A Study of Vedolizumab in Children With Ulcerative Colitis (UC) or Crohn's Disease (CD)

Study Overview
=================
Brief Summary
-----------------
The study is an extension of two parent studies (MLN0002-3024 [NCT04779307] and MLN0002-3025 [NCT04779320]). Participants must have participated in one of the previous studies. The purpose of this study is to collect the long-term safety of vedolizumab in children with UC or CD.

Detailed Description
-----------------
This multi-center trial will be conducted worldwide. Up to 240 patients would be enrolled from Studies MLN0002-3024 [participants with UC] and MLN0002-3025 [participants with CD], either in the Treatment Cohort or in the Observational Cohort. Approximately 93 participants who have previously participated either in study MLN0002-3024 or MLN0002-3025, referred to as parent study, are expected to roll over to the MLN0002-3029 study in the treatment cohort. Treatment Cohort: The drug being tested in this study is called vedolizumab, being studied to treat pediatric patients who have UC or CD. Participants eligible for the Treatment Cohort can be administered vedolizumab intravenous (IV) at Week 54 visit of parent study or up to 1 week after Week 54 of the parent study based on the availability of test results needed to assess eligibility of the participant. At this study entry, participants will be administered the same blinded dose of vedolizumab IV that was received at Week 46 in the parent study and will then continue to receive vedolizumab IV at a frequency of once every 8 weeks (Q8W) in the following treatment groups: Participants 10 to ≤15 kilogram (kg), Vedolizumab 150 milligram (mg) (High dose) Participants 10 to ≤15 kg, Vedolizumab 100 mg (Low dose) Participants >15 to <30 kg, Vedolizumab 200 mg (High dose) Participants >15 to <30 kg, Vedolizumab 100 mg (Low dose) Participants ≥30 kg, Vedolizumab 300 mg (High dose) Participants ≥30 kg, Vedolizumab 150 mg (Low dose) Blinding of dose group assignment of the parent study will continue until the last participant from MLN0002-3024 or MLN0002-3025 rolls over to MLN0002-3029 in order to protect the blinding of the parent study. The overall time to participate in the Treatment Cohort of this study is up to participant withdrawal, or until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available, or Sponsor's decision for study closure, or for up to approximately 5 years, whichever comes first. Participants who complete or are discontinued from the study for any reason will complete the final safety/end of study (EOS) visit 18 weeks after their last dose of study drug. Observational Cohort: Participants who received at least 1 dose of study drug during parent study and early terminated or are not eligible for the Treatment Cohort of this study after completion of the Week 54 visit of parent study, will be enrolled in the Observational Cohort of this study as part of a long-term follow-up period to assess prespecified safety events of interest and will not receive continued treatment with vedolizumab IV. The overall time to participate in the Observational Cohort is up to approximately 2 years.

Official Title
-----------------
A Phase 3b Extension Study to Evaluate the Long-term Safety of Vedolizumab Intravenous in Pediatric Patients With Ulcerative Colitis or Crohn's Disease

Conditions
-----------------
Ulcerative Colitis, Crohn's Disease

Intervention / Treatment
-----------------
* Drug: Vedolizumab IV
* Other: No Intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: For Treatment Cohort: The participant should have completed Study MLN0002-3024 or Study MLN0002-3025 and achieved corticosteroid-free clinical response at Week 54 (and has tapered off of steroids, as applicable, at least 12 weeks before Week 54) as defined by a reduction of partial Mayo score of ≥2 points and ≥25% from baseline for participants with UC, or by a decrease of pediatric Crohn's disease activity index (PCDAI) of ≥15 points for participants with CD. A male participant who is sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (e.g., condom with or without spermicide) from signing of informed consent throughout the duration of the study and for 18 weeks after last dose. The female partner of a male participant should also be advised to use a highly effective method of contraception. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective method of contraception from signing of informed consent throughout the duration of the study and 18 weeks after the last dose. For Observational Cohort: 1. The participant has received at least 1 dose of vedolizumab during Study MLN0002-3024 or Study MLN0002-3025 and early terminated OR completed the Week 54 visit of Study MLN0002-3024 or Study MLN0002-3025 but was not eligible to enroll in the treatment cohort of this study. Main Exclusion Criteria: For Treatment Cohort only: The participant currently requires major surgical intervention for UC or CD (e.g., bowel resection), or is anticipated to require major surgical intervention for UC or CD during the study. The participant has developed any new unstable or uncontrolled cardiovascular, heart failure moderate to severe (New York Class Association III or IV), pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurological, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety. The participant has other serious comorbidities that will limit their ability to complete the study. The participant is unable to comply with all study assessments. The participant has hypersensitivity or allergies to any of the vedolizumab excipients. The participant is lactating or pregnant.

Ages Eligible for Study
-----------------
Minimum Age: 3 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Treatment Cohort: Participants 10 to ≤15 kg, Vedolizumab 150 mg<br>Eligible participants from studies MLN0002-3024 or MLN0002-3025 weighing 10 to ≤15 kg will receive vedolizumab 150 mg, IV infusion, Q8W, (same as their Week 46 dose in parent study) in this study for up to approximately 5 years. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>* Other names: KYNTELES;|
| Experimental: Treatment Cohort: Participants 10 to ≤15 kg, Vedolizumab 100 mg<br>Eligible participants from studies MLN0002-3024 or MLN0002-3025 weighing 10 to ≤15 kg will receive vedolizumab 100 mg, IV infusion, Q8W, (same as their Week 46 dose in parent study) in this study for up to approximately 5 years. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>* Other names: KYNTELES;|
| Experimental: Treatment Cohort: Participants >15 to <30 kg, Vedolizumab 200 mg<br>Eligible participants from studies MLN0002-3024 or MLN0002-3025 weighing >15 to <30 kg will receive vedolizumab 200 mg, IV infusion, Q8W, (same as their Week 46 dose in parent study) in this study for up to approximately 5 years. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>* Other names: KYNTELES;|
| Experimental: Treatment Cohort: Participants >15 to <30 kg, Vedolizumab 100 mg<br>Eligible participants from studies MLN0002-3024 or MLN0002-3025 weighing >15 to <30 kg will receive vedolizumab 100 mg, IV infusion, Q8W, (same as their Week 46 dose in parent study) in this study for up to approximately 5 years. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>* Other names: KYNTELES;|
| Experimental: Treatment Cohort: Participants ≥30 kg, Vedolizumab 300 mg<br>Eligible participants from studies MLN0002-3024 or MLN0002-3025 weighing ≥30 kg will receive vedolizumab 300 mg, IV infusion, Q8W, (same as their Week 46 dose in parent study) in this study for up to approximately 5 years. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>* Other names: KYNTELES;|
| Experimental: Treatment Cohort: Participants ≥30 kg, Vedolizumab 150 mg<br>Eligible participants from studies MLN0002-3024 or MLN0002-3025 weighing ≥30 kg will receive vedolizumab 150 mg, IV infusion, Q8W, (same as their Week 46 dose in parent study) in this study for up to approximately 5 years. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>* Other names: KYNTELES;|
| Other: Observational Cohort: Early Terminated Participants From Parent Studies<br>Participants will have assessment visits at Day 1 and Weeks 8, 34, 60, and 86 as part of a long-term follow-up period to assess prespecified safety events of interest and to monitor growth and pubertal development for approximately 2 years after their last dose of study drug in parent study. | Other: No Intervention<br>* Participants will not receive any intervention in the Observational Cohort.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Cohort: Number of Participants With at Least One Adverse Event (AE) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have causal relationship with this treatment. AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether or not it is considered related to drug. | From first dose of study drug up to approximately 5 years | 
| Observational Cohort: Number of Participants With Prespecified Safety Events | Prespecified safety events will include serious infections, malignancies, progressive multifocal leukoencephalopathy (PML), concerns about growth and pubertal development, and bowel surgery. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Cohort: Time to Major Inflammatory Bowel Disease (IBD)-related Events | Major IBD-related events include hospitalizations, surgeries, and procedures in pediatric participants with UC or CD. | Up to approximately 5 years | 
| Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Total Score for Participants Aged 9 to 17 Years for Every 24 Weeks | The IMPACT-III questionnaire is a self-reported measure with 35 closed questions encompassing 6 domains: Bowel Symptoms (7 items), Systemic Symptoms (3 items), Social Functioning (12 items), Body Image (3 items), Treatment/Interventions (3 items), and Emotional Functioning (7 items). The IMPACT-III uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The total score is an average of all item scores. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025. | Baseline, every 24 weeks in this study (up to approximately 5 years) | 
| Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Bowel Symptom Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks | The IMPACT-III Bowel Symptom Subscale is a self-reported measure with 7 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The bowel symptom subscale score ranges from 1 to 35, with higher scores indicating lesser bowel symptoms. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025. | Baseline, every 24 weeks in this study (up to approximately 5 years) | 
| Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Systemic Symptom Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks | The IMPACT-III Systemic Symptom Subscale is a self-reported measure with 3 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The Systemic symptom subscale score ranges from 1 to 15, with higher scores indicating lesser systemic symptoms. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025. | Baseline, every 24 weeks in this study (up to approximately 5 years) | 
| Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Social Functioning Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks | The IMPACT-III Social Functioning Subscale is a self-reported measure with 12 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The social functioning subscale score ranges from 1 to 60, with higher scores indicating better social functioning. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025. | Baseline, every 24 weeks in this study (up to approximately 5 years) | 
| Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Body Image Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks | The IMPACT-III Body Image Subscale is a self-reported measure with 3 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The body image subscale score ranges from 1 to 15, with higher scores indicating better body image. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025. | Baseline, every 24 weeks in this study (up to approximately 5 years) | 
| Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Treatment/Intervention Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks | The IMPACT-III Treatment/Intervention Subscale is a self-reported measure with 3 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The treatment/intervention subscale score ranges from 1 to 15, with higher scores indicating ease of administration of treatment/interventions. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025. | Baseline, every 24 weeks in this study (up to approximately 5 years) | 
| Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Emotional Functioning Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks | The IMPACT-III Emotional Functioning Subscale is a self-reported measure with 7 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The emotional functioning subscale score ranges from 1 to 35, with higher scores indicating better emotional functioning. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025. | Baseline, every 24 weeks in this study (up to approximately 5 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy