Study for Participants With Ulcerative Colitis Previously Enrolled in Etrolizumab Phase II/III Studies

Study Overview
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Brief Summary
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This two-part, part 1: open-label extension (OLE) and part 2: safety monitoring (SM) study will examine the efficacy and safety of continued etrolizumab treatment in moderate to severe ulcerative colitis (UC) participants previously enrolled in etrolizumab Phase II/III studies. Participants with moderate to severe UC who were enrolled in the Phase II OLE study (GA27927 [NCT01461317]) or the Phase III studies (GA28948 [NCT02163759], GA28949 [NCT02171429], GA28950 [NCT02100696], GA29102 [NCT02165215], and GA29103 [NCT02136069]) were included. Participants from the Phase II OLE study or the Phase III studies who are not eligible or willing to receive etrolizumab in the OLE-SM study, and who have completed the 12-week safety follow-up period will be enrolled in Part 2. Part 1 of OLE-SM will continue for up to 9 years after the first participant is enrolled into the study. Following Part 1, participants will enter Part 2 for a period of 92 weeks.

Official Title
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An Open-Label Extension and Safety Monitoring Study of Moderate to Severe Ulcerative Colitis Patients Previously Enrolled in Etrolizumab Phase II/III Studies

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Etrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1 (Open-label Extension) - Participants previously enrolled in the Phase II OLE study or Phase III controlled studies who meet the eligibility criteria for open-label etrolizumab for those studies as described in the protocol Part 2 (Safety Monitoring) Participants whose safety follow-up or PML follow-up is not completed within Study GA27927 and participants who had their last dose of etrolizumab in July 2016 in Study GA27927 and are not eligible or willing to enroll in Part 1 (OLE) Participants who participated in one of the etrolizumab Phase III studies and are not eligible or willing to enter Part 1 (OLE) Participants who transfer from Part 1 (OLE) Completion of the 12-week safety follow-up prior to entering. Exclusion Criteria: Part 1 (Open-label Extension) Withdrawal of consent from and participant not compliant in the Phase II OLE study or any of the Phase III studies Participant who discontinued etrolizumab/etrolizumab placebo prior to Week 10 or did not perform the Week 10 visit of the Phase III Studies GA28948, GA28949, GA29102, and GA29103 Participant who discontinued etrolizumab/etrolizumab placebo prior to Week 14 or did not perform the Week 14 visit of the Phase III Study GA28950 Any new, significant, uncontrolled condition

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Open-label Extension<br>Participants with moderate to severe UC who were enrolled in the Phase II OLE study or the Phase III studies, and who meet the eligibility criteria for enrollment will receive open-label etrolizumab in Part 1 (OLE). | Drug: Etrolizumab<br>* Participants will receive etrolizumab 105 milligrams (mg), administered subcutaneously (SC) every 4 weeks for up to 9 years or until either commercial availability or the Sponsor's decision to terminate the study.<br>* Other names: rhuMAb Beta7;|
| No Intervention: Part 2: Safety Monitoring<br>All participants from Part 1 (OLE), participants whose PML follow-up is not completed within the Phase II OLE study, and participants transferring from the Phase III double-blind studies after the 12-week safety follow-up will be monitored for PML (92 weeks). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Remission as Determined by the Partial Mayo Clinic Score (pMCS) - Part 1 |  | Baseline up to 9 years (assessed at Baseline, Week 4, 8, 12 thereafter every 12 weeks up to 9 years after the first participant is enrolled or until commercial availability, whichever is earlier, or until sponsor's decision to terminate the study) | 
| Percentage of Participants With Remission as Determined by the Mayo Clinic Score (MCS) - Part 1 |  | Week 108 | 
| Percentage of Participants With Endoscopic Remission |  | Week 108 | 
| Percentage of Participants With Anti-therapeutic Antibodies to Etrolizumab - Part 1 |  | Baseline, Week 12, every 48 weeks, week 108, at early withdrawal from treatment up to 9 years after first participant enrolled or until commercial availability, whichever is earlier, or until sponsor's decision to terminate the study) | 
| Percentage of Participants With Adverse Events - Part 1 |  | Baseline up to 9 years after the first participant is enrolled or until commercial availability, whichever is earlier, or until the Sponsor's decision to terminate the study | 
| Percentage of Participants With Progressive Multifocal Leukoencephalopathy (PML) - Part 2 |  | 104 weeks | 
| Change From Baseline in pMCS at Year 9 |  | Baseline, Year 9 |