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

Phase 4

Recruiting

• Conditions: Moderately to Severely Active Crohn’s Disease

• Registration Number: 2023-509096-16-00
• Lead Sponsor: Alimentiv Inc.

Brief Summary

To demonstrate that treating to achieve a target of corticosteroid-free TMH + IUS outcomes clinical remission + biomarker remission is superior to a target of corticosteroid-free clinical remission + biomarker remission after 48 weeks

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-07-03
• Last Update Posted: 2025-06-02

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 171

Inclusion Criteria

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);

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

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 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 Criteria

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

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;

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;

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).

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Corticosteroid-free endoscopic remission at Week 48		Corticosteroid-free endoscopic remission at Week 48

Secondary Outcome Measures

Name	Time	Method
Corticosteroid-free TMH + endoscopic remission + clinical remission at Week 48; Corticosteroid-free IUS response + endoscopic remission + clinical remission at Week 48; Corticosteroid-free endoscopic remission + clinical remission at Week 48; Corticosteroid-free endoscopic response + clinical response at Week 48		Corticosteroid-free TMH + endoscopic remission + clinical remission at Week 48; Corticosteroid-free IUS response + endoscopic remission + clinical remission at Week 48; Corticosteroid-free endoscopic remission + clinical remission at Week 48; Corticosteroid-free endoscopic response + clinical response at Week 48
Corticosteroid-free clinical remission at Weeks 14, 22, and 48; Corticosteroid-free clinical response at Weeks 14, 22, and 48; CDAI total score and corresponding change from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48)		Corticosteroid-free clinical remission at Weeks 14, 22, and 48; Corticosteroid-free clinical response at Weeks 14, 22, and 48; CDAI total score and corresponding change from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48)
Corticosteroid-free endoscopic response at Week 48; SES-CD total score and corresponding change from baseline to Week 48		Corticosteroid-free endoscopic response at Week 48; SES-CD total score and corresponding change from baseline to Week 48
TMH at Week 48; IUS response at Week 48; BWT and corresponding change from baseline at Week 48; CDS and corresponding change from baseline at Week 48; International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at Week 48		TMH at Week 48; IUS response at Week 48; BWT and corresponding change from baseline at Week 48; CDS and corresponding change from baseline at Week 48; International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at Week 48
TMH at Weeks 14, 22, 30, 38, and 48; IUS response at Weeks 14, 22, 30, 38, and 48; BWT and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48; CDS and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48; IBUS-SAS and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48		TMH at Weeks 14, 22, 30, 38, and 48; IUS response at Weeks 14, 22, 30, 38, and 48; BWT and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48; CDS and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48; IBUS-SAS and corresponding change from baseline at Weeks 14, 22, 30, 38, and 48
Histologic remission at Week 48; Histologic response at Week 48		Histologic remission at Week 48; Histologic response at Week 48
Biomarker remission at Week 48; Biomarker response at Week 48; CRP response during follow-up (Weeks 6, 14, 22, 30, 38, and 48); FCal response during follow-up (Weeks 6, 14, 22, 30, 38, and 48); CRP and FCal and their corresponding changes from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48)		Biomarker remission at Week 48; Biomarker response at Week 48; CRP response during follow-up (Weeks 6, 14, 22, 30, 38, and 48); FCal response during follow-up (Weeks 6, 14, 22, 30, 38, and 48); CRP and FCal and their corresponding changes from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48)
2-item Patient-Reported Outcome (PRO 2) score, Symptoms and Impacts Questionnaire for CD (SIQ-CD) score, and Urgency Numerical Rating Score (NRS) and their corresponding changes from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48); Inflammatory Bowel Disease Questionnaire (IBDQ) score and corresponding changes from baseline during follow-up (Weeks 30 and 48)		2-item Patient-Reported Outcome (PRO 2) score, Symptoms and Impacts Questionnaire for CD (SIQ-CD) score, and Urgency Numerical Rating Score (NRS) and their corresponding changes from baseline during follow-up (Weeks 6, 14, 22, 30, 38, and 48); Inflammatory Bowel Disease Questionnaire (IBDQ) score and corresponding changes from baseline during follow-up (Weeks 30 and 48)
Time to CD-related complication from randomization through Week 96.; Time to each component of CD-related complication; Switched to an alternate biologic (yes/no) by Week 48 and Week 96; Endpoints related to CDAI, CRP, FCal, and patient-reported measures (as specified above) at Weeks 64, 80, and 96.		Time to CD-related complication from randomization through Week 96.; Time to each component of CD-related complication; Switched to an alternate biologic (yes/no) by Week 48 and Week 96; Endpoints related to CDAI, CRP, FCal, and patient-reported measures (as specified above) at Weeks 64, 80, and 96.
Exposure-adjusted incidence rates of serious adverse events (SAEs), all adverse events (AEs), and AEs of special interest (AESIs)		Exposure-adjusted incidence rates of serious adverse events (SAEs), all adverse events (AEs), and AEs of special interest (AESIs)

Trial Locations

Locations (37)

Elisabeth-Tweesteden Ziekenhuis; 🇳🇱 Tilburg, Netherlands

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC); 🇳🇱 Rotterdam, Netherlands

Radboud universitair medisch centrum / RADBOUDUMC; 🇳🇱 Nijmegen, Netherlands

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Region Midtjylland; 🇩🇰 Aarhus N, Denmark

Region Sjaelland; 🇩🇰 Koege, Denmark

Copenhagen University Hospital; 🇩🇰 Copenhagen Nv, Denmark

Nordsjaellands Hospital; 🇩🇰 Hilleroed, Denmark

Region Hovedstaden; 🇩🇰 Herlev, Denmark

Universitaetsklinikum Schleswig-Holstein AöR; 🇩🇪 Kiel, Germany

Scroll for more (27 remaining)

Elisabeth-Tweesteden Ziekenhuis

🇳🇱Tilburg, Netherlands

Robert Laheij

Site contact

+310132218466

r.laheij@etz.nl