Allergic asthma and an anti-CD23 mAb (IDEC-152) : Results of a phase I, single-dose, dose-escalating clinical trial - 29/08/11

Doi : 10.1016/S0091-6749(03)01861-X

Lanny J Rosenwasser, MD ^a,^⁎,^{^{1
Drs Rosenwasser and Busse contributed equally to this research.}}, William W Busse, MD ^{^{1
Drs Rosenwasser and Busse contributed equally to this research.},}^b, Richard G Lizambri, MD ^c, Teresa A Olejnik ^c, Mark C Totoritis, MD ^c
^a National Jewish Medical and Research Center and the University of Colorado Health Science Center, Denver, Colo, USA
^b University of Wisconsin Medical School, Madison, Wis, USA
^c IDEC Pharmaceuticals Corporation, San Diego, Calif, USA

Reprint requests: Lanny J. Rosenwasser, MD, University of Colorado Health Science Center and the Division of Allergy and Clinical Immunology, National Jewish Medical and Research Center, Allergy and Clinical Immunology, 1400 Jackson St, Denver, CO 80206

Abstract

Background

CD23, a cell-surface molecule, is involved in a variety of pathways likely to influence IgE production and inflammation in allergic disorders, such as allergic rhinitis and allergic asthma.

Objective

This study investigated the safety, clinical activity, and pharmacokinetic profile of IDEC-152, an IgG1 anti-CD23 antibody, in patients with mild-to-moderate persistent allergic asthma.

Methods

This single-dose, dose-escalating, placebo-controlled study involved 30 patients. Cohorts of 3 to 6 patients received single intravenous infusions of either placebo or IDEC-152 (0.05, 0.25, 1.0, 4.0, 10.0, or 15.0 mg/kg) on study day 1. Safety, clinical activity, and pharmacokinetics were assessed for 12 weeks after treatment.

Results

IDEC-152 was well tolerated. Adverse events (AEs) were mild, no grade 4 or serious AEs were reported, and no relationships were apparent between the dose of IDEC-152 and the frequency, severity, or type of event. The most common AEs in the IDEC-152 group included ecchymosis at the injection site, sinusitis, headache, arthralgia, cold syndrome, infection, throat irritation, and dysmenorrhea. Commonly reported AEs in the placebo group included headache, abdominal pain, and infection. Sustained and dose-dependent decreases in mean IgE concentrations were noted. The mean maximum concentration and area under the curve of IDEC-152 were proportional to the dose administered for the dose range 4.0 to 15.0 mg/kg. The serum half-life of the IDEC-152 antibody increased from 2 to 10 days with increasing doses. After single-dose administration of IDEC-152, no dose-dependent change in FEV₁ was observed, and most changes in peak expiratory flow rate were within 10% of baseline values.