A Study of Vedolizumab in Adult Participants With Moderate to Severe Crohn's Disease

Study Overview
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Brief Summary
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This is a study to evaluate vedolizumab for injection (300 mg) as a safe and active treatment for Crohn's Disease in adults in China. Participants will receive an injection of Vedolizumab 300 mg at scheduled weeks 0, 2, and 6, and starting at week 14, every 8 weeks over 58 weeks or starting at week 18, every 4 weeks over 54 weeks. There will be up to 20 study visits over 58 weeks to complete assessments.

Detailed Description
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The drug being tested in this study is called vedolizumab. Vedolizumab will be administered as an intravenous (IV) infusion in Chinese participants. This study will investigate the efficacy and safety of vedolizumab IV in participants with moderately to severely active Crohn's Disease (CD). The study will enroll approximately 408 patients. Participants will be randomized into 2:1 in the Induction Period to receive: Vedolizumab IV 300 mg Placebo All participants completing the Week 14 visit, irrespective of their response status, will continue in the OLE without unblinding of their baseline treatment group and will receive 300 mg vedolizumab once every 8 weeks (Q8W) starting from Week 14. Starting at Week 18 and throughout the remainder of the OLE, participants who are nonresponders or who have disease worsening based on the assessment by visit every 4 weeks, are eligible to receive 300 mg vedolizumab once every 4 weeks (Q4W). This multi-center trial will be conducted in China. The overall time participants will be in this study is approximately 58 weeks. Participants will make a final safety follow-up visit at 18 weeks after the last dose of study drug. Participants will also be followed-up for a long-term follow-up safety survey after completion of or early termination from study via telephone, 6 months after last dose of study drug.

Official Title
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A Phase 3, Multicenter, Randomized, Parallel-Group, Double-blind, Placebo-Controlled Induction Study Followed by an Open-label Extension Period to Evaluate the Efficacy and Safety of Intravenous Vedolizumab (300 mg) Infusion Treatment in Subjects in China With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Vedolizumab IV
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: The participant has a diagnosis of CD established at least 3 months before screening by clinical and endoscopic evidence corroborated by a histopathology report. Cases of CD established at least 6 months before randomization for which a histopathology report is not available will be considered based on the weight of evidence supporting the diagnosis and excluding other potential diagnoses, and must be discussed with the sponsor on a case-by-case basis before randomization. The participant has moderately to severely active CD as determined by a 2-component patient-reported outcome (PRO2) score of 14 to 34 points and a Simple Endoscopic Score for Crohn's Disease (SES-CD) score of ≥6 (or ≥4 in cases of isolated ileitis) on screening ileocolonoscopy. The participant has CD involvement of the ileum and/or colon, at a minimum. A participant with extensive colitis or pancolitis of >8 years duration or limited colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months before initial screening (may be performed during screening if not performed in previous 12 months). A participant with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during screening). The participant has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below: Corticosteroids. Immunomodulators. TNF-α antagonists. Exclusion Criteria: I. Gastrointestinal (GI) Exclusion Criteria: The participant has evidence of abdominal abscess at the initial screening visit. The participant has had extensive colonic resection, subtotal or total colectomy. The participant has a history of >3 small bowel resections or diagnosis of short bowel syndrome. The participant has received tube feeding, defined formula diets, or parenteral alimentation within 21 days before administration of the first dose of study drug. The participant has had ileostomy, colostomy, known fixed symptomatic stenosis of the intestine, or evidence of fixed stenosis, or small bowel stenosis with prestenotic dilation. Within 30 days before randomization, the participant has received any of the following for the treatment of underlying disease: Nonbiologic therapies (eg, cyclosporine, thalidomide) other than those specifically listed in the Permitted Medications and Treatments section. An approved or investigational nonbiologic therapy in an investigational protocol. The participant has received traditional Chinese medication (TCMs) within 30 days before randomization. The participant has had previous exposure to approved or investigational anti-integrins including, but not limited to natalizumab, efalizumab, etrolizumab, or abrilumab (AMG-181), or mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) antagonists, or rituximab. The participant has had previous exposure to vedolizumab. The participant has used topical (rectal) treatment with 5-aminosalicylic acid (5-ASA), corticosteroid enemas/suppositories or traditional Chinese medications for CD treatment within 2 weeks of the administration of the first dose of study drug. The participant requires currently or is anticipated to require surgical intervention for CD during the study. The participant has a history or evidence of adenomatous colonic polyps that have not been removed. The participant has a history or evidence of colonic mucosal dysplasia including low or high-grade dysplasia, as well as indeterminate for dysplasia. II. Infectious Disease Exclusion Criteria The participant has evidence of active infection during the screening period. The participant has evidence of treatment for Clostridioides difficile (C difficile) infection or other intestinal pathogen within, 28 days before first dose of study drug. The participant has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection. The participant has active or latent tuberculosis (TB). The participant has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation). The participants has received any live vaccinations within 30 days before screening. The participant has a clinically significant active infection (eg, pneumonia, pyelonephritis, or coronavirus disease 2019 [COVID-19]) within 30 days before screening or during screening, or has an ongoing chronic infection or any ongoing COVID-19-related symptom(s), if previously diagnosed as having COVID-19. III. General Exclusion Criteria The participant has had any surgical procedure requiring general anesthesia within 30 days before enrollment or is planning to undergo major surgery during the study period. The participant has any history of malignancy, except for the following: (a) adequately-treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and has not recurred for at least 1 year before randomization; and (c) history of cervical carcinoma in situ that has been adequately treated and has not recurred for at least 3 years before randomization. Participants with remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis before randomization. The participant has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction Period: Vedolizumab 300 mg<br>Participants will receive vedolizumab 300 mg IV infusion on Days 1,15, and 43 (Weeks 0, 2, and 6) in the 14-week Induction Period. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>|
| Placebo Comparator: Induction Period: Placebo<br>Participants will receive vedolizumab placebo-matching IV, infusion on Days 1,15, and 43 (Weeks 0, 2, and 6) in the 14-week Induction Period. | Drug: Placebo<br>* Vedolizumab placebo-matching IV infusion<br>|
| Experimental: Open-label Extension (OLE) Period: Vedolizumab 300 mg<br>All participants completing the Week 14 visit, irrespective of their response status, will continue in the OLE without unblinding of their baseline treatment group and will receive vedolizumab 300 mg, IV infusion, Q8W, on Days 99, 155, 211, 267, 323, and 379 (Weeks 14, 22, 30, 38, 46 and 54). Starting from Day 127 (Week 18) until the end of OLE Period up to approximately 58 weeks, participants who are nonresponders or who have disease worsening are eligible to receive 300 mg vedolizumab Q4W. | Drug: Vedolizumab IV<br>* Vedolizumab IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Response at Week 14 | Clinical response is defined as ≥8 point decrease in 2-component patient-reported outcome (PRO2) score from baseline. The PRO2 is constituted by abdominal pain and number of liquid stools components of the Crohn's Disease Activity Index (CDAI). The PRO-2 score is the sum of the abdominal pain and stool frequency subscores of the CDAI score. The average daily number of liquid or very soft stools and abdominal pain score (with 0 indicating no pain and 3 indicating severe pain) are weighted according to the CDAI multiplication factors (2 for stool frequency and 5 for abdominal pain). | Up to Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Remission at Week 14 | Clinical remission is defined as PRO2 score <8 from baseline. The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI. The PRO-2 score is the sum of the abdominal pain and stool frequency subscores of the CDAI score. The average daily number of liquid or very soft stools and abdominal pain score (with 0 indicating no pain and 3 indicating severe pain) are weighted according to the CDAI multiplication factors (2 for stool frequency and 5 for abdominal pain). | Up to Week 14 | 
| Percentage of Participants Achieving Endoscopic Response at Week 14 | Endoscopic response is defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) reduction by ≥50%. The SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable is sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 60, where higher scores indicate more severe disease. | Up to Week 14 | 
| Percentage of Participants Achieving Both Clinical Response and Endoscopic Response at Week 14 | Clinical response:≥8 point decrease in PRO2 score from baseline. Endoscopic response:SES-CD reduction by ≥50%.PRO2:number of liquid stools and abdominal pain components of the CDAI. PRO-2 score:sum of the abdominal pain and stool frequency subscores of the CDAI score.Average daily number of liquid or very soft stools and abdominal pain score (0=no pain and 3=severe pain) are weighted according to the CDAI multiplication factors (2= stool frequency;5= abdominal pain).Negative change indicates clinical response achieved.SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and presence of narrowings) in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum).Score for each endoscopic variable=sum of values obtained for each segment.SES-CD total=sum of the 4 endoscopic variable scores from 0 to 60, where higher scores=more severe disease. | Up to Week 14 | 
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Discontinuation | AE:any untoward medical occurrence in clinical investigation participants administered a drug;it does not necessarily have to have causal relationship with treatment.SAE:any untoward medical occurrence that:1)results in death,2)is life-threatening,3)requires inpatient hospitalization or prolongation of existing hospitalization,4)results in persistent or significant disability/incapacity,5)leads to a congenital anomaly/birth defect in offspring of participant or6)is medically important event that satisfies any of following:a)May require intervention to prevent items 1 through 5 above.b)May expose participant to danger,even though event is not immediately life threatening or fatal or does not result in hospitalization.AESI:serious infections,opportunistic infections such as progressive multifocal leukoencephalopathy(PML);liver injury;malignancies;infusion-related reactions,injection site reactions,systemic reactions,and hypersensitivity. | From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks) | 
| Percentage of Participants With Abnormal Change from Baseline in Vital Sign Values | Vital signs assessment will include body temperature, respiratory rate, blood pressure, and pulse (beats per minute). Abnormal values will be determined by the investigator. | From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks) | 
| Percentage of Participants With Abnormal Change from Baseline in Laboratory Values | Laboratory parameter assessment will include hematology, serum chemistry, and urinalysis. Abnormal values will be determined by the central lab. | From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks) | 
| Percentage of Participants With Abnormal Change from Baseline in Electrocardiogram (ECG) Values | The ECG results will be interpreted using 1 of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant. Abnormal values are determined by the investigator. | From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks) | 

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