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An Open Label Phase 4 Study to Evaluate Efficacy of Early Versus Late Use of Vedolizumab in Ulcerative Colitis (LOVE-UC)

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ClinicalTrials.gov Identifier: NCT02646657
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 120 patients in 2 cohorts: 60 patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids and 60 patients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih 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 and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will make sure recruitment in either study group is comparable for number and profile of patients (extent of disease and on/off corticosteroids).

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: Vedolizumab 300 mg Phase 4

Detailed Description:

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Symptoms include bloody diarrhea, weight loss, and fever. There is no known cause or cure for UC. The aim of current UC treatments is to induce and maintain remission, to reduce the need of corticosteroids and avoid colectomy.

Treatment options include 5-Aminosalicylates (5-ASA), systemic and/or topical corticosteroids, purine analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery. In 2013, results from the GEMINI I, phase 3, randomized controlled trial demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining remission in adult patients with active UC.

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 UC.

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 UC. 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 UC patients with active disease: 1. patients who have been diagnosed < 4 years ago and who only have 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.

VDZ has been shown to be efficacious at inducing and maintaining remission in UC. However, data about the endoscopic and histological effects of VDZ in 'early UC' are lacking. Therefore, the investigators propose to perform an interventional study in early and late UC patients including endoscopic and histological assessment


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 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 Ulcerative Colitis: the LOVE-UC Study (LOw Countries VEdolizumab in UC Study)
Study Start Date : July 2015
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Vedolizumab

Arm Intervention/treatment
Early UC
Patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids
Drug: Vedolizumab 300 mg
Open-label VEDOLIZUMAB 300 mg at week 0,2,6, 14, 22, 30, 38, 46
Other Name: Entyvio

Late UC
Patients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih intolerance to IS AND anti-TNF will also be allowed in the latter group.
Drug: Vedolizumab 300 mg
Open-label VEDOLIZUMAB 300 mg at week 0,2,6, 14, 22, 30, 38, 46
Other Name: Entyvio




Primary Outcome Measures :
  1. Clinical and endoscopic remission [ Time Frame: Change in Mayo score from baseline to week 26 ]
    Defined as a Mayo Clinic score ≤2 and no subscore >1


Secondary Outcome Measures :
  1. Proportion of patients with endoscopic response [ Time Frame: Week 26 and week 52 ]
    Change in endoscopic Mayo score of 1 or more than 1

  2. Proportion of patients with clinical response [ Time Frame: 52 weeks ]
    Mayo score < 6

  3. Proportion of patients with clinical remission [ Time Frame: 52 weeks ]
    Mayo Clinic score ≤2 and no subscore >1

  4. Proportion of patients with corticosteroid- free clinical remission [ Time Frame: 52 weeks ]
    Mayo remission score ≤2 and no subscore >1

  5. Proportion of patients with normalized serum C-reactive protein (CRP) [ Time Frame: 52 weeks ]
    Normal CRP

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

  7. Proportion of patients with sustained clinical response [ Time Frame: After week 10. ]
    A Mayo score < 6

  8. Proportion of patients with sustained clinical remission [ Time Frame: After week 10. ]
    Mayo Clinic score ≤2 and no subscore >1.

  9. Proportion of patients that need to be hospitalized [ Time Frame: 52 weeks ]
    hospitalization

  10. Quality of life measured by Inflammatory Bowel Disease Questionnaire ( IBDQ ) [ Time Frame: At enrollment, week 26 and week 52 ]
    Questionnaire

  11. Work productivity Index [ Time Frame: At enrollment, week 26 and week 52 ]
    Questionnaire

  12. Serum concentrations of vedolizumab and antibodies to vedolizumab [ Time Frame: Before every infusion ]
    through concentration

  13. Quality of life measured by and Euroquol [ Time Frame: At enrollment, week 26 and week 52 ]
    Questionnaire



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 ulcerative colitis with histopathological confirmation available in the record of the patient.
  6. Moderate to severe active UC (total Mayo score > 6) with objective evidence of inflammation that can be visualized on endoscopy. All endoscopies will be video-taped for later review, rereading and quality assurance. Patients must have an endoscopic Mayo score of 2 or 3.
  7. Anti-TNF discontinued for at least 6 weeks
  8. Written informed consent must be obtained and documented

GROUP 1 (EARLY UC)

  1. Diagnosis of UC < 4 years prior to enrollment confirmed by clinical, endoscopic and histopathological evidence.
  2. Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to topical or systemic corticosteroids or intolerance to corticosteroids or: need for > 1 course of steroids per year or: steroid dependency at any dose and additionally, but not mandatory, lack of efficacy of thiopurines or intolerance to thiopurines (azathioprine, 6-mercaptopurine or 6-thioguanine) (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 UC)

  1. Diagnosis of UC confirmed by clinical, endoscopic and histopathological evidence.
  2. Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to at least 3 months of thiopurines (TP) or intolerance to TP 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. Loss of response to anti-TNF is defined as recurrence of symptoms during maintenance dosing following prior clinical benefit.

May continue stable dose of conventional therapies for Inflammatory Bowel Disease ( IBD) including aminosalicylates and thiopurines and corticosteroids. Steroids will be tapered by protocol by week 14. Anti-TNF must be discontinued for > 6 weeks.

Exclusion Criteria:

  1. Prior treatment with vedolizumab.
  2. Contraindication for endoscopy.
  3. History of colonic dysplasia/cancer
  4. Extensive colonic resection, i.e. subtotal or total colectomy with <15 cm colon remaining
  5. Received other biologics within the last 4 weeks of baseline
  6. Use of 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

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): NCT02646657


Contacts
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Contact: Esme Clasquin, Drs 0031-20 5661125 e.clasquin@amc.uva.nl

Locations
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Belgium
St. Vincentius ziekenhuis Withdrawn
Antwerpen, Belgium
UZ Antwerpen Withdrawn
Antwerpen, Belgium
Imeldahospital Recruiting
Bonheiden, Belgium
Principal Investigator: Dr. P Bossuyt         
AZ Sint-Lucas Withdrawn
Brugge, Belgium
ULB Erasme Recruiting
Brussels, Belgium
Principal Investigator: Prof D Franchimont         
Ziekenhuis Oost-Limburg Completed
Genk, Belgium
AZ Sint-Lucas Recruiting
Gent, Belgium
Principal Investigator: Prof H Peeters         
UZ Gent Recruiting
Gent, Belgium
Principal Investigator: Dr. P Hindryckx         
AZ Groeninge Recruiting
Kortrijk, Belgium
Principal Investigator: Dr W van Moerkercke         
Leuven AcademicHospital Recruiting
Leuven, Belgium
Contact: Ganel Schops       ganel.schops@uzleuven.be   
Principal Investigator: Severine Vermeire, Prof         
CHC Clinique Saint-Joseph Completed
Liege, Belgium
CHU Liege 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         
Hungary
Semmelweis University Recruiting
Budapest, Hungary
Principal Investigator: Pal Miheller, Dr         
University of Debrechen Recruiting
Debrecen, Hungary
Principal Investigator: Karoly Palatka, Dr.         
University of Szeged Recruiting
Szeged, Hungary
Principal Investigator: Tamas Molnar, Dr         
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands
Principal Investigator: Prof G D'Haens         
OLVG Recruiting
Amsterdam, Netherlands
Principal Investigator: Dr. J Jansen         
Ziekenhuis Gelderse Vallei Recruiting
Ede, Netherlands
Principal Investigator: Dr. W Mares         
Catharina ziekenhuis Recruiting
Eindhoven, Netherlands
Principal Investigator: L Gillisen, Dr.         
LUMC Withdrawn
Leiden, Netherlands
Radboud UMC Recruiting
Nijmegen, Netherlands
Principal Investigator: Dr F. Hoentjes         
Erasmus MC Recruiting
Rotterdam, Netherlands
Principal Investigator: Prof 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 Sponsor Investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02646657     History of Changes
Other Study ID Numbers: 2014-100756
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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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Vedolizumab
Gastrointestinal Agents