ESPE Yearbook of Paediatric Endocrinology

Brief summary: This randomized, multicenter, controlled, phase II study compared the effects of high-dose (HD) once-weekly PEGylated-recombinant human growth hormone (PEG-rhGH) to low-dose (LD) and to an untreated control group of children with idiopathic short stature (ISS) over a period of 52 weeks. PEG-rhGH was effective in increasing height gain in a dose dependent manner with both doses being well tolerated during the observation period.

PEG-rhGH is a once-weekly long-acting rhGH obtained by adding a hydrophilic polyethylene glycol residue to rhGH, in order to extend half-life and reduce antigenicity and immunogenicity (1). Previous phase I–III studies established the safety and efficacy of weekly PEG-rhGH in children with GHD, supporting its approval in China (2).

The authors reported the results of the Phase 2 randomized, multicenter, controlled study in ISS children comparing two different dose-regimens of PEG-rhGH with a control group.

Study population included 360 children with idiopathic short stature randomized 1:1:1 to weekly s.c. injections of PEG-rhGH 0.1 (LD) or 0.2 mg/kg/week (HD) or untreated controls for 52 weeks.

The study was completed by 118/120 patients in LD arm, 116/120 patients in HD arm and 117/120 controls.

At week 52, the height improvement (HT-SDS) was 0.56±0.26, 0.98±0.35, and 0.20±0.26 in the LD, HD, and control groups, respectively (P < 0.0001). Statistically significant increase in height velocity, IGF-1, IGF-1/ IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P < 0.0001) with a dose-dependent response for all auxological variables. Adverse events occurring during treatment were reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. A total of 27 (8.7%) children experienced mild to moderate drug-related adverse effects that did not affect treatment efficacy and compliance. There was no significant change in the other safety parameters, such as complete blood count and glucose metabolism during treatment. To our knowledge, this is the first study reporting efficacy and safety of a long acting formulation of GH in ISS children. Preliminary results look encouraging but a phase 3 trial and a longer observation time are needed to confirm these results.

References: 1. Hou L, Chen ZH, Liu D, Cheng YG & Luo XP. Comparative pharmacokinetics and pharmacodynamics of a pegylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children. Drug Design, Development and Therapy. 2016; (10):13–21. doi: 10.2147/DDDT.S93183. 2. Luo X, Hou L, Liang L, Dong G, Shen S, Zhao Z, Gong CX, Li Y, Du ML, Su Z et al. Long-acting pegylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies. Eur J of Endocrinology. 2017; (177)195–205. doi: 10.1530/EJE-16-0905.