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. (1st February 2023)

• Record Type: Journal Article
• Authors: Yan, Diqin; Niu, Suping; Hu, Dingyuan; Dong, Wenliang; Sun, Yunjuan; Wang, Qian; Wang, Simin; Gu, Qun; Liu, Gang; Wang, Jiaxue; Chen, Liming; Lv, Jie; Zheng, Qingshan; Song, Haifeng; Fang, Yi
• Is Part Of: Expert opinion on investigational drugs. Volume 32:Number 2(2023)
• Page Start: 161
• Page End: 170
• Publication Date: 2023-02-01
• Subjects: Pharmacokinetics -- pharmacodynamics -- interleukin-6 -- IL-6 -- tocilizumab -- phase I study; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2023.2178894
• Languages: English
• ISSNs: 1354-3784

Abstract

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.