Asthma and lower airway diseaseSafety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti–IL-5 receptor α antibody, in a phase I study of subjects with mild asthma
Section snippets
Subjects
Adults (age 18-45 years) with mild atopic asthma (nighttime symptoms ≤1/wk and daytime symptoms <1/d, FEV1 or peak expiratory flow ≥80% of predicted, and peak expiratory flow variability ≤30%) were eligible. A methacholine provocation dose causing 20% decrease in FEV1 (PC20) of ≤8 mg/mL was required during the first visit (day −14 to −7) or documented within 6 months previously. Women were eligible if postmenopausal, surgically sterile, or willing to use birth control for the duration of the
Demographics and baseline characteristics
Of the 44 subjects enrolled, 39 (88.6%) completed the study. Three subjects withdrew consent (0.1 mg/kg, n = 1; 1 mg/kg, n = 1; 3 mg/kg, n = 1), and 2 subjects (0.0003 mg/kg) were lost to follow-up. Baseline characteristics were generally comparable among all treatment groups (Table I).
Three additional subjects were added to the 1 mg/kg group (n = 9) when half of the 6 subjects in the 3 mg/kg group experienced a cluster of AEs after infusion with MEDI–563 (see Safety profile). All of these
Discussion
MEDI-563 produced depletion of circulating PB eosinophil levels within 24 hours at all doses administered. This effect persisted for at least 2 to 3 months in subjects dosed in the 0.03 mg/kg to 3 mg/kg range. Basophil counts were not reported in this study because of the known difficulties of obtaining a reliable measurement using standard techniques.22 Future studies will use flow cytometry to assess changes in basophils counts. In addition to the biological effect observed, no deterioration
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Supported by MedImmune, LLC, Gaithersburg, Md, and Biowa, Inc, Princeton, NJ.
Disclosure of potential conflict of interest: W. W. Busse is a consultant for and is on the advisory board of Altair, GlaxoSmithKline, Merck, Wyeth, Pfizer, Centocor, Amgen, UCB, Johnson & Johnson, Novartis, AstraZeneca, Eisai, TEVA, CompleWare, KaloBios, Boehringer Ingelheim, and Sandoz and has received research support from NIH-NIAID, NIH-NHLBI, Novartis, Centocor, GlaxoSmithKline, MedImmune, and Ception. D. Gossage, S. Sari, B. Wang, R. Kolbeck, A. J. Coyle, G. P. Geba, and N. A. Molfino are employed by MedImmune. P. A. Kiener was employed by MedImmune at the time of the study conduct. M. Koike and G. L. Spitalny are employed by Biowa, Inc. R. Katial declares no conflict of interest.
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S. Sari is currently employed by Emergent BioSolutions, Rockville, Md.
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P. A. Kiener is currently employed by Zyngenia, Inc, Gaithersburg, Md.