The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics.
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.
Corne
J
J
University Medicine, Southampton General Hospital, United Kingdom.
Djukanovic
R
R
Thomas
L
L
Warner
J
J
Botta
L
L
Grandordy
B
B
Gygax
D
D
Heusser
C
C
Patalano
F
F
Richardson
W
W
Kilchherr
E
E
Staehelin
T
T
Davis
F
F
Gordon
W
W
Sun
L
L
Liou
R
R
Wang
G
G
Chang
T W
TW
Holgate
S
S
D000293:Adolescent; D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001491:Basophils / Q000378:metabolism; D002678:Chimera / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis* / Q000097:blood / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011058:Pollen / Q000276:immunology; D011852:Radioallergosorbent Test; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*; D012882:Skin Tests
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007073:Immunoglobulin E