Effect of Growth Hormone Therapy on Height Velocity in Korean Children with Idiopathic Short Stature: A Phase III Randomised Controlled Trial

Abstract

Background/aims: The SYNERGY (Saizen® for Your New Life and Brighter Tomorrow without Growth Deficiency) study is the first randomised multi-centre, open-label study to assess the short-term efficacy and safety of this recombinant human growth hormone (r-hGH) preparation for prepubertal children with idiopathic short stature in South Korea.

Methods: The SYNERGY study (ClinicalTrials.gov NCT01746862) was conducted at 9 centres throughout South Korea between December 2012 and March 2015. The primary endpoint was difference in height velocity from baseline to 6 months in the treatment and control arms.

Results: 97 children were screened; 90 were randomly assigned: 60 children to 0.067 mg/kg/day r-hGH for 12 months (treatment) and 30 children to 6 months of no treatment followed by 0.067 mg/kg/day r-hGH for 6 months (control). The 6-month mean height velocity in the treatment group increased from 5.63 cm/year (SD 1.62) to 10.08 cm/year (SD 1.92) (p < 0.0001) and from 4.94 cm/year (SD 1.91) to 5.92 cm/year (SD 2.01) (p = 0.0938) in the control group (between-group difference 3.47 cm/year, 95% CI 2.17-4.78; p < 0.0001). Adherence was > 90% throughout the study. The safety profile was consistent with that already known for r-hGH.

Conclusion: Treatment with r-hGH in the SYNERGY study demonstrated a statistically significant increase in height velocity at 6 months.

Keywords: Efficacy; Height velocity; Idiopathic short stature; Recombinant human growth hormone; Safety.

© 2018 S. Karger AG, Basel.

Figures

Fig. 1

SYNERGY study design. * Seven children did not meet the screening criteria; therefore, 90 patients were enrolled and randomised in the intention-to-treat population. EOT, end of treatment; r-hGH, recombinant human growth hormone.

Fig. 2

Flow of children through the study. LOCF, last observation carried forward; r-hGH, recombinant human growth hormone.

Fig. 3

Change in height velocity at 6 months. Data are mean (SD); only positive SD are shown. p values are for within- group comparisons. Intention-to-treat with LOCF. Treatment group: n = 59 (1 patient was excluded from the baseline and change from baseline analyses owing to no height value recorded for 6 months prior to screening; this patient withdrew and there were no data after visit 1). Control group: n = 29 (6-month height measurements were missing for 3 children; these were replaced by measurements at withdrawal for 2 children; 1 child had no post-baseline measurement and, therefore, was not included in the analysis). LOCF, last observation carried forward; r-hGH, recombinant human growth hormone; SD, standard deviation.

Fig. 4

Change in height (a) and height SDS (b) at 6 and 12 months. Data are mean (SD); only positive SD are shown. Children completing the study at 12 months: treatment, n = 52; control, n = 27. Reasons for discontinuation in the treatment group: 5 parents/guardians withdrew consent; 1 child withdrew consent; 1 child had serious noncompliance with the study drug; 1 girl entered puberty (breast Tanner stage ≥2). Reasons for discontinuation in the control group: 2 parents/guardians withdrew consent; 1 child withdrew consent. SD, standard deviation; SDS, standard deviation score.

Fig. 5

Change in IGF-1 SDS (a) and IGFBP-3 SDS (b) from baseline at 6 months and 12 months. Data are mean (SD). Children completing the study at 12 months: treatment, n = 52; control, n = 27. Reasons for discontinuation in the treatment group: 5 parents/guardians withdrew consent, 1 child withdrew consent, 1 child had serious noncompliance with the study drug, and 1 girl entered puberty (breast Tanner stage ≥2). Reasons for discontinuation in the control group: 2 parents/guardians withdrew consent and 1 child withdrew consent. SD, standard deviation; SDS, standard deviation score.