A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC)

• ClinicalTrials.gov Identifier: NCT02819635
• Recruitment Status: Active, not recruiting
• First Posted: June 30, 2016
• Last Update Posted: January 7, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: June 28, 2016
• First Posted Date: June 30, 2016
• Last Update Posted Date: January 7, 2021
• Actual Study Start Date: September 26, 2016
• Estimated Primary Completion Date: February 28, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 26, 2020)

• Substudy 1/Substudy 2: Percentage Of Participants Who Achieve Clinical Remission Per Adapted Mayo Score [ Time Frame: At Week 8 ]
  Clinical remission per Adapted Mayo score.
• Substudy 3: Percentage Of Participants Who Achieve Clinical Remission Per Adapted Mayo Score [ Time Frame: At Week 52 ]
  Clinical remission per Adapted Mayo score.

Original Primary Outcome Measures (submitted: June 28, 2016)

• Substudy 1/Substudy 2: Proportion of participants who achieve clinical remission per adapted Mayo score [ Time Frame: At Week 8 ]
  Clinical remission is defined as stool frequency subscore (SFS) <= 1, rectal bleeding subscore (RBS) of 0, and endoscopic subscore <= 1.
• Substudy 3: Proportion of participants who achieve clinical remission per adapted Mayo score [ Time Frame: At Week 44 ]
  Clinical remission is defined as stool frequency subscore (SFS) <= 1, rectal bleeding subscore (RBS) of 0, and endoscopic subscore <= 1.

Current Secondary Outcome Measures (submitted: May 26, 2020)

• Substudy 1: Percentage Of Participants With Endoscopic Improvement [ Time Frame: At Week 8 ]
  Endoscopic improvement defined by endoscopic subscore.
• Substudy 1: Percentage Of Participants Achieving Clinical Remission Per Full Mayo Score [ Time Frame: At Week 8 ]
  Clinical remission per Full Mayo score.
• Substudy 1: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score [ Time Frame: At Week 8 ]
  Clinical response per Adapted Mayo.
• Substudy 1: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score [ Time Frame: At Week 2 ]
  Percentage of participants achieving clinical response per Partial Mayo score.
• Substudy 1: Change in Full Mayo Score [ Time Frame: Baseline (Week 0) to Week 8 ]
  Change from baseline in Full Mayo score.
• Substudy 1: Percentage Of Participants With Endoscopic Remission [ Time Frame: At Week 8 ]
  Remission defined by endoscopic subscore.
• Substudy 1: Percentage Of Participants Who Achieved Histologic Improvement [ Time Frame: At Week 8 ]
  Histologic improvement defined by Geboes score.
• Substudy 2: Percentage Of Participants With Endoscopic Improvement [ Time Frame: At Week 8 ]
  Endoscopic improvement defined by endoscopic subscore.
• Substudy 2: Percentage Of Participants With Endoscopic Remission [ Time Frame: At Week 8 ]
  Remission defined by endoscopic subscore.
• Substudy 2: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score [ Time Frame: At Week 8 ]
  Clinical response per Adapted Mayo.
• Substudy 2: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score [ Time Frame: At Week 2 ]
  Percentage of participants achieving clinical response per Partial Mayo score.
• Substudy 2: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement [ Time Frame: At Week 8 ]
  Histologic-endoscopic mucosal improvement defined by Endoscopic subscore and Geboes score.
• Substudy 2: Percentage Of Participants Who Report No Bowel Urgency [ Time Frame: At Week 8 ]
  Percentage of participants who report no bowel urgency.
• Substudy 2: Percentage Of Participants Who Reported No Abdominal Pain [ Time Frame: At Week 8 ]
  Percentage of participants who reported no abdominal pain.
• Substudy 2: Percentage Of Participants Who Achieved Histologic Improvement [ Time Frame: At Week 8 ]
  Histologic improvement defined by Geboes score.
• Substudy 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score [ Time Frame: Baseline (Week 0) to Week 8 ]
  The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.
• Substudy 2: Percentage Of Participants With Mucosal Healing [ Time Frame: At Week 8 ]
  Percentage of participants with mucosal healing.
• Substudy 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Questionnaire Score [ Time Frame: Baseline (Week 0) to Week 8 ]
  The FACIT system is a collection of quality of life (QOL) questionnaires targeted to the management of cancer and other chronic illnesses.
• Substudy 3: Percentage Of Participants With Endoscopic Improvement [ Time Frame: At Week 52 ]
  Endoscopic improvement defined by endoscopic subscore.
• Substudy 3: Percentage Of Participants Who Maintain Clinical Remission Per Adapted Mayo Score Among Participants Who Received Clinical Remission Per Adapted Mayo Score in Study M14-234 (Substudy 1 or 2) Or M14-675 [ Time Frame: At Week 52 ]
  Percentage of participants who maintain clinical remission per Adapted Mayo score among participants who received clinical remission per Adapted Mayo score in Study M14-234 (Substudy 1 or 2) or M14-675.
• Substudy 3: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo score And Were Corticosteroid Free ≥ 90 days [ Time Frame: At Week 52 ]
  Percentage of participants who achieved clinical remission per Adapted Mayo score and were corticosteroid free ≥ 90 days among participants in clinical remission in the end of the induction treatment in Study M14-234 (Substudy 1 or 2) or M14-675.
• Substudy 3: Percentage Of Participants With Endoscopic Improvement Among Participants Who Had Endoscopic Improvement In Study M14-234 (Substudy 1 or 2) Or Study M14-675 [ Time Frame: At Week 52 ]
  Percentage of participants with endoscopic improvement among participants who had endoscopic improvement in Study M14-234 (Substudy 1 or 2) or Study M14-675.
• Substudy 3: Percentage Of Participants With Endoscopic Remission [ Time Frame: At Week 52 ]
  Percentage of participants with endoscopic remission.
• Substudy 3: Percentage Of Participants Who Maintain Clinical Response Per Adapted Mayo Score [ Time Frame: At Week 52 ]
  Percentage of participants who maintain clinical response per Adapted Mayo score.
• Substudy 3: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement [ Time Frame: At Week 52 ]
  Histologic-endoscopic mucosal improvement defined by Endoscopic subscore and Geboes score.
• Substudy 3: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score [ Time Frame: Baseline (Week 0) to Week 52 ]
  The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.
• Substudy 3: Percentage Of Participants With Mucosal Healing [ Time Frame: At Week 52 ]
  Percentage of participants with mucosal healing.
• Substudy 3: Percentage Of Participants Who Reported No Bowel Urgency [ Time Frame: At Week 52 ]
  Percentage of participants who reported no bowel urgency.
• Substudy 3: Percentage Of Participants Who Reported No Abdominal Pain [ Time Frame: At Week 52 ]
  Percentage of participants who reported no abdominal pain.
• Substudy 3: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score [ Time Frame: Baseline (Week 0) to Week 52 ]
  The FACIT-F is a validated tool that measures an individual's level of fatigue during their usual daily activities.
• Substudy 3: Incidence Rate Of Ulcerative Colitis (UC)-Related Hospitalization [ Time Frame: At Week 52 ]
  Incidence of UC-related hospitalization.
• Substudy 3: Incidence Rate of Ulcerative Colitis (UC)-Related Surgeries [ Time Frame: At Week 52 ]
  Incidence rate of UC-related surgeries.

Original Secondary Outcome Measures (submitted: June 28, 2016)

• Substudy 1/Substudy 2: Proportion of participants with endoscopic improvement at Week 8 [ Time Frame: At Week 8 ]
  Endoscopic improvement is defined as an endoscopic subscore <= 1
• Substudy 1/Substudy 2: Proportion of participants achieving clinical remission per Full Mayo score at Week 8 [ Time Frame: At Week 8 ]
  Clinical remission is defined as a Full Mayo score <= 2 with no subscore > 1
• Substudy 1/Substudy 2: Proportion of participants achieving clinical response per Adapted Mayo score at Week 8 [ Time Frame: At Week 8 ]
  Clinical response per Adapted Mayo is defined as a decrease from baseline in the Adapted Mayo score >= 2 points and >= 30% from baseline, PLUS a decrease in rectal bleeding subscore (RBS) >= 1 or an absolute RBS <= 1.
• Substudy 3: Proportion of participants with endoscopic improvement at Week 44 [ Time Frame: At Week 44 ]
  Endoscopic improvement is defined as an endoscopic subscore <= 1
• Substudy 3: Proportion of participants achieving clinical remission per Full Mayo score at Week 44 [ Time Frame: At Week 44 ]
  Clinical remission per Full Mayo score is defined as a Full Mayo score <= 2 with no subscore > 1
• Substudy 3: Proportion of participants who discontinued corticosteroid use that achieved clinical remission per Adapted Mayo score at Week 44 [ Time Frame: At Week 44 ]
  Participants who discontinued corticosteroid use and achieved clinical remission per Adapted Mayo score, defined as Stool Frequency Subscore (SFS) <= 1, Rectal Bleeding Subscore (RBS) of 0, and endoscopic subscore <= 1.

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

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC)
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
• Brief Summary: This study comprises three sub-studies. The objective of sub-study 1 is to characterize the dose-response, efficacy, and safety of upadacitinib compared to placebo in inducing clinical remission in order to identify the induction dose of upadacitinib for further evaluation in sub-study 2. The objective of sub-study 2 is to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission in participants. The objective of sub-study 3 is to evaluate the efficacy and safety of upadacitinib compared to placebo in achieving clinical remission in participants who had a response following induction with upadacitinib.
• 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: Ulcerative Colitis (UC)

Intervention

• Drug: Placebo
  Tablet; Oral
• Drug: Updacitinib (ABT-494)
  Tablet; Oral
  Other Names:

  • Upadacitinib
  • RINVOQ

Study Arms

• Placebo Comparator: Placebo
  Administered once daily.
  Intervention: Drug: Placebo
• Experimental: Updacitinib (ABT-494) Dose A
  Administered once daily.
  Intervention: Drug: Updacitinib (ABT-494)
• Experimental: Updacitinib (ABT-494) Dose B
  Administered once daily.
  Intervention: Drug: Updacitinib (ABT-494)
• Experimental: Updacitinib (ABT-494) Dose C
  Administered once daily.
  Intervention: Drug: Updacitinib (ABT-494)
• Experimental: Updacitinib (ABT-494) Dose D
  Administered once daily.
  Intervention: Drug: Updacitinib (ABT-494)

• Publications *: Sandborn WJ, Ghosh S, Panes J, Schreiber S, D'Haens G, Tanida S, Siffledeen J, Enejosa J, Zhou W, Othman AA, Huang B, Higgins PDR. Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis. Gastroenterology. 2020 Jun;158(8):2139-2149.e14. doi: 10.1053/j.gastro.2020.02.030. Epub 2020 Feb 22. Erratum in: Gastroenterology. 2020 Sep;159(3):1192.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 6, 2021): 1267
• Original Estimated Enrollment (submitted: June 28, 2016): 1055
• Estimated Study Completion Date: June 1, 2022
• Estimated Primary Completion Date: February 28, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Note: Adolescent participants at the age of 16 or 17 years old will be eligible to participate if approved by the country or regulatory/health authority. If approval has not been granted, only participants >= 18 years old will be enrolled.

Adolescents must weigh >= 40 kilograms and meet the definition of Tanner Stage 5 at Screening Visit.

• Diagnosis of ulcerative colitis for 90 days or greater prior to Baseline, confirmed by colonoscopy during the Screening Period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available.
• Active ulcerative colitis with an Adapted Mayo score of 5 to 9 points and endoscopic sub score of 2 to 3 (confirmed by central reader).
• Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following treatments including: oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies in the opinion of the investigator.

Note: Participants who have had inadequate response, loss of response to conventional therapy, but have not failed biologic therapy (Non-bio-IR) and have received a prior biologic for up to 1 year may be enrolled, however they must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease) and must meet criteria for inadequate response, loss of response or intolerance to aminosalicylates, corticosteroids, and/or immunosuppressants as defined above.

• If female, participant must meet the criteria for Contraception Recommendations.
• Female participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit prior to study drug dosing.

Exclusion Criteria:

• Participant with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC).
• Current diagnosis of fulminant colitis and/or toxic megacolon.
• Participant with disease limited to the rectum (ulcerative proctitis) during the Screening endoscopy.
• Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline.
• Participant on azathioprine or 6-mercaptopurine within 10 days of baseline.
• Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
• Participant with previous exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib).
• Screening laboratory and other analyses show any abnormal results.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 75 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, Brazil, Canada, Chile, China, Colombia, Croatia, Czechia, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Puerto Rico, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Egypt, Romania

Administrative Information

• NCT Number: NCT02819635
• Other Study ID Numbers: M14-234; 2016-000641-31 ( 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: January 2021