Pharmacokinetic bioequivalence, safety, and immunogenicity of GB222, a bevacizumab biosimilar candidate, and bevacizumab in Chinese healthy males: a randomized clinical trial

ABSTRACT

Background

This study was conducted to compare the similarity of the pharmacokinetics (PKs), safety, and immunogenicity of GB222, a potential bevacizumab biosimilar, to that of reference bevacizumab in Chinese healthy males.

Research design and methods

This was a randomized, double-blind, single-dose, parallel-group clinical trial performed in 84 Chinese healthy males, who were randomly assigned to receive a single infusion dose of 1 mg/kg GB222 or bevacizumab with an 84-days follow-up. The primary endpoint was the area under the plasma concentration-time curve (AUC) from zero to the last quantifiable concentration at time t (AUC_0-t). The second endpoints were the safety and immunogenicity evaluation. The PK bioequivalence was verified by the 90% confidence intervals (CIs) of the geometrical mean (GM) ratio for AUC_0-t falling within the bioequivalence margin, 80–125%.

Results

The PK profiles of GB222 and bevacizumab were comparable. The 90% CIs of GM ratio of GB222 to bevacizumab for AUC_0-t was within the pre-specified bioequivalence margin. The most common treatment-related adverse event was sinus bradycardia. Seventeen subjects (20.2%) tested positive for anti-drug antibodies (ADAs).

Conclusion

GB222 was found to be comparable to bevacizumab in terms of PKs, safety, and immunogenicity for Chinese healthy males.

Trial registration

ChiCTR-IIR-17,011,143.

KEYWORDS:

• Bevacizumab
• biosimilar
• pharmacokinetics
• sinus bradycardia
• immunogenicity
• study design

Highlights

• The pharmacokinetic bioequivalence of GB222 and reference bevacizumab was demonstrated in this study.

• The most common reported treatment-related adverse event was sinus bradycardia.

• Despite the high ADAs positive rate, there were no clinically meaningful changes in pharmacokinetics and safety.

Acknowledgments

Genor Biopharma Co. Ltd. (Shanghai, China) provided the test drugs (GB222 and reference bevacizumab). Beijing United-Power Pharma Tech Co., Ltd., provided the methodology and platform for drug concentration and drug immunogenicity testing. The authors would like to extend sincere appreciation to all enrolled subjects, investigators, and people who contributed to this study.

Declaration of interest

Fan Xie is the employee of Genor Biopharma Co. Ltd. (Shanghai, China). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Authors’ contributions

Yi Fang, Haifeng Song, Qingshan Zheng, Youzhong An, and Fan Xie contributed to the design of the study; Suping Niu, Jie Lv, Huaying Fan, Zhenwei Xie, and Huiying Rao contributed to the monitoring of the study; Bianzhen Wang contributed to the drug testing methodology of the study; Qian Wang contributed to the subjects blood drawing; Gang Liu contributed to the drug preparation; Lin Xia, Jiaxue Wang, and Tiantian Shen contributed to the blood samples collection and treatment; Wenliang Dong and Min Chen contributed to the analysis and interpretation of the results; Wenliang Dong contributed to the manuscript writing. All authors contributed to the manuscript and approved its publication.

Data availability statement

All original data and related documents such as the statistical analysis plan, protocol and amendments are available from the corresponding author, Yi Fang, upon reasonable request.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was funded by Genor Biopharma Co. Ltd. (Shanghai, China).