PMID- 34899612
OWN - NLM
STAT- MEDLINE
DCOM- 20220215
LR  - 20220215
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 12
DP  - 2021
TI  - 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.
PG  - 779365
LID - 10.3389/fendo.2021.779365 [doi]
LID - 779365
AB  - CONTEXT: Long-acting recombinant human growth hormone (rhGH) has transformed 
      growth hormone deficiency (GHD) treatment. However, the possibility and 
      rationality for flexible time regimen are pending. OBJECTIVE: We studied the 
      efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD 
      children. DESIGN SETTING AND PATIENTS: This multicenter, phase IV trial with a 
      non-inferiority threshold >/=20% enrolled 585 Tanner stage I GHD children. 
      INTERVENTION: Subjects 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 MEASURE: The 
      primary outcome was height SD scores for chronological age (HtSDS(CA)) at week 26 
      and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 
      changes. RESULTS: At week 26, the median HtSDS(CA) 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 HtSDS(CA) 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. CONCLUSIONS: Although 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 REGISTRATION: clinicaltrials.gov, identifier 
      NCT02976675.
CI  - Copyright (c) 2021 Sun, Lu, Liu, Zhang, Wei, Hu, Hu, Zhao, Liu, Ye, Wang, Gu, Liu, 
      Ye, Zhang, Zhu, Jiang, Liu, Wan, Yan, Yin, Ying, Huang, Yin, Xi, Luo and Cheng.
FAU - Sun, Chengjun
AU  - Sun C
AD  - Department of Pediatric Endocrinology and Inherited Metabolic Diseases, 
      Children's Hospital of Fudan University, Shanghai, China.
FAU - Lu, Biao
AU  - Lu B
AD  - Department of Pediatrics, General Hospital of Ningxia Medical University, 
      Yinchuan, China.
FAU - Liu, Yu
AU  - Liu Y
AD  - Department of Endocrine and Genetic Metabolism, Maternal and Child Health-Care 
      Hospital in Guiyang, Guiyang, China.
FAU - Zhang, Yaqin
AU  - Zhang Y
AD  - Department of Child Health, Maternal and Child Health Care Hospital of Hainan 
      Province, Haikou, China.
FAU - Wei, Haiyan
AU  - Wei H
AD  - Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Henan 
      Provincial Hospital, Affiliated to Zhengzhou University, Zhengzhou, China.
FAU - Hu, Xu
AU  - Hu X
AD  - Department of Pediatrics, Lu'an People's Hospital, Lu'an, China.
FAU - Hu, Pei
AU  - Hu P
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      State Key Laboratory of Complex Severe and Rare Diseases, National Medical 
      Products Administration (NMPA) Key Laboratory for Clinical Research and 
      Evaluation of Drug, Beijing Key Laboratory of Clinical Pharmacokinetics and 
      Pharmacodynamics (PK & PD) Investigation for Innovative Drugs, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, China.
FAU - Zhao, Qian
AU  - Zhao Q
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      State Key Laboratory of Complex Severe and Rare Diseases, National Medical 
      Products Administration (NMPA) Key Laboratory for Clinical Research and 
      Evaluation of Drug, Beijing Key Laboratory of Clinical Pharmacokinetics and 
      Pharmacodynamics (PK & PD) Investigation for Innovative Drugs, Chinese Academy of 
      Medical Sciences & Peking Union Medical College, Beijing, China.
FAU - Liu, Yanling
AU  - Liu Y
AD  - Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, China.
FAU - Ye, Kan
AU  - Ye K
AD  - Department of Child Health, The Affiliated Suzhou Hospital of Nanjing Medical 
      University, Suzhou, China.
FAU - Wang, Kan
AU  - Wang K
AD  - Department of Pediatrics, Jinhua Hospital, Zhejiang University School of 
      Medicine, Jinhua, China.
FAU - Gu, Zaiyan
AU  - Gu Z
AD  - Department of Pediatrics, Jiaxing First Hospital, Jiaxing, China.
FAU - Liu, Zheng
AU  - Liu Z
AD  - Department of Pediatrics, Tai'an Maternal and Child Health Care Hospital, Tai'an, 
      China.
FAU - Ye, Jin
AU  - Ye J
AD  - Department of Pediatrics, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 
      China.
FAU - Zhang, Hongxiao
AU  - Zhang H
AD  - Department of Pediatrics, Second Hospital of Lanzhou University, Lanzhou, China.
FAU - Zhu, Hong
AU  - Zhu H
AD  - Department of Pediatrics, The First People's Hospital of Changzhou, Changzhou, 
      China.
FAU - Jiang, Zhihong
AU  - Jiang Z
AD  - Department of Pediatrics, The First Affiliated Hospital of Henan University of 
      Science and Technology, Luoyang, China.
FAU - Liu, Yanjie
AU  - Liu Y
AD  - Department of Pediatrics, Inner Mongolia People's Hospital, Hohhot, China.
FAU - Wan, Naijun
AU  - Wan N
AD  - Department of Pediatrics, Jishuitan Hospital, Beijing, China.
FAU - Yan, Chengming
AU  - Yan C
AD  - Department of Pediatrics, Anhui Province Maternity and Child Health Hospital, 
      Anhui Medical University Maternal and Child Health Clinic College, Hefei, China.
FAU - Yin, Jianying
AU  - Yin J
AD  - Department of Pediatrics, Hebei General Hospital, Shijiazhuang, China.
FAU - Ying, Lirong
AU  - Ying L
AD  - Department of Pediatrics, Cixi People's Hospital, Cixi, China.
FAU - Huang, Feng
AU  - Huang F
AD  - Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Yin, Qingjin
AU  - Yin Q
AD  - Department of Internal Medicine, Chengdu Children's Specialized Hospital, 
      Chengdu, China.
FAU - Xi, Li
AU  - Xi L
AD  - Department of Pediatric Endocrinology and Inherited Metabolic Diseases, 
      Children's Hospital of Fudan University, Shanghai, China.
FAU - Luo, Feihong
AU  - Luo F
AD  - Department of Pediatric Endocrinology and Inherited Metabolic Diseases, 
      Children's Hospital of Fudan University, Shanghai, China.
FAU - Cheng, Ruoqian
AU  - Cheng R
AD  - Department of Pediatric Endocrinology and Inherited Metabolic Diseases, 
      Children's Hospital of Fudan University, Shanghai, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT02976675
PT  - Clinical Trial, Phase IV
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211125
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Recombinant Proteins)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
EIN - Front Endocrinol (Lausanne). 2021 Dec 28;12:830469. PMID: 35027911
MH  - Child
MH  - Child, Preschool
MH  - China
MH  - Drug Administration Schedule
MH  - Dwarfism, Pituitary/drug therapy
MH  - Equivalence Trials as Topic
MH  - Female
MH  - Growth Disorders/*drug therapy
MH  - Human Growth Hormone/*administration & dosage/*adverse effects/deficiency
MH  - Humans
MH  - Male
MH  - Polyethylene Glycols/chemistry
MH  - Recombinant Proteins/administration & dosage/adverse effects/chemistry
MH  - Treatment Outcome
PMC - PMC8655095
OTO - NOTNLM
OT  - IGF-2
OT  - PEG-rhGH
OT  - PEGylated recombinant human growth hormone
OT  - children
OT  - growth hormone deficiency
COIS- CS, RC, and FL received lecture fees from GeneScience Pharmaceuticals. The 
      remaining authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/14 06:00
MHDA- 2022/02/16 06:00
PMCR- 2021/01/01
CRDT- 2021/12/13 17:55
PHST- 2021/09/18 00:00 [received]
PHST- 2021/11/03 00:00 [accepted]
PHST- 2021/12/13 17:55 [entrez]
PHST- 2021/12/14 06:00 [pubmed]
PHST- 2022/02/16 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2021.779365 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2021 Nov 25;12:779365. doi: 
      10.3389/fendo.2021.779365. eCollection 2021.