Supplementary Material for: Once-weekly Lonapegsomatropin was Efficacious and Well Tolerated in Chinese Children with Growth Hormone Deficiency: Results from a Phase 3 Randomized Trial

Introduction: Lonapegsomatropin, a prodrug of somatropin, is approved for once-weekly treatment of paediatric growth hormone deficiency (GHD) in the USA and Europe. Here, we report the first trial to assess the efficacy and safety of weekly lonapegsomatropin compared to daily somatropin in treatment-naive Chinese children with GHD. Methods: The briGHt trial was a randomized, open-label, active-controlled, 52-week, phase 3 trial (NCT04326374; CTR20200399) conducted at 17 sites across China. Treatment-naive, prepubertal children with GHD were enrolled and randomized 2:1 to either lonapegsomatropin 0.24 mg hGH/kg/week or equivalent weekly dose of daily somatropin 0.034 mg/kg/day. The primary endpoint was annualized height velocity (AHV) at week 52. Secondary endpoints included change in height standard deviation score (∆HT SDS) from baseline, insulin-like growth factor 1, and safety. Results: 153 participants received treatment. Least-squares (LS) mean ± standard error (±SE) of AHV at week 52 was 10.66 ± 0.22 cm/year for weekly lonapegsomatropin and 9.75 ± 0.26 cm/year for daily somatropin; weekly lonapegsomatropin demonstrated non-inferiority and superiority over daily somatropin, with a difference of 0.91 ± 0.28 cm/year (95% confidence interval: 0.37–1.45; p = 0.0010). LS mean (±SE) of ∆HT SDS was 1.01 ± 0.04 for weekly lonapegsomatropin and 0.83 ± 0.05 for daily somatropin at week 52, favouring lonapegsomatropin from week 13 (p < 0.05) onward. The safety profile was similar between treatment groups. Conclusions: Weekly lonapegsomatropin demonstrated non-inferiority and superiority in efficacy compared to daily somatropin among treatment-naive Chinese children with GHD. The treatment groups showed comparable safety and tolerability profiles.

引言：洛那培生长激素（lonapegsomatropin）是生长激素（somatropin）的前体药物，已在美国和欧洲获批用于儿童生长激素缺乏症（paediatric growth hormone deficiency, GHD）的每周一次治疗。本研究首次评估了每周一次洛那培生长激素对比每日给予生长激素，在初治中国儿童生长激素缺乏症患者中的疗效与安全性。
方法：本项briGHt试验为一项随机、开放标签、阳性对照的52周3期临床试验（临床试验注册号：NCT04326374；CTR20200399），在中国17家研究中心开展。纳入初治的青春前期生长激素缺乏症患儿，以2:1的比例随机分配至洛那培生长激素组（0.24 mg生长激素当量/kg/周），或每日给予生长激素组（0.034 mg/kg/日，对应每周等效剂量）。本试验的主要终点为第52周时的年化身高增长速率（annualized height velocity, AHV）；次要终点包括较基线的身高标准差评分变化（ΔHT SDS）、胰岛素样生长因子1（insulin-like growth factor 1）水平及安全性。
结果：共计153例受试者接受了治疗。第52周时，洛那培生长激素组的最小二乘均值±标准误（±SE）年化身高增长速率为10.66±0.22 cm/年，每日生长激素组为9.75±0.26 cm/年；洛那培生长激素较每日生长激素不仅显示出非劣效性，同时具有优效性，组间差值为0.91±0.28 cm/年（95%置信区间：0.37~1.45；p=0.0010）。第52周时，洛那培生长激素组的身高标准差评分变化最小二乘均值（±SE）为1.01±0.04，每日生长激素组为0.83±0.05，自第13周起洛那培生长激素组的获益即优于对照组（p<0.05）。两组的安全性特征相似。
结论：在初治中国儿童生长激素缺乏症患者中，每周一次洛那培生长激素的疗效较每日给予生长激素兼具非劣效性与优效性，两组的安全性与耐受性特征相当。