A Study of Vedolizumab in People With Ulcerative Colitis and Crohn's Disease

Study Overview
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Brief Summary
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Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system. In this study, people with ulcerative colitis or Crohn's disease will be treated with vedolizumab. The main aim of the study is to check for side effects from vedolizumab. At the first visit, the study doctor will check who can take part. Participants will receive vedolizumab slowly through a vein (infusion). Participants will regularly visit the clinic for up to 46 weeks for more infusions of Vedolizumab. During these visits, the study doctor will check if there are any side effects from this treatment. Participants will visit the clinic for a final check-up up to 16 weeks after their final infusion of Vedolizumab. Clinic staff will arrange a phone call 6 months after their final infusion of Vedolizumab for a further check-up.

Detailed Description
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The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have active UC or CD. The study will enroll approximately 150 patients. Participants will be assigned to the vedolizumab treatment group. •Vedolizumab 300 mg Vedolizumab 300 mg IV infusion will be administered once in Weeks 0, 2, 6 and 10 (CD-participants who have not shown a response can receive a dose at Week 10) during induction phase and in Weeks 14, 22, 30, 38 and 46 during maintenance phase. This multicentre trial will be conducted in India. The overall time to participate in this study is 74 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone plus a final visit after receiving their last dose of drug for a follow-up assessment.

Official Title
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A Multicenter, Single-arm, Open-label, Phase 4 Study to Evaluate the Safety and Efficacy of Vedolizumab in Indian Patients With Ulcerative Colitis and Crohn's Disease

Conditions
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Ulcerative Colitis, Crohn Disease

Intervention / Treatment
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* Drug: Vedolizumab IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a diagnosis of moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) at least 3 months prior to screening, with a Full Mayo Score of 6-12 for UC and a Harvey Bradshaw Index (HBI) score of >=8 for CD at the time of enrolment. Has demonstrated, an inadequate response to, loss of response to, or intolerance to at least 1 of the following agents: Conventional therapy TNF-α alpha antagonist Exclusion Criteria: Has undergone an ileostomy, colostomy, or has known fixed symptomatic stenosis of the intestine. Has active or latent tuberculosis (TB). Has had a prior exposure to vedolizumab or a history of hypersensitivity or allergies to vedolizumab, natalizumab, efalizumab, or rituximab. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist during screening or prior to the administration of study drug on Day 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Vedolizumab 300 mg<br>Vedolizumab 300 mg IV infusion will be administered once in Weeks 0, 2 and 6 during induction phase and in Weeks 14, 22, 30, 38 and 46 during maintenance phase. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>* Other names: Kynteles;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs), Serious Adverse events (SAEs), Adverse Events of Special Interest (AESIs), Adverse Drug Reactions (ADRs) and Unexpected ADRs | An AE is defined as any untoward medical occurrence in a clinical investigation patient administered a drug; it does not necessarily have to have a causal relationship with the treatment. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. AESIs occurs during the treatment or follow-up period, are recorded in the special interest such as opportunistic infections, gastrointestinal infections, respiratory infections, other clinically significant infections, malignancies, infusion-related reactions and hypersensitivity, and hepatic injury. ADRs are defined as AEs which are in the investigator's opinion of causal relationship to the study treatment. An Unexpected ADR is an ADR with the nature, severity, or outcome which is not consistent with summary of product characteristics. | From first dose of study drug up to 6 months after the last dose of study drug (Up to approximately 70 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Ulcerative Colitis (UC) and Crohn's Disease (CD) Who Achieved Clinical Response | Clinical response is defined as decrease in Simple Clinical Colitis Activity Index (SCCAI) of ≥3 from baseline or by physician assessment of clinical response (UC participants) or decrease in Harvey Bradshaw Index (HBI) of ≥3 points from baseline (CD participants). SCCAI is composed of six domains: bowel frequency (during day) ranges 0 to >9; bowel frequency (during night) ranges 0 to 6; urgency of defecation ranges none to incontinence; blood in stool ranges none to usually frank (>50% of defecation); general well-being ranges very well to terrible (0-10); and a number of defined extracolonic features of UC (i.e. arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis). The score of <5 is considered as inactive and ≥5 is active disease. HBI is composed of five clinical parameters: general well-being, abdominal pain, number of liquid stools/day, abdominal mass, and complications. The score <5 is considered as clinical remission, 5-7 mild, 8-16 moderate, and >16 severe disease. | Weeks 14, 30 and 46 | 
| Percentage of Participants with UC and CD Who Achieved Clinical Remission | Clinical remission is defined as SCCAI of ≤2 from baseline (UC participants) or a HBI ≤4 (CD participants). SCCAI is composed of six domains: bowel frequency (during day) ranges 0 to >9; bowel frequency (during night) ranges 0 to 6; urgency of defecation ranges none to incontinence; blood in stool ranges none to usually frank (>50% of defecation); general well-being ranges very well to terrible (0-10); and a number of defined extracolonic features of UC (i.e. arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis). The score of <5 is considered as inactive and ≥5 is active disease. HBI is composed of five clinical parameters: general well-being, abdominal pain, number of liquid stools/day, abdominal mass, and complications. The score <5 is considered as clinical remission, 5-7 mild, 8-16 moderate, and >16 severe disease. | Weeks 14, 30 and 46 | 
| Percentage of Participants with UC and CD Who Had Vedolizumab Discontinuation | Vedolizumab discontinuation is defined as ceasing vedolizumab, or a treatment gap ≥90 days between consecutive doses. | Up to 46 weeks | 
| Percentage of Participants with UC and CD Who Achieved Mucosal Healing | Mucosal healing is based on endoscopic evidence of no inflammation and healing of the mucosa as defined by a Mayo endoscopic subscore of ≤1 point or Simple Endoscopic Score for Crohn Disease (SES-CD) 0-2 or SES-CD ≤4 and at least a 2 point reduction from baseline with no sub-score >1. Full Mayo Score evaluates ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation, and Physician's global assessment. Each parameter of the score (including Mayo endoscopic subscore) ranges from 0 (normal or inactive disease) to 3 (severe activity) yielding a total score of 0-12. The scores 0-2 are considered as clinical remission, 3-5 mild, 6-10 moderate, and 11-12 severe. SES-CD assesses the size of mucosal ulcers, ulcerated surface, endoscopic extension, and the presence and type of narrowings. Each of the four SES-CD variables is scored from 0 to 3, with the sum of scores for each variable ranging from 0 to 15 yielding a total SES-CD score of 0-60. | Week 46 | 
| Percentage of Participants with UC and CD Who Achieved Endoscopic Response | Endoscopic response is defined as decrease in Mayo endoscopic subscore of ≥1 point in UC and >50% decrease in SES-CD in CD. Full Mayo Score evaluates ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation, and Physician's global assessment. Each parameter of the score (including Mayo endoscopic subscore) ranges from 0 (normal or inactive disease) to 3 (severe activity) yielding a total score of 0-12. The scores 0-2 are considered as clinical remission, 3-5 mild, 6-10 moderate, and 11-12 severe. SES-CD assesses the size of mucosal ulcers, ulcerated surface, endoscopic extension, and the presence and type of narrowings. Each of the four SES-CD variables is scored from 0 to 3, with the sum of scores for each variable ranging from 0 to 15 yielding a total SES-CD score of 0-60. | Week 46 | 
| Change From Baseline in Patient-reported Quality of Life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]) | The SIBDQ is a valid and reliable instrument used to assess quality of life in adult participants with Inflammatory Bowel Disease (IBD). It is a 10-item questionnaire that includes questions on 4 domains of health-related quality of life (HRQoL): bowel systems, emotional function, social function, and systemic function and is scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). A total SIBDQ score is calculated by summing the scores from each domain; the total SIBDQ score ranges from 10 (poor HRQoL) to 70 (optimum HRQoL). | From Baseline and Weeks 14, 30 and 46 | 

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