A Study to Evaluate Whether Healing all Bowel Wall Layers is a Superior Treatment Target in Patients with Active Crohn’s Disease (CD).

Prior treatment

• Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;
• Known HIV or hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required;
• Known active or latent tuberculosis (TB); if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization;
• Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization;
• Unwillingness to withhold protocol-prohibited medications during the trial;
• Previously exposed to 2 or more compounds or classes of an advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD;
• Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days prior to randomization;
• Prior enrolment in the current study and had received study treatment;
• Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination with a live or live-attenuated vaccine during participation in the study;
• Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of >40 mg of prednisone or equivalent at randomization;
• Previous extensive colonic resection or missing >2 segments out of 5 (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum), ileorectal anastomosis, or a proctocolectomy

Other illness

• Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the participant’s ability to participate fully in the study or would compromise participant safety;
• Positive stool test for Clostridioides difficile infection (as demonstrated by positive toxin);
• Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization;
• Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab;
• Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection.
• History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant’s ability to comply with the study procedures;
• Short bowel syndrome;

Other

• Abscess >2 cm, detected by IUS or endoscopy; participants with draining fistulas are not excluded;
• Pregnant, lactating, or intending to become pregnant/impregnate a partner before, during, or within 18 weeks after the last dose; or intending to donate ova or sperm during such time period;
• Any person performing mandatory military service, deprived of liberty, in a residential care setting, or any person who, due to a judicial decision, cannot take part in clinical studies;
• The person is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling).
• Only have inflammation proximal to the terminal ileum that cannot be reached by ileocolonoscopy;
• Have a CD complication, such as symptomatic strictures in the small bowel with >3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention;
• Ostomy or ileoanal pouch;
• Fibrotic-only stricture in the ileum or colon without evidence of active inflammation (in the investigator’s judgment), including any impassable stenosis

• Adults aged 18 to 80 years, inclusive, at the time of consent;
• Moderately to severely active CD at baseline defined by a CDAI score of 220 to 450 inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 for participants with isolated ileal disease);
• BWT on IUS of >4.0 mm in the terminal ileum or any colonic segment (excluding the rectum) as assessed by the mean of 2 longitudinal and 2 cross-sectional measurements of the same segment;
• Biologic-naïve or have previous exposure (within the last 5 years of the screening date) to no more than 1 advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD. Note: only approximately 15% to 30% of the enrolled population will have had prior exposure to an advanced therapeutic;
• Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD;
• Persons of childbearing potential must have a negative serum pregnancy test prior to randomization and must use a highly effective method of contraception throughout the study. Females unable to bear children must have documentation of such in the source records;
• Able to participate fully in all aspects of this clinical trial;
• Written informed consent must be obtained and documented