Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease.
OBJECTIVE
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.
Schreiber
S
S
First Medical Department, University Hospital Kiel, Germany. s.schreiber@mucosa.de
Nikolaus
S
S
Malchow
H
H
Kruis
W
W
Lochs
H
H
Raedler
A
A
Hahn
E G
EG
Krummenerl
T
T
Steinmann
G
G
D000328:Adult; D002908:Chronic Disease; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020319:Oligodeoxyribonucleotides, Antisense / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054735:Phosphorothioate Oligonucleotides; D011446:Prospective Studies; D013873:Thionucleotides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D020319:Oligodeoxyribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D013873:Thionucleotides; D018799:Intercellular Adhesion Molecule-1; C089753:alicaforsen