AUTHOR=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 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.694375

DOI=10.3389/fphar.2021.694375

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> This study was conducted to compare the pharmacokinetics, safety and immunogenicity of HOT-1010 with bevacizumab (Avastin®) in Chinese healthy male subjects.</p><p><bold>Methods:</bold> 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<sub>max</sub>, AUC<sub>0-t</sub> and AUC<sub>0-∞,</sub> were calculated and evaluated the bioequivalence between HOT-1010 and Avastin®, the safety and immunogenicity of investigational drugs were also assessed.</p><p><bold>Results:</bold> A total of 82 subjects completed the study. The 90% Confidence Intervals for geometric mean ratios of C<sub>max</sub>, AUC<sub>0-t</sub> and AUC<sub>0-∞</sub> 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.</p><p><bold>Conclusion:</bold> HOT-1010 exhibited the similar pharmacokinetics, safety and immunogenicity profiles of bevacizumab (Avastin®) in Chinese healthy male subjects.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="http://www.chinadrugtrials.org.cn/index.html" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.chinadrugtrials.org.cn/index.html</ext-link>, CTR20181610.</p>