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

JAMA. 1999 May 19;281(19):1797-804. doi: 10.1001/jama.281.19.1797.


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 microg 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.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Adult
  • Antibodies / analysis
  • Antibodies, Viral / biosynthesis
  • Common Cold / diagnosis
  • Common Cold / immunology
  • Common Cold / prevention & control*
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / immunology*
  • Interleukin-8 / biosynthesis
  • Male
  • Middle Aged
  • Nasal Mucosa / immunology
  • Neutralization Tests
  • Powders
  • Rhinovirus / immunology*
  • Rhinovirus / isolation & purification
  • Severity of Illness Index
  • Solutions
  • Virus Shedding


  • Antibodies
  • Antibodies, Viral
  • Interleukin-8
  • Powders
  • Solutions
  • Intercellular Adhesion Molecule-1