A 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 (UC)

• ClinicalTrials.gov Identifier: NCT02819635
• Recruitment Status: Recruiting
• First Posted: June 30, 2016
• Last Update Posted: October 14, 2019
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis (UC)	Drug: Placebo; Drug: Updacitinib (ABT-494)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 844 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 26, 2016
• Estimated Primary Completion Date: April 27, 2021
• Estimated Study Completion Date: February 24, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Updacitinib (ABT-494) Dose B; Administered orally, once daily.	Drug: Updacitinib (ABT-494); Tablet; Other Name: Upadacitinib
Experimental: Updacitinib (ABT-494) Dose A; Administered orally, once daily.	Drug: Updacitinib (ABT-494); Tablet; Other Name: Upadacitinib
Experimental: Updacitinib (ABT-494) Dose C; Administered orally, once daily.	Drug: Updacitinib (ABT-494); Tablet; Other Name: Upadacitinib
Experimental: Updacitinib (ABT-494) Dose D; Administered orally, once daily.	Drug: Updacitinib (ABT-494); Tablet; Other Name: Upadacitinib
Placebo Comparator: Placebo; Administered orally, once daily.	Drug: Placebo; Tablet

Outcome Measures

Primary Outcome Measures :

1. 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
2. Substudy 3: Percentage of participants who achieve clinical remission per Adapted Mayo score [ Time Frame: At Week 44 or Week 52 ]
   Clinical remission per Adapted Mayo score

Secondary Outcome Measures :

1. Substudy 1: Change in Full Mayo score [ Time Frame: Week 0 to Week 8 ]
   Change in Full Mayo score
2. Substudy 1/Substudy 2: Percentage of participants achieving clinical response per Adapted Mayo score [ Time Frame: At Week 8 ]
   Clinical response per Adapted Mayo
3. Substudy 1/Substudy 2: Percentage of participants achieving clinical remission per Full Mayo score [ Time Frame: At Week 8 ]
   Clinical remission per Full Mayo score
4. Substudy 1/Substudy 2: Percentage of participants with endoscopic improvement [ Time Frame: At Week 8 ]
   Endoscopic improvement defined by endoscopic subscore
5. Substudy 1/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
6. Substudy 1/Substudy 2: Percentage of participants with endoscopic remission [ Time Frame: At Week 8 ]
   Remission defined by endoscopic subscore
7. Substudy 1/Substudy 2: Percentage of participants who achieved histologic improvement [ Time Frame: At Week 8 ]
   Histologic improvement defined by Geboes score
8. Substudy 2: Percentage of participants who report no bowel urgency [ Time Frame: At Week 8 ]
   Percentage of participants who report no bowel urgency
9. Substudy 2: Percentage of participants who reported no abdominal pain [ Time Frame: At Week 8 ]
   Percentage of participants who reported no abdominal pain
10. Substudy 2: Percentage of participants achieving response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom domain [ Time Frame: At Week 8 ]
    Response defined by IBDQ Bowel Symptom domain
11. Substudy 2: Percentage of participants achieving clinical response per Adapted Mayo score [ Time Frame: At Week 8 ]
    Percentage of participants achieving clinical response per Adapted Mayo score
12. Substudy 2: Percentage of participants with mucosal healing [ Time Frame: At Week 8 ]
    Percentage of participants with mucosal healing
13. Substudy 2: Percentage of participants achieving response in Inflammatory Bowel Disease Questionnaire (IBDQ) fatigue item [ Time Frame: At Week 8 ]
    Defined by IBDQ fatigue item scores
14. Substudy 2: Percentage of participants with UC-related hospitalizations [ Time Frame: Through Week 8 ]
    Percentage of participants with UC-related hospitalizations
15. Substudy 2: Percentage of participants with UC-related surgeries [ Time Frame: Through Week 8 ]
    Percentage of participants with UC-related surgeries
16. Substudy 3: Percentage of participants with endoscopic improvement [ Time Frame: At Week 44 or Week 52 ]
    Endoscopic improvement defined by endoscopic subscore
17. Substudy 3: Percentage of participants who discontinued corticosteroid use, remained corticosteroid free for >= 90 days and achieved clinical remission per Adapted Mayo score [ Time Frame: At Week 44 or Week 52 ]
    Percentage of participants who discontinued corticosteroid use, remained corticosteroid free and achieved clinical remission per Adapted Mayo score
18. 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 44 or 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
19. 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 44 or 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
20. Substudy 3: Percentage of participants with endoscopic remission [ Time Frame: At Week 44 or Week 52 ]
    Percentage of participants with endoscopic remission
21. Substudy 3: Percentage of participants with mucosal healing [ Time Frame: At Week 44 or Week 52 ]
    Percentage of participants with mucosal healing
22. Substudy 3: Percentage of participants who reported no bowel urgency [ Time Frame: At Week 44 or Week 52 ]
    Percentage of participants who reported no bowel urgency
23. Substudy 3: Percentage of participants who reported no abdominal pain [ Time Frame: At Week 44 or Week 52 ]
    Percentage of participants who reported no abdominal pain
24. Substudy 3: Incidence of Ulcerative Colitis (UC)-related hospitalization [ Time Frame: At Week 44 or Week 52 ]
    Incidence of UC-related hospitalization
25. Substudy 3: Percentage of participants achieving response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom domain [ Time Frame: At Week 44 or Week 52 ]
    Defined by IBDQ bowel symptom domain scores
26. Substudy 3: Incidence rate of Ulcerative Colitis (UC)-related surgeries [ Time Frame: At Week 44 or Week 52 ]
    Incidence rate of UC-related surgeries
27. Substudy 3: Percentage of participants achieving response in Inflammatory Bowel Disease Questionnaire (IBDQ) fatigue item [ Time Frame: At Week 44 or Week 52 ]
    Defined by IBDQ fatigue item scores
28. Substudy 3: Percentage of participants who maintain clinical response per Adapted Mayo score [ Time Frame: At Week 44 or Week 52 ]
    Percentage of participants who maintain clinical response per Adapted Mayo score
29. Substudy 3: Percentage of participants who discontinued corticosteroid use that achieved clinical remission per Adapted Mayo score [ Time Frame: At Week 44 or Week 52 ]
    Clinical remission per Adapted Mayo score

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

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

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Sponsors and Collaborators

AbbVie

Investigators

• Study Director: AbbVie Inc.; AbbVie

More Information

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02819635 History of Changes
• Other Study ID Numbers: M14-234; 2016-000641-31 ( EudraCT Number )
• First Posted: June 30, 2016
• Last Update Posted: October 14, 2019
• Last Verified: October 2019

Individual Participant Data (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; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); 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

• 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

Keywords provided by AbbVie:

Upadacitinib (ABT-494); Moderately to Severely Active UC

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases; Upadacitinib; Janus Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents