Efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, an anti-immunoglobulin E chimeric monoclonal antibody, in patients with seasonal allergic rhinitis

Clin Pharmacol Ther. 1997 Dec;62(6):675-90. doi: 10.1016/S0009-9236(97)90087-4.

Abstract

The efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, a recombinant monoclonal mouse-human chimeric anti-human immunoglobulin E (IgE) antibody were evaluated for 153 patients with seasonal allergic rhinitis treated with placebo or with 15, 30, or 60 mg CGP 51901 in six biweekly doses. Seasonal allergic rhinitis was chosen to validate the concept of anti-IgE therapy because the causal and temporal relation between allergen confrontation and IgE-mediated evocation of symptoms is firmly established. A sustained 85% or greater reduction of serum free IgE levels was shown to be effective in improving clinical symptoms. The concentration of CGP 51901 needed to maintain 85% or greater reduction of IgE was estimated to be about 5000 ng/ml. Baseline IgE levels and body weights of the patients greatly influenced the pharmacokinetic and pharmacodynamic profiles of CGP 51901. A population model was developed and refined to take into account patient baseline IgE level and body weight. The model was able to help predict multiple-dose pharmacokinetic and pharmacodynamic profiles on the basis of single-dose pharmacokinetic and pharmacodynamic measurements in the therapeutically effective dose range.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use*
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology*
  • Male
  • Middle Aged
  • Models, Biological
  • Rhinitis, Allergic, Seasonal / blood
  • Rhinitis, Allergic, Seasonal / metabolism*
  • Rhinitis, Allergic, Seasonal / therapy*

Substances

  • Antibodies, Monoclonal
  • CGP 51901
  • Immunoglobulin E