Journal of Clinical Pediatrics >
Phase Ⅲ clinical trial of recombinant human growth hormone for injection in treatment of idiopathic short stature
Received date: 2022-07-25
Online published: 2023-10-08
Objective To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) for injection in the treatment of prepubertal children with idiopathic short stature (ISS) in China. Methods This study was a randomized, open-label, controlled, multicenter, phase Ⅲ clinical trial of prepubertal ISS from December 27, 2016 to July 30, 2020. Participants were randomly assigned to the high-dose group, low-dose group and control group in a ratio of 3:3:1, and the administration cycle of rhGH was 52 weeks. Changes in height standard deviation scores (ΔHT-SDS) of actual age before and after treatment, annual height velocity (HV) and bone maturity at the end of treatment were observed. At the same time, the rhGH safety during treatment was investigated. Results A total of 150 participants completed the trial. At baseline, there were no significant differences in age, bone age, sex, height, weight, body mass index, HT-SDS, annual HV and insulin-like growth factor 1 levels among all groups (P>0.05). Both full analysis set (FAS) and per protocol set (PPS) analysis found statistically significant differences in ΔHT SDS among the high-dose, low-dose and control groups at week 26, 39 and 52 (P<0.001). Pairwise comparison showed that ΔHT SDS in the high-dose and low-dose groups were higher than those in the control group, and the differences were statistically significant (P<0.05). FAS analysis showed statistically significant differences in HV among the high-dose, low-dose and control groups at week 13, 26, 39, and 52 (P<0.001). Pairwise comparison showed that HV in the high-dose and low-dose groups was higher than that in the control group, and the differences were statistically significant (P<0.05). At week 52, there was no significant difference in bone maturity among all groups (P>0.05). During the study, no serious adverse reaction occurred in each group. Conclusions The rhGH injection is effective in treating ISS, and there is a significant growth in stature after 52 weeks of treatment, but more observation and evaluation of the effect and safety of lifetime height are needed.
Huan LIANG , Hai SHENG , Haiyan WEI , Yu YANG , Hongwei DU , Fang LIU , Li YANG , Meina WANG , Li WANG , Qin MA , Huiwen ZHANG , Xuefan GU . Phase Ⅲ clinical trial of recombinant human growth hormone for injection in treatment of idiopathic short stature[J]. Journal of Clinical Pediatrics, 2023 , 41(10) : 685 -691 . DOI: 10.12372/jcp.2023.22e1018
| [1] | Wit JM, Clayton PE, Rogol AD, et al. Idiopathic short stature: definition, epidemiology, and diagnostic evaluation[J]. Growth Horm IGF Res, 2008, 18(2): 89-110. |
| [2] | Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop[J]. J Clin Endocrinol Metab, 2008, 93(11): 4210-4217. |
| [3] | Wu S, Liu QQ, Gu W, et al. A Retrospective analysis of patients with short stature in the south of China between 2007 and 2015[J]. Biomed Res Int, 2018, 2018: 5732694. |
| [4] | 陈伟伟, 刘焕欣, 刘晶, 等. 儿童身材矮小的病因分析及遗传学诊断[J]. 中国当代儿科杂志, 2019, 21(4): 381-386. |
| [5] | Finkelstein BS, Imperiale TF, Speroff T, et al. Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis[J]. Arch Pediatr Adolesc Med, 2002, 156(3): 230-240. |
| [6] | Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-i treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-Ⅰdeficiency[J]. Horm Res Paediatr, 2016, 86(6): 361-397. |
| [7] | Lee MM. Clinical practice. Idiopathic short stature[J]. N Engl J Med, 2006, 354(24): 2576-2582. |
| [8] | Wu D, Chen RM, Chen SK, et al. Final adult height of children with idiopathic short stature: a multicenter study on GH therapy alone started during peri-puberty[J]. BMC Pediatr, 2020, 20(1): 138. |
| [9] | Ying YQ, Hou L, Liang Y, et al. Efficacy and safety of recombinant human growth hormone in treating Chinese children with idiopathic short stature[J]. Growth Horm IGF Res, 2018, 42-43: 80-85. |
| [10] | Gubitosi-Klug RA, Cuttler L. Idiopathic short stature[J]. Endocrinol Metab Clin North Am, 2005, 34(3): 565-580. |
| [11] | 中华医学会儿科学分会内分泌遗传代谢学组, 中华儿科杂志编辑委员会, 梁雁. 基因重组人生长激素儿科临床规范应用的建议[J]. 中华儿科杂志, 2013, 51(6): 426-432. |
| [12] | Albertsson-Wikland K, Aronson AS, Gustafsson J, et al. Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency[J]. J Clin Endocrinol Metab, 2008, 93(11): 4342-4350. |
| [13] | Common Terminology Criteria for Adverse Events (CTCAE) Version 5[EB/OL]. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, 2017 [2022-07-25]. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. |
| [14] | Chung WY, Yoo HW, Hwang JS, et al. Effect of growth hormone therapy on height velocity in Korean children with idiopathic short stature: a phase Ⅲ randomised controlled trial[J]. Horm Res Paediatr, 2018, 90(1): 44-53. |
| [15] | Kim J, Suh BK, Ko CW, et al. Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase Ⅲ randomized trial[J]. J Endocrinol Invest, 2018, 41(4): 475-483. |
| [16] | Kim HS, Yang SW, Yoo HW, et al. Efficacy of short-term growth hormone treatment in prepubertal children with idiopathic short stature[J]. Yonsei Med J, 2014, 55(1): 53-60. |
| [17] | Child CJ, Quigley CA, Cutler GB Jr, et al. Height gain and safety outcomes in growth hormone-treated children with idiopathic short stature: experience from a prospective observational study[J]. Horm Res Paediatr, 2019, 91(4): 241-251. |
| [18] | Yuan J, Fu J, Wei H, et al. A randomized controlled phase 3 Study on the efficacy and safety of recombinant human growth hormone in children with idiopathic short stature[J]. Front Endocrinol (Lausanne), 2022, 13: 864908. |
| [19] | Deodati A, Cianfarani S. Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review[J]. BMJ, 2011, 342: c7157. |
| [20] | Maniatis AK, Casella SJ, Nadgir UM, et al. Safety and efficacy of lonapegsomatropin in children with growth hormone deficiency: enliGHten trial 2-year results[J]. J Clin Endocrinol Metab, 2022, 107(7): e2680-e2689. |
| [21] | Mauras N, Attie KM, Reiter EO, et al. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. Genentech, Inc., Cooperative Study Group[J]. J Clin Endocrinol Metab, 2000, 85(10): 3653-3660. |
| [22] | Darendeliler F, Ranke MB, Bakker B, et al. Bone age progression during the first year of growth hormone therapy in pre-pubertal children with idiopathic growth hormone deficiency, Turner syndrome or idiopathic short stature, and in short children born small for gestational age: analysis of data from KIGS (Pfizer International Growth Database)[J]. Horm Res, 2005, 63(1):40-47. |
| [23] | Ross JL, Lee PA, Gut R, et al. Attaining genetic height potential: analysis of height outcomes from the ANSWER Program in children treated with growth hormone over 5 years[J]. Growth Horm IGF Res, 2015, 25(6): 286-293. |
/
| 〈 |
|
〉 |
