贝那鲁肽在中国健康受试者中的安全性、耐受性和药代动力学：一项随机、单盲的 1 期研究。
Safety, Tolerability, and Pharmacokinetics of Benralizumab: A Phase 1, Randomized, Single-Blind Study of Healthy Chinese Participants.
机构信息
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, People's Republic of China.
Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, South San Francisco, CA, USA.
出版信息
Drug Des Devel Ther. 2023 Jan 26;17:209-218. doi: 10.2147/DDDT.S392155. eCollection 2023.
PURPOSE
Biological therapies targeting eosinophils have been shown to be effective in treating patients with severe eosinophilic asthma. Benralizumab (Fasenra, 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 maintained throughout the study to Day 85.
CONCLUSION
A single SC injection of benralizumab was well tolerated by healthy Chinese participants, with no new or unexpected safety findings. The pharmacokinetics of benralizumab in Chinese participants was dose-proportional and consistent with those of non-Chinese participants observed in previous studies.
CLINICAL TRIAL REGISTRATION
NCT03928262 (https://clinicaltrials.gov/ct2/show/NCT03928262).
目的
针对嗜酸性粒细胞的生物疗法已被证明可有效治疗严重嗜酸性粒细胞性哮喘患者。贝那鲁肽（Fasenra，阿斯利康）是一种与人白细胞介素-5 受体的α亚单位结合的人源化单克隆抗体，通过抗体依赖性细胞毒性迅速耗尽嗜酸性粒细胞。本 1 期研究的目的是评估贝那鲁肽在健康中国人体内的安全性、耐受性和药代动力学。
材料和方法
在这项随机、单盲研究（NCT03928262）中，18 至 45 岁、体重 50 至 100 公斤的健康中国成年参与者按 1:1:1 的比例随机分配，在第 1 天接受单次皮下（SC）注射贝那鲁肽 10mg、30mg 或 100mg 于上臂。在整个研究期间（直至第 85 天）监测安全性，并采集血样以确定血清贝那鲁肽浓度和检测抗药物抗体。采用非房室分析估算药代动力学参数。
结果
共纳入 36 名健康参与者，每组 12 名（平均[标准差]年龄 26[6]岁）。单次 SC 注射贝那鲁肽后，10 名参与者（28%）报告了 13 起不良事件，其中 1 起轻度注射部位反应评估为相关。贝那鲁肽的平均血清浓度呈剂量依赖性增加，随后呈指数下降。10mg 剂量的平均终末半衰期为 15.1 天，30mg 剂量的半衰期为 14.4 天，100mg 剂量的半衰期为 15.4 天。所有剂量均导致第 2 天嗜酸性粒细胞几乎完全耗尽，并在整个研究期间（直至第 85 天）保持。
结论
单次 SC 注射贝那鲁肽在健康中国参与者中耐受良好，无新的或意外的安全性发现。贝那鲁肽在中国参与者中的药代动力学与之前研究中观察到的非中国参与者一致，呈剂量依赖性。
临床试验注册
NCT03928262（https://clinicaltrials.gov/ct2/show/NCT03928262）。
Zotero 插件