Endocrine Abstracts

Objective: GH replacement therapy currently requires daily injections, which may cause poor compliance and distress for patients. CTP-modified hGH (MOD-4023) is being developed for once-weekly administration in GH Deficient adults and children. The present study evaluated the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of MOD-4023 in GHD adults.

Design and methods: 39 normalized GHDA patients currently treated with daily GH were randomized and switched to 3 dose levels of once-weekly MOD-4023 (30%, 45% or 100% of each patient’s cumulative weekly hGH dose) to evaluate safety and PK/PD profile. The study was comprised of two stages. Stage I included an optimization period and 4 weeks of once-weekly subcutaneously administered MOD-4023. Stage II is an optional 16 week extension period of once weekly MOD-4023 administration to collect further safety information and confirm the results obtained in Stage I. Here we present the results of Stage I.

Results: MOD-4023 was well-tolerated and a dose dependent response of IGF1 concentration was demonstrated. In most patients, IGF1 levels were maintained within ±2 SDS during the 4 weeks, without exceeding +2 SDS at peak levels. In two cohorts (45% and 100%) the mean IGF1 values were comparable to those obtained with daily hGH at steady state. The adverse effects reported were consistent with known hGH related side-effects, and were mostly mild. MOD-4023 was not immunogenic.

Conclusions: Once-weekly, repeated doses of long-acting MOD-4023 were safe and well tolerated in adult GHD patients. IGF1 levels were maintained within the normal range in most MOD-4023 treated patients for the entire 4 weeks of treatment.

Based on the positive results of Stage I, an estimated target dose range for a Phase III study has been established and the 16-week extension study was initiated to further confirm the estimated dose range and to provide additional safety information.

Declaration of interest: The authors declare that there is a conflict of interest.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.