vectors - a study to evaluate transmural healing as a treatment target in crohn's disease

Conditions: Moderately to Severely Active Crohn's Disease; Crohn Disease; Disease Crohn

Summary: transmural healing (tmh) is recognized as a potentially important measure of crohn's disease (cd) activity but not a formal target. observational studies suggest that tmh may be associated with better long-term outcomes. the study will evaluate tmh using noninvasive intestinal ultrasound (ius), a patient-friendly technique that can be performed routinely in clinical practice. the aim of the study is to determine if treating to a target of corticosteroid-free (cs-free) ius outcomes + clinical symptoms + biomarkers is superior to a target of clinical symptoms + biomarkers alone in achieving cs-free endoscopic remission measured by the simple endoscopic score for crohn's disease (ses-cd). qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different target treatment groups. group 1: participants will be treated over 48 weeks to achieve a target of corticosteroid-free ius-based outcomes + clinical remission + biomarker remission. at week 22 and 30, the ius-based component of the target will be ius response and at week 38, the final treatment target will be tmh. group 2: participants will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.


Eligibility criteria:
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 450 inclusive and ses-cd, excluding the presence of narrowing component, ≥6 (or ≥4 for participants 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 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; 6. participants may continue stable dose (initiated at least 4 weeks prior to screening) of 5-asa for cd; 7. 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; 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 randomization or 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 by ileocolonoscopy; 5. have a cd complication, such as symptomatic strictures in the small bowel with \>3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention; 6. 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; 7. ostomy or ileoanal pouch; 8. short bowel syndrome; 9. fibrotic only stricture in the ileum or colon without evidence of active inflammation (in the investigator's judgment), including any impassable stenosis; 10. abscess \>2 cm, detected incidentally by ius, but participants with draining fistulas are 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 or would compromise participant safety; 12. positive stool test for clostridioides difficile infection (as demonstrated by positive toxin); 13. 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; 14. 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; 15. other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization; 16. has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (pml) prior to randomization; 17. hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab; 18. active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection; 19. unwillingness to withhold protocol-prohibited medications during the trial; 20. concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days or 5 half-lives (whichever is longer) prior to randomization; 21. 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; 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 sperm during such time period; 24. 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; 25. 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; 26. 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).