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

NCT ID: NCT02646683

Last Updated: 2023-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2023-05-26

Brief 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).

Detailed 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 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.

Conditions

Crohn Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early Crohn's disease

VEDOLIZUMAB 300 mg at week 0,2,6, (10), 14, 22, 30,(34), 38, (42), 46, (50)

week 10 = only required for subjects not responding week 34, 42 and 50- only required for subjects who have no endoscopic improvement at week 26

Group Type: OTHER

vedolizumab

Intervention Type: DRUG

Late Crohn's disease

VEDOLIZUMAB 300 mg at week 0,2,6, (10), 14, 22, 30,(34), 38, (42), 46, (50)

week 10 = only required for subjects not responding week 34, 42 and 50- only required for subjects who have no endoscopic improvement at week 26

Group Type: OTHER

vedolizumab

Intervention Type: DRUG

Interventions

vedolizumab

Intervention Type: DRUG

Other Intervention Names

Entyvio

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Geert D'Haens

OTHER

Sponsor Role: lead

Responsible Party

Geert D'Haens

Coordinating Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Geert D'Haens, Prof

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

UZ Antwerpen

Antwerp, , Belgium

Imeldahospital

Bonheiden, , Belgium

AZ Sint-Lucas

Bruges, , Belgium

ULB Erasme

Brussels, , Belgium

Ziekenhuis Oost-Limburg

Genk, , Belgium

AZ Sint Lucas

Ghent, , Belgium

UZ Gent

Ghent, , Belgium

AZ Groeninge

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

CHC Clinique Saint-Joseph

Liège, , Belgium

CHU de Liège

Liège, , Belgium

ZNA Jan Palfijn

Merksem, , Belgium

AZ Damiaan

Ostend, , Belgium

AZ Delta Roeselare

Roeselare, , Belgium

St Vincentius

Wilrijk, , Belgium

Semmelweis University

Budapest, , Hungary

University of Debrecen

Debrecen, , Hungary

Universtiy of Szeged

Szeged, , Hungary

Academisch Medisch Centrum

Amsterdam, , Netherlands

Ziekenhuis Gelderse Vallei

Ede, , Netherlands

OLVG

Leiden, , Netherlands

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Countries

Belgium; Hungary; Netherlands

References

Hanzel J, Dreesen E, Vermeire S, Lowenberg M, Hoentjen F, Bossuyt P, Clasquin E, Baert FJ, D'Haens GR, Mathot R. Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study. Inflamm Bowel Dis. 2022 May 4;28(5):689-699. doi: 10.1093/ibd/izab143.

Reference Type: DERIVED

PMID: 34137430 (View on PubMed)

Other Identifiers

2014-100757

Identifier Type: -

Identifier Source: org_study_id