Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Gerilimzumab (GB224), a recombinant humanized interleukin-6 monoclonal antibody, in healthy Chinese adults: A randomized controlled dose–escalation study

ABSTRACT

Objectives

This study aimed to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of Gerilimzumab (GB224), a recombinant humanized IgG1λ monoclonal antibody against interleukin-6, in healthy Chinese adults.

Methods

Fifty-eight subjects were randomly assigned to receive a single subcutaneous dose of 2, 5, 10, 15, 20, 30 mg GB224 or placebo. Safety assessments were performed, and blood samples were collected for PK, PD, and immunogenicity analyses during a follow-up of 112 days.

Results

The most frequent adverse event was decreased fibrinogen (43.1%). GB224 was absorbed relatively fast with a median T_max of 48 h (24–168 h) but eliminated slowly with a long mean half-life (839.38–981.63 h). Dose proportionality was shown to be in the dose range of 10–30 mg. A dose-dependent increase in serum interleukin-6 concentration from baseline was observed in the subjects receiving GB224. Only two subjects tested positive for antidrug antibodies after administration of GB224.

Conclusion

GB224 had a well-tolerated safety profile, desirable PK, and a low immunogenicity following a single-dose subcutaneous administration in healthy Chinese subjects. These findings warrant further investigation.

KEYWORDS:

• Pharmacokinetics
• pharmacodynamics
• interleukin-6
• IL-6
• tocilizumab
• phase I study

Acknowledgments

Genor Biopharma Co. Ltd. (Shanghai, China) provided the test drugs (GB224). Beijing United-Power Pharma Tech Co., Ltd. (Beijing, China) provided the methodology and platform for PK, PD, and immunogenicity testing. The authors would like to extend their thanks to all enrolled participants, investigators, and people who contributed to this study.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Diqin Yan, Suping Niu, Dingyuan Hu, Yunjuan Sun, Qian Wang, Qun Gu, Gang Liu, and Jiaxue Wang. The first draft of the manuscript was written by Diqin Yan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Data availability statement

The data that support the findings of this study are available from the corresponding author, Y Fang, at https://doi.org/10.6084/m9.figshare.22104764 upon reasonable request.

Clinical trial registration

https://www.chinadrugtrials.org.cn/index.html identifier is ChiCTR-IIR-17013205, and https://clinicaltrials.gov identifier is NCT04178070.

Additional information

Funding

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