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.
Highlights
Hypothalamic–pituitary diseases and/or injury can lead to adult growth hormone deficiency (AGHD) (1)
This was a Phase 2 multi-center, randomized, openlabel, parallel group, active-controlled trial of three different doses of weekly TransCon GH compared to daily Omnitrope
In Cohort 2, each subject withdrew due to adverse events with their withdrawal occurring before Day 28; both were excluded from the PK and PD analyses, leaving 35 subjects
Summary
Hypothalamic–pituitary diseases and/or injury can lead to adult growth hormone deficiency (AGHD) (1). Recombinant human GH, known as somatropin, is produced by inserting cDNA coding for human GH into Escherichia coli. It became commercially available in the mid-1980s and is identical to endogenous GH. A significant portion of patients are poorly adherent to treatment (7), up to 65% in one study, attributed to the inconvenience and discomfort of daily injections, concerns about efficacy and treatment length beyond 2 years (8). A safe and efficacious product with less frequent dosing would be a considerable improvement over currently available daily regimens and may lead to increased adherence, with consequent positive physiological effects and better quality of life
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
