title: A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency.
abstract: BACKGROUND
  Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD).
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens.
  
  
  METHODS
  Twenty-five United States pediatric endocrinology centers.
  
  
  METHODS
  Naive-to-treatment, prepubertal children with GHD (n = 68).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Wayne V
authors.initials: WV
authors.lastname: Moore
authors.affiliation: 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.
authors.forename: Huong Jil
authors.initials: HJ
authors.lastname: Nguyen
authors.affiliation: 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.
authors.forename: Gad B
authors.initials: GB
authors.lastname: Kletter
authors.affiliation: 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.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: Douglas
authors.initials: D
authors.lastname: Rogers
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Ng
authors.affiliation: 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.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Moore
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Humphriss
authors.affiliation: 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.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Cleland
authors.affiliation: 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.
authors.forename: George M
authors.initials: GM
authors.lastname: Bright
mesh_terms: D001827:Body Height; D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency* / Q000493:pharmacokinetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D011627:Puberty; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I