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.
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.
Yacyshyn
Bruce
B
Rochester Institute for Digestive Diseases and Science, Rochester, New York, USA. yacyshyn.br@pg.com
Chey
William Y
WY
Wedel
Mark K
MK
Yu
Rosie Z
RZ
Paul
David
D
Chuang
Emil
E
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*
D007166:Immunosuppressive Agents; D020319:Oligodeoxyribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D013873:Thionucleotides; D018799:Intercellular Adhesion Molecule-1; C089753:alicaforsen