Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Endocrinology, Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
Front Endocrinol (Lausanne). 2022 Aug 11;13:922304. doi: 10.3389/fendo.2022.922304. eCollection 2022.
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).
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.
A dose-dependent response of maximum plasma concentration (C) and area under the concentration-time curves from 0 to 168 hours (AUC) were observed for YPEG-rhGH. The ratio of C and the ratio of AUC from the first to the last dosing were 1.091.11 and 1.221.26 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.
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.
ClinicalTrials.gov, identifier [NCT04513171].
研究 Y 型分支聚乙二醇化重组人生长激素（YPEG-rhGH）的药代动力学（PK）和药效动力学（PD），并评估其在生长激素缺乏症（GHD）儿童中的短期疗效和安全性。
本研究为一项在中国 12 个中心开展的、随机、多中心、阳性药物对照、双盲（YPEG-rhGH 剂量）试验，共纳入 43 例 GHD 患儿。患儿按照 1:1:1:1 的比例随机分配至 YPEG-rhGH 100、120 和 140μg/kg/周组和每日 rhGH 35μg/kg/天组。治疗持续 12 周。主要结局为胰岛素样生长因子-1（IGF-1）变化的曲线下面积（AUC）。次要结局为第 12 周时的身高增长速度（HV）增量。
观察到 YPEG-rhGH 的最大血浆浓度（C）和 0 至 168 小时浓度-时间曲线下面积（AUC）呈剂量依赖性增加。C 和首剂量至末剂量 AUC 的比值分别为 1.091.11 和 1.221.26。观察到 YPEG-rhGH 剂量依赖性增加 IGF-1 折叠变化的 AUC。模型推导的平均 IGF-1 SDS 在所有三种 YPEG-rhGH 剂量下均处于正常范围内。第 12 周时，YPEG-rhGH 100、120 和 140μg/kg/周及每日 rhGH 的 HV 分别为 7.07、10.39、12.27cm/年和 11.58cm/年。依从性和安全性与每日 rhGH 一致。未报告与治疗相关的严重不良事件。
PK/PD 提示 YPEG-rhGH 适用于儿童 GHD 的每周 1 次治疗。与每日 rhGH 35μg/kg/天相比，YPEG-rhGH 120~140μg/kg/周提供了最接近的 HV 增量，且具有相似的安全性和耐受性。
ClinicalTrials.gov，标识符 [NCT04513171]。
