Effects of recombinant human growth hormone treatment on growth, body composition, and safety in infants or toddlers with Prader-Willi syndrome: a randomized, active-controlled trial

Abstract

Background: Prader-Willi syndrome (PWS) is a rare complex genetic disorder and is characterized by short stature, muscular hypotonia, abnormal body composition, psychomotor retardation, and hyperphagia. Recombinant human growth hormone (rhGH) treatment improves the symptoms in children with PWS, and early treatment results in more favorable outcomes. However, systematic studies in infants and toddlers under 2 years of age are lacking. This multicenter, randomized, active-controlled, parallel-group, open-label, Phase III study aimed to evaluate the safety of rhGH (Eutropin, LG Chem, Ltd.) and its efficacy on growth, body composition, and motor and cognitive development in infants and toddlers with PWS compared with a comparator treatment (Genotropin, Pfizer, Inc.). Eligible Korean infants or toddlers with PWS were randomly assigned to receive Eutropin or comparator (both 0.24 mg/kg/week, 6 times/week) for 1 year. Height standard deviation score (SDS), body composition, and motor and cognitive development were measured.

Results: Thirty-four subjects (less than 24 months old) were randomized into either the Eutropin (N = 17) group or the comparator (N = 17) group. After 52 weeks of rhGH treatment, height SDS and lean body mass increased significantly from baseline in both groups: the mean height SDS change (SD) was 0.75 (0.59) in the Eutropin group and 0.95 (0.66) in the comparator group, and the mean lean body mass change (SD) was 2377.79 (536.25) g in the Eutropin group and 2607.10 (641.36) g in the comparator group. In addition, percent body fat decreased significantly: the mean (SD) change from baseline was - 8.12% (9.86%) in the Eutropin group and - 7.48% (10.26%) in the comparator group. Motor and cognitive developments were also improved in both groups after the 1-year treatment. The incidence of adverse events was similar between the groups.

Conclusions: rhGH treatment for 52 weeks in infants and toddlers with PWS improved growth, body composition, and motor and cognitive development, and efficacy and safety outcomes of Eutropin were comparable to those of Genotropin. Hence, Eutropin is expected to provide safe and clinically meaningful improvements in pediatric patients with PWS.

Trial registration: The study was registered at ClinicalTrials.gov (identifier: NCT02204163) on July 30, 2014. URL: https://ichgcp.net/clinical-trials-registry/NCT02204163?term=NCT02204163&rank=1.

Keywords: Body composition; Growth hormone therapy; Infants and toddlers; Prader-Willi syndrome; Psychomotor development.

Conflict of interest statement

YE and JL are employed by LG Chem, Ltd. The other authors declare that they have no competing interests.

Figures

Fig. 1

Flow chart. * The subjects (one in the Eutropin group and two in the comparator group) required the use of a prohibited medication for the treatment of adverse events, and hence, they were withdrawn from the study at the discretion of the investigator because of expected protocol deviation (use of prohibited medications)

Fig. 2

a Mean change in height SDS at week 52 from baseline b Height SDS over time. P-value was obtained from Paired t-test. b The lower and upper boundaries are the 25th percentile and the 75th percentile, respectively. The horizontal line in the box shows the median. Filled squares are mean values. SDS, standard deviation score; CI, confidence interval; SE, standard error

Fig. 3

a Mean change in lean body mass at week 52 from baseline b Mean change in percent body fat at week 52 from baseline. * P-value was obtained from Paired t-test. ‡P-value was obtained from Wilcoxon’s signed rank test. CI, confidence interval; SE, standard error

Fig. 4

a Height velocity over time b Weight SDS over time c Head circumference over time. The lower and upper boundaries are the 25th percentile and 75th percentile, respectively. The horizontal line in the box shows the median. Filled squares are mean values. SDS, standard deviation score

Fig. 5

a Mean change in bone mineral density at week 52 from baseline b Mean change in bone age at week 52 from baseline. P-value was obtained from Paired t-test. CI, confidence interval; SE, standard error

Fig. 6

a Motor development score over time b Cognitive development score over time. The lower and upper boundaries are the 25th percentile and 75th percentile, respectively. The horizontal line in the box shows the median. Filled squares are mean values.

Fig. 7

a IGF-I SDS over time b IGFBP-3 SDS over time. The lower and upper boundaries are the 25th percentile and 75th percentile, respectively. The horizontal line in the box shows the median. Filled squares are mean values. IGF-I, insulin-like growth factor I; SDS, standard deviation score; IGFBP-3, IGF-binding protein 3