A Study of Long-term Effects of Vedolizumab Subcutaneous in Adults With Ulcerative Colitis and Crohn's Disease

Study Overview
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Brief Summary
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The main aim of the study is to check for long-term side effects of Vedolizumab Subcutaneous (also known as Vedolizumab SC) in people with ulcerative colitis and Crohn's disease. Vedolizumab SC will be given as an injection just under the skin. This type of injection is called a subcutaneous injection or SC for short. Another aim of the study is to collect information on whether the participant's condition remains under control or improves during and after treatment with Vedolizumab SC. Participants who previously took part in studies MLN0002SC-3027 or MLN0002SC-3031 will be invited to visit the study clinic. At this visit, the study doctor will check if each participant can take part in this study. For those who can take part, participants will receive a subcutaneous injection of vedolizumab SC either once a week or once every 2 weeks. How often each participant receives vedolizumab SC will depend on their results from the previous study and on how active their condition is. Participants might be able to self-inject vedolizumab SC after being trained by the study doctors. During this study, the dose of vedolizumab SC might be increased for participants whose condition worsens. Participants will continue treatment with vedolizumab SC until it is approved in their particular country, the participant decides to stop treatment, or the sponsor stops the study. If the sponsor stops the study before vedolizumab SC is approved in all countries, the sponsor will make sure all affected participants will have access to vedolizumab SC outside of the study. After their final dose of vedolizumab SC, participants will visit the clinic 18 weeks later for a final check-up. Then, the clinic will telephone the participants 6 months after their final dose of vedolizumab SC to check if they have any health problems.

Detailed Description
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The drug being tested in this study is called vedolizumab subcutaneous (vedolizumab SC). Vedolizumab SC is being tested to assess its long-term safety and effectiveness in treating participants with UC or CD. This study will look at the long-term side effects and response/remission of UC and CD in participants who received vedolizumab SC in a prior vedolizumab SC study. The study will enroll up to 692 patients. All participants enrolled in this study will have previously participated in the MLN0002SC-3027 or MLN0002SC-3031 study. Participants who completed the Maintenance Period (Week 52) in their previous study, or who did not achieve a clinical response at Week 6 but who did achieve a clinical response at Week 14 after having received a third vedolizumab IV infusion at Week 6 in their previous study, will receive open-label vedolizumab SC 108 mg, once every 2 weeks (Q2W). Participants who withdrew early from the Maintenance Period of their previous study due to disease worsening or need for rescue medications will receive open-label vedolizumab SC 108 mg, once every week (QW). Participants receiving SC 108 mg Q2W who experience treatment failure (disease worsening or need for rescue medications while in the current study will be dose escalated to vedolizumab SC 108 mg QW. This multi-center trial will be conducted worldwide. Participation in this vedolizumab SC study will continue until vedolizumab SC becomes commercially available, the participant withdraws from the study, or the sponsor decides to close the study. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after last dose of study drug for a follow-up assessment. Participants will also participate in a long-term safety follow-up, by phone, at 6 months after the last dose of study drug.

Official Title
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A Phase 3b Open-label Study to Determine the Long-term Safety and Efficacy of Vedolizumab Subcutaneous in Subjects With Ulcerative Colitis and Crohn's Disease

Conditions
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Colitis, Ulcerative, Crohn's Disease

Intervention / Treatment
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* Drug: Vedolizumab SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Prior participation in Study MLN0002SC-3027 or MLN0002SC-3031, and, in the opinion of the investigator, tolerated the study drug well. Early withdrawal from Study MLN0002SC-3027 or MLN0002SC-3031 must have been due to treatment failure during the Maintenance Period. Exclusion Criteria: Surgical intervention for IBD during or after participation in Study MLN0002SC-3027 or MLN0002SC-3031, or at any time during this study. Chronic or severe infection, or, any new, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, oncologic, or other medical disorder developed during or after participation in a prior vedolizumab study that, in the opinion of the investigator, would confound the study results or compromise participant safety. Withdrawal from Study MLN0002SC-3027 or MLN0002SC-3031 due to a study-drug related adverse event (AE).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Vedolizumab SC 108 mg Q2W<br>Participants from studies MLN0002SC-3027 and MLN0002SC-3031 who: Completed the Maintenance Period (Week 52), or Were not randomized into Maintenance Period and achieved response at Week 14 after having received a third vedolizumab IV infusion at Week 6. | Drug: Vedolizumab SC<br>* Vedolizumab SC 108 mg injection<br>|
| Experimental: Group B: Vedolizumab SC 108 mg QW<br>Participants from studies MLN0002SC-3027 and MLN0002SC-3031 who withdrew early from the Maintenance Period due to treatment failure. •Participants from current study who experience treatment failure while on study. | Drug: Vedolizumab SC<br>* Vedolizumab SC 108 mg injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | Number of TEAEs and SAEs adjusted by duration of exposure to study treatment scaled such that it provides an incidence rate of TEAEs and SAEs per 100-participant-years. | From start of study medication through 18 weeks after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events of Special Interest (AESIs) Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | Number of AESIs adjusted by duration of exposure to study treatment scaled such that it provides an incidence rate of AESIs per 100-participant-years. AESIs include hypersensitivity reactions (including injections site reactions), serious infections, malignancies, hepatotoxicity (abnormal liver function test) and progressive multifocal leukoencephalopathy (PML). | From start of study medication through 18 weeks after the last dose | 
| Percentage of Participants with Ulcerative Colitis Achieving Partial Mayo Scoring Clinical Response | Clinical response is defined as a decrease in the partial Mayo Score of at least 2 points and ≥25% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥1 point from baseline or absolute rectal bleeding subscore of ≤1 point. | From Week 0 (Day 1) up to availability of vedolizumab SC, withdrawal by participant, or study closure, Up to 7 years | 
| Percentage of Participants with Crohn's Disease Achieving Clinical Response | Clinical response is defined as a decrease in HBI score of ≥3 points from baseline in CD participants (randomized early terminator CD participants only [defined as randomized CD participants withdrawn from the parent study between Week 6 and Week 52]). | From Week 0 (Day 1) up to availability of vedolizumab SC, withdrawal by participant, or study closure, Up to 7 years | 
| Percentage of Participants with Ulcerative Colitis Achieving Clinical Remission | Clinical remission is defined as a partial Mayo score of ≤ 2 with no individual subscore >1. | From Week 0 (Day 1) up to availability of vedolizumab SC, withdrawal by participant, or study closure, up to 7 years | 
| Percentage of Participants with Crohn's Disease (CD) Achieving Clinical Remission | Clinical remission is defined as total HBI score of ≤4 points in CD participants only (defined as randomized CD participants withdrawn from the parent study between Week 6 and Week 52). | From Week 0 (Day 1) up to availability of vedolizumab SC, withdrawal by participant, or study closure, Up to 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy