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

Alimentiv

Status and phase: Enrolling; Phase 4

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

Treatments: Biological: Vedolizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06257706

TAK01769

Details and patient eligibility

About

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.

Enrollment: 304 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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304 participants in 2 patient groups

Group 1: Corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission

Other group

Description:

Group 1 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.

Treatment:

Biological: Vedolizumab

Group 2: Corticosteroid-free clinical remission + biomarker remission.

Other group

Description:

Group 2 will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.

Treatment:

Biological: Vedolizumab

Sponsors of this trial

Lead Sponsor

Alimentiv

Collaborating Sponsor

Takeda