Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection - A randomized clinical trial

Context Attachment of most rhinovirus subtypes to cells depends on a cellul ar receptor, the intercellular adhesion molecule 1 (ICAM-1). A recombinant soluble ICAM-1 (tremacamra, formerly BIRR 4) has shown possible efficacy in early studies. Objective To determine the efficacy and safety of intranasal administration of tremacamra in experimental rhinovirus colds in humans. Design Four randomized, double-blind, placebo-controlled trials conducted i n January to March 1996, Setting and Subjects Volunteers between the ages of 18 and 60 years who had an antibody titer of 1:4 or less to the challenge virus. Subjects were iso lated in a hotel room during study days 0 to 8; symptoms were recorded thro ugh day 14, A total of 198 subjects were randomized, of whom 196 received d rug or placebo and were included in the safety analysis. A total of 177 sub jects were included in the efficacy analysis. Interventions Tremacamra or placebo was given beginning 7 hours before inoc ulation with rhinovirus type 39 (preinoculation studies) or 12 hours after (postinoculation studies). Tremacamra as an inhaled solution or as a powder (each given preinoculation and postinoculation for a total of 4 studies) a nd placebo were given in 6 doses at 3-hour intervals daily during days 1 th rough 7, Recipients of active treatment received 367 mu g of tremacamra per nostril per dose for a total of 4.4 mg/d. Main Outcome Measures Effect of tremacamra on infection, as determined by v irus isolation and seroconversion, and on illness, as determined by symptom scores, clinical colds, and nasal mucus weights. Treatment-by-study intera ction was not significant, so results were pooled for the main analysis. Results A total of 88 (92%) of the 96 subjects in the placebo groups and 69 (85%) of the 81 subjects in the active treatment groups were infected (P=. 19). For placebo vs tremacamra, respectively, the total symptom score (+/- 95% confidence interval [CI]) was 17.6 (+/- 2.7) vs 9.6 (+/- 2.9), the prop ortion of clinical colds was 64/96 (67% +/- 9%) vs 36/81 (44% +/- 11%), and the nasal mucus weight was 32.9 (+/- 8.8) g vs 14.5 (+/- 9.4) g (P<.001 fo r all comparisons). Tremacamra was not associated with adverse effects or e vidence of absorption through the nasal mucosa and did not interfere with d evelopment of neutralizing antibody. Conclusion Tremacamra reduced the severity of experimental rhinovirus colds . Whether tremacamra will be useful clinically will require further study.