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BioDrugs

, Volume 33, Issue 2, pp 173–181 | Cite as

A Randomized, Double-Blind Trial Comparing the Pharmacokinetics of CT-P16, a Candidate Bevacizumab Biosimilar, with its Reference Product in Healthy Adult Males

  • Sang-Heon Cho
  • Seunghoon Han
  • Jong-Lyul Ghim
  • Moon-Suk Nam
  • Sunyoung Yu
  • Taehong Park
  • Sinhye Kim
  • Jihun Bae
  • Jae-Gook ShinEmail author
Original Research Article
  • 103 Downloads

Abstract

Background

CT-P16 is a candidate biosimilar of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor that is used in the treatment of a range of advanced solid cancers.

Objective

The objective of this study was to demonstrate the pharmacokinetic equivalence of CT-P16 and European Union (EU)-approved bevacizumab (EU-bevacizumab) and US-licensed bevacizumab (US-bevacizumab) reference products.

Methods

In this double-blind, parallel-group phase I trial (ClinicalTrials.gov identifier NCT03247673), healthy adult males were randomized (1:1:1) to receive a single dose of CT-P16 5 mg/kg, EU-bevacizumab 5 mg/kg, or US-bevacizumab 5 mg/kg. Primary study endpoints were area under the concentration–time curve (AUC) from time zero to infinity (AUC), AUC from time zero to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean (GM) ratios of the AUC, AUClast, and Cmax were within the predefined bioequivalence margin of 80–125%. Safety and immunogenicity were also evaluated.

Results

A total of 144 subjects were randomized: 47 to CT-P16, 49 to EU-bevacizumab, and 48 to US-bevacizumab. The 90% CIs for the GM ratios of AUC, AUClast, and Cmax for CT-P16/EU-bevacizumab, CT-P16/US-bevacizumab, and EU-bevacizumab/US-bevacizumab comparisons were all within the bioequivalence margin. Mean serum concentration–time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across all three treatment groups.

Conclusion

CT-P16 demonstrated pharmacokinetic equivalence to EU-bevacizumab and US-bevacizumab. Safety and immunogenicity profiles were similar for CT-P16, EU-bevacizumab, and US-bevacizumab. These data support the further clinical evaluation of CT-P16 as a bevacizumab biosimilar.

Clinical Trials Registration

NCT03247673.

Notes

Acknowledgements

We thank all study investigators, staff, and subjects who contributed to this study. Medical writing support (including development of a draft outline and subsequent drafts in consultation with the authors, assembling tables and figures, collating author comments, copyediting, fact checking, and referencing) was provided by Emma Evans Ph.D., CMPP and Rick Flemming Ph.D., CMPP at Aspire Scientific Limited (Bollington, UK), and funded by CELLTRION, Inc. (Incheon, Republic of Korea).

Author Contributions

S-HC, SH, SY, TP, M-SN, and J-GS were involved in the conception and/or design of this study. J-LG, SY, TP, SK, and JB were involved in the acquisition, analysis, and/or interpretation of the data. All authors contributed to development of the manuscript and approved the final version for submission.

Compliance with Ethical Standards

Funding

This study was sponsored by CELLTRION, Inc. (Incheon, Republic of Korea).

Conflict of Interest

SY, TP, SK, and JB are employees of CELLTRION, Inc. SY has stock in CELLTRION, Inc. S-HC, SH, J-LG, M-SN, and J-GS have no conflicts of interest to declare.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

40259_2019_340_MOESM1_ESM.docx (60 kb)
Supplementary material 1 (DOCX 60 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Inha University HospitalInha University School of MedicineIncheonRepublic of Korea
  2. 2.The Catholic University of Korea Seoul St. Mary’s HospitalSeoulRepublic of Korea
  3. 3.Inje University and Inje University Busan Paik HospitalBusanRepublic of Korea
  4. 4.CELLTRION, Inc.IncheonRepublic of Korea

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