title: A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency.
abstract: TransCon growth hormone is a sustained-release human growth hormone prodrug under development in which unmodified growth hormone is transiently linked to a carrier molecule. It is intended as an alternative to daily growth hormone in the treatment of growth hormone deficiency. This was a multi-center, randomized, open-label, active-controlled trial designed to compare the safety (including tolerability and immunogenicity), pharmacokinetics and pharmacodynamics of three doses of weekly TransCon GH to daily growth hormone (Omnitrope). Thirty-seven adult males and females diagnosed with adult growth hormone deficiency and stable on growth hormone replacement therapy for at least 3 months were, following a wash-out period, randomized (regardless of their pre-study dose) to one of three TransCon GH doses (0.02, 0.04 and 0.08 mg GH/kg/week) or Omnitrope 0.04 mg GH/kg/week (divided into 7 equal daily doses) for 4 weeks. Main outcomes evaluated were adverse events, immunogenicity and growth hormone and insulin-like growth factor 1 levels. TransCon GH was well tolerated; fatigue and headache were the most frequent drug-related adverse events and reported in all groups. No lipoatrophy or nodule formation was reported. No anti-growth hormone-binding antibodies were detected. TransCon GH demonstrated a linear, dose-dependent increase in growth hormone exposure without accumulation. Growth hormone maximum serum concentration and insulin-like growth factor 1 exposure were similar after TransCon GH or Omnitrope administered at comparable doses. The results suggest that long-acting TransCon GH has a profile similar to daily growth hormone but with a more convenient dosing regimen. These findings support further TransCon GH development.
authors.affiliation: Department of EndocrinologyMetabolism and Diabetology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden charlotte.hoybye@sll.se.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Höybye
authors.affiliation: Charité Universitätsmedizin BerlinCampus Benjamin Franklin, Klinik für Endokrinologie & Stoffwechselmedizin, Berlin, Germany.
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.affiliation: IRCCS AOU San Martino-ISTUniversità di Genova - Endocrinologia DiMI, Dipartimento di Medicina Interna e Specialità Mediche, & CEBR, Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ferone
authors.affiliation: Medicinsk Endokrinologist Afd.MEA, NBG, Århus Sygehus, Århus, Denmark.
authors.forename: Jens Sandahl
authors.initials: JS
authors.lastname: Christiansen
authors.affiliation: Ascendis Pharma A/SHellerup, Denmark.
authors.forename: David
authors.initials: D
authors.lastname: Gilfoyle
authors.affiliation: Ascendis Pharma A/SHellerup, Denmark.
authors.forename: Eva Dam
authors.initials: ED
authors.lastname: Christoffersen
authors.affiliation: Ascendis Pharma Inc.Palo Alto, California, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Mortensen
authors.affiliation: Ascendis Pharma Inc.Palo Alto, California, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Leff
authors.affiliation: Ascendis Pharma A/SHellerup, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Beckert
keywords: adult growth hormone deficiency; daily growth hormone; insulin-like growth factor 1; long-acting growth hormone