QL0902, a proposed etanercept biosimilar: pharmacokinetic and immunogenicity profile to its reference product in healthy Chinese male subjects

ABSTRACT

Objectives: To study the pharmacokinetics, safety and immunogenicity of Recombinant Human Tumor Necrosis Factor-α Receptor II: IgG Fc Fusion Protein for Injection (QL0902) and evaluate the pharmacokinetic similarity between QL0902 and reference Etanercept in healthy male subjects.

Methods: A randomized, double-blinded, single-dose, two-period, two-sequence and crossover study was conducted in healthy males. Sixty-eight subjects were randomized at 1:1 ratio to receive a single 50-mg subcutaneous injection of QL0902 or reference Etanercept. The statistical analysis was conducted by SAS Enterprise Guide statistical software.

Results: The main pharmacokinetic parameters of QL0902 were as follows: AUC_0-∞ was 461861.60 ± 126861.42 (h*ng/mL), AUC_0-t was 453304.68 ± 124424.94 (h*ng/mL), C_max was (2634.03 ± 833.82)ng/mL; The main pharmacokinetic parameters of reference Etanercept were as follows: AUC_0-∞ was 537977.72 ± 153295.70 (h*ng/mL), AUC_0-t was 528817.19 ± 150910.05 (h*ng/mL), C_max was (2874.21 ± 822.31) ng/mL.

Conclusions: After a single subcutaneous injection of QL0902 and reference Etanercept, the 90% confidence intervals of the ratios of AUC_0-∞, AUC_0-t, C_max of healthy subjects were respectively 82.76% to 89.15%, 82.66% to 89.00%, 87.30% to 93.95%, which were between 80.00% and 125.00%. It indicts that their pharmacokinetic characteristics were similar. No serious adverse events occurred and the immunogenicity of QL0902 was lower.

Trial Registration: The trial is registered at www.chictr.org.cn (ChiCTR1900023 437).

KEYWORDS:

• Biosimilars
• etanercept
• pharmacokinetic
• phase I

Ethics

The trial was approved by the Institutional Review Board of the Third Xiangya Hospital, Central South University. The study was conducted in full accordance with the ethical principles of the Declaration of Helsinki and Korean Good Clinical Practices and other applicable regulations. Informed consent was obtained from all individual participants included in the study.

Acknowledgments

The authors thank all the staff members in the Center of Clinical Trial Research, The Third Xiangya Hospital, Central South of University.

Declaration of interest

All authors are employees of the Third Xiangya Hospital. 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.

Reviewer disclosures

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

Author contributions

Yun Zeng and Jie Huang drafted and revised this manuscript, Chang Cui and Shuang Yang were involved in process of trial, Jie Huang and Zhi-jun Huang made contributions to analysis and interpretation of the data, Saqib Ali and Ze-yu Zhang provided language help, Guo-ping Yang was involved in the conception, design and the final approval of the version to be published. All authors made substantial contributions to concept and design of the study, revised the manuscript, and gave their approval to the final version of the manuscript.

Additional information

Funding

This study was supported by International Science & Technology Cooperation Program of China [No.2014DFA30900], and National Natural Science Foundation of China [81673519].