{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:12:47Z","timestamp":1787026367068,"version":"build-2736575974"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 \u03bcg\/kg\/week of YPEG-rhGH groups and daily rhGH 35 \u03bcg\/kg\/day groups. The treatment lasted 12 weeks. The primary outcome was the area under the curve of the change of insulin-like growth factor-1 (IGF-1). The secondary outcome was the height velocity (HV) increment at week 12.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A dose-dependent response of maximum plasma concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) and area under the concentration-time curves from 0 to 168 hours (AUC\n                      <jats:sub>0-168h<\/jats:sub>\n                      ) were observed for YPEG-rhGH. The ratio of C\n                      <jats:sub>max<\/jats:sub>\n                      and the ratio of AUC\n                      <jats:sub>0-168h<\/jats:sub>\n                      from the first to the last dosing were 1.09~1.11 and 1.22~1.26 respectively. A YPEG-rhGH dose-dependent increase in area under effect curve (AUEC) of IGF-1 fold change was observed. Model-derived mean IGF-1 SDS was in the normal range for all three YPEG-rhGH doses. At week 12, HV was 7.07, 10.39, 12.27 cm\/year, and 11.58 cm\/year for YPEG-rhGH 100, 120, and 140 \u03bcg\/kg\/week and daily rhGH respectively. Adherence and safety were consistent with the profile of daily rhGH. No related serious adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The PK\/PD suggests that YPEG-rhGH is suitable for the once-weekly treatment of pediatric GHD. YPEG-rhGH 120 ~ 140 \u03bcg\/kg\/week provides the closest HV increment with similar safety and tolerability compared to daily rhGH 35 \u03bcg\/kg\/day in children with GHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>ClinicalTrials.gov<\/jats:uri>\n                      , identifier [NCT04513171].\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2022.922304","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T08:53:30Z","timestamp":1660208010000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone 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