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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3 Multicenter, Long-Term Extension Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) in Subjects With Ulcerative Colitis

Conditions
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Ulcerative Colitis (UC)

Intervention / Treatment
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* Drug: Upadacitinib (ABT-494)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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. During the COVID-19 pandemic, for participants with missing endoscopy at Week 8, Week 16 or Week 52 due to the COVID-19 pandemic in Studies M14-234 Substudy 2, M14-234 Substudy 3 and M14-675, participants may be enrolled if certain criteria are met. If female, participant must meet the contraception criteria. 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. Known hypersensitivity to upadacitinib or its excipients or had any adverse event (AE) during the preceding studies, that in the investigator's judgment makes the participant unsuitable for this study. 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 tuberculosis (TB); current evidence of latent tuberculosis and for any reason the participant cannot take full course of TB prophylaxis treatment as required per protocol. 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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving Upadacitinib (ABT-494) Dose A<br>The participants in this arm will receive Upadacitinib (ABT-494) dose A. | Drug: Upadacitinib (ABT-494)<br>* Upadacitinib (ABT-494) will be administered orally.<br>* Other names: RINVOQ;|
| Experimental: Participants receiving Upadacitinib (ABT-494) Dose B<br>The participants in this arm will receive Upadacitinib (ABT-494) dose B. | Drug: Upadacitinib (ABT-494)<br>* Upadacitinib (ABT-494) will be administered orally.<br>* Other names: RINVOQ;|
| Experimental: Participants receiving Upadacitinib (ABT-494) Dose C<br>The participants in this arm will receive Upadacitinib (ABT-494) dose C. | Drug: Upadacitinib (ABT-494)<br>* Upadacitinib (ABT-494) will be administered orally.<br>* Other names: RINVOQ;|
| Experimental: Participants receiving Placebo<br>The participants in this arm will receive placebo until study is unblinded. | Drug: Placebo<br>* Placebo will be administered orally.<br>|
| Experimental: Participants receiving Upadacitinib (ABT-494) Dose A or Dose B<br>The participants in this arm will receive Upadacitinib (ABT-494) dose A or dose B. | Drug: Upadacitinib (ABT-494)<br>* Upadacitinib (ABT-494) will be administered orally.<br>* Other names: RINVOQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing Treatment-Emergent Adverse Events | 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. | Up to 288 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis (UC), Upadacitinib (ABT-494), Long Term Extension (LTE), Safety, Efficacy, RINVOQ