The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency
Yan Liang, Cai Zhang, Haiyan Wei, Hongwei Du, Gaixiu Zhang, Yu Yang, Hua Zhang, Haihong Gong, Pin Li, Fuying Song, Zhuangjian Xu, Ruoyi He, Weidong Zhou, Heng Zheng, Li Sun, Xiaoping Luo, Yan Liang, Cai Zhang, Haiyan Wei, Hongwei Du, Gaixiu Zhang, Yu Yang, Hua Zhang, Haihong Gong, Pin Li, Fuying Song, Zhuangjian Xu, Ruoyi He, Weidong Zhou, Heng Zheng, Li Sun, Xiaoping Luo
Abstract
Objectives: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD).
Methods: A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 μg/kg/week of YPEG-rhGH groups and daily rhGH 35 μg/kg/day groups. The treatment lasted 12 weeks. The primary outcome was the area under the curve of the change of insulin-like growth factor-1 (IGF-1). The secondary outcome was the height velocity (HV) increment at week 12.
Results: A dose-dependent response of maximum plasma concentration (Cmax) and area under the concentration-time curves from 0 to 168 hours (AUC0-168h) were observed for YPEG-rhGH. The ratio of Cmax and the ratio of AUC0-168h from the first to the last dosing were 1.09~1.11 and 1.22~1.26 respectively. A YPEG-rhGH dose-dependent increase in area under effect curve (AUEC) of IGF-1 fold change was observed. Model-derived mean IGF-1 SDS was in the normal range for all three YPEG-rhGH doses. At week 12, HV was 7.07, 10.39, 12.27 cm/year, and 11.58 cm/year for YPEG-rhGH 100, 120, and 140 μg/kg/week and daily rhGH respectively. Adherence and safety were consistent with the profile of daily rhGH. No related serious adverse events were reported.
Conclusion: The PK/PD suggests that YPEG-rhGH is suitable for the once-weekly treatment of pediatric GHD. YPEG-rhGH 120 ~ 140 μg/kg/week provides the closest HV increment with similar safety and tolerability compared to daily rhGH 35 μg/kg/day in children with GHD.
Clinical trial registration: ClinicalTrials.gov, identifier [NCT04513171].
Keywords: Y-shape branched PEGylation; clinical trial; growth hormone deficiency; long-acting growth hormone; prepubertal children.
Conflict of interest statement
LS is the president of Xiamen Amoytop Biotech Co., Ltd. RH and WZ are employees of Xiamen Amoytop Biotech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Copyright © 2022 Liang, Zhang, Wei, Du, Zhang, Yang, Zhang, Gong, Li, Song, Xu, He, Zhou, Zheng, Sun and Luo.
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