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

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.

• Authors: Sang-Heon Cho, Seunghoon Han, Jong-Lyul Ghim, Moon-Suk Nam, Sunyoung Yu, Taehong Park, Sinhye Kim, Jihun Bae, Jae-Gook Shin
• Journal: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy (BioDrugs) Vol. 33 Issue 2 Pg. 173-181 (Apr 2019) ISSN: 1179-190X [Electronic] New Zealand
• PMID: 30850957 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal
• Biosimilar Pharmaceuticals
• Bevacizumab

Topics

• Adult
• Antibodies, Monoclonal (adverse effects, blood, pharmacokinetics)
• Bevacizumab (adverse effects, blood, pharmacokinetics)
• Biosimilar Pharmaceuticals (adverse effects, blood, pharmacokinetics)
• Double-Blind Method
• Healthy Volunteers
• Humans
• Male
• Middle Aged
• Therapeutic Equivalency
• Young Adult