VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease
An Interventional Study to Evaluate Treating to a Target of Transmural Healing in Patients With Moderately to Severely Active Crohn's Disease
Alimentiv Inc.
304 participants
Aug 7, 2024
INTERVENTIONAL
Conditions
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
Inclusion Criteria8
- 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.
Exclusion Criteria26
- Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;
- 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;
- 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;
- 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;
- 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;
- Ostomy or ileoanal pouch;
- Short bowel syndrome;
- Fibrotic-only stricture in the ileum or colon without evidence of active inflammation (in the investigator's judgment), including any impassable stenosis;
- Abscess \>2 cm, detected by IUS or endoscopy; participants with draining fistulas are not excluded;
- 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);
- 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;
- Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization;
- Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to 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.
- Unwillingness to withhold protocol-prohibited medications during the trial;
- Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days prior to randomization;
- 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;
- Prior enrolment in the current study and had received study treatment;
- 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;
- 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;
- 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).
Interventions
All participants will begin a vedolizumab induction regimen of 300 mg IV at Weeks 0, 2, 6, and 10 followed by vedolizumab 300 mg IV every 8 weeks starting at Week 14. Treatment may be modified at Weeks 22, 30, and/or 38 based on the results of the target assessment at each of these time points.
Locations(69)
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NCT06257706