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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

Tracking Information
First Submitted Date  ICMJE December 20, 2016
First Posted Date  ICMJE December 30, 2016
Last Update Posted Date May 16, 2019
Actual Study Start Date  ICMJE January 31, 2017
Estimated Primary Completion Date January 7, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 27, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03006068 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: December 27, 2016)
  • Proportion of participants achieving clinical remission per Adapted Mayo score [ Time Frame: Up to Week 48 ]
    It is defined as stool frequency subscore (SFS) <= 1, rectal bleeding subscore (RBS) of 0, and endoscopy subscore <= 1.
  • Proportion of participants achieving clinical response per Adapted Mayo score [ Time Frame: Up to Week 48 ]
    It is defined as decrease from baseline in Adapted Mayo score >= 2 points and >= 30%, accompanied by a decrease in RBS of >= 1 or an absolute RBS of 0 or 1.
  • Proportion of participants achieving clinical remission per Full Mayo score [ Time Frame: Up to 48 Weeks ]
    Clinical remission per full mayo score is defined as a Full Mayo score <= 2 with no subscore > 1.
  • Proportion of participants achieving clinical remission per Partial Mayo score [ Time Frame: Up to 48 Weeks ]
    It is defined as a Partial Mayo score <= 2 with no subscore > 1.
  • Proportion of participants achieving clinical response per Partial Mayo score [ Time Frame: Up to 48 Weeks ]
    It is defined as decrease from baseline in the Partial Mayo score >= 2 points and >= 30% from Baseline, PLUS a decrease in RBS >= 1 or an absolute RBS <= 1.
  • Proportion of participants in clinical remission per Adapted Mayo score at Week 0 who maintain remission at Week 48 [ Time Frame: At Week 48, and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Adapted Mayo score is defined as SFS <= 1, RBS of 0, and endoscopy subscore <= 1.
  • Proportion of participants in clinical remission per Full Mayo score at Week 0 who maintain remission at Week 48 [ Time Frame: At Week 48, and every 48 weeks thereafter through 288 weeks ]
    Clinical remission per Full Mayo score is defined as a Full Mayo score <= 2 with no subscore > 1.
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Long-Term Safety and Efficacy of Upadacitinib (ABT-494) in Subjects With Ulcerative Colitis (UC)
Official Title  ICMJE A Phase 3 Multicenter, Long-Term Extension Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) in Subjects With Ulcerative Colitis
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis (UC)
Intervention  ICMJE
  • Drug: Upadacitinib (ABT-494)
    Upadacitinib (ABT-494) will be administered orally.
    Other Name: Upadacitinib
  • Drug: Placebo
    Placebo will be administered orally.
Study Arms  ICMJE
  • Experimental: Participants receiving Upadacitinib (ABT-494) Dose A
    The participants in this arm will receive Upadacitinib (ABT-494) dose A.
    Intervention: Drug: Upadacitinib (ABT-494)
  • Experimental: Participants receiving Upadacitinib (ABT-494) Dose B
    The participants in this arm will receive Upadacitinib (ABT-494) dose B.
    Intervention: Drug: Upadacitinib (ABT-494)
  • Experimental: Participants receiving Upadacitinib (ABT-494) Dose C
    The participants in this arm will receive Upadacitinib (ABT-494) dose C.
    Intervention: Drug: Upadacitinib (ABT-494)
  • Experimental: Participants receiving Placebo
    The participants in this arm will receive placebo until study is unblinded.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Upadacitinib (ABT-494)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: December 27, 2016)
950
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 28, 2024
Estimated Primary Completion Date January 7, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03006068
Other Study ID Numbers  ICMJE M14-533
2016-000674-38 ( EudraCT Number )
Has Data Monitoring Committee No
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  ICMJE
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  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP