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

Prior treatment

• The participant has had extensive colonic resection, subtotal or total colectomy.
• The participant has received tube feeding, defined formula diets, or parenteral alimentation within 21 days before administration of the first dose of study drug.
• 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 evidence of treatment for Clostridioides difficile (C difficile) infection or other intestinal pathogen within, 28 days before first dose of study drug.
• 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.
  • 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.

Other illness

• The participant has a history of \>3 small bowel resections or diagnosis of short bowel syndrome.
• The participant has a history or evidence of colonic mucosal dysplasia including low or high-grade dysplasia, as well as indeterminate for dysplasia.
  • Infectious Disease Exclusion Criteria
• The participant has evidence of active infection during the screening period.
• 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 participant has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.

Age

• 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.

Other

• Gastrointestinal (GI) Exclusion Criteria:
• The participant has evidence of abdominal abscess at the initial screening visit.
• 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.
• The participant has a history or evidence of adenomatous colonic polyps that have not been removed.

• 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.