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Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects

Cellular & Molecular Immunology volume 16, pages 473–482 (2019)Cite this article

Abstract

F-652 is a recombinant fusion protein consisting of two human interleukin-22 (IL-22) molecules linked to an immunoglobulin constant region (IgG2-Fc). IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection. The safety, pharmacokinetics (PK), tolerability, and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized, double-blind, placebo-controlled study. Following single-dose subcutaneous (SC) injection of F-652 at 2.0 µg/kg into healthy subjects, six out of six subjects experienced delayed injection site reactions, which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing. F-652 was then administered to the healthy subjects via an intravenous (IV) infusion at 2.0, 10, 30, and 45 µg/kg. No severe adverse event (SAE) was observed during the study. Among the IV-dosed cohorts, eye and skin treatment emergent adverse events (TEAEs) were observed in the 30 and 45 µg/kg cohorts. F-652 IV dosing resulted in linear increases in Cmax and AUC(0–t), and the T1/2 ranged from 39.4 to 206 h in the cohorts. An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A, C-reactive protein, and FIB, and decreased serum triglycerides. The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45 μg/kg. In conclusion, IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties. These results warrant further clinical development of F-652 to treat inflammatory diseases.

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Acknowledgements

The authors thank Dr. Bin Gao and Dr. Ada Kung for their review and comments and Dr. Stewart Leung for organizing and editing the manuscript. This project is supported by funding from the Generon (Shanghai) Corporation.

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  1. Generon (Shanghai) Corporation Ltd., Zhangjiang Hi-Tech Park, Shanghai, China

    Kai-Yang Tang, Zhi-Hua Huang, Zong-Shu Xian, Han-Yang Chen, Cheng Huang, Chong Xiao, Yu-Peng Wang, Ying Tan, Lin-Feng Xu, Yu-Liang Huang & Xiao-Qiang Yan

  2. Nucleus Network, Melbourne, VIC, Australia

    Jason Lickliter

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Correspondence to Xiao-Qiang Yan.

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X.Q.Y., K.Y.T., C.H., C.X., Y.L.H., Z.H.H., H.L., Z.S.X., H.Y.C., Y.P.W., Y.T., and L.F.X. are employees of the Generon (Shanghai) Corporation, which is involved in the development of F-652. J.L. was sponsored by Generon and has no potential conflict of interest.

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Tang, KY., Lickliter, J., Huang, ZH. et al. Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects. Cell Mol Immunol 16, 473–482 (2019). https://doi.org/10.1038/s41423-018-0029-8

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