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). Secondary endpoints were AUC from time zero to last quantifiable concentration (AUC), maximum concentration (C), 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 and C 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 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.