A Study of Intravenous Vedolizumab Administered Every 4 Weeks in Japanese Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease

Study Overview
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Brief Summary
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The main aim of the study is to learn if 4-weekly vedolizumab improves symptoms of Japanese participants with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD). Vedolizumab is commercially available in Japan for 8-weekly treatment but not for 4-weekly treatment. The study doctors will also monitor side effects from the study treatment. This study will take place in Japan. At the first visit, the study doctor will check if each person can take part. For those who can take part, participants will receive vedolizumab intravenously once every 4 weeks. After 3 infusions of vedolizumab (which will be 12 weeks of treatment), the study doctor will assess if symptoms of the participants have improved. Participants who do not have improved symptoms after 12 weeks of treatment with vedolizumab will stop this treatment. Then, they will visit the study clinic 16 weeks after their last infusion of vedolizumab for a final check-up. Participants who have improved symptoms after 12 weeks of treatment with vedolizumab will continue to receive vedolizumab every 4 weeks. Then, after their last infusion of vedolizumab, the participants will visit the study clinic 16 weeks later for a final check-up. Finally, the study clinic will make a phone call to each participant 6 months after their last infusion to check if they have any health problems.

Official Title
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An Open-Label, Phase 3 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Intravenous (IV) Vedolizumab Administered Every 4 Weeks (Q4W) in Japanese Patients With Moderate to Severe Ulcerative Colitis or Crohn's Disease Who Experienced Secondary Loss of Response During Maintenance Therapy With Vedolizumab IV Administered Every 8 Weeks (Q8W)

Conditions
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Ulcerative Colitis, Crohn's Disease

Intervention / Treatment
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* Drug: Vedolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: UC cohort The participant has moderate to severe UC, who had previously shown clinical response in initial treatment with commercially available vedolizumab IV, then experienced secondary loss of response during maintenance therapy with commercially available vedolizumab IV Q8W. Previous clinical response is to be judged by the investigators referring to one of the following criteria. Reduction of >=2 points and >=25% in modified Mayo score, and a decrease of >=1 point in rectal bleeding subscore or rectal bleeding subscore of =<1, from the start of initial treatment with commercially available vedolizumab IV. Reduction of >=2 points and >=25% in partial Mayo score, and a decrease of >=1 point in rectal bleeding subscore or rectal bleeding subscore of =<1, from the start of initial treatment with commercially available vedolizumab IV. Significant improvement on endoscopy (i.e., a decrease of >=2 points in Mayo endoscopic subscore). Secondary loss of response is to be judged by the investigators referring to one of the following criteria. Increase of >=2 points in modified Mayo score, and an increase of >=1 point in rectal bleeding subscore or rectal bleeding subscore >=2, from the start of maintenance therapy with commercially available vedolizumab IV. Increase of >=2 points in partial Mayo score, and an increase of >=1 point in rectal bleeding subscore or rectal bleeding subscore >=2, from the start of maintenance therapy with commercially available vedolizumab IV. Significant deterioration on endoscopy (i.e., an increase of >=2 points in Mayo endoscopic subscore). The participant has active UC as determined by a modified Mayo score of >=5 at baseline (within 10 days prior to the start of treatment phase), with a Mayo rectal bleeding subscore of >=1 at baseline (within 10 days prior to the start of treatment phase) and a Mayo endoscopic subscore of >=1 as assessed by the central reader. CD cohort The participant has moderate to severe CD, who had previously shown clinical response in initial treatment with commercially available vedolizumab IV, then experienced secondary loss of response during maintenance therapy with commercially available vedolizumab IV Q8W. Previous clinical response is to be judged by the investigators referring to one of the following criteria. Reduction of >=70 points in CDAI score from the start of initial treatment with commercially available vedolizumab IV. Reduction of >=3 points in HBI score from the start of initial treatment with commercially available vedolizumab IV. Secondary loss of response is to be judged by the investigators referring to one of the following criteria. Increase of >=70 points in CDAI score from the start of maintenance therapy with commercially available vedolizumab IV. Increase of >=3 points in HBI score from the start of maintenance therapy with commercially available vedolizumab IV. The participant has active CD as determined by a CDAI score of >=220 at baseline (within 10 days prior to the start of treatment phase). The participant has a C-reactive protein (CRP) level >3.0 mg/L during the screening phase. Exclusion Criteria: The participant has had extensive colonic resection, subtotal or total colectomy. The participant has received any of the investigational or approved non-biologic therapies (e.g., cyclosporine, tacrolimus or tofacitinib, except for those specifically listed as permitted medications) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer). The participant has received any investigational or approved biologic or biosimilar agent other than vedolizumab within 60 days or 5 half-lives of screening (whichever is longer). The participant has a clinically significant active infection (e.g., pneumonia, pyelonephritis or coronavirus disease 2019 [COVID-19]) within 30 days prior to screening or during screening, or has an ongoing chronic infection. The participant has known or suspected intolerance or hypersensitivity to vedolizumab or closely related compounds, or any of the vedolizumab IV excipients. The participant has active cerebral/meningeal disease, or signs/symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML at screening.

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: Vedolizumab 300 mg in UC cohort<br>Vedolizumab 300 mg, IV infusion, for up to 12 weeks Q4W for Treatment phase, and until the date of marketing approval of vedolizumab IV Q4W or study termination for Extension phase. | Drug: Vedolizumab<br>* Vedolizumab 300 mg, IV infusion<br>|
| Experimental: Vedolizumab 300 mg in CD cohort<br>Vedolizumab 300 mg, IV infusion, for up to 12 weeks Q4W for Treatment phase, and until the date of marketing approval of vedolizumab IV Q4W or study termination for Extension phase. | Drug: Vedolizumab<br>* Vedolizumab 300 mg, IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Clinical Response at Week 12 Based on Modified Mayo Score in UC Cohort | Clinical response is defined as a reduction of >=2 points and >=25% in modified Mayo score, and a decrease of >=1 point in rectal bleeding subscore or rectal bleeding subscore of =<1 from baseline (Week 0). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy), each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease. | Week 12 | 
| Percentage of Participants with Clinical Response at Week 12 in CD Cohort | Clinical response is defined as a reduction of =>70 points in CDAI score from baseline (Week 0). CDAI assesses CD based on clinical signs and symptoms such as number of liquid stools, intensity of abdominal pain, general well being, presence of comorbid conditions, use of antidiarrheal, physical examination and laboratory findings. Total score ranges from 0 to 600 points. Higher score indicates more severe disease. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Clinical Remission at Week 12 Based on Modified Mayo Score in UC Cohort | Clinical remission is defined as a modified Mayo score of =<2, and no individual subscore >1. Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy), each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease. | Week 12 | 
| Percentage of Participants with Mucosal Healing at Week 12 in UC Cohort | Mucosal healing is defined as a Mayo endoscopic subscore of =<1, in participants with baseline Mayo endoscopic subscore of >=2. Mayo score is an instrument designed to measure disease activity of UC. | Week 12 | 
| Percentage of Participants with Corticosteroid-Free Remission Based on Partial Mayo Score in UC Cohort | Corticosteroid-free remission is defined as participants using oral corticosteroids at baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission based on partial Mayo score at Week 52. Clinical remission based on partial Mayo score is defined as a partial Mayo score of =<2, and no individual subscore >1. Mayo score is an instrument designed to measure disease activity of UC. Partial Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and physician's global assessment, each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher scores indicates more severe disease. | Week 12 | 
| Percentage of Participants with Clinical Remission at Week 12 in CD Cohort | Clinical remission is defined as a CDAI score of =<150. CDAI assesses CD based on clinical signs and symptoms such as number of liquid stools, intensity of abdominal pain, general well being, presence of comorbid conditions, use of antidiarrheal, physical examination and laboratory findings. Total score ranges from 0 to 600 points. Higher score indicates more severe disease. | Week 12 | 
| Percentage of Participants with Enhanced Clinical Response at Week 12 in CD Cohort | Enhanced clinical response is defined as a reduction of >=100 points in CDAI score from baseline (Week 0). CDAI assesses CD based on clinical signs and symptoms such as number of liquid stools, intensity of abdominal pain, general well being, presence of comorbid conditions, use of antidiarrheal, physical examination and laboratory findings. Total score ranges from 0 to 600 points. Higher score indicates more severe disease. | Week 12 | 
| Percentage of Participants with Corticosteroid-Free Remission in CD Cohort | Corticosteroid-free remission is defined as participants using oral corticosteroids at baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. | Week 12 |