A randomized, double-masked, placebo-controlled study of alicaforsen, an antisense inhibitor of intercellular adhesion molecule 1, for the treatment of subjects with active Crohn's disease

Clin Gastroenterol Hepatol. 2007 Feb;5(2):215-20. doi: 10.1016/j.cgh.2006.11.001.

Abstract

Background & aims: The aim of this study was to compare the safety and efficacy of alicaforsen, a first-generation antisense inhibitor of intercellular adhesion molecule 1, with placebo in subjects with active Crohn's disease, a disorder in which intercellular adhesion molecule 1 is overexpressed.

Methods: In 2 identical double-masked, placebo-controlled studies, 331 subjects with active Crohn's disease were treated with either alicaforsen (221 subjects) or placebo (110 subjects) administered via 2-hour intravenous infusion 3 times a week for 4 weeks. Patients then returned for follow-up every 2 weeks. The primary end point was clinical remission by week 12. Secondary end points included clinical response and remission in relation to previous use of other biologics including tumor necrosis factor-alpha antagonists and presence of fistulous disease.

Results: The results, whether combined or analyzed individually, failed to demonstrate statistical significance as a measure of its primary outcome (alicaforsen 33.9% vs placebo 34.5%; P = .89). In addition, no statistical differences in response were observed between alicaforsen and placebo in subjects who were previously treated with anti-tumor necrosis factor-alpha therapy or had baseline fistulizing disease. There were no significant differences in adverse events from placebo apart from a higher infusion reaction rate.

Conclusions: In the subject population studied, alicaforsen failed to demonstrate efficacy in any of its primary outcome measures. Alicaforsen was well-tolerated.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Crohn Disease / drug therapy*
  • Crohn Disease / physiopathology
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Intercellular Adhesion Molecule-1 / physiology
  • Male
  • Oligodeoxyribonucleotides, Antisense / therapeutic use*
  • Phosphorothioate Oligonucleotides
  • Thionucleotides / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Oligodeoxyribonucleotides, Antisense
  • Phosphorothioate Oligonucleotides
  • Thionucleotides
  • Intercellular Adhesion Molecule-1
  • alicaforsen