A Randomized Controlled Phase 3 Study on the Efficacy and Safety of Recombinant Human Growth Hormone in Children With Idiopathic Short Stature

Background: To evaluate the safety and efficacy of daily somatropin (Jintropin (R)), a recombinant human growth hormone, in prepubertal children with ISS in China. Methods: This study was a multicenter, randomized, controlled, open-label, phase 3 study. All subjects were randomized 3:1 to daily somatropin 0.05 mg/kg/day or no treatment for 52 weeks. A total of 481 subjects with a mean baseline age of 5.8 years were enrolled in the study. The primary endpoint was change in (Delta) height standard deviation score (HT-SDS) for chronological age (CA). Secondary endpoints included Delta height from baseline; Delta bone age (BA)/CA; Delta height velocity (HV) and Delta insulin-like growth factor 1 (IGF-1 SDS). Results: Delta HT-SDS at week 52 was 1.04 +/- 0.31 in the treatment group and 0.20 +/- 0.33 in the control group (P < 0.001). At week 52, statistical significance was observed in the treatment group compared with control for Delta height (10.19 +/- 1.47 cm vs. 5.85 +/- 1.80 cm; P < 0.001), Delta BA/CA (0.04 +/- 0.09 vs. 0.004 +/- 0.01; P < 0.001), Delta HV (5.17 +/- 3.70 cm/year vs. 0.75 +/- 4.34 cm/year; P < 0.001), and Delta IGF-1 SDS (2.31 +/- 1.20 vs. 0.22 +/- 0.98; P < 0.001). The frequencies of treatment-emergent adverse events (TEAEs) were similar for the treatment and the control groups (89.8% vs. 82.4%); most TEAEs were mild to moderate in severity and 23 AEs were considered study-drug related. Conclusions: Daily subcutaneous administration of somatropin at 0.05 mg/kg/day for 52 weeks demonstrated improvement in growth outcomes and was well tolerated with a favorable safety profile.