title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Rochester Institute for Digestive Diseases and Science, Rochester, New York, USA. yacyshyn.br@pg.com
authors.forename: Bruce
authors.initials: B
authors.lastname: Yacyshyn
authors.forename: William Y
authors.initials: WY
authors.lastname: Chey
authors.forename: Mark K
authors.initials: MK
authors.lastname: Wedel
authors.forename: Rosie Z
authors.initials: RZ
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Paul
authors.forename: Emil
authors.initials: E
authors.lastname: Chuang
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use*; D054735:Phosphorothioate Oligonucleotides; D013873:Thionucleotides / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D020319:Oligodeoxyribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D013873:Thionucleotides; D018799:Intercellular Adhesion Molecule-1; C089753:alicaforsen