment (submitted: November 15, 2017): 855
• Estimated Study Completion Date: March 17, 2021
• Estimated Primary Completion Date: January 9, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed 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.
• Evidence of mucosal inflammation based on the Simplified Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader.
• Demonstrated an inadequate response or intolerance to any biologic therapy for infliximab, adalimumab, certolizumab pegol, vedolizumab, and ustekinumab.
• If female, subject must meet the contraception recommendations

Exclusion Criteria:

• Participant with a current diagnosis of ulcerative colitis or indeterminate colitis.
• Participant not on stable doses of CD related antibiotics, oral aminosalicylates, corticosteroids or methotrexate (MTX).
• Participant with the following known complications of CD: abscess (abdominal or peri-anal), symptomatic bowel strictures, fulminant colitis, toxic megacolon, or any other manifestation that might require surgery while enrolled in the study.
• Participant with ostomy or ileoanal pouch
• Participant diagnosed with short gut or short bowel syndrome
• Screening laboratory and other analyses show abnormal results.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 847.283.8955; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: American Samoa, Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Egypt, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Belarus

Administrative Information

• NCT Number: NCT03345836
• Other Study ID Numbers: M14-431; 2017-001226-18 ( 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)
• Supporting Materials: Analytic Code
• 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: May 2019