Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial
Abstrakt
Background PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis.
Methods This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (>= 3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score >= 6 and a Mayo endoscopic subscore >= 2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNF alpha treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7.5 mg, 22.5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks.
Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score 1 and rectal bleeding subscore <= 1) at week 12.
The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted.
This study is registered with ClinicalTrials.gov, number NCT01620255.