Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial

ContextLong-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending.ObjectiveWe studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD chi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chengjun Sun, Biao Lu, Yu Liu, Yaqin Zhang, Haiyan Wei, Xu Hu, Pei Hu, Qian Zhao, Yanling Liu, Kan Ye, Kan Wang, Zaiyan Gu, Zheng Liu, Jin Ye, Hongxiao Zhang, Hong Zhu, Zhihong Jiang, Yanjie Liu, Naijun Wan, Chengming Yan, Jianying Yin, Lirong Ying, Feng Huang, Qingjin Yin, Li Xi, Feihong Luo, Ruoqian Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	growth hormone deficiency PEGylated recombinant human growth hormone PEG-rhGH IGF-2 children Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/342716233f3f4e22bd958dab3aed79f3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:342716233f3f4e22bd958dab3aed79f3
record_format	dspace
spelling	oai:doaj.org-article:342716233f3f4e22bd958dab3aed79f32021-11-30T21:46:25ZReduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial1664-239210.3389/fendo.2021.779365https://doaj.org/article/342716233f3f4e22bd958dab3aed79f32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.779365/fullhttps://doaj.org/toc/1664-2392ContextLong-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending.ObjectiveWe studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children.Design, Setting, and PatientsThis multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children.InterventionSubjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks.Main Outcome MeasureThe primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes.ResultsAt week 26, the median HtSDSCA changed from −2.75, −2.82, and −2.78 to −2.31, −2.43, and −2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%–90.34% and 76.08%–90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups.ConclusionsAlthough notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02976675.Chengjun SunBiao LuYu LiuYaqin ZhangHaiyan WeiXu HuPei HuQian ZhaoYanling LiuKan YeKan WangZaiyan GuZheng LiuJin YeHongxiao ZhangHong ZhuZhihong JiangYanjie LiuNaijun WanChengming YanJianying YinLirong YingFeng HuangQingjin YinLi XiFeihong LuoRuoqian ChengFrontiers Media S.A.articlegrowth hormone deficiencyPEGylated recombinant human growth hormonePEG-rhGHIGF-2childrenDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	growth hormone deficiency PEGylated recombinant human growth hormone PEG-rhGH IGF-2 children Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	growth hormone deficiency PEGylated recombinant human growth hormone PEG-rhGH IGF-2 children Diseases of the endocrine glands. Clinical endocrinology RC648-665 Chengjun Sun Biao Lu Yu Liu Yaqin Zhang Haiyan Wei Xu Hu Pei Hu Qian Zhao Yanling Liu Kan Ye Kan Wang Zaiyan Gu Zheng Liu Jin Ye Hongxiao Zhang Hong Zhu Zhihong Jiang Yanjie Liu Naijun Wan Chengming Yan Jianying Yin Lirong Ying Feng Huang Qingjin Yin Li Xi Feihong Luo Ruoqian Cheng Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial
description	ContextLong-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending.ObjectiveWe studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children.Design, Setting, and PatientsThis multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children.InterventionSubjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks.Main Outcome MeasureThe primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes.ResultsAt week 26, the median HtSDSCA changed from −2.75, −2.82, and −2.78 to −2.31, −2.43, and −2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%–90.34% and 76.08%–90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups.ConclusionsAlthough notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02976675.
format	article
author	Chengjun Sun Biao Lu Yu Liu Yaqin Zhang Haiyan Wei Xu Hu Pei Hu Qian Zhao Yanling Liu Kan Ye Kan Wang Zaiyan Gu Zheng Liu Jin Ye Hongxiao Zhang Hong Zhu Zhihong Jiang Yanjie Liu Naijun Wan Chengming Yan Jianying Yin Lirong Ying Feng Huang Qingjin Yin Li Xi Feihong Luo Ruoqian Cheng
author_facet	Chengjun Sun Biao Lu Yu Liu Yaqin Zhang Haiyan Wei Xu Hu Pei Hu Qian Zhao Yanling Liu Kan Ye Kan Wang Zaiyan Gu Zheng Liu Jin Ye Hongxiao Zhang Hong Zhu Zhihong Jiang Yanjie Liu Naijun Wan Chengming Yan Jianying Yin Lirong Ying Feng Huang Qingjin Yin Li Xi Feihong Luo Ruoqian Cheng
author_sort	Chengjun Sun
title	Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial
title_short	Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial
title_full	Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial
title_fullStr	Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial
title_full_unstemmed	Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial
title_sort	reduced effectiveness and comparable safety in biweekly vs. weekly pegylated recombinant human growth hormone for children with growth hormone deficiency: a phase iv non-inferiority threshold targeted trial
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/342716233f3f4e22bd958dab3aed79f3
work_keys_str_mv	AT chengjunsun reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT biaolu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT yuliu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT yaqinzhang reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT haiyanwei reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT xuhu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT peihu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT qianzhao reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT yanlingliu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT kanye reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT kanwang reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT zaiyangu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT zhengliu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT jinye reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT hongxiaozhang reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT hongzhu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT zhihongjiang reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT yanjieliu reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT naijunwan reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT chengmingyan reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT jianyingyin reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT lirongying reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT fenghuang reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT qingjinyin reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT lixi reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT feihongluo reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial AT ruoqiancheng reducedeffectivenessandcomparablesafetyinbiweeklyvsweeklypegylatedrecombinanthumangrowthhormoneforchildrenwithgrowthhormonedeficiencyaphaseivnoninferioritythresholdtargetedtrial
_version_	1718406254521483264

Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial

Ejemplares similares