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

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, Cmax, AUC0-t and AUC0-∞, 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 Cmax, AUC0-t and AUC0-∞ 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.

A Randomized, Double-Blind, Parallel-Controlled Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of SCT510 to Bevacizumab (Avastin®) in Healthy Chinese Males

“…The mean t 1/2 (15 days) for STC510 was similar to that of the reference product, which was consistent with the t 1/2 reported in another bevacizumab study in healthy volunteers [ 22 – 24 ]. According to reports, this antibody has a small inter-CV among Chinese patients, but a large volume of distribution and a 14- to 16-day half-life [ 25 – 28 ]. A similar pattern of elimination for STC510 was also observed in this study, beginning with a rapid blood clearance stage lasting about 7 days, and then followed by a gradual clearance phase.…”

Comparative Pharmacokinetics, Safety, and Immunogenicity Study of the Prefilled Syringe and Lyophilized Formulation of a Recombinant Human Tumor Necrosis Factor‐α Receptor II:lgG Fc Fusion Protein in Healthy Chinese Male Subjects

“…Second, healthy subjects were used in the PK similarity study to ensure the study population's homogeneity and represent the most sensitive population for evaluating the PK similarity, as patients have potentially complicated factors that possibly influence PK profiles, such as disease complications and concomitant medications. 18 Third, as an immunocompetent population, healthy subjects are more suitable for comparing the safety and immunogenicity of biological agents.…”

“…The 2‐period, crossover study conducted in healthy male subjects is based on the following design considerations: First, the short half‐life (≈75 hours) and low immunogenicity of rhTNFR:Fc, as well as the smaller sample size, suggested that the crossover study is preferred to a parallel design. Second, healthy subjects were used in the PK similarity study to ensure the study population's homogeneity and represent the most sensitive population for evaluating the PK similarity, as patients have potentially complicated factors that possibly influence PK profiles, such as disease complications and concomitant medications 18 . Third, as an immunocompetent population, healthy subjects are more suitable for comparing the safety and immunogenicity of biological agents.…”