Open-Label Extension and Safety Study for Participants With Crohn's Disease Previously Enrolled in the Etrolizumab Phase III Study GA29144

Study Overview
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Brief Summary
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This open-label extension and safety monitoring study is composed of two parts: Part 1 will evaluate the long-term safety and efficacy of continued etrolizumab treatment in participants with moderately to severely active Crohn's disease who were previously enrolled in the etrolizumab Phase III Study GA29144 (NCT02394028) and who meet eligibility criteria for enrollment into Part 1. In Part 2, participants who have stopped etrolizumab treatment (either by exiting Part 1 of this study or by entering directly from Study GA29144 [NCT02394028]) will be monitored for 92 weeks for progressive multifocal leukoencephalopathy (PML) and other safety events.

Official Title
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An Open-Label Extension and Safety Monitoring Study of Patients With Moderately to Severely Active Crohn's Disease Previously Enrolled in the Etrolizumab Phase III Protocol GA29144

Conditions
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Crohn Disease

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: Patients previously enrolled in etrolizumab Phase III study GA29144 (NCT02394028) who meet the eligibility criteria for open-label etrolizumab as described in the protocol Part 2 Safety Monitoring: Patients who participated in etrolizumab Phase III study GA29144 (NCT02394028) and are not eligible or choose not to enter Part 1 Patients who transfer from Part 1 Completion of the 12-week safety follow-up period prior to entering Exclusion Criteria: Part 1 Open-Label Extension: Any new, significant, uncontrolled condition Part 2 Safety Monitoring: No exclusion criteria

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Etrolizumab Open-Label Extension<br>Participants will receive open-label treatment with etrolizumab once every 4 weeks until commercial availability in their country or sponsor's decision to terminate the study, whichever is earlier (up to approximately 10 years after the first patient is enrolled). | Drug: Etrolizumab<br>* 105 mg etrolizumab subcutaneous administration once every 4 weeks<br>* Other names: RG7413;|
| No Intervention: Part 2: Safety Monitoring<br>Participants who have stopped etrolizumab treatment (either by exiting Part 1 of this study or by entering directly from Study GA29144 [NCT02394028]) will be monitored for 92 weeks for progressive multifocal leukoencephalopathy (PML) and other safety events. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants with Crohn's Disease Activity Index (CDAI) Remission Over Time |  | Weeks 0, 12, 24, and every 12 weeks thereafter until study completion or early withdrawal, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Number of Participants with Clinical Remission Over Time | Clinical remission is defined by a loose/soft stool frequency (SF) mean daily score ≤3 and an abdominal pain mean daily score ≤1 with no worsening in either subscore compared to baseline, averaged over 7 days prior to visit. | Weeks 0, 12, 24, and every 12 weeks thereafter until study completion or early withdrawal, commercial availability of etrolizumab, or study termination, whichever is earlier (up to approximately 10 years) | 
| Part 1: Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 108 |  | Week 108 (or at early withdrawal, if prior to Week 108) | 
| Part 1: Overall Number of Participants who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Overall Number of Participants with Adverse Events Leading to Etrolizumab Discontinuation |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Overall Number of Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Number of Infection-Related Adverse Events per Patient-Year |  | From Week 0 until study completion or early withdrawal, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Overall Number of Participants who Experienced at Least One Infection-Related Serious Adverse Event |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Overall Number of Participants who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Overall Number of Participants who Develop Malignancies |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Number of Malignancies per Patient-Year |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Overall Number of Participants who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 |  | From Week 0 until completion of safety follow-up, commercial availability of etrolizumab, or study termination, whichever is earliest (up to approximately 10 years) | 
| Part 1: Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Etrolizumab |  | Weeks 0 and 12, and every 48 weeks thereafter until study completion or early withdrawal (up to approximately 10 years) | 
| Part 2: Number of Participants who Experienced at Least One Suspected or Confirmed Event of Progressive Multifocal Leukoencephalopathy (PML) |  | From end of safety follow-up until completion of 92-week safety monitoring in Part 2 (up to 92 weeks) |