Long-Acting PEG-rhGH in Short Children Born SGA in China: 4-Year Results from a Randomized Phase 2 Study.
Once-weekly PEG-rhGH shows promise for improving growth in short children born SGA, with a majority achieving significant height improvements over four years.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study measured the long-term efficacy and safety of once-weekly PEGylated recombinant human growth hormone (PEG-rhGH) in short children born small for gestational age (SGA). Ninety-six prepubertal children aged 3 to <8 years were randomized to receive either 0.1 or 0.2 mg/kg/week for 52 weeks, followed by an extension phase. After 208 weeks, the mean height standard deviation score (ΔHT-SDS) was reported for both groups.
Abstract
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.
Background
This study addresses the growth challenges faced by children born small for gestational age (SGA) who do not achieve catch-up growth. Prior research has shown that daily recombinant human growth hormone (rhGH) can improve growth but adherence to daily therapy is often problematic. The introduction of a long-acting formulation, such as PEG-rhGH, could potentially enhance adherence and improve outcomes in this population.
Methods
This multicenter, randomized, open-label, dose-response phase 2 study involved 96 GH treatment-naïve, non-GH-deficient, prepubertal children born SGA, aged 3 to <8 years. Participants were randomized (1:1) to receive either PEG-rhGH 0.1 mg/kg/week or 0.2 mg/kg/week for 52 weeks. After this period, 66 children continued into an extension phase with an initial dose of 0.2 mg/kg/week, which could be increased to a maximum of 0.4 mg/kg/week until near-adult height was reached.
Results
After 208 weeks, the mean ΔHT-SDS was 1.746 (0.488) for the 0.2 mg/kg/week group and 1.660 (0.710) for the 0.1 mg/kg/week group. Additionally, 90.9% of participants achieved height > -2 SDS, and 53.0% reached target height SDS. The mean annualized height velocity remained within the normal range, indicating sustained growth.
Interpretation
The observed improvements in height SDS are statistically significant, but the clinical significance may vary based on individual patient contexts. The findings align with previous literature suggesting that long-acting GH can be effective, though the open-label design and small sample size may limit the generalizability of the results. Further studies with larger cohorts and longer follow-up are needed to confirm these findings and assess long-term safety.
Key findings
- Mean ΔHT-SDS was 1.746 (0.488) in the 0.2 mg/kg/week group and 1.660 (0.710) in the 0.1 mg/kg/week group after 208 weeks.
- 90.9% (60/66) achieved height > -2 SDS.
- 53.0% (35/66) reached target height SDS.
- Mean annualized height velocity remained within the normal range.
Limitations
- Open-label design may introduce bias.
- Small sample size of 96 participants.
- Long-term effects beyond the study duration are not reported.
- Single-site and multicenter nature may affect consistency.