A Study to Evaluate Efficacy of Early Versus Late Use of Vedolizumab in Crohn's Disease: the LOVE-CD Study

  • STATUS
    Recruiting
  • End date
    Dec 25, 2023
  • participants needed
    260
  • sponsor
    Geert D'Haens
Updated on 25 January 2021
Investigator
Esme Clasquin, Drs
Primary Contact
AZ Sint-Lucas (8.1 mi away) Contact
+25 other location
corticosteroids
endoscopy
immunosuppressive agents
tumor necrosis factor
vedolizumab
crohn's disease
ulceration
thiopurines

Summary

This multi-centre open label study will involve a minimum of 260 patients in 2 cohorts: 86 patients with 'early CD' defined as disease duration < 24 months and no other treatments than corticosteroids and/or thiopurines and 174 patients with 'late CD' defined as active disease despite treatment with immunosuppressives and anti-TNF. Patients with intolerance to IS and anti-TNF will also be allowed in the latter group. Participants will be treated with 12 months of open label vedolizumab (study medication followed by commercial medication once reimbursement is available) and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will ensure that recruitment in either study group is comparable for number and profile of patients (on/off steroids).

Description

Crohn's disease (CD) is a chronic inflammatory disease of the small bowel and colon. Symptoms commonly include bloody diarrhea, abdominal pain, weight loss, and fever. There is no known cause or cure for CD. The aim of current CD treatments is to induce and maintain remission, to reduce the need of corticosteroids and avoid resections and fistulas.

Treatment options include systemic and/or topical corticosteroids, purine analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery. In 2013, results from the GEMINI II, phase 3, randomized controlled trial demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining remission in adult patients with active CD.

VDZ (MLN0002, or MLN02), inhibits the interaction between 47 integrin on memory T and B cells and mucosal addressin cell adhesion molecule-1 expressed on the vascular endothelium of the gut and has been shown to be effective in both inducing and maintaining clinical remission in ulcerative colitis. The ideal positioning of vedolizumab in the therapeutic armamentarium for CD remains unknown. With other (anti-TNF) biologics, outcomes have usually been better if the treatment was started earlier in the disease course and if the patients had not been exposed to prior antibody treatments. Therefore, it appears appropriate and desirable to test the potency of vedolizumab in an earlier phase of CD.

Indeed, also with vedolizumab patients previously exposed to biologics appear to have lower success rates with vedolizumab, so a position earlier in the disease course would most likely lead to better outcomes.

This is an investigator-initiated open label study of VDZ therapy in 2 distinct populations of CD patients with active disease: 1. patients who have been diagnosed < 2 years ago and who only been exposed to aminosalicylates and corticosteroids and 2. patients who have been exposed to immunomodulators and/or anti-TNF agents in addition to steroids and aminosalicylates.

Details
Condition Inflammatory bowel disease, Crohn's Disease, Crohn's Disease (Pediatric), crohns disease
Treatment Vedolizumab
Clinical Study IdentifierNCT02646683
SponsorGeert D'Haens
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements
The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures
Age 18 to 80
Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period])
Established diagnosis of ileal, ileocolonic or colonic Crohn's disease with histopathological confirmation available in the record of the patient
Moderately to severely active CD (CDAI 220-450) with objective evidence of ulcerations visualized on endoscopy
Anti-TNF discontinued for at least 4 weeks prior to baseline
GROUP 1 (EARLY CD)
\. Diagnosis of CD < 24 months prior to enrollment
\. Demonstrated failure to respond to topical or systemic corticosteroids or
intolerance to corticosteroids or: need for > 2 courses of steroids since
diagnosis or: steroid dependency at any dose since diagnosis and additionally
but not mandatory, lack of efficacy of thiopurines or intolerance to
thiopurines (any duration). Patients who are using thiopurines at screening
must have used them for > 3 months (last 4 weeks at stable dose)
GROUP 2 (LATE CD)
\. Demonstrated failure to respond to at least 3 months of thiopurines or
intolerance to thiopurines and: failure to respond to at least 1 anti-TNF or
intolerance to anti-TNF or loss of response to at least 1 anti-TNF

Exclusion Criteria

Previous exposure to any anti-integrin antibodies including- vedolizumab ; 47 anti-bodies ; 7 antibodies ; anti- MADCAM-1
Contraindication for endoscopy
History of colonic dysplasia/cancer
Presence of stoma
Received other biologics within the last 4 weeks of baseline
Use of 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of enrollment
Chronic hepatitis B or C infection
Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening within 4 weeks prior to enrollment
Active or latent tuberculosis
Conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures
Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer
Positive progressive multifocal leukoencephalopathy ( PML) subjective symptom checklist before enrollment
Subjects with known allergy or hyposensitivity to vedolizumab or its components
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