VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease

Inclusion Criteria:

Participants must meet all of the following criteria for enrolment into the study:

1. Adults aged 18 to 80 years, inclusive, at the time of consent;

2. Moderately-to-severely active CD at baseline defined by a CDAI score of 220 to 450inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 forparticipants with isolated ileal disease);

3. CRP of ≥5 mg/L and/or FCal ≥250 μg/g at Screening;

4. BWT on IUS of >4.0 mm in the ileum or any colonic segment (excluding the rectum);

5. Biologic-naïve or have previous exposure to no more than 1 advanced therapeuticcompound (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 priorexposure to an advanced therapeutic;

6. Participants may continue stable dose (initiated at least 4 weeks prior toScreening) of 5-ASA for CD;

7. Persons of childbearing potential must have a negative serum pregnancy test prior torandomization and must use a highly effective method of contraception throughout thestudy. Females unable to bear children must have documentation of such in the sourcerecords;

8. Able to participate fully in all aspects of this clinical trial;

9. Written informed consent must be obtained and documented.

Exclusion Criteria:

Participants who exhibit any of the following conditions are to be excluded from the study:

1. Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;

2. Previously exposed to 2 or more compounds of an advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD;

3. Change to oral corticosteroid therapy dosing within 2 weeks prior to randomizationor a corticosteroid dose of >40 mg of prednisone or equivalent at randomization;

4. Only have inflammation proximal to the terminal ileum that cannot be reached byileocolonoscopy;

5. Have a CD complication, such as symptomatic strictures in the small bowel with >3 cmprestenotic dilatation on any imaging modality, requiring procedural intervention;

6. Previous extensive colonic resection or missing >2 segments out of 5 (terminalileum, right colon, transverse colon, sigmoid and left colon, and rectum),ileorectal anastomosis, or a proctocolectomy;

7. Ostomy or ileoanal pouch;

8. Short bowel syndrome;

9. Fibrotic only stricture in the ileum or colon without evidence of activeinflammation (in the investigator's judgment), including any impassable stenosis;

10. Abscess >2 cm, detected incidentally by IUS, but participants with draining fistulasare not excluded;

11. 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 orwould compromise participant safety;

12. Positive stool test for Clostridioides difficile infection (as demonstrated bypositive toxin);

13. Known HIV or hepatitis B or C infection. If a negative test result is available inthe 12 months prior to randomization, retesting is not required;

14. Known active or latent tuberculosis (TB); if a negative test result is available inthe 12 months prior to randomization, confirmatory testing (per standard of care) isnot required before randomization;

15. Other systemic or opportunistic infection (including cytomegalovirus), any otherclinically significant extraintestinal infection, or recurring infection within 6months of randomization;

16. Has active cerebral/meningeal disease, signs, symptoms, or any history ofprogressive multifocal leukoencephalopathy (PML) prior to randomization;

17. Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or anyother contraindication to vedolizumab;

18. Active severe infection such as sepsis, cytomegalovirus, listeriosis, oropportunistic infection;

19. Unwillingness to withhold protocol-prohibited medications during the trial;

20. Concurrent or previous participation in another clinical trial and received anyinvestigational therapy within 30 days or 5 half-lives (whichever is longer) priorto randomization;

21. History of alcohol or drug abuse that in the opinion of the investigator mayinterfere with the participant's ability to comply with the study procedures;

22. Prior enrolment in the current study and had received study treatment;

23. 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 spermduring such time period;

24. Vaccination with a live or live-attenuated vaccine within 4 weeks prior torandomization, or planned vaccination with a live or live-attenuated vaccine duringparticipation in the study;

25. Any person performing mandatory military service, deprived of liberty, in aresidential care setting, or any person who, due to a judicial decision, cannot takepart in clinical studies;

26. The person is an immediate family member, study site employee, or is in a dependentrelationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling).