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

Study Purpose

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).

Recruitment Criteria

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Accepts Healthy Volunteers
No

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Study Type
Interventional
Eligible Ages 18 Years - 80 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 2. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Age 18 to 80 4. 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]). 5. Established diagnosis of ileal, ileocolonic or colonic Crohn's disease with histopathological confirmation available in the record of the patient. 6. Moderately to severely active CD (CDAI 220-450) with objective evidence of ulcerations visualized on endoscopy. 7. Anti-TNF discontinued for at least 4 weeks prior to baseline. GROUP 1 (EARLY CD): 8. Diagnosis of CD < 24 months prior to enrollment 9. 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) 10. 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:

1. Previous exposure to any anti-integrin antibodies including- vedolizumab ; α4β7 anti-bodies ; β7 antibodies ; anti- MADCAM-1 2. Contraindication for endoscopy. 3. History of colonic dysplasia/cancer 4. Presence of stoma 5. Received other biologics within the last 4 weeks of baseline 6. Use of 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of enrollment 7. Chronic hepatitis B or C infection 8. Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening within 4 weeks prior to enrollment 9. Active or latent tuberculosis 10. Conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures. 11. Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer. 12. Positive progressive multifocal leukoencephalopathy ( PML) subjective symptom checklist before enrollment. 13. Subjects with known allergy or hyposensitivity to vedolizumab or its components

Trial Details

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

Trial ID:
NCT02646683

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase
Phase 4

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Lead Sponsor
Geert D'Haens

The person who is responsible for the scientific and technical direction of the entire clinical study.

Principal Investigator
Geert D'Haens, Prof
Principal Investigator Affiliation Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Agency Class
OtherIndustry
Overall Status Recruiting
Countries Belgium, Hungary, Netherlands

The disease, disorder, syndrome, illness, or injury that is being studied.

Conditions
Crohn Disease
Additional Details

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 α4β7 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Erasmus MC, Rotterdam, Netherlands

Status

Recruiting

Address

Erasmus MC

Rotterdam, ,

Radboud Universitair Medisch Centrum, Nijmegen, Netherlands

Status

Recruiting

Address

Radboud Universitair Medisch Centrum

Nijmegen, ,

OLVG, Leiden, Netherlands

Status

Recruiting

Address

OLVG

Leiden, ,

LUMC, Leiden, Netherlands

Status

Withdrawn

Address

LUMC

Leiden, ,

Catharina ziekenhuis, Eindhoven, Netherlands

Status

Recruiting

Address

Catharina ziekenhuis

Eindhoven, ,

Site Contact

Gilissen

e.clasquin@amc.uva.nl

0031205666545

Ziekenhuis Gelderse Vallei, Ede, Netherlands

Status

Recruiting

Address

Ziekenhuis Gelderse Vallei

Ede, ,

Academisch Medisch Centrum, Amsterdam, Netherlands

Status

Recruiting

Address

Academisch Medisch Centrum

Amsterdam, ,

Universtiy of Szeged, Szeged, Hungary

Status

Recruiting

Address

Universtiy of Szeged

Szeged, ,

University of Debrecen, Debrecen, Hungary

Status

Recruiting

Address

University of Debrecen

Debrecen, ,

Semmelweis University, Budapest, Hungary

Status

Recruiting

Address

Semmelweis University

Budapest, ,

St Vincentius, Wilrijk, Belgium

Status

Completed

Address

St Vincentius

Wilrijk, ,

AZ Delta Roeselare, Roeselare, Belgium

Status

Recruiting

Address

AZ Delta Roeselare

Roeselare, ,

AZ Damiaan, Oostende, Belgium

Status

Recruiting

Address

AZ Damiaan

Oostende, ,

ZNA Jan Palfijn, Merksem, Belgium

Status

Recruiting

Address

ZNA Jan Palfijn

Merksem, ,

CHU de Liège, Liege, Belgium

Status

Recruiting

Address

CHU de Liège

Liege, ,

CHC Clinique Saint-Joseph, Liege, Belgium

Status

Completed

Address

CHC Clinique Saint-Joseph

Liege, ,

UZ Leuven, Leuven, Belgium

Status

Recruiting

Address

UZ Leuven

Leuven, , 3000

Site Contact

Severine Vermeire, Prof

e.clasquin@amc.uva.nl

0031205666545

AZ Groeninge, Kortrijk, Belgium

Status

Recruiting

Address

AZ Groeninge

Kortrijk, ,

UZ Gent, Gent, Belgium

Status

Recruiting

Address

UZ Gent

Gent, ,

AZ Sint Lucas, Gent, Belgium

Status

Recruiting

Address

AZ Sint Lucas

Gent, ,

Ziekenhuis Oost-Limburg, Genk, Belgium

Status

Completed

Address

Ziekenhuis Oost-Limburg

Genk, ,

ULB Erasme, Brussels, Belgium

Status

Recruiting

Address

ULB Erasme

Brussels, ,

AZ Sint-Lucas, Brugge, Belgium

Status

Completed

Address

AZ Sint-Lucas

Brugge, ,

Imeldahospital, Bonheiden, Belgium

Status

Recruiting

Address

Imeldahospital

Bonheiden, ,

UZ Antwerpen, Antwerpen, Belgium

Status

Completed

Address

UZ Antwerpen

Antwerpen, ,

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