A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency

Endocrine Connections

Michael Beckert¹  David Gilfoyle¹  Eva Dam Christoffersen¹  Jonathan A Leff²  Eva Mortensen²  Andreas F H Pfeiffer³  Charlotte Höybye⁴  Diego Ferone⁵  Jens Sandahl Christiansen⁶ 

[1] Ascendis Pharma A/S, Hellerup, Denmark;Ascendis Pharma Inc., Palo Alto, California, USA;Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Endokrinologie & Stoffwechselmedizin, Berlin, Germany;Department of Endocrinology, Metabolism and Diabetology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden;IRCCS AOU San Martino-IST, Università di Genova – Endocrinologia DiMI, Dipartimento di Medicina Interna e Specialità Mediche, & CEBR, Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy;Medicinsk Endokrinologist Afd., MEA, NBG, Århus Sygehus, Århus, Denmark;

关键词: daily growth hormone;    adult growth hormone deficiency;    long-acting growth hormone;    insulin-like growth factor 1;   

DOI  :  10.1530/EC-17-0007

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown