Phase I, Randomized, Placebo-Controlled, Dose-Escalation Study of GB223, a Fully-Humanized Monoclonal Antibody to RANKL, in Healthy Chinese Adults

Overview

Journal BioDrugs

Specialties Allergy & Immunology
Genetics
Pharmacology

Date 2023 Jun 6

PMID 37278972

Authors

Chen Li

Haiyan Liu

Yixiang Liao

Yu Zhu

Jingyuan Tian

Xuan Wang

Zhiqin Hu

Yaoxuan Zhan

Xianbo Li

Xintong Liang

Jin He

Yongmei Li

Dewei Shang

Qingshan Zheng

Tenghua Wang

Haifeng Song

Yi Fang

Affiliations

Soon will be listed here.

Abstract

Background: GB223 is a novel, fully-humanized monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL). In this phase I study, the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of GB223 were investigated.

Patients And Methods: This was a randomized, double-blinded, placebo-controlled, single-dose escalation study conducted in 44 healthy Chinese adults. Participants were randomly assigned to receive a single subcutaneous injection dose of 7, 21, 63, 119, or 140 mg of GB223 (n = 34) or placebo (n = 10) and were followed up for 140-252 days.

Results: The results of noncompartmental analysis showed that GB223 was slowly absorbed after dosing, with a time to reach maximum concentration (T) ranging from 5 to 11 days. Serum GB223 concentrations decreased slowly, with a long half-life ranging from 7.91 to 19.60 days. A two-compartment Michaelis-Menten model was found to best describe the pharmacokinetics of GB223, and the absorption rate of GB223 differed between males (0.0146 h) and females (0.0081 h). Serum C-terminal telopeptide of type I collagen decreased significantly postdose, and the inhibition lasted 42-168 days. No deaths or drug-related serious adverse events occurred. The most frequent adverse events were blood parathyroid hormone increased (94.1%), blood phosphorus decreased (67.6%) and blood calcium decreased (58.8%). In the GB223 group, 44.1% (15/34) of subjects were antidrug antibody positive after dosing.

Conclusion: In this study, we demonstrated for the first time that a single subcutaneous injection of GB223, from 7 to 140 mg, is safe and well tolerated in healthy Chinese subjects. GB223 has a nonlinear pharmacokinetic profile, and sex was a potential covariate that may affect the absorption rate of GB223.

Clinical Trial Registration: NCT04178044 and ChiCTR1800020338.

Citing Articles

The clinical trial landscape of anti-RANKL agents for osteoporosis: current status and future directions.

Li X, Cheng L Osteoporos Int. 2025; 36(3):573-575.

PMID: 39812674 DOI: 10.1007/s00198-025-07389-1.

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