A phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis

Abstract

Background: Alicaforsen is an antisense oligonucleotide designed to inhibit expression of human intercellular adhesion molecule 1. Previous clinical studies have demonstrated activity of alicaforsen enema in ulcerative colitis and pouchitis.

Aim: To determine the minimally effective dosing regimen of alicaforsen enema in subjects with mild to moderate left-sided ulcerative colitis.

Methods: Randomized, placebo-controlled, double-blind, two-dose ranging multicentre study. One hundred and twelve subjects were equally randomized to receive one of four alicaforsen enema regimens or placebo daily for 6 weeks. Primary end point was Disease Activity Index at week 6. Secondary end points included evaluation of clinical improvement, relapse rates and durability of response. Analysis of data were performed on the intent-to-treat population.

Results: No significant difference was observed between treatment arms and placebo in the primary end point. A prolonged reduction in mean% Disease Activity Index relative to baseline was observed in the daily 240 mg alicaforsen enema treatment arm in comparison with placebo from week 18 (51% vs. 18%, P=0.04) to week 30 (50% vs. 11%, P=0.03).

Conclusions: Alicaforsen enema was safe and well tolerated at all doses studied. The durability of the response to alicaforsen enema treatment may suggests a disease-modifying effect.