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

BMC Pharmacology and Toxicology

Research

Yuanyuan Liu¹  Bingyan Liu¹  Yuzhou Ding¹  Jing Xie¹  Yunqiu Xie²  Hongtao Li³  Cuixia He⁴  Rongfang Shan⁴  Ying Wang⁴  Xingyu Zhu⁴  Xiangdi Zhao⁴  Yuanyuan Xu⁴  Minhui Zhu⁴  Huan Zhou⁵  Jiaxiang Ding⁶  Yue Su⁶ 

[1] National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;Department of Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, China;National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, China;School of Public Foundation, Bengbu Medical College, Bengbu, Anhui, China;National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China;School of Public Foundation, Bengbu Medical College, Bengbu, Anhui, China;

关键词: Bevacizumab;    Biosimilarity;    Immunogenicity;    Pharmacokinetics;    Recombinant humanized anti-vascular endothelial growth factor monoclonal antibody injection;   

DOI  :  10.1186/s40360-023-00673-y

 received in 2022-09-05, accepted in 2023-05-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsA 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).ResultsThe 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.ConclusionIn 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.Trial registrationRegistered 08/10/2019, CTR20191923.

【 授权许可】

CC BY   
© The Author(s) 2023

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