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

  • Expert Opin Investig Drugs. 2023 Feb;32(2):161-170. doi: 10.1080/13543784.2023.2178894.
Diqin Yan  1  2 ,  Suping Niu  1 ,  Dingyuan Hu  1  2 ,  Wenliang Dong  1  2 ,  Yunjuan Sun  3 ,  Qian Wang  1 ,  Simin Wang  1  4 ,  Qun Gu  1 ,  Gang Liu  5 ,  Jiaxue Wang  6 ,  Liming Chen  1 ,  Jie Lv  7 ,  Qingshan Zheng  8 ,  Haifeng Song  9 ,  Yi Fang  1
Affiliations
  • 1. Clinical Trial Institution, Peking University People's Hospital, Beijing, China.
  • 2. Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
  • 3. Beijing United-Power Pharma Tech Co., Ltd, Beijing, China.
  • 4. Department of Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
  • 5. Department of Pharmacy, Peking University People's Hospital, Beijing, China.
  • 6. Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, China.
  • 7. Department of Intensive Care Units, Peking University People's Hospital, Beijing, China.
  • 8. The Center for Drug Clinical Research of Shanghai University of TCM, Shanghai, China.
  • 9. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
PMID: 36755413 DOI: 10.1080/13543784.2023.2178894
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 Tmax 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
IL-6; Pharmacokinetics; interleukin-6; pharmacodynamics; phase I study; tocilizumab.
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