A Phase I, Randomized, Double-Blinded, Single-Dose Study Evaluating The Pharmacokinetic Equivalence Of The Biosimilar Ibi305 And Bevacizumab In Healthy Male Subjects

Objective: To compare the pharmacokinetic (PK) profiles, immunogenicity, and safety of the proposed biosimilar IBI305 with those of bevacizumab in healthy male subjects. Design: A phase I. randomized, double-blinded, two-arm, parallel-group study. Settings: The study was conducted in The First Hospital of Jilin University, Changchun, China, from March 2017 to November 2017. Participants: A total of 100 healthy male subjects were enrolled, with 48 in the IBI305 group and 50 in bevacizumab group included in the final analysis. Intervention: In a 16-week study course, participants were randomized at a 1:1 ratio to receive intravenous administration of either a single dose of 3 mg/kg IBI305 (n = 50) or bevacizumab (n = 50). Outcome measures: The primary endpoints were area under the concentration-time curve from zero to the time of the last measurable concentration (AUC(0-t)) and AUC curve from zero to infinity (AUC(0-infinity)). The secondary endpoints include the other PK parameters, immunogenicity, and safety measurements. Results: AUC(0-t), AUC(0-infinity) maximum concentration observed (C-m(ax)), half-life (T-1/2), drug clearance, and volume of distribution were similar between IBI305- and bevacizumab-treated subjects. For AUC(0-infinity), AUC(0-t), and C-max, the 90% confidence intervals for the ratios of geometric means were fully within the range 0.80 -1.25, confirming the bioequivalence of the two investigational agents. Furthermore, no apparent difference in adverse events was found between the two groups. Conclusion: This study demonstrated the similarity of PK, immunogenicity, and safety profiles of IBI305 to those of bevacizumab.