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A Randomized Clinical Trial

Ronald B. Turner, MD; Margaret T. Wecker, PhD; Gerhardt Pohl, PhD; Theodore J. Witek, DrPH; Eugene McNally, PhD; Roger St. George, MS; Birgit Winther, MD; Frederick G. Hayden, MD

JAMA. 1999;281:1797-1804.

Context  Attachment of most rhinovirus subtypes to cells depends on a cellular 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 in 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 isolated in a hotel room during study days 0 to 8; symptoms were recorded through day 14. A total of 198 subjects were randomized, of whom 196 received drug or placebo and were included in the safety analysis. A total of 177 subjects were included in the efficacy analysis.

Interventions  Tremacamra or placebo was given beginning 7 hours before inoculation 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) and placebo were given in 6 doses at 3-hour intervals daily during days 1 through 7. Recipients of active treatment received 367 µg 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 virus isolation and seroconversion, and on illness, as determined by symptom scores, clinical colds, and nasal mucus weights. Treatment-by-study interaction 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 proportion 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 for all comparisons). Tremacamra was not associated with adverse effects or evidence of absorption through the nasal mucosa and did not interfere with development of neutralizing antibody.

Conclusion  Tremacamra reduced the severity of experimental rhinovirus colds. Whether tremacamra will be useful clinically will require further study.

Author Affiliations: Departments of Pediatrics and Laboratory Medicine, Medical University of South Carolina, Charleston (Dr Turner); Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Conn (Drs Wecker, Pohl, Witek, and McNally, and Mr St. George); and Departments of Otolaryngology (Dr Winther) and Internal Medicine and Pathology (Dr Hayden), University of Virginia Health Sciences Center, Charlottesville.

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