Last updated on May 2019

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

Brief description of study

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).

Detailed Study 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 47 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

Clinical Study Identifier: NCT02646657

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