Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease

Gastroenterology. 2001 May;120(6):1339-46. doi: 10.1053/gast.2001.24015.


Background & aims: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD).

Methods: A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI <150) at week 14.

Results: Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups.

Conclusions: The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chronic Disease
  • Crohn Disease / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Subcutaneous
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / physiology*
  • Male
  • Middle Aged
  • Oligodeoxyribonucleotides, Antisense / adverse effects
  • Oligodeoxyribonucleotides, Antisense / pharmacokinetics
  • Oligodeoxyribonucleotides, Antisense / therapeutic use*
  • Phosphorothioate Oligonucleotides
  • Prospective Studies
  • Thionucleotides / adverse effects
  • Thionucleotides / pharmacokinetics
  • Thionucleotides / therapeutic use*


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