Document Detail


The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics.
MedLine Citation:
PMID:  9062345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J Corne; R Djukanovic; L Thomas; J Warner; L Botta; B Grandordy; D Gygax; C Heusser; F Patalano; W Richardson; E Kilchherr; T Staehelin; F Davis; W Gordon; L Sun; R Liou; G Wang; T W Chang; S Holgate
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  99     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-04     Completed Date:  1997-04-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  879-87     Citation Subset:  AIM; IM    
Affiliation:
University Medicine, Southampton General Hospital, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Animals
Antibodies, Anti-Idiotypic / administration & dosage,  adverse effects,  therapeutic use*
Antibodies, Monoclonal / administration & dosage,  adverse effects,  therapeutic use
Basophils / secretion
Chimera / immunology*
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Dose-Response Relationship, Immunologic
Double-Blind Method
Histamine Release
Humans
Immunoglobulin E / analysis*,  blood,  immunology*
Male
Mice
Middle Aged
Pollen / immunology
Radioallergosorbent Test
Rhinitis, Allergic, Seasonal / drug therapy*
Skin Tests
Chemical
Reg. No./Substance:
0/Antibodies, Anti-Idiotypic; 0/Antibodies, Monoclonal; 37341-29-0/Immunoglobulin E
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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