Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis

doi:10.1016/S0091-6749(97)70202-1

Journal of Allergy and Clinical Immunology

Volume 100, Issue 1, July 1997, Pages 110-121

https://doi.org/10.1016/S0091-6749(97)70202-1 Get rights and content

Abstract

Background: Increased serum levels of antigen-specific IgE are often associated with allergic respiratory disorders. RhuMAb-E25, a recombinant humanized monoclonal antibody, decreases free serum IgE by forming biologically inactive immune complexes with free IgE. Objective: We hypothesized that rhuMAb-E25 would decrease total serum IgE and reduce symptoms. Methods: Two hundred forty subjects were enrolled into five groups to determine the safety, tolerance, and efficacy of repeated administration of rhuMAb-E25 in adults with ragweed-induced allergic rhinitis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE. One hundred eighty-one subjects received an initial intravenous loading dose (day 0, 1 month before ragweed season), followed by administration of rhuMAb-E25 (in mg/kg body weight) of 0.15 mg/kg subcutaneously, 0.15 mg/kg intravenously, or 0.5 mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo group and an intravenous placebo group were included. The total evaluation time included the 84-day treatment period, followed by a 42-day observation period. Results: Adverse events were mild, and no differences were observed in the rates between the three active and two placebo treatment groups. Ragweed-specific IgE levels correlated with symptom scores. RhuMAb-E25 decreased serum free IgE levels in a dose- and baseline IgE–dependent fashion. However, only 11 subjects had IgE levels that were suppressed to undetectable levels (≤24 ng/ml), a sample too small to demonstrate significant differences and clinical efficacy. Thus the case for efficacy was not proven. Nonetheless, the study confirms that it is safe to repeatedly administer rhuMAb-E25 over a period of months. Conclusions: Because rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because symptom scores correlated with antigen-specific IgE levels, the results suggest that if given in adequate doses, rhuMAb-E25 should be an effective therapy for allergic diseases. (J Allergy Clin Immunol 1997;100:110-21.)

Section snippets

Study design

The study was a double-blind, placebo-controlled trial of 240 patients at seven centers, randomized into five arms: three active treatment and two placebo (Table I). Study drug administration occurred over a 12-week period (4 weeks before and during the 1994 ragweed season), followed by an 8-week follow-up period. Treatment was allocated according to a computerized randomization scheme prepared by the Genentech Biostatistics Department. A separate scheme for each study center allocated

Demographics

A total of 240 patients were enrolled at seven centers located in the Midwest and on the East Coast of the United States. Patients were treated with rhuMAb-E25 or placebo weekly for the first 2 weeks, then biweekly through day 84 (Table I). All treatment groups were well balanced except for the 0.15 IV group, which had a slightly higher proportion of Caucasian patients and a higher rate of asthma at study entry (Table II).

. Selected baseline characteristics of enrolled patients

Empty Cell	Placebo*(n = 59)	Empty Cell

Discussion

The results of this phase II, multicenter, double-blind, placebo-controlled study in adults with a history of seasonal ragweed-induced allergic rhinitis indicate that prolonged administration of a humanized recombinant monoclonal antibody directed against human IgE is safe in a large number of patients and demonstrates an important biologic dose-response effect and functional comparability of SC and IV administration. Although the data do not demonstrate statistically significant differences in

Acknowledgements

We thank the study coordinators, nurses, and pharmacists for their assistance in carrying out these studies and the following Genentech individuals for their invaluable contributions: John Curd, MD, Juergen Froehlich, MD, Paula Jardieu, PhD, V. Miles Rios, Jr., CCRA, Jane Ruppel, BA, Monika Schoenhoff, PhD, and Thomas M. Tremblay, RN. We also thank Darla Bartels and Vicki Sears for secretarial and editorial support.

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^☆: From ^athe Department of Internal Medicine, University of Iowa; ^bCincinnati; ^cUniversity of Wisconsin, Madison; ^dRaleigh; ^eDenver; ^fEvansville; ^gLenexa, Kansas; ^hGenentech, Inc., South San Francisco.

^☆☆: Supported by Genentech, Inc., San Francisco, Calif.

^★: Reprint requests: Thomas B. Casale, MD, Nebraska Medical Research Institute, 401 E. Gold Coast Rd., Suite 124, Papillion, NE 68046-4796.

^★★: 1/1/81429

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Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis☆,☆☆,★,★★

Abstract

Section snippets

Study design

Demographics

Discussion

Acknowledgements

Immunol Allergy Clin North Am

J Allergy Clin Immunol

Rhinitis and asthma

JAMA

Allergic rhinitis [review]

N Engl J Med

Epidemiology and natural history of asthma, allergic rhinitis, and atopic dermatitis

Immunologic analysis of steroid-dependent asthma

Ann Allergy