Wayne V Moore1, Huong Jil Nguyen1, Gad B Kletter1, Bradley S Miller1, Douglas Rogers1, David Ng1, Jerome A Moore1, Eric Humphriss1, Jeffrey L Cleland1, George M Bright1. 1. Department of Endocrinology and Diabetes (W.V.M.), University of Missouri-Kansas City School of Medicine, Kansas City, Missouri 64111; Sierra Medical Research (H.J.N.), Clovis, California 93612; Mary Bridge Children's Hospital (G.B.K.), Tacoma, Washington 98405; Department of Pediatrics (B.S.M.), University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota 55454; Center for Pediatric Endocrinology (D.R.), Cleveland Clinic, Cleveland, Ohio 44195; ResearchPoint Global, Inc (D.N.), Austin, Texas 78735; Pacific BioDevelopment (J.A.M.), Emeryville, California 94608; and Versartis, Inc (E.H., J.L.C., G.M.B.), Menlo Park, California 94025.
Abstract
CONTEXT: Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD). OBJECTIVES: 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. DESIGN: Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens. SETTING:Twenty-five United States pediatric endocrinology centers. PATIENTS: Naive-to-treatment, prepubertal children with GHD (n = 68). INTERVENTION(S): 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. MAIN OUTCOME MEASURES: Safety, pharmacokinetics, pharmacodynamics, 6-month height velocity (HV). RESULTS: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. CONCLUSIONS: 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.
RCT Entities:
CONTEXT: Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD). OBJECTIVES: 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. DESIGN: Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens. SETTING: Twenty-five United States pediatric endocrinology centers. PATIENTS: Naive-to-treatment, prepubertal children with GHD (n = 68). INTERVENTION(S): 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. MAIN OUTCOME MEASURES: Safety, pharmacokinetics, pharmacodynamics, 6-month height velocity (HV). RESULTS: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. CONCLUSIONS: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.
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