A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.

<h4>Purpose</h4>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 bevacizuma...

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Autores principales: Martin Demarchi, Pierre Coliat, Philippe Barthelemy, Roland Schott, Meher BenAbdelghani, Michael Kim, Jocelyn Chung Shii Hii, Peggy Feyaerts, Felicia Rui Xia Ang, Marie Paule Derde, Filip Deforce, Thierry Petit, Chris Schwabe, Chris Wynne, Lisa Soyeon Park, Xavier Pivot
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:45bef64f51cc46f89c05d51ff10823152021-12-02T20:08:05ZA randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.1932-620310.1371/journal.pone.0248222https://doaj.org/article/45bef64f51cc46f89c05d51ff10823152021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0248222https://doaj.org/toc/1932-6203<h4>Purpose</h4>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 (NCT03390673).<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Implications</h4>HD204 demonstrates equivalent pharmacokinetic profiles compared to those of both US-sourced and EU-sourced bevacizumab. (NCT03390673).Martin DemarchiPierre ColiatPhilippe BarthelemyRoland SchottMeher BenAbdelghaniMichael KimJocelyn Chung Shii HiiPeggy FeyaertsFelicia Rui Xia AngMarie Paule DerdeFilip DeforceThierry PetitChris SchwabeChris WynneLisa Soyeon ParkXavier PivotPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0248222 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Martin Demarchi
Pierre Coliat
Philippe Barthelemy
Roland Schott
Meher BenAbdelghani
Michael Kim
Jocelyn Chung Shii Hii
Peggy Feyaerts
Felicia Rui Xia Ang
Marie Paule Derde
Filip Deforce
Thierry Petit
Chris Schwabe
Chris Wynne
Lisa Soyeon Park
Xavier Pivot
A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
description <h4>Purpose</h4>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 (NCT03390673).<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Implications</h4>HD204 demonstrates equivalent pharmacokinetic profiles compared to those of both US-sourced and EU-sourced bevacizumab. (NCT03390673).
format article
author Martin Demarchi
Pierre Coliat
Philippe Barthelemy
Roland Schott
Meher BenAbdelghani
Michael Kim
Jocelyn Chung Shii Hii
Peggy Feyaerts
Felicia Rui Xia Ang
Marie Paule Derde
Filip Deforce
Thierry Petit
Chris Schwabe
Chris Wynne
Lisa Soyeon Park
Xavier Pivot
author_facet Martin Demarchi
Pierre Coliat
Philippe Barthelemy
Roland Schott
Meher BenAbdelghani
Michael Kim
Jocelyn Chung Shii Hii
Peggy Feyaerts
Felicia Rui Xia Ang
Marie Paule Derde
Filip Deforce
Thierry Petit
Chris Schwabe
Chris Wynne
Lisa Soyeon Park
Xavier Pivot
author_sort Martin Demarchi
title A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
title_short A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
title_full A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
title_fullStr A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
title_full_unstemmed A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
title_sort randomized phase i study comparing the pharmacokinetics of a bevacizumab (hd204) biosimilar to european union- and united states of america-sourced bevacizumab.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/45bef64f51cc46f89c05d51ff1082315
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