{"title":"在中国健康男性受试者中比较重组人源抗血管内皮生长因子单克隆抗体注射液与阿瓦斯汀®的药代动力学生物相似性和安全性的I期研究。","authors":"Hongtao Li, Xiangdi Zhao, Jing Xie, Xingyu Zhu, Yue Su, Cuixia He, Jiaxiang Ding, Minhui Zhu, Yuanyuan Xu, Ying Wang, Rongfang Shan, Bingyan Liu, Yuzhou Ding, Yuanyuan Liu, Huan Zhou, Yunqiu Xie","doi":"10.1186/s40360-023-00673-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The biosimilar landscape for malignancies continues to grow, with several biosimilars for reference product bevacizumab currently available. Bevacizumab has been shown to be well tolerated; however, the safety of recombinant humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody injection remains unclear. This study aimed to compare the pharmacokinetics (PK), safety, and immunogenicity of recombinant humanized anti-VEGF monoclonal antibody injection to that of Avastin® in healthy Chinese male volunteers.</p><p><strong>Methods: </strong>A randomized, double-blind, single-dose, and parallel-group study was performed on 88 healthy men who randomly (1:1) received either the test drug as an intravenous infusion of 3 mg/kg or Avastin®. The primary PK parameter was area under the serum concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC<sub>0-t</sub>). Secondary endpoints included maximum observed serum concentration (C<sub>max</sub>), AUC from 0 extrapolated to infinity (AUC<sub>inf</sub>), safety, and immunogenicity. Serum bevacizumab concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The baseline characteristics were similar among the two groups. The 90% confidence interval (CI) for the geometric mean ratio of AUC<sub>0-t</sub>, C<sub>max</sub> and AUC<sub>inf</sub> between the test group and reference group were 91.71%-103.18%, 95.72%-107.49% and 91.03%-103.43%, respectively. These values were within the predefined bioequivalence margin of 80.00%-125.00%, demonstrating the biosimilarity of the test drug and Avastin®. Eighty-one treatment-emergent adverse events were reported, with a comparable incidence among the test group (90.91%) and the reference group (93.18%). No serious adverse events were reported. The incidence of ADA antibodies in the two groups was low and similar.</p><p><strong>Conclusion: </strong>In healthy Chinese men, PK similarity of recombinant humanized anti-VEGF monoclonal antibody injection to Avastin® was confirmed, with comparable safety and immunogenicity. Subsequent studies should investigate recombinant humanized anti-VEGF monoclonal antibody injection in patients setting.</p><p><strong>Trial registration: </strong>Registered 08/10/2019, CTR20191923.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10223897/pdf/","citationCount":"0","resultStr":"{\"title\":\"A phase I study comparing the biosimilarity of the pharmacokinetics and safety of recombinant humanized anti-vascular endothelial growth factor monoclonal antibody injection with Avastin<sup>®</sup> in healthy Chinese male subjects.\",\"authors\":\"Hongtao Li, Xiangdi Zhao, Jing Xie, Xingyu Zhu, Yue Su, Cuixia He, Jiaxiang Ding, Minhui Zhu, Yuanyuan Xu, Ying Wang, Rongfang Shan, Bingyan Liu, Yuzhou Ding, Yuanyuan Liu, Huan Zhou, Yunqiu Xie\",\"doi\":\"10.1186/s40360-023-00673-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The biosimilar landscape for malignancies continues to grow, with several biosimilars for reference product bevacizumab currently available. Bevacizumab has been shown to be well tolerated; however, the safety of recombinant humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody injection remains unclear. This study aimed to compare the pharmacokinetics (PK), safety, and immunogenicity of recombinant humanized anti-VEGF monoclonal antibody injection to that of Avastin® in healthy Chinese male volunteers.</p><p><strong>Methods: </strong>A randomized, double-blind, single-dose, and parallel-group study was performed on 88 healthy men who randomly (1:1) received either the test drug as an intravenous infusion of 3 mg/kg or Avastin®. The primary PK parameter was area under the serum concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC<sub>0-t</sub>). Secondary endpoints included maximum observed serum concentration (C<sub>max</sub>), AUC from 0 extrapolated to infinity (AUC<sub>inf</sub>), safety, and immunogenicity. Serum bevacizumab concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The baseline characteristics were similar among the two groups. The 90% confidence interval (CI) for the geometric mean ratio of AUC<sub>0-t</sub>, C<sub>max</sub> and AUC<sub>inf</sub> between the test group and reference group were 91.71%-103.18%, 95.72%-107.49% and 91.03%-103.43%, respectively. These values were within the predefined bioequivalence margin of 80.00%-125.00%, demonstrating the biosimilarity of the test drug and Avastin®. Eighty-one treatment-emergent adverse events were reported, with a comparable incidence among the test group (90.91%) and the reference group (93.18%). No serious adverse events were reported. The incidence of ADA antibodies in the two groups was low and similar.</p><p><strong>Conclusion: </strong>In healthy Chinese men, PK similarity of recombinant humanized anti-VEGF monoclonal antibody injection to Avastin® was confirmed, with comparable safety and immunogenicity. Subsequent studies should investigate recombinant humanized anti-VEGF monoclonal antibody injection in patients setting.</p><p><strong>Trial registration: </strong>Registered 08/10/2019, CTR20191923.</p>\",\"PeriodicalId\":9023,\"journal\":{\"name\":\"BMC Pharmacology & Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10223897/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Pharmacology & Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40360-023-00673-y\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Pharmacology & Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40360-023-00673-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A phase I study comparing the biosimilarity of the pharmacokinetics and safety of recombinant humanized anti-vascular endothelial growth factor monoclonal antibody injection with Avastin® in healthy Chinese male subjects.
Background: The biosimilar landscape for malignancies continues to grow, with several biosimilars for reference product bevacizumab currently available. Bevacizumab has been shown to be well tolerated; however, the safety of recombinant humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody injection remains unclear. This study aimed to compare the pharmacokinetics (PK), safety, and immunogenicity of recombinant humanized anti-VEGF monoclonal antibody injection to that of Avastin® in healthy Chinese male volunteers.
Methods: A randomized, double-blind, single-dose, and parallel-group study was performed on 88 healthy men who randomly (1:1) received either the test drug as an intravenous infusion of 3 mg/kg or Avastin®. The primary PK parameter was area under the serum concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC0-t). Secondary endpoints included maximum observed serum concentration (Cmax), AUC from 0 extrapolated to infinity (AUCinf), safety, and immunogenicity. Serum bevacizumab concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA).
Results: The baseline characteristics were similar among the two groups. The 90% confidence interval (CI) for the geometric mean ratio of AUC0-t, Cmax and AUCinf between the test group and reference group were 91.71%-103.18%, 95.72%-107.49% and 91.03%-103.43%, respectively. These values were within the predefined bioequivalence margin of 80.00%-125.00%, demonstrating the biosimilarity of the test drug and Avastin®. Eighty-one treatment-emergent adverse events were reported, with a comparable incidence among the test group (90.91%) and the reference group (93.18%). No serious adverse events were reported. The incidence of ADA antibodies in the two groups was low and similar.
Conclusion: In healthy Chinese men, PK similarity of recombinant humanized anti-VEGF monoclonal antibody injection to Avastin® was confirmed, with comparable safety and immunogenicity. Subsequent studies should investigate recombinant humanized anti-VEGF monoclonal antibody injection in patients setting.
期刊介绍：
BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
