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

NCT02646683 | Completed Phase 4

• 1 other identifier: 2014-100757
• Study Type: interventional
• Target: 260
• Locations: 3 countries
• Sites: 23

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).

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with clinical and endoscopic remission at Week 26

  Crohns disease activity index (CDAI) of 150 or lower and Simple endoscopic score for Crohn's disease (SES-CD) \< 4.

  week 26

Secondary Outcomes (16)

• Proportion of patients with endoscopic response at Weeks 26 and 52

  26 and 52 weeks

• Proportion of patients with 25% and 75% reduction of SES-CD at Weeks 26 and 52

  26 and 52 weeks

• Proportion of patients with clinical response

  52 weeks

• Proportion of patients with clinical remission

  52 weeks

• Proportion of patients with corticosteroid- free clinical remission

  52 weeks

Study Arms (2)

Early Crohn's disease

OTHER

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

Drug: vedolizumab

Late Crohn's disease

OTHER

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

Drug: vedolizumab

Interventions

vedolizumab DRUG

Also known as: Entyvio

Early Crohn's disease; Late Crohn's disease

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Previous exposure to any anti-integrin antibodies including- vedolizumab ; α4β7 anti-bodies ; β7 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

Sponsors & Collaborators

• Geert D'Haens: lead
• Takeda: collaborator

Study Sites (23)

UZ Antwerpen

Antwerp, Belgium

Location

Imeldahospital

Bonheiden, Belgium

Location

AZ Sint-Lucas

Bruges, Belgium

Location

ULB Erasme

Brussels, Belgium

Location

Ziekenhuis Oost-Limburg

Genk, Belgium

Location

AZ Sint Lucas

Ghent, Belgium

Location

UZ Gent

Ghent, Belgium

Location

AZ Groeninge

Kortrijk, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHC Clinique Saint-Joseph

Liège, Belgium

Location

CHU de Liège

Liège, Belgium

Location

ZNA Jan Palfijn

Merksem, Belgium

Location

AZ Damiaan

Ostend, Belgium

Location

AZ Delta Roeselare

Roeselare, Belgium

Location

St Vincentius

Wilrijk, Belgium

Location

Semmelweis University

Budapest, Hungary

Location

University of Debrecen

Debrecen, Hungary

Location

Universtiy of Szeged

Szeged, Hungary

Location

Academisch Medisch Centrum

Amsterdam, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, Netherlands

Location

OLVG

Leiden, Netherlands

Location

Radboud Universitair Medisch Centrum

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 34137430 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Geert D'Haens, Prof

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating Investigator

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: January 6, 2016
• Study Start: July 1, 2015
• Primary Completion: May 26, 2023
• Study Completion: May 26, 2023
• Last Updated: June 23, 2023

Record last verified: 2023-06

Locations

NL (5); BE (15); HU (3)