Dataset Information

A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency.

ABSTRACT: Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD).To determine the optimal somavaratan dose regimen to normalize IGF-1 in pediatric GHD and to evaluate safety and efficacy of somavaratan over 6 months.Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens.Twenty-five United States pediatric endocrinology centers.Naive-to-treatment, prepubertal children with GHD (n = 68).Patients received single sc doses of somavaratan (0.8, 1.2, 1.8, 2.7, 4.0, or 6.0 mg/kg) during the 30-day dose-finding phase, then were randomized to somavaratan 1.15 mg/kg weekly, 2.5 mg/kg twice monthly, or 5.0 mg/kg monthly for 6 months.Safety, pharmacokinetics, pharmacodynamics, 6-month height velocity (HV).Somavaratan pharmacokinetics was linearly proportional to dose; dose-dependent increases in the magnitude and duration of IGF-1 responses enabled weekly, twice-monthly or monthly dosing. A single dose of somavaratan sustained IGF-1 responses for up to 1 month. No somavaratan or IGF-1 accumulation occurred with repeat dosing. Mean annualized HVs for somavaratan administered monthly, twice monthly, or weekly (7.86 ± 2.5, 8.61 ± 2.7, and 7.58 ± 2.5 cm/y, respectively) were similar between groups. Adverse events were mostly mild and transient.Somavaratan demonstrated clinically meaningful improvements in HV and IGF-1 in prepubertal children with GHD, with no significant differences between monthly, twice-monthly, or weekly dosing.

SUBMITTER: Moore WV

PROVIDER: S-EPMC4803167 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency.

Moore Wayne V WV Nguyen Huong Jil HJ Kletter Gad B GB Miller Bradley S BS Rogers Douglas D Ng David D Moore Jerome A JA Humphriss Eric E Cleland Jeffrey L JL Bright George M GM

The Journal of clinical endocrinology and metabolism 20151216 3

<h4>Context</h4>Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD).<h4>Objectives</h4>To determine the optimal somavaratan dose regimen to normalize IGF-1 in pediatric GHD and to evaluate safety and efficacy of somavaratan over 6 months.<h4>Design</h4>Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens.<h4>Setting</h4>Twenty-five United States pediat ...[more]

PMID: 26672637

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Project description:Abstract TransCon Growth Hormone in the Treatment of Pediatric Growth Hormone Deficiency: Results of the Phase 3 heiGHt TrialBackground TransCon Growth Hormone is a sustained-release recombinant human growth hormone (hGH; somatropin) prodrug in development as a long-acting GH (LAGH) for children with growth hormone deficiency (GHD). In its prodrug form, TransCon hGH is inactive with hGH transiently bound to a TransCon carrier via a TransCon linker. Upon injection and triggered by physiological pH and temperature, unmodified recombinant hGH is sustainably released and thus designed to maintain the same mode-of-action and distribution as daily hGH replacement therapy but with once-weekly dosing. In a 6-month phase 2 trial of TransCon hGH vs. a daily hGH in children with GHD, mean annualized height velocity (AHV) for TransCon hGH was 12.9 cm/y compared to 11.6 cm/y for a daily hGH at an equivalent hGH dose (0.21 mg/kg/wk). The subsequent pivotal phase 3 global heiGHt Trial (ClinicalTrials.gov: NCT02781727) was designed to investigate the safety, tolerability, and efficacy of weekly TransCon hGH versus daily hGH over 52 weeks in treatment-naive prepubertal children with GHD. Methods Subjects were randomized in a 2:1 ratio and received either once-weekly TransCon hGH 0.24 mg hGH/kg/wk or dose-equivalent once-daily Genotropin over 52 weeks. Key baseline demographics variables included age, gender, height standard deviation score (SDS), IGF-1 SDS, peak stimulated GH, and bone age delay. Study endpoints included AHV, IGF-1 response, immunogenicity, and safety. Results At baseline, the mean age of study participants, of whom 82% were male, was 8.5 years. Mean height SDS was -2.93, and mean IGF-1 SDS was -2.04. Mean peak stimulated GH was 5.77 µg/L, and mean bone delay was 2.63 years. The final sample size (n=161) was larger than planned (n=150) which strengthens the study power for noninferiority. Top-line results, including AHV, change in height SDS, serum IGF-1 levels, change in bone age, and adverse events, will be available for presentation at ENDO 2019. Conclusion Only LAGHs based on unmodified hGH have obtained approval in Europe or the United States. By February 2019, all subjects will have completed their participation in this pivotal trial of a LAGH designed to release unmodified hGH, with top-line analyses available in March. The heiGHt Trial was well-powered to demonstrate noninferiority between TransCon hGH and a daily hGH, with baseline demographic variables in the range of recent GH trials.

Dataset Information

A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency.

Publications

A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency.

Similar Datasets

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