Objectives: This trial (NCT01927861) evaluated the growth-promoting effect and safety of Norditropin® (somatropin; recombinant human growth hormone) in Japanese children with short stature due to Noonan syndrome over four years of treatment.
Methods: Pre-pubertal children diagnosed with Noonan syndrome were randomized 1:1 to receive Norditropin® 0.033 mg/kg/day or 0.066 mg/kg/day. Change in height standard deviation score (SDS) from baseline to 208 weeks (four years) of treatment was analyzed using an ANCOVA model.
Results: Fifty-one children were randomized to Norditropin® 0.033 mg/kg/day (n=25, mean age [mean±SD] 6.57±2.42 years, 11 female) or 0.066 mg/kg/day (n=26, mean age 6.06±2.25 years, 8 female). Baseline height SDS was similar between groups, relative to a Japanese reference standard (0.033 mg/kg/day: 3.24±0.76; 0.066 mg/kg/day: 3.25±0.71] or a Japanese Noonan reference standard (0.033 mg/kg/day: 0.73±0.74; 0.066 mg/kg/day: 0.80±0.72). After 208 weeks of treatment, the estimated change (95% CI) in height SDS relative to the Japanese reference standard was 0.85 (0.59; 1.12) in the 0.033 mg/kg/day group and 1.84 (1.58; 2.10) in the 0.066 mg/kg/day group, with an estimated mean difference of 0.99 (95% CI:0.62; 1.36) (p<0.0001). Rates and patterns of adverse events (AEs) and the frequency of serious AEs were similar between groups. Mean insulin-like growth factor-I SDS increased from 1.71 at baseline to 0.75 (0.033 mg/kg/day) and to 0.57 (0.066 mg/kg/day). HbA1c increased slightly in both groups. Glucose profiles were almost unchanged and insulin profiles increased in both groups using an oral glucose tolerance test. Three patients in the 0.066 mg/kg/day group withdrew from the trial, two due to adverse events (polymyositis and scoliosis).
Conclusions: Japanese children with short stature due to Noonan syndrome treated with Norditropin® 0.033 or 0.066 mg/kg/day over 208 weeks showed significantly improved height SDS and a favorable safety profile. The increase in height SDS was statistically significant in the 0.066 mg/kg/day group compared with the 0.033 mg/kg/day group.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology