ObjectiveTo evaluate the safety and efficacy of weekly PEGylated-recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS) in China. Design and methodsThis was a multicenter, phase II study in which all subjects were randomized 1:1:1 to weekly s.c. injections of PEG-rhGH 0.1 (low-dose (LD) group) or 0.2 mg/kg/week (high-dose (HD) group) or control for 52 weeks. The primary end point was change (Delta) in height s.d. score (HT-SDS) from baseline to week 52. Secondary end points were height velocity (HV), bone maturity, insulin-like growth factor-1 (IGF-1) SDS, and IGF-1/insulin-like growth factor-binding protein-3 (IGFBP-3) molar ratio. ResultsA total of 360 children with ISS were recruited in the study (n = 120 in each group). At week 52, Delta HT-SDS was 0.56 +/- 0.26, 0.98 +/- 0.35, and 0.20 +/- 0.26 in the LD, HD, and control groups, respectively (within-group P < 0.0001; intergroup P < 0.0001). Statistically significant values of Delta HV, IGF-1, IGF-1/IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P < 0.0001). There were clear dose-dependent responses for all auxological variables. PEG-rhGH was well tolerated throughout the treatment period with treatment-emergent adverse events (TEAEs) reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. The incidence of TEAEs was similar in all treatment groups despite the difference in doses. A total of 27 (8.7%) children experienced drug-related TEAEs. ConclusionFifty-two-week treatment with PEG-rhGH 0.1 or 0.2 mg/kg/week achieved significant improvement in HT-SDS and other growth-related variables, including HV, IGF-1 SDS, and IGF-1/IGFBP-3 ratio, in a dose-dependent manner. Both doses were well tolerated with similar safety profiles.