The aim of the study was to evaluate the safety and efficacy of an enema formulation of alicaforsen, an antisense inhibitor of intercellular adhesion molecule, after 1, 3, and 6 months.
This was a randomized, placebo controlled, double blind, escalating dose multicenter study in 40 patients with mild to moderately active distal ulcerative colitis (disease activity index (DAI) 4–10).
Patients were assigned to 4 dosing cohorts of 10 patients each (8 active, 2 placebo).
Each patient received 60 ml of alicaforsen enema (0.1, 0.5, 2, or 4 mg/ml or placebo) once daily for 28 consecutive days.
Safety and efficacy (DAI and clinical activity index) scores were evaluated up to six months after initiation of dosing.
At day 29, alicaforsen enema resulted in dose dependent improvement in DAI (overall p = 0.003).
Alicaforsen 4 mg/ml improved DAI by 70% compared with the placebo response of 28% (p = 0.004).
Alicaforsen 2 and 4 mg/ml improved DAI status by 72% and 68% compared with a placebo response of 11.5% at month 3 (p = 0.016 and 0.021, respectively).
Specifically, DAI improved from 5.6 to 1.6 and from 6.3 to 2.5 in the 2 and 4 mg/ml groups compared with placebo (7.5 to 6.1).
None of the patients in the 4 mg/ml group compared with 4/8 placebo patients required additional medical or surgical intervention over baseline during the 6 month period after starting the enema treatment.
The safety profile was favorable.
Alicaforsen enema showed promising acute and long term benefit in patients with mild to moderate descending ulcerative colitis.
Alicaforsen enemas had a favorable safety profile.
These findings require verification in larger randomized controlled clinical trials.