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A Study to Evaluate the Long-Term Safety and Efficacy of Upadacitinib (ABT-494) in Subjects With Ulcerative Colitis (UC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03006068
Recruitment Status : Enrolling by invitation
First Posted : December 30, 2016
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This study is designed to evaluate the long-term safety and efficacy of Upadacitinib in participants with ulcerative colitis (UC) who have not responded at the end of the induction period in Study M14-234 Substudy 1, who have had loss of response during the maintenance period of Study M14-234 Substudy 3, or who have successfully completed Study M14-234 Substudy 3.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 950 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Multicenter, Long-Term Extension Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) in Subjects With Ulcerative Colitis
Actual Study Start Date : January 31, 2017
Estimated Primary Completion Date : January 7, 2022
Estimated Study Completion Date : August 28, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Participants receiving Upadacitinib (ABT-494) Dose A
The participants in this arm will receive Upadacitinib (ABT-494) dose A.
Drug: Upadacitinib (ABT-494)
Upadacitinib (ABT-494) will be administered orally.
Other Name: Upadacitinib

Experimental: Participants receiving Upadacitinib (ABT-494) Dose B
The participants in this arm will receive Upadacitinib (ABT-494) dose B.
Drug: Upadacitinib (ABT-494)
Upadacitinib (ABT-494) will be administered orally.
Other Name: Upadacitinib

Experimental: Participants receiving Upadacitinib (ABT-494) Dose C
The participants in this arm will receive Upadacitinib (ABT-494) dose C.
Drug: Upadacitinib (ABT-494)
Upadacitinib (ABT-494) will be administered orally.
Other Name: Upadacitinib

Experimental: Participants receiving Placebo
The participants in this arm will receive placebo until study is unblinded.
Drug: Placebo
Placebo will be administered orally.

Experimental: Participants receiving Upadacitinib (ABT-494) Dose A or Dose B
The participants in this arm will receive Upadacitinib (ABT-494) dose A or dose B.
Drug: Upadacitinib (ABT-494)
Upadacitinib (ABT-494) will be administered orally.
Other Name: Upadacitinib




Primary Outcome Measures :
  1. Assessing Treatment-Emergent Adverse Events [ Time Frame: Up to 288 Weeks ]
    Treatment-emergent adverse events are defined as events that begin or worsen either on or after the first dose of the study drug and within 30 days after the last dose of the study drug in the analysis period.


Secondary Outcome Measures :
  1. Percentage of participants achieving clinical response per Partial Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical response per Partial Mayo score

  2. Percentage of participants achieving clinical remission per Adapted Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Adapted Mayo score

  3. Percentage of participants in clinical remission per Full Mayo score at Week 0 who maintain remission at Week 48 [ Time Frame: At Week 0, Week 48, and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Full Mayo score

  4. Percentage of participants achieving clinical remission per Partial Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Partial Mayo score

  5. Percentage of participants in clinical remission per Adapted Mayo score at Week 0 who maintain remission at Week 48 [ Time Frame: At Week 0, Week 48, and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Adapted Mayo score

  6. Percentage of participants achieving clinical remission per Full Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Full Mayo score

  7. Percentage of participants achieving clinical response per Adapted Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical response per Adapted Mayo score

  8. Percentage of participants with Stool Frequency Subscore (SFS) of 0, Rectal Bleeding Subscore (RBS) of 0, and endoscopic subscore of <=1 [ Time Frame: At Week 48 and every 48 Weeks thereafter through 288 weeks ]
    Percentage of participants with specific Stool Frequency Subscore (SFS), Rectal Bleeding Subscore (RBS), and endoscopic subscore

  9. Percentage of participants who had upadacitinib dose-escalation and achieved clinical remission per Full Mayo Score [ Time Frame: At Week 8 in Cohort 2 ]
    Clinical remission per Full Mayo score

  10. Percentage of participants who had upadacitinib dose-escalation and achieved endoscopic improvement [ Time Frame: At Week 8 in Cohort 2 ]
    Endoscopic improvement defined by endoscopic subscore

  11. Percentage of participants who had upadacitinib dose-escalation and achieved endoscopic remission [ Time Frame: At Week 8 in Cohort 2 ]
    Endoscopic remission identified by endoscopic subscore

  12. Percentage of participants achieving clinical remission [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical remission will be assessed by Stool Frequency Subscore (SFS), Rectal Bleeding Subscore (RBS), and endoscopic subscore

  13. Percentage of participants who had upadacitinib dose-escalation and achieved clinical response per Adapted Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical response per Adapted Mayo score

  14. Percentage of participants who had upadacitinib dose-escalation and achieved clinical remission (after dose-escalation) per Adapted Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical response per Adapted Mayo score

  15. Percentage of participants who had upadacitinib dose-escalation and achieved clinical remission (after dose-escalation) per Full Mayo score [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Full Mayo score

  16. Percentage of participants with endoscopic improvement [ Time Frame: At Week 0, Week 48, and every 48 weeks thereafter through 288 Weeks ]
    Endoscopic improvement assessed by endoscopic subscore

  17. Percentage of participants with endoscopic remission [ Time Frame: At Week 0, Week 48, and every 48 Weeks thereafter through 288 Weeks ]
    Endoscopic remission defined by endoscopic subscore

  18. Percentage of Participants with endoscopic remission at Week 0 and maintained at Week 48 and every 48 Weeks [ Time Frame: At Week 0, Week 48 and every 48 Weeks thereafter through 288 Weeks ]
    Endoscopic remission defined by endoscopic subscore

  19. Percentage of participants taking steroids at Baseline (Week 0) who are steroid-free over time [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Percentage of participants taking steroids who are steroid-free over time

  20. Percentage of participants taking steroids at Baseline (Week 0) who discontinued corticosteroid use and achieved clinical remission per Adapted Mayo score [ Time Frame: At Week 48 and every 48 Weeks thereafter through 288 Weeks ]
    Percentage of participants who discontinued corticosteroids and achieved clinical remission per Adapted Mayo score

  21. Percentage of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) response [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Percentage of participants achieving IBDQ response

  22. Percentage of participants with Inflammatory Bowel Disease Questionnaire (IBDQ) remission [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Remission defined by IBDQ total score

  23. Percentage of participants who reported no abdominal pain [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Percentage of participants who reported no abdominal pain

  24. Percentage of participants who reported no bowel urgency [ Time Frame: At Week 48 and every 48 weeks thereafter through 288 weeks ]
    Percentage of participants who reported no bowel urgency

  25. Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total and domain score [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in IBDQ total and domain score

  26. Change from Baseline in individual Inflammatory Bowel Disease Questionnaire (IBDQ) item under Bowel Symptom domain (for Q1, Q5, Q9, Q13, Q17, Q20, Q22, Q24, Q26, and Q29) [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in individual IBDQ item under Bowel Symptom domain

  27. Change from Baseline in corticosteroid dose [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in corticosteroid dose

  28. Change from Baseline in Adapted Mayo score, Full Mayo score, Partial Mayo score, and Mayo subscores [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in Adapted Mayo score, Full Mayo score, Partial Mayo score, and Mayo subscores

  29. Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in hs-CRP

  30. Change from Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) scores [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in WPAI scores

  31. Change from Baseline in fecal calprotectin [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in fecal calprotectin

  32. Change from Baseline in European Quality of Life 5 -Dimensions 5 Levels (EQ-5D-5L) score [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in EQ-5D-5L score

  33. Change from Baseline in subject-reported stool frequency (absolute values) [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in subject-reported stool frequency

  34. Change from Baseline in Short Form 36 (SF-36) scores [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in SF-36 scores

  35. Percentage of participants by Patient Global Impression of Severity (PGIS) category [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Percentage of participants by PGIS category

  36. Change from Baseline in Ulcerative Colitis Symptoms Questionnaire (UC-SQ) score [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in UC-SQ score

  37. Percentage of participants by Patient Global Impression of Change (PGIC) category [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Percentage of participants by PGIC category

  38. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Change in FACIT-F score

  39. Health care resource utilization (HCRU), including all-cause and UC-related hospitalizations and surgeries [ Time Frame: At Week 0, Week 48 and every 48 weeks thereafter through 288 weeks ]
    Health care resource utilization



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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: Participants aged 16 or 17 may enroll in M14-234 or M14-675 where locally permissible

  • Participant has not achieved clinical response at the end of the induction period (Week 8) in Study M14-234 Substudy 1, has had loss of response during the maintenance period of Study M14-234 Substudy 3, or has successfully completed Study M14-234 Substudy 3.
  • If female, participant must meet the criteria for Contraception Recommendations.
  • Women of childbearing potential must have a negative urine pregnancy test at Week 0 visit.
  • Participant is judged to be in otherwise good health as determined by the principal investigator based upon clinical evaluations performed during the preceding study (Study M14-234).
  • Must be able and willing to give written informed consent and to comply with the requirements of this study protocol.

Exclusion Criteria:

  • For any reason participant is considered by the investigator to be an unsuitable candidate.
  • Female participant with a positive pregnancy test at the final visit of Study M14-234 or who is considering becoming pregnant during the study or within 30 days after the last dose of study drug.
  • Participant with an active or recurrent infection that based on the investigator's clinical assessment makes the participant an unsuitable candidate for the study. Participants with ongoing infections undergoing treatment may be enrolled BUT NOT dosed until the infection has been successfully treated.
  • Current evidence of active or untreated latent tuberculosis.
  • Participant with a poorly controlled medical condition, such as uncontrolled diabetes, unstable ischemic heart disease, moderate or severe congestive heart failure (New York Heart Association class III or IV), recent cerebrovascular accidents and any other condition which, in the opinion of the investigator or sponsor, would put the subject at risk by participation in this study.
  • Participants have malignancy, high-grade dysplasia, un-removed low-grade dysplasia of the gastrointestinal tract diagnosed at the endoscopy performed at the final visit of Study M14-234.
  • History of any malignancy except for successfully treated nonmelanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix from evaluations performed in Study M14-234.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03006068


  Show 467 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03006068     History of Changes
Other Study ID Numbers: M14-533
2016-000674-38 ( EudraCT Number )
First Posted: December 30, 2016    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 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

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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:
Ulcerative Colitis (UC)
Upadacitinib (ABT-494)
Long Term Extension (LTE)
Safety
Efficacy

Additional relevant MeSH terms:
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Colitis
Ulcer
Colitis, Ulcerative
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