title: A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency.
abstract: TransCon Growth Hormone (GH) (Ascendis Pharma) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency (GHD).
  
  
  
  To compare the pharmacokinetics, pharmacodynamics, safety, and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD.
  
  
  
  Randomized, open-label, active-controlled study of three doses of weekly TransCon GH versus daily Genotropin (Pfizer).
  
  
  
  Thirty-eight centers in 14 European countries and Egypt.
  
  
  
  Prepubertal male and female treatment-naïve children with GHD (n = 53).
  
  
  
  Subjects received one of three TransCon GH doses (0.14, 0.21, or 0.30 mg GH/kg/wk) or Genotropin 0.03 mg GH/kg/d for 26 weeks.
  
  
  
  GH and insulinlike growth factor-1 (IGF-1) levels, growth, adverse events, and immunogenicity.
  
  
  
  Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses. A dose response was observed, with IGF-1 standard deviation scores increasing into the normal range for all three TransCon GH doses. Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm, which was not statistically different from 11.6 cm for Genotropin. Adverse events were mild to moderate, and most were unrelated to the study drug. Injection site tolerance was good. One TransCon GH subject developed a low-titer, nonneutralizing antibody response to GH.
  
  
  
  The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH (pharmacokinetics) and IGF-1 (pharmacodynamics) levels, safety, and efficacy and support advancement into phase 3 development.
authors.affiliation: Collège of Paediatrics, Université Claude Bernard Lyon 1, 69230 Saint-Genis-Laval, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chatelain
authors.affiliation: Department of Pediatrics, Bashkir State Medical University, Ufa, 450000, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Malievskiy
authors.affiliation: Department of Psychophysiology, Belarusian Institute of Law, 220004 Minsk, Belarus.|Department of Endocrinology, Second City Children Clinical Hospital, 220090 Minsk, Belarus.
authors.forename: Klaudziya
authors.initials: K
authors.lastname: Radziuk
authors.affiliation: Pediatrics 1 and Neonatology, Kharkiv National Medical University, Kharkiv, 61093, Ukraine.
authors.forename: Ganna
authors.initials: G
authors.lastname: Senatorova
authors.affiliation: Endocrinology Department, El Shatby University Hospital, 21526 Alexandria, Egypt.
authors.forename: Magdy O
authors.initials: MO
authors.lastname: Abdou
authors.affiliation: Endocrinology Department, Children's Hospital P. A. Kyriakou, 11527 Athens, Greece.
authors.forename: Elpis
authors.initials: E
authors.lastname: Vlachopapadopoulou
authors.affiliation: Pediatrics and Endocrinology, St. Petersburg State Pediatric Medical University, St. Petersburg, 194100, Russia.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Skorodok
authors.affiliation: Endocrinology Centre of Science, Federal Official Body of RosMedTechnology, Institute of Children's Endocrinology, Moscow, 117036, Russia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Peterkova
authors.affiliation: Ascendis Pharma, Palo Alto, California 94301.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Leff
authors.affiliation: Ascendis Pharma, 2900 Hellerup, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Beckert
mesh_terms: D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage*
chemical_list: D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I