학술논문
Weekly Lonapegsomatropin in Treatment-Naive Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Thornton, Paul S.; Maniatis, Aristides K.; Aghajanova, Elena; Chertok, Elena; Vlachopapadopoulou, Elpis; Lin, Zhengning; Song, Wenjie; Christoffersen, Eva Dam; Breinholt, Vibeke Miller; Kovalenko, Tatiana; Giorgadze, Elene; Korpal-Szczyrska, Maria; Hofman, Paul L.; Karpf, David B.; Shu, Aimee D.; Beckert, Michael
Source
Journal of Clinical Endocrinology & Metabolism. November 2021, Vol. 106 Issue 11, p3184, 12 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Growth hormone (GH) promotes growth, maintenance of normal body composition, and overall endocrine health. GH exerts its effects both by directly binding to specific cell surface receptors and indirectly via [...]
Context: For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD. Objective: The objective of this study was to evaluate the efficacy and safety of onceweekly lonapegsomatropin vs daily somatropin. Design: The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3trial(NCT02781727). Setting: This trial took place at 73 sites across 15 countries. Patients: This trial enrolled and dosed 161 treatment-naive, prepubertal patients with GHD. Interventions: Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily. Main Outcome Measure: The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS). Results: Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P - 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P - 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups. Conclusions: The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naive children with GHD.
Context: For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD. Objective: The objective of this study was to evaluate the efficacy and safety of onceweekly lonapegsomatropin vs daily somatropin. Design: The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3trial(NCT02781727). Setting: This trial took place at 73 sites across 15 countries. Patients: This trial enrolled and dosed 161 treatment-naive, prepubertal patients with GHD. Interventions: Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily. Main Outcome Measure: The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS). Results: Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P - 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P - 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups. Conclusions: The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naive children with GHD.