AUTHOR=Sun Chengjun , Lu Biao , Liu Yu , Zhang Yaqin , Wei Haiyan , Hu Xu , Hu Pei , Zhao Qian , Liu Yanling , Ye Kan , Wang Kan , Gu Zaiyan , Liu Zheng , Ye Jin , Zhang Hongxiao , Zhu Hong , Jiang Zhihong , Liu Yanjie , Wan Naijun , Yan Chengming , Yin Jianying , Ying Lirong , Huang Feng , Yin Qingjin , Xi Li , Luo Feihong , Cheng Ruoqian 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.779365

DOI=10.3389/fendo.2021.779365

ISSN=1664-2392

ABSTRACT=<sec><title>Context</title><p>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.</p></sec><sec><title>Objective</title><p>We studied the efficacy of biweekly <italic>versus</italic> weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children.</p></sec><sec><title>Design, Setting, and Patients</title><p>This multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children.</p></sec><sec><title>Intervention</title><p>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.</p></sec><sec><title>Main Outcome Measure</title><p>The primary outcome was height SD scores for chronological age (HtSDS<sub>CA</sub>) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes.</p></sec><sec><title>Results</title><p>At week 26, the median HtSDS<sub>CA</sub> 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<sub>CA</sub> 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.</p></sec><sec><title>Conclusions</title><p>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.</p></sec><sec><title>Clinical Trial Registration</title><p><uri xlink:href="https://clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">clinicaltrials.gov</uri>, identifier NCT02976675.</p></sec>