The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics
| Autor: | Luigi Botta, T. Staehelin, C H Heusser, G. Wang, Tse Wen Chang, F. Davis, Ruey-Shyan Liou, E. Kilchherr, L. Sun, W. Richardson, L. Thomas, Daniel Gygax, Jane Warner, F. Patalano, Ratko Djukanovic, Stephen T. Holgate, W. Gordon, Jonathan M Corne, B. Grandordy |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Adolescent Dose-Response Relationship Immunologic Pharmacology Immunoglobulin E Placebo Histamine Release Serum ige Mice Radioallergosorbent Test Pharmacokinetics Double-Blind Method Animals Humans Receptor Anti-IgE Antibody Chromatography High Pressure Liquid Skin Tests biology Dose-Response Relationship Drug Chemistry Chimera Total ige Antibodies Monoclonal Rhinitis Allergic Seasonal General Medicine Middle Aged Antibodies Anti-Idiotypic Basophils Immunology biology.protein Pollen sense organs Antibody Research Article |
| Popis: | CGP 51901 is a non-anaphylactogenic mouse/human chimeric anti-human IgE antibody that binds to free IgE and surface IgE of IgE-expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilonR1) on mast cells and basophils or low affinity IgE receptors (Fc epsilonR2) on other cells. A phase 1 double-blind, placebo-controlled, single dose study with doses of 3, 10, 30, and 100 mg of CGP 51901 was conducted in 33 pollen-sensitive subjects who had raised levels of serum IgE and received either intravenous CGP 51901 or placebo. The administration of CGP 51901 was well tolerated and resulted in a decrease of serum free IgE levels in a dose-dependent manner, with suppression after 100 mg of CGP 51901 reaching > 96%. Time of recovery to 50% of baseline IgE correlated with the dose of administered antibody and ranged from a mean of 1.3 d for the 3 mg to 39 d for the 100 mg dose. Total IgE, comprised of free and complexed IgE, increased as stored and newly synthesized IgE bound to CGP 51901. Complexed IgE was eliminated at a rate comparable with the terminal half-life of free CGP 51901 (11-13 d at all doses). Only one subject showed a weak antibody response against CGP 51901. We conclude that the use of anti-human IgE antibody is safe and effective in reducing serum IgE levels in atopic individuals and provides a potential therapeutic approach to the treatment of atopic diseases. |
| Databáze: | OpenAIRE |
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