An Open Label Phase 4 Study to Evaluate Efficacy of Early Versus Late Use of Vedolizumab in Ulcerative Colitis

NCT02646657 | Completed Phase 4

• 1 other identifier: 2014-100756
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 20

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).

Conditions

Colitis, Ulcerative

Outcome Measures

Primary Outcomes (1)

• Clinical and endoscopic remission

  Defined as a Mayo Clinic score ≤2 and no subscore \>1

  Change in Mayo score from baseline to week 26

Secondary Outcomes (13)

• Proportion of patients with endoscopic response

  Week 26 and week 52

• 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

• Proportion of patients with normalized serum C-reactive protein (CRP)

  52 weeks

Study Arms (2)

Early UC

OTHER

Patients with 'early UC' defined as disease duration \< 4 years and no other treatments than aminosalicylates and/or corticosteroids

Drug: Vedolizumab 300 mg

Late UC

OTHER

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

Interventions

Vedolizumab 300 mg DRUG

Open-label VEDOLIZUMAB 300 mg at week 0,2,6, 14, 22, 30, 38, 46

Also known as: Entyvio

Early UC; Late UC

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 ulcerative colitis with histopathological confirmation available in the record of the patient.
• 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.
• Anti-TNF discontinued for at least 6 weeks
• Written informed consent must be obtained and documented
• GROUP 1 (EARLY UC)
• Diagnosis of UC \< 4 years prior to enrollment confirmed by clinical, endoscopic and histopathological evidence.
• 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)
• Diagnosis of UC confirmed by clinical, endoscopic and histopathological evidence.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Geert D'Haens: lead
• Takeda: collaborator

Study Sites (20)

Imeldahospital

Bonheiden, 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

Leuven AcademicHospital

Leuven, Belgium

Location

CHC Clinique Saint-Joseph

Liège, Belgium

Location

CHU Liege

Liège, Belgium

Location

ZNA Jan Palfijn

Merksem, Belgium

Location

AZ Damiaan

Ostend, Belgium

Location

AZ Delta- Roeselare

Roeselare, Belgium

Location

Semmelweis University

Budapest, Hungary

Location

University of Debrechen

Debrecen, Hungary

Location

University of Szeged

Szeged, Hungary

Location

Academic Medical Center

Amsterdam, Netherlands

Location

OLVG

Amsterdam, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic 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 Sponsor Investigator

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: January 6, 2016
• Study Start: July 1, 2015
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

HU (3); NL (5); BE (12)