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

Kai Huang; Linling Que; Ying Ding; Nannan Chu; Zhenzhong Qian; Yunfei Shi; Wei Qin; Zhenni Li; Yuanxin Chen; Xianghong Gu; Jiakun Wang; Lin Zhang; Jisheng Zhang; Xiangyang Zhu; Yongmin Yang; Yuan Tang; Qing He

doi:10.3389/fphar.2021.694375

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

Front Pharmacol. 2021 Jun 17:12:694375. doi: 10.3389/fphar.2021.694375. eCollection 2021.

Authors

Kai Huang¹, Linling Que¹, Ying Ding¹, Nannan Chu¹, Zhenzhong Qian¹, Yunfei Shi¹, Wei Qin¹, Zhenni Li¹, Yuanxin Chen¹, Xianghong Gu¹, Jiakun Wang¹, Lin Zhang¹, Jisheng Zhang¹, Xiangyang Zhu², Yongmin Yang², Yuan Tang², Qing He¹

Affiliations

¹ Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
² Shanghai Huaota Biopharmaceutical Co., Ltd., Shanghai, China.

Abstract

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.

Keywords: Avastin®; HOT-1010; Immunogenicity; bevacizumab; biosimilarity; pharmacokinetics.