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- Title
A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
- Authors
Demarchi, Martin; Coliat, Pierre; Barthelemy, Philippe; Schott, Roland; BenAbdelghani, Meher; Kim, Michael; Hii, Jocelyn Chung Shii; Feyaerts, Peggy; Ang, Felicia Rui Xia; Derde, Marie Paule; Deforce, Filip; Petit, Thierry; Schwabe, Chris; Wynne, Chris; Park, Lisa Soyeon; Pivot, Xavier
- Abstract
Purpose: This first-in-human study was designed to evaluate the pharmacokinetic (PK) equivalence between HD204 and the European Union (EU)-sourced bevacizumab, between HD204 and the United States of America (US)-sourced bevacizumab, and between EU-sourced and US-sourced bevacizumab (NCT 03390673). Methods: In this randomized, double-blind, 3-way parallel group, single-dose comparative PK study, healthy male subjects were randomized to receive a single 1 mg/kg intravenous dose of HD204, EU-sourced bevacizumab or US-sourced bevacizumab. PK parameters were calculated using non-compartmental methods. PK equivalence was determined using the pre-defined equivalence margin of 0.8–1.25 in terms of AUC(0-∞) for the pairwise comparisons. Findings: Baseline demographics for the 119 randomized subjects were similar across the three groups. The 90% CIs for the ratio of the geometric means of HD204 to US-sourced bevacizumab, HD204 to EU-sourced bevacizumab, and EU-sourced to US-sourced bevacizumab were all within the interval of 80% to 125% for AUC0-inf, thus demonstrating equivalency in the PK properties for all three treatment groups. Similarly, the ratio of the geometric means for AUC0-last and Cmax were all within the 80% and 125% margins, supporting the robustness of the primary findings. All other PK parameters, including the half-life (t1⁄2) clearance (CL), volume of distribution (Vd) and time of maximum concentration (tmax), were comparable. There was no difference between the 3 treatment arms in terms of vital signs, laboratory tests and adverse events. None of the subjects treated with HD204 had positive ADA results. Implications: HD204 demonstrates equivalent pharmacokinetic profiles compared to those of both US-sourced and EU-sourced bevacizumab. (NCT 03390673).
- Subjects
EUROPEAN Union; BEVACIZUMAB; PHARMACOKINETICS; VITAL signs
- Publication
PLoS ONE, 2021, Vol 16, Issue 9, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0248222