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. Epub 2023 Feb 20.

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.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized* / immunology
  • Antibodies, Monoclonal, Humanized* / pharmacokinetics
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • East Asian People
  • Humans
  • Interleukin-6

Substances

  • Antibodies, Monoclonal, Humanized
  • Interleukin-6