注射用重组人生长激素治疗特发性矮小症Ⅲ期临床试验研究

doi:10.12372/jcp.2023.22e1018

Abstract

Abstract:

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.

Key words: idiopathic short stature, recombinant human growth hormone, efficacy, safety

LIANG Huan, SHENG Hai, WEI Haiyan, YANG Yu, DU Hongwei, LIU Fang, YANG Li, WANG Meina, WANG Li, MA Qin, ZHANG Huiwen, GU Xuefan. 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.

Figures/Tables 4

References 23

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项目	对照组(n=24)	低剂量组(n=72)	高剂量组(n=72)	统计量	P
年龄($\bar{x}±s$)/岁	6.8±1.9	7.3±2.0	7.4±2.2	F=0.81	0.446
男性[n(%)]	17(70.8)	49(68.1)	53(73.6)	χ²=0.54	0.765
汉族[n(%)]	24(100.0)	68(94.4)	71(98.6)	χ²=3.01	0.223
骨龄($\bar{x}±s$)/岁	5.8±1.9	5.9±2.1	5.9±1.9	F=0.02	0.985
身高($\bar{x}±s$)/cm	110.8±10.0	113.4±10.1	114.4±11.0	F=1.04	0.356
HT-SDS($\bar{x}±s$)	-2.4±0.5	-2.4±0.6	-2.3±0.5	F=0.56	0.574
HV[M(P₂₅~P₇₅)]/cm·a^-1	2.6(1.8~3.7)	2.9(1.9~3.8)	3.1(2.4~3.8)	H=3.24	0.198
体重($\bar{x}±s$)/kg	19.5±5.0	20.3±5.1	20.1±4.6	F=0.25	0.780
体质指数($\bar{x}±s$)/kg·m^-2	15.6±2.0	15.5±2.2	15.1±1.3	F=1.10	0.334
IGF-1[M(P₂₅~P₇₅)]/ng·mL^-1	102.5(66.9~127.5)	89.55(68.7~117.0)	89.70(59.0~110.0)	H=1.59	0.451
IGFBP3[M(P₂₅~P₇₅)]/ng·mL^-1	2 670.0(2 130.0~2 850.0)	2 630.0(2 220.0~3 040.0)	2 220.0(1 840.0~2 760.0)	H=6.61	0.037

项目	对照组	低剂量组	高剂量组	F值	P
ΔHT-SDS(PPS)
第13周	0.3±0.3	0.4±0.4	0.4±0.3	1.08	0.343
第26周	0.1±0.2	0.5±0.3¹⁾	0.5±0.2¹⁾	28.35	<0.001
第39周	0.3±0.3	0.7±0.4¹⁾	0.8±0.4¹⁾	16.36	<0.001
第52周	0.1±0.2	0.8±0.3¹⁾	0.9±0.3¹⁾	63.45	<0.001
ΔHT-SDS(FAS)
第13周	0.2±0.3	0.4±0.4	0.3±0.3	1.19	0.306
第26周	0.1±0.2	0.5±0.3¹⁾	0.5±0.2¹⁾	22.71	<0.001
第39周	0.3±0.3	0.7±0.4¹⁾	0.7±0.4¹⁾	13.47	<0.001
第52周	0.1±0.2	0.8±0.4¹⁾	0.8±0.4¹⁾	41.89	<0.001
HV(FAS)/cm·a^-1
第13周	7.4±2.7	11.5±4.3¹⁾	12.3±3.3¹⁾	15.20	<0.001
第26周	6.6±1.7	10.3±2.6¹⁾	10.7±2.1¹⁾	29.98	<0.001
第39周	6.1±1.3	9.8±1.9¹⁾	10.4±1.8¹⁾	56.05	<0.001
第52周	5.8±1.1	9.3±1.6¹⁾	10.1±1.3¹⁾	75.45	<0.001
ΔBA/ΔCA(FAS)
第26周	-	1.1±0.4	1.1±0.5	-	-
第52周	0.97±0.4	1.1±0.3	1.2±0.5	2.40	0.094

指标	对照组(n=24)	低剂量组(n=72)	高剂量组(n=72)	χ²值	P
TEAE	14(58.3)	64(88.9)	62(86.1)	12.80	0.002
ADR	0(0)	14(19.4)	12(16.7)	5.34	0.069
SAE	0(0)	3(4.2)	4(5.6)	-	0.680¹⁾
SADR	0(0)	0(0)	0(0)	-	-
导致退出试验TEAE	0(0)	0(0)	1(1.4)	-	-
导致退出试验ADR	0(0)	0(0)	1(1.4)	-	-
导致剂量调整TEAE	0(0)	0(0)	0(0)	-	-
导致剂量调整ADR	0(0)	0(0)	0(0)	-	-
导致药物暂停TEAE	0(0)	42(58.3)	41(56.9)	27.37	<0.001
导致药物暂停ADR	0(0)	10(13.9)	11(15.3)	4.06	0.131
严重程度≥3级TEAE	0(0)	3(4.2)	4(5.6)	-	0.680¹⁾
严重程度≥3级ADR	0(0)	0(0)	1(1.4)	-	-

Phase Ⅲ clinical trial of recombinant human growth hormone for injection in treatment of idiopathic short stature

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