OBJECTIVE: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of bevacizumab biosimilars (MIL60, BAT1706, IBI305) in Chinese healthy male subjects. METHODS: This randomized, double-blind, two-arm, parallel studies included three separate investigations, which were conducted by three sponsors to investigate the bioequivalence of bevacizumab biosimilars (MIL60, BAT1706, IBI305) with that of bevacizumab-EU as a reference drug. Subjects received a single-dose of 1 or 3 mg/kg of the bevacizumab biosimilars or bevacizumab-EU and were followed up for 70-99 days. Serum concentrations of bevacizumab, antidrug antibody (ADA), and neutralizing antibody (NAb) were measured using electrochemiluminescence. In addition, the PK parameters were determined using non-compartmental methods. The safety assessments included adverse events, hematology tests, and biochemistry tests. RESULTS: The three bevacizumab biosimilars exhibited similar PK properties to that of bevacizumab-EU. Bevacizumab demonstrated linear PK properties and a concentration-dependent disposition. When comparing the three biosimilars with bevacizumab-EU, the 90% CIs of the ratios for Cmax, AUC0-t, and AUC0-∞ were within 80-125%. The inter-CV ranged from 12.6 to 23.3%. Three subjects in the biosimilar groups and bevacizumab-EU were positive for the ADA and negative for the NAb. Treatment-related mild or moderate adverse events were reported in 56-80 and 36-80% of subjects in the biosimilar and bevacizumab treatment arms, respectively. CONCLUSIONS: The bevacizumab biosimilars exhibit similar PK characteristics to that of the reference product bevacizumab-EU. The inter-CV is moderate and less than 25% in all cases. The safety profile was similar among bevacizumab biosimilars and bevacizumab-EU with significant adverse events.
RCT Entities:
OBJECTIVE: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of bevacizumab biosimilars (MIL60, BAT1706, IBI305) in Chinese healthy male subjects. METHODS: This randomized, double-blind, two-arm, parallel studies included three separate investigations, which were conducted by three sponsors to investigate the bioequivalence of bevacizumab biosimilars (MIL60, BAT1706, IBI305) with that of bevacizumab-EU as a reference drug. Subjects received a single-dose of 1 or 3 mg/kg of the bevacizumab biosimilars or bevacizumab-EU and were followed up for 70-99 days. Serum concentrations of bevacizumab, antidrug antibody (ADA), and neutralizing antibody (NAb) were measured using electrochemiluminescence. In addition, the PK parameters were determined using non-compartmental methods. The safety assessments included adverse events, hematology tests, and biochemistry tests. RESULTS: The three bevacizumab biosimilars exhibited similar PK properties to that of bevacizumab-EU. Bevacizumab demonstrated linear PK properties and a concentration-dependent disposition. When comparing the three biosimilars with bevacizumab-EU, the 90% CIs of the ratios for Cmax, AUC0-t, and AUC0-∞ were within 80-125%. The inter-CV ranged from 12.6 to 23.3%. Three subjects in the biosimilar groups and bevacizumab-EU were positive for the ADA and negative for the NAb. Treatment-related mild or moderate adverse events were reported in 56-80 and 36-80% of subjects in the biosimilar and bevacizumab treatment arms, respectively. CONCLUSIONS: The bevacizumab biosimilars exhibit similar PK characteristics to that of the reference product bevacizumab-EU. The inter-CV is moderate and less than 25% in all cases. The safety profile was similar among bevacizumab biosimilars and bevacizumab-EU with significant adverse events.