Long-Acting C-Terminal Peptide–Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children

Abstract Context: Daily injections are required for growth hormone (GH) replacement therapy, which may cause low compliance as a result of inconvenience and distress in patients. Objective: C-terminal peptide–modified human GH (MOD-4023) is developed for once-a-week dosing regimen in GH-deficient (GHD) adults and children. The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children. Design: A multicenter, open-label, randomized, controlled phase 2 study in children with GHD, evaluating the safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy of three different weekly MOD-4023 doses, compared with daily recombinant human GH (r-hGH). Setting: The trial was conducted in 14 endocrinology centers in Europe. Patients: Fifty-three prepubertal children with GHD completed 12 months of treatment with either MOD-4023 (N = 42) or r-hGH (N = 11). Interventions: C-terminal peptide–modified hGH (MOD-4023) was administered weekly at a dose of either 0.25, 0.48, or 0.66 mg/kg/wk and compared with daily hGH at a dose of 0.24 mg/kg/wk. Results: MOD-4023 showed an estimated half-life approximately fivefold to 10-fold longer when compared with daily r-hGH. Insulin-like growth factor (IGF)-I and IGF-binding peptide 3 showed a dose-dependent increase during MOD-4023 treatment. IGF-I standard deviation score for MOD-4023 did not exceed +2. All MOD-4023 cohorts demonstrated adequate catch-up growth. The 0.66 mg/kg/wk dose demonstrated efficacy closest to daily r-hGH. No serious adverse events were observed during MOD-4023 treatment, and its tolerability was consistent with known properties of r-hGH. Conclusions: This study confirms the long-acting properties of MOD-4023 and shows a promising safety and tolerability profile. This provides support for initiation of a phase 3 study in GHD children using a single weekly injection of MOD-4023. A phase 2 clinical study of long-acting, CTP-modified GH (MOD-4023) in GHD children using a once-weekly regimen confirms its safety profile and supports the initiation of a pivotal phase 3 study.