HLX14与参考药物地诺单抗在健康男性中的药代动力学、药效学、安全性和免疫原性:随机 I 期研究

IF 3.1 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Nanyang Li, Nannan Chu, Leilei Zhu, Xiaojie Wu, Qiong Wei, Jiahui Wang, Xuhui Hu, Haoyu Yu, Qingyu Wang, Wei'an Yuan, Kai Huang, Jing Zhang
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引用次数: 0

摘要

地诺单抗是一种针对核因子卡巴-B 配体受体激活剂(RANKL)的人类 IgG2 单克隆抗体,用于治疗骨质疏松症和骨质流失。HLX14 是一种拟议的地诺单抗生物类似物。这项随机、平行分组、两部分组成的I期研究旨在比较HLX14与参考药物地诺单抗在中国健康成年男性参与者中的药代动力学、药效学、安全性和免疫原性。在第一部分中,参与者按1:1的比例随机分组,接受HLX14或来自欧盟(EU)的参考药物地诺单抗治疗。在双盲的第二部分中,参与者按1:1:1:1:1的比例随机接受HLX14或来自美国、欧盟或中国的地诺单抗。所有研究药物均通过皮下注射给药,单次剂量为60毫克。主要终点是血清药物浓度-时间曲线下的面积(从时间 0 到最后一次浓度-可量化时间 t)、最大血清药物浓度(Cmax)和血清药物浓度-时间曲线下的面积(从时间 0 到无穷大)(AUC0-inf)。24 名参与者被随机分配到第一部分,228 名参与者被随机分配到第二部分。不同来源的HLX14和地诺单抗的AUC0-t、Cmax和AUC0-inf的几何平均比值的90%置信区间均在0.80-1.25的预设相似度范围内(AUC0-t,0.91-1.13;Cmax,0.91-1.13;AUC0-inf,0.91-1.12),显示了药代动力学的相似性。在药效学、安全性或免疫原性方面,各治疗组之间未发现明显差异。HLX14显示出与地诺单抗高度相似的药代动力学特征,并具有可比的药效学、安全性和免疫原性,支持将其作为一种潜在的地诺单抗生物仿制药进行进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 versus reference denosumab in healthy males: A randomized phase I study

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 versus reference denosumab in healthy males: A randomized phase I study

Denosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel-group, two-part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants. In Part 1, participants were randomized 1:1 and given HLX14 or reference denosumab sourced from the European Union (EU). In double-blind Part 2, participants were randomized 1:1:1:1 to receive HLX14 or denosumab sourced from the United States, EU, or China. All study drugs were administered via subcutaneous injection at a single dose of 60 mg. The primary endpoints were area under the serum drug concentration–time curve from time 0 to the last concentration-quantifiable time t (AUC0–t), maximum serum drug concentration (Cmax), and area under the serum drug concentration–time curve from time 0 to infinity (AUC0–inf). Twenty-four participants were randomized in Part 1 and 228 in Part 2. The 90% confidence intervals of geometric mean ratio of AUC0–t, Cmax, and AUC0–inf between HLX14 and denosumab from different sources fell within the pre-specified similarity margins of 0.80–1.25 (AUC0–t, 0.91–1.13; Cmax, 0.91–1.13; AUC0–inf, 0.91–1.12), demonstrating pharmacokinetic similarity. No notable difference was observed among treatment groups in pharmacodynamics, safety, or immunogenicity. HLX14 demonstrated highly similar pharmacokinetic characteristics with comparable pharmacodynamics, safety, and immunogenicity to denosumab, supporting its further investigation as a potential denosumab biosimilar.

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来源期刊
Cts-Clinical and Translational Science
Cts-Clinical and Translational Science 医学-医学:研究与实验
CiteScore
6.70
自引率
2.60%
发文量
234
审稿时长
6-12 weeks
期刊介绍: Clinical and Translational Science (CTS), an official journal of the American Society for Clinical Pharmacology and Therapeutics, highlights original translational medicine research that helps bridge laboratory discoveries with the diagnosis and treatment of human disease. Translational medicine is a multi-faceted discipline with a focus on translational therapeutics. In a broad sense, translational medicine bridges across the discovery, development, regulation, and utilization spectrum. Research may appear as Full Articles, Brief Reports, Commentaries, Phase Forwards (clinical trials), Reviews, or Tutorials. CTS also includes invited didactic content that covers the connections between clinical pharmacology and translational medicine. Best-in-class methodologies and best practices are also welcomed as Tutorials. These additional features provide context for research articles and facilitate understanding for a wide array of individuals interested in clinical and translational science. CTS welcomes high quality, scientifically sound, original manuscripts focused on clinical pharmacology and translational science, including animal, in vitro, in silico, and clinical studies supporting the breadth of drug discovery, development, regulation and clinical use of both traditional drugs and innovative modalities.
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