A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizum
- PDF / 745,639 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 90 Downloads / 180 Views
CLINICAL TRIAL REPORT
A phase I, randomized, single‑dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers Donghoon Shin1 · Yoon Jung Lee2 · Jihye Choi3 · Dahyoung Lee4 · Minjeong Park1 · Magdalena Petkova5 Received: 17 June 2020 / Accepted: 6 September 2020 © The Author(s) 2020
Abstract Purpose To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US). Methods In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUC last), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00–125.00%. Safety and immunogenicity were also investigated. Results The 90% CIs for the geometric LSMean ratios of AUCinf, AUClast and Cmax were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/ bevacizumab-US were 88.01%, 88.48% and 100.54% for AUCinf, 88.65%, 89.08% and 100.49% for AUClast and 99.59%, 101.15% and 101.56% for Cmax, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected. Conclusion This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. Clinicaltrials.gov identifier NCT02453672 (submitted date); EudraCT number: 2015-001,026-41. Keywords SB8 · Bevacizumab · Biosimilar · Pharmacokinetics · Immunogenicity
Introduction
* Donghoon Shin [email protected] 1
Medical Affairs, Samsung Bioepis Co., Ltd, Incheon, Korea
2
Clinical Development, Samsung Bioepis Co., Ltd, Incheon, Korea
3
Biometrics, Samsung Bioepis Co., Ltd, Incheon, Korea
4
Clinical Bioanalysis, Samsung Bioepis Co., Ltd, Incheon, Korea
5
Clinical Pharmacology Unit, SGS LSS, Antwerpen, Lange Beeldekensstraat 267, 2060 Antwerpen, Belgium
Bevacizumab is a recombinant humanized monoclonal immunoglobulin G1 antibody that inhibits angiogenesis, a hallmark of solid tumor development, by targeting the vascular endothelial growth factor A (VEGF
Data Loading...
