A randomized, double-blind, single-dose, parallel phase I clinical trial to compare the bioequivalence, immunogenicity, and safety of bevacizumab biosimilar and bevacizumab in healthy Chinese subjects.

IF 3.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-07-01 Epub Date: 2022-08-18 DOI:10.1080/17425255.2022.2113382

Zhengzhi Liu, Zhenyue Gao, Wei Yang, Lixiu Zhang, Nan Xiao, Dongmei Qu, Zhengjie Su, Kaibo Xu, Guangwen Liu, Yanli Wang, Qing Ren, Shuang Yu, Yang Cheng, Yannan Zhou, Qiaohuan Deng, Yicheng Zhao, Zeyu Wang, Haimiao Yang

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引用次数: 0

Abstract

Background: Bevacizumab, a humanized monoclonal antibody against VEGF, can be used as a target therapy for colorectal cancer. A phase I clinical trial was conducted to compare the bioequivalence, immunogenicity, and safety of bevacizumab biosimilar (Chia Tai Tianqing Pharmaceutical Group Co., Ltd.) and Bevacizumab (Roche Diagnostics GmbH) in healthy Chinese males.

Research design & method: Healthy Chinese subjects (N = 98) were randomly divided into two groups. A single-dose bevacizumab biosimilar or Bevacizumab was given per cycle. Plasma drug concentrations were detected by liquid chromatography-tandem mass spectrometry (LC-MC/MS) assay. We detected the levels of anti-drug antibody (ADA) to evaluate drug immunogenicity and the safety of drugs throughout the study.

Results: The geometric mean ratios (GMRs) of AUC_0-t, C_max, and AUC_0-∞ for bevacizumab biosimilar and Bevacizumab were 96.27%, 93.69%, and 97.01%, respectively. The 90% CIs were all within 80-125%, meeting the bioequivalence standards. The levels of ADA were similar. In addition, the two drugs both demonstrated excellent safety in the trial.

Conclusion: This study showed that bevacizumab biosimilar and Bevacizumab had similar pharmacokinetics (PK) parameters and safety in healthy Chinese subjects.

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一项随机、双盲、单剂量、平行的I期临床试验，比较贝伐单抗生物仿制药和贝伐单抗在中国健康受试者中的生物等效性、免疫原性和安全性。

背景:贝伐单抗是一种抗VEGF的人源化单克隆抗体，可作为结直肠癌的靶向治疗药物。本研究开展了贝伐单抗生物仿制药(正大天庆药业集团有限公司)和贝伐单抗(罗氏诊断有限公司)在中国健康男性中的生物等效性、免疫原性和安全性的I期临床试验。研究设计与方法:健康中国受试者98例，随机分为两组。每个周期给予单剂量贝伐单抗生物类似药或贝伐单抗。采用液相色谱-串联质谱(LC-MC/MS)法检测血浆药物浓度。在整个研究过程中，我们通过检测抗药物抗体(ADA)水平来评价药物的免疫原性和药物的安全性。结果:贝伐单抗生物仿制药和贝伐单抗的AUC0-t、Cmax和AUC0-∞的几何平均比值(GMRs)分别为96.27%、93.69%和97.01%。90%的ci值均在80 ~ 125%范围内，符合生物等效性标准。ADA的水平是相似的。此外，这两种药物在试验中都表现出极好的安全性。结论:本研究表明贝伐单抗生物仿制药与贝伐单抗在中国健康受试者体内具有相似的药代动力学参数和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.