Safety, Tolerability, and Pharmacokinetics of Benralizumab: A Phase 1, Randomized, Single-Blind Study of Healthy Chinese Participants

作者：TT Cheung, Tu H., Yen Lin Chia, Desmond YH Yap, Chi‐Ho Lee, Cecil Chi-Keung Chen, Ying Huang, Yuwen Jin, James B. Johnston, Viktoría Werkström, Yuhui Yao, Xiaoyun Ge, Wenying Zheng · 发表于：Drug Design Development and Therapy · 年份：2023 · DOI：10.2147/dddt.s392155 · 被引用次数：10 · 研究领域：Urticaria and Related Conditions、Rheumatoid Arthritis Research and Therapies、Eosinophilic Disorders and Syndromes

Purpose: , AstraZeneca) is a humanized monoclonal antibody binding to the alpha subunit of the interleukin-5 receptor, which rapidly depletes eosinophils via antibody-dependent cellular cytotoxicity. The aim of this Phase 1 study was to assess the safety, tolerability, and pharmacokinetics of benralizumab in healthy Chinese individuals. Materials and Methods: In this randomized, single-blind study (NCT03928262), healthy Chinese adult participants aged 18 to 45 years, weighing 50 to 100 kg, were randomized 1:1:1 to receive a single subcutaneous (SC) injection of benralizumab 10 mg, 30 mg, or 100 mg in the upper arms on Day 1. Safety was monitored throughout the study (up to Day 85), and blood samples were taken to determine serum benralizumab concentrations and for detection of anti-drug antibody. A non-compartmental analysis was conducted to estimate the pharmacokinetic parameters. Results: Thirty-six healthy participants were enrolled, 12 in each dose group (mean [SD] age 26 [6] years). Following a single SC injection of benralizumab, 13 adverse events were reported by 10 participants (28%), with one mild injection-site reaction assessed as related. The mean serum benralizumab concentrations increased in a dose proportional manner, followed by exponential decreases. The mean terminal half-lives were 15.1 days for the 10 mg dose, 14.4 days for the 30 mg dose, and 15.4 days for the 100 mg dose. All doses resulted in near-complete depletion of eosinophils on Day 2, which was ma...