A Randomized, Double-Blind, Single-Dose Study Comparing the Biosimilarity of HOT-1010 With Bevacizumab (Avastin®) in Chinese Healthy Male Subjects

• Published in: Frontiers in pharmacology 2021-06, Vol.12, p.694375-694375
• Main Authors: Huang, Kai, Que, Linling, Ding, Ying, Chu, Nannan, Qian, Zhenzhong, Shi, Yunfei, Qin, Wei, Li, Zhenni, Chen, Yuanxin, Gu, Xianghong, Wang, Jiakun, Zhang, Lin, Zhang, Jisheng, Zhu, Xiangyang, Yang, Yongmin, Tang, Yuan, He, Qing
• Format: Article
• Language: English
• Subjects: Avastin; bevacizumab; biosimilarity; HOT-1010; Immunogenicity; pharmacokinetics; Pharmacology
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.694375

Objective: This study was conducted to compare the pharmacokinetics, safety and immunogenicity of HOT-1010 with bevacizumab (Avastin®) in Chinese healthy male subjects. Methods: A single-center, randomized, double-blind, single-dose, parallel trial was performed in 84 Chinese healthy male subjects who randomly (1:1) received a single intravenous infusion of 1 mg/kg HOT-1010 or Avastin® for 90 min and followed up for 85 days. Serum concentrations of bevacizumab were analyzed by enzyme-linked immunosorbent assay. Primary pharmacokinetic parameters, C max , AUC 0-t and AUC 0-∞, were calculated and evaluated the bioequivalence between HOT-1010 and Avastin®, the safety and immunogenicity of investigational drugs were also assessed. Results: A total of 82 subjects completed the study. The 90% Confidence Intervals for geometric mean ratios of C max , AUC 0-t and AUC 0-∞ were 91.81–103.64%, 85.19–95.39% and 85.04–95.36%, which were all within the bioequivalence margin. Treatment-emergent adverse events were reported in 27 (65.9%) subjects in HOT-1010 group and 23 (56.1%) subjects in Avastin® group. Most TEAEs were mild or moderate. No TEAEs, Serious Adverse Events or deaths leading to discontinuation was reported. Subjects were all tested negative for Anti-drug Antibody. Conclusion: HOT-1010 exhibited the similar pharmacokinetics, safety and immunogenicity profiles of bevacizumab (Avastin®) in Chinese healthy male subjects. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html , CTR20181610.