Objective: Growth hormone (GH) replacement therapy currently requires daily injections. This may cause poor compliance, inconvenience and distress for patients. CTP-modified human GH (MOD-4023) has been developed for once-weekly administration in growth hormone-deficient (GHD) adults and children. In the present Phase 2 study, the safety and tolerability of once-weekly subcutaneous (SC) administration of MOD-4023 were evaluated in GHD children.
Design and methods: Randomized, controlled Phase 2 study conducted in 53 pre-pubertal GHD children receiving SC injections of one of three MOD-4023 doses once-weekly (0.25, 0.48, and 0.66 mg/kg/week) or daily hGH (34 μg/kg/day) as control arm for 12 months. Safety assessments included monitoring of adverse events, injection site reactions, vital signs and physical condition, as well as laboratory assessments, such as glucose and lipid metabolism, blood biochemistry and immunogenicity.
Results: The analysis included safety data for all 53 patients that completed 12 months of treatment with either MOD-4023 (n=42 patients) or hGH (n=11). No severe adverse events (AEs) were reported during treatment with MOD-4023. Twenty-eight patients (66.7%) reported 101 AEs during treatment with MOD-4023. This rate was similar to that observed for the daily arm, in which 8 patients (72.7%) reported a total of 30 AEs. No evidence was found of injection site-related AEs such as local discomfort, swelling, erythema or lipoatrophy. Laboratory assessments supported the tolerability of MOD-4023 treatment, and no significant overall changes were observed in glucose levels, insulin, HbA1c, or vital signs. No anti-CTP Abs were detected and no neutralizing activity was observed.
Conclusions: MOD-4023 demonstrated an excellent safety and tolerability profile during treatment for up to 12 months using a dose ranging from 0.25 to 0.66 mg/kg/week, with no unexpected AEs considered to be related to MOD-4023. These results support the continued clinical development of once-weekly MOD-4023 for the treatment of children suffering from GHD.