SUN-259 Recombinant Growth Hormone Therapy for Children with Turner Syndrome in Korea: A Phase III Randomized Trial

Abstract

Background: Short stature is the most consistent characteristic feature of Turner syndrome (TS). Several studies have been performed to evaluate growth response to growth hormone (GH) for children with TS and shown that earlier and proper treatment with GH improves growth. Objective: The objectives of this study were to determine whether the efficacy and safety of Growtropin®-II (recombinant human GH) are non-inferior to those of Genotropin® in Korean children with TS. Methods: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible 58 patients were randomized to one of groups administrated with Growtropin®-II or Genotropin® at a dose of 0.14 IU(0.045-0.050 mg)/kg/day by subcutaneous injection and 55 of whom completed the study. Results: Annualized height velocity (HV) after 52-week treatment was 8.73±0.21 cm/year in Growtropin®-II treatment group and was 8.70±0.21 cm/year in Genotropin® group. The lower bound of the 95% two-sided confidence interval for group difference for the annualized HV(-0.56 cm/year) satisfied the non-inferiority margin(-1.5 cm/year). The change in height standard deviation score (SDS) at 52-week was calculated at 0.70±0.23 in Growtropin®-II administered group and 0.66±0.39 in Genotropin® group. The change from baseline in height SDS between two groups at 52-week was not statistically different (p=0.6849). Skeletal maturity, which was defined as change in bone age / change in chronological age between the two groups was also not significantly different (1.25±0.58 in Growtropin®-II group, 1.47±0.45 in Genotropin® group, p=0.1336). The changes of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks with subjects received Growtropin®-II therapy were 206.59±105.76 ng/ml and 1.30±0.93 mg/ml, respectively. Genotropin® group showed 222.60±95.15 ng/ml and 1.42±1.31 mg/ml, respectively. (p=0.5645, p=0.3882). Adverse events were not significant in either group. Conclusion: This study demonstrated that annualized HV of Growtropin®-II treatment at 52 week is non-inferior to that of Genotropin® in children with TS and there were no significant differences in the change of height SDS, IGF-1 and IGFBP-3 between two groups. Growtropin®-II is well tolerated and its safety profile was comparable with Genotropin® over 1 year of treatment.