A Randomized, Double-Blind Trial Comparing the Pharmacokinetics of CT-P16, a Candidate Bevacizumab Biosimilar, with its Reference Product in Healthy Adult Males

초록

BackgroundCT-P16 is a candidate biosimilar of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor that is used in the treatment of a range of advanced solid cancers.ObjectiveThe objective of this study was to demonstrate the pharmacokinetic equivalence of CT-P16 and European Union (EU)-approved bevacizumab (EU-bevacizumab) and US-licensed bevacizumab (US-bevacizumab) reference products.MethodsIn this double-blind, parallel-group phaseI trial (ClinicalTrials.gov identifier NCT03247673), healthy adult males were randomized (1:1:1) to receive a single dose of CT-P16 5mg/kg, EU-bevacizumab 5mg/kg, or US-bevacizumab 5mg/kg. Primary study endpoints were area under the concentration-time curve (AUC) from time zero to infinity (AUC), AUC from time zero to the last quantifiable concentration (AUC(last)), and maximum serum concentration (C-max). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean (GM) ratios of the AUC, AUC(last), and C-max were within the predefined bioequivalence margin of 80-125%. Safety and immunogenicity were also evaluated.ResultsA total of 144 subjects were randomized: 47 to CT-P16, 49 to EU-bevacizumab, and 48 to US-bevacizumab. The 90% CIs for the GM ratios of AUC, AUC(last), and C-max for CT-P16/EU-bevacizumab, CT-P16/US-bevacizumab, and EU-bevacizumab/US-bevacizumab comparisons were all within the bioequivalence margin. Mean serum concentration-time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across all three treatment groups.ConclusionCT-P16 demonstrated pharmacokinetic equivalence to EU-bevacizumab and US-bevacizumab. Safety and immunogenicity profiles were similar for CT-P16, EU-bevacizumab, and US-bevacizumab. These data support the further clinical evaluation of CT-P16 as a bevacizumab biosimilar.Clinical Trials RegistrationNCT03247673.

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