Department of Women's and Children's Health, Karolinska Institute and Pediatric Endocrinology Unit, Karolinska University Hospital, Stockholm, Sweden.
UMC-University Children's Hospital, and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1847-61. doi: 10.1210/clinem/dgz310.
Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD).
The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH.
REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562).
This study took place at 29 sites in 11 countries.
Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial.
Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously.
The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS.
At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week-daily GH): 1.7 [95% CI -0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was -1.62 (0.86), -1.09 (0.78), and 0.31 (1.06), respectively, vs -0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH.
In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).
每日给予生长激素（GH）注射可能会给患者和照护者带来负担。Somapacitan 是一种正在开发中的长效、可逆的白蛋白结合型 GH 衍生物，每周给药一次，用于治疗生长激素缺乏症（GHD）患者。
本研究旨在评估每周一次 somapacitan 与每日 GH 相比的疗效、安全性和耐受性。
REAL 3 是一项多中心、随机、对照、双盲（somapacitan 剂量）的 2 期研究，有 26 周的主要和 26 周的扩展阶段（NCT02616562）。
该研究在 11 个国家的 29 个地点进行。
59 例 GH 初治青春期前 GHD 患儿被随机分配；58 例完成了试验。
干预措施包括 3 种 somapacitan 剂量（0.04[ n = 16]、0.08[ n = 15]或 0.16 mg/kg/周[n = 14]）和每日 GH（0.034 mg/kg/d [ n = 14]），均皮下给药。
主要终点是 26 周时的身高速度（HV）。次要疗效终点包括 HV SDS 评分和胰岛素样生长因子-I（IGF-I）SDS。
在 26 周时，somapacitan 组的年平均 HV 分别为 8.0（2.0）、10.9（1.9）和 12.9（3.5）cm/年，而每日 GH 组为 11.4（3.3）cm/年；估计治疗差异（somapacitan 0.16 mg/kg/周-每日 GH）：1.7[95%CI-0.2 至 3.6]cm/年。在第 52 周时 HV 仍持续，somapacitan 0.16 mg/kg/周与每日 GH 相比显著更高。在第 52 周时，HV SDS 的平均（SD）变化分别为 somapacitan 组 4.72（2.79）、6.14（3.36）和 8.60（3.15），每日 GH 组为 7.41（4.08）。somapacitan 组模型推导的平均（SD）IGF-I SDS 分别为-1.62（0.86）、-1.09（0.78）和 0.31（1.06），而每日 GH 组为-0.40（1.50）。安全性和耐受性与每日 GH 的特征一致。
在 GHD 患儿中，每周一次的 somapacitan 0.16 mg/kg/周与每日 GH 相比具有最接近的疗效，在 26 和 52 周的治疗后，其安全性和耐受性相似。我们的工作有一个简短的可视化总结（1）。
