Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects

Jane R Parnes, John T Sullivan, Li Chen, Clapton Dias, Jane R Parnes, John T Sullivan, Li Chen, Clapton Dias

Abstract

Tezepelumab (AMG 157) is a monoclonal antibody that targets thymic stromal lymphopoietin and has shown benefits in treating asthma. We assessed the safety, tolerability, and pharmacokinetics of single-ascending and multiple-ascending doses in two randomized, double-blind, placebo-controlled phase I studies. Healthy and atopic dermatitis subjects were enrolled in the single-dose study, and healthy subjects in the multiple-dose study. Tezepelumab showed linear pharmacokinetics in both healthy and atopic dermatitis subjects. The half-life after a subcutaneous or intravenous administration ranged from 19.9 to 25.7 days. After multiple doses, the mean area under the curve accumulation ratio was 1.82, 1.64, and 1.59 for the 35 mg, 105 mg, and 210 mg monthly subcutaneous doses, respectively. The mean maximum serum concentration (Cmax ) accumulation ratio was 1.59, 2.84, and 6.74 for the 210 mg dose given every 28, 14, and 7 days, respectively. Tezepelumab was well tolerated in both studies with no evidence of immunogenicity.

Conflict of interest statement

J.R.P., J.T.S., L.C., and C.D. were employees of Amgen at the time the studies were conducted.

© 2019 Amgen Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1
Figure 1
Design and treatment schema of the single‐ascending dose (SAD) and multiple‐ascending dose (MAD) studies of tezepelumab. (a) SAD study. Subjects in cohorts 1–8 were randomized 6:2 and subjects in cohort 9 were randomized 9:3 to either tezepelumab or placebo, administered intravenously (IV) or subcutaneously (SC). The end of study was day 113. (b) MAD Study. In each multi dose (MD) cohort, eight healthy subjects were randomized 6:2 to either tezepelumab or placebo IV or SC once every 7, 14, or 28 days (Q7D, Q14D, Q28D, respectively) from study day 1 (D1) through the end of study (EOS) on day 169 (D169). [Colour figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Mean (standard deviation) serum concentration‐time profiles (Semilog) following tezepelumab administration in healthy subjects and subjects with atopic dermatitis. (a) Single SC dose (all healthy subjects). (b) Single IV dose (cohorts 7 and 8: healthy subjects; cohort 9: subjects with atopic dermatitis). (c) Multiple SC or IV doses (all healthy subjects). IV, intravenous; PK, pharmacokinetic; SC, subcutaneous.

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