An Open Label Phase 4 Study to Evaluate Efficacy of Early Versus Late Use of Vedolizumab in Ulcerative Colitis
Condition: Colitis, Ulcerative
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 4

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).
    

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
    

Intervention name(s): Vedolizumab 300 mg
Intervention type(s): Drug
Intervention description(s): Open-label VEDOLIZUMAB 300 mg at week 0,2,6, 14, 22, 30, 38, 46
Other intervention name(s): Entyvio
Intervention MeSH terms: Vedolizumab
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment