A randomized, double-blind, parallel-group, single‑dose, pharmacokinetic bioequivalence study of INTP24 and bevacizumab in healthy adult men

Purpose To demonstrate pharmacokinetic (PK) equivalence and to compare safety of INTP24 (bevacizumab biosimilar) with that of US-bevacizumab and EU-bevacizumab in healthy male subjects. Methods In this randomized, parallel-group, double-blind study, male subjects were randomized (1:1:1) to receive a single 1 mg/kg intravenous infusion of either INTP24, US-bevacizumab, or EU-bevacizumab. The primary endpoint was area under serum concentration (AUC) from time zero to infinity (AUC 0-∞ ). Secondary endpoints were AUC from time zero to last quantifiable concentration (AUC 0-t ), maximum concentration (C max ), other PK parameters, immunogenicity, and safety. Results A total of 117 subjects (39/group) were dosed; 113 subjects (37, 37, and 39 in INPT24, US-bevacizumab, and EU-bevacizumab groups, respectively) completed the study and were included in the PK analysis. Baseline demographics were similar across the three groups. The 90% confidence intervals (CI) of geometric mean ratios (GMR) of ln-transformed AUC 0-∞ and C max of INTP24 relative to US-bevacizumab and EU-bevacizumab were within the acceptance range of 80%-125% (INTP24 vs. US-bevacizumab, 96.55–112.51% and 99.16–112.79%: INTP24 vs. EU-bevacizumab, 94.84–110.17% and 96.32–109.28%). The 90% CIs of GMRs for AUC 0-t was also within 80–125% for INTP24 vs. US-bevacizumab and INTP24 vs. EU-bevacizumab. Safety and immunogenicity profiles were similar across the three groups. Twenty-one (17.95%) subjects experienced at least one AE and 9 (7.69%) were ADA positive. One treatment-related serious adverse event (varicella zoster infection) was reported in INTP24 group. Conclusion This study demonstrated PK bioequivalence of INTP24 to US-bevacizumab and EU-bevacizumab in healthy male subjects and showed similar safety and immunogenicity profiles across the treatment groups.