Long-Acting PEG-rhGH in Short Children Born SGA in China: 4-Year Results from a Randomized Phase 2 Study

Introduction Children born small for gestational age (SGA) who failed to achieve catch-up growth are at risk of persistent short stature and associated metabolic complications. Daily recombinant human growth hormone (rhGH) therapy improves growth but is limited by adherence challenges. This study evaluated the long-term efficacy and safety of once-weekly PEGylated recombinant human growth hormone (PEG-rhGH; Jintrolong) in short children born SGA. Methods This multicenter, randomized, open-label, dose-response phase 2 study, comprised a 52-week main phase and an ongoing extension (NCT02375620), across 9 and 7 sites in China, respectively. Ninety-six GH treatment-naïve, non-GH-deficient, prepubertal children born SGA (age 3 to <8 years) were randomized (1:1) to PEG-rhGH 0.1 or 0.2 mg/kg/week for 52 weeks. After 52 weeks, sixty-six children proceeded to the extension phase continuing PEG-rhGH treatment (initial dose: 0.2 mg/kg/week, maximum: 0.4 mg/kg/week) until near-adult height (NAH). Results After 208 weeks, the mean (SD) ΔHT-SDS was 1.746 (0.488) and 1.660 (0.710) in the original 0.2 and 0.1 mg/kg/week groups respectively. Overall, 90.9% (60/66) achieved height > -2 SDS and 53.0% (35/66) reached target height SDS. The mean annualized height velocity remained within the normal range. Long-term PEG-rhGH treatment was well tolerated, with most treatment-emergent adverse events (TEAEs) being mild and consistent with known GH-related effects. Conclusion Once-weekly PEG-rhGH provides sustained improvement in height and growth velocity over four years in short children born SGA. It's favorable safety and adherence profile observed supports long-acting GH as an alternative to daily GH therapy for managing growth failure in SGA children.