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

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ClinicalTrials.gov Identifier: NCT02646683
Recruitment Status : Recruiting
First Posted : January 6, 2016
Last Update Posted : May 1, 2019
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Geert D'Haens, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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).

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: vedolizumab Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Interventional Phase 4 Study to Evaluate Efficacy, Safety and Mucosal Healing of Early Versus Late Use of Vedolizumab in Crohn's Disease: the LOVE-CD Study (LOw Countries VEdolizumab in CD Study)
Study Start Date : July 2015
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Vedolizumab

Arm Intervention/treatment
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

Drug: vedolizumab
Other Name: Entyvio

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

Drug: vedolizumab
Other Name: Entyvio




Primary Outcome Measures :
  1. The proportion of patients with clinical and endoscopic remission at Week 26 [ Time Frame: week 26 ]
    Crohns disease activity index (CDAI) of 150 or lower and Simple endoscopic score for Crohn's disease (SES-CD) < 4.


Secondary Outcome Measures :
  1. Proportion of patients with endoscopic response at Weeks 26 and 52 [ Time Frame: 26 and 52 weeks ]
    SES-CD reduction by ≥ 50 %

  2. Proportion of patients with 25% and 75% reduction of SES-CD at Weeks 26 and 52 [ Time Frame: 26 and 52 weeks ]
    SES-CD reduction

  3. Proportion of patients with clinical response [ Time Frame: 52 weeks ]
    CDAI decrease of ≥ 70 points from baseline

  4. Proportion of patients with clinical remission [ Time Frame: 52 weeks ]
    (CDAI <=150) at all time other points

  5. Proportion of patients with corticosteroid- free clinical remission [ Time Frame: 52 weeks ]
    (CDAI <=150) at all other time points

  6. Proportion of patients with normalized serum C-reactive protein (CRP) at all time points [ Time Frame: 52 weeks ]
    CRP

  7. Proportion of patients with no granulocytes in the biopsies at Weeks 26 and 52. [ Time Frame: Week 26 and week 52 ]
    No granulocytes

  8. Proportion of patients with 25%, 50% and 75% reduction in the Geboes histology score at Weeks 26 and 52 [ Time Frame: Week 26 and week 52 ]
    Geboes score

  9. Proportion of patients with sustained clinical response (response at all time points after week 10) [ Time Frame: After week 10 ]
    Geboes score reduction

  10. Proportion of patients with sustained clinical remission [ Time Frame: After week 10 ]
    (remission at all time points after week 10)

  11. Proportion of patients with draining fistulas [ Time Frame: 52 weeks ]
    Fistula

  12. Proportion of patients that need to be hospitalized [ Time Frame: 52 weeks ]
  13. Quality of life measured by Inflammatory Bowel Disease Questionnaire ( IBDQ) [ Time Frame: Screening, week 10, week 26 and week 52 ]
    Questionnaire

  14. Work productivity Index [ Time Frame: Screening, week 10, week 26 and week 52 ]
    Questionnaire

  15. Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion [ Time Frame: 52 weeks ]
    through concentration

  16. Quality of life measured by Euroqol (EQ-5D) [ Time Frame: Screening, week 10, week 26 and week 52 ]
    Questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02646683


Contacts
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Contact: Esmé Clasquin, Drs. 0031205666545 e.clasquin@amc.uva.nl

Locations
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Belgium
UZ Antwerpen Completed
Antwerpen, Belgium
Imeldahospital Recruiting
Bonheiden, Belgium
Principal Investigator: Dr. P. Bossuyt         
AZ Sint-Lucas Completed
Brugge, Belgium
ULB Erasme Recruiting
Brussels, Belgium
Principal Investigator: Dr. D. Franchimont         
Ziekenhuis Oost-Limburg Completed
Genk, Belgium
AZ Sint Lucas Recruiting
Gent, Belgium
Principal Investigator: Dr. H Peeters         
UZ Gent Recruiting
Gent, Belgium
Principal Investigator: Dr. P Hindryckx         
AZ Groeninge Recruiting
Kortrijk, Belgium
Principal Investigator: Dr. W van Moerkercke         
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: Severine Vermeire, Prof         
CHC Clinique Saint-Joseph Completed
Liege, Belgium
CHU de Liège Recruiting
Liege, Belgium
Principal Investigator: Dr. E Louis         
ZNA Jan Palfijn Recruiting
Merksem, Belgium
Principal Investigator: Dr. J Dutré         
AZ Damiaan Recruiting
Oostende, Belgium
Principal Investigator: Dr. G. Lambrecht         
AZ Delta Roeselare Recruiting
Roeselare, Belgium
Principal Investigator: Dr. F Baert         
St Vincentius Completed
Wilrijk, Belgium
Hungary
Semmelweis University Recruiting
Budapest, Hungary
Principal Investigator: Pal Miheller, Dr.         
University of Debrecen Recruiting
Debrecen, Hungary
Principal Investigator: Karoly Palatka, Dr.         
Universtiy of Szeged Recruiting
Szeged, Hungary
Principal Investigator: Tamas Molnar         
Netherlands
Academisch Medisch Centrum Recruiting
Amsterdam, Netherlands
Principal Investigator: Prof G D'Haens         
Ziekenhuis Gelderse Vallei Recruiting
Ede, Netherlands
Principal Investigator: Dr. W Mares         
Catharina ziekenhuis Recruiting
Eindhoven, Netherlands
Contact: Gilissen         
LUMC Withdrawn
Leiden, Netherlands
OLVG Recruiting
Leiden, Netherlands
Principal Investigator: Dr. J. Jansen         
Radboud Universitair Medisch Centrum Recruiting
Nijmegen, Netherlands
Principal Investigator: Dr. F. Hoentjen         
Erasmus MC Recruiting
Rotterdam, Netherlands
Principal Investigator: Dr. J van der Woude         
Sponsors and Collaborators
Geert D'Haens
Takeda
Investigators
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Principal Investigator: Geert D'Haens, Prof Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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Responsible Party: Geert D'Haens, Coordinating Investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02646683     History of Changes
Other Study ID Numbers: 2014-100757
First Posted: January 6, 2016    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Vedolizumab
Gastrointestinal Agents