Long-acting pegylated human GH in children with GH deficiency: a single-dose, dose-escalation trial investigating safety, tolerability, pharmacokinetics and pharmacodynamics

Objective: GH replacement therapy currently requires daily injections, which may be inconvenient and distressing for young patients. This study determined the safety, tolerability, pharmacokinetics and pharmacodynamics of escalating single doses of a pegylated GH (NNC126-0083) developed for once-weekly administration, in children with GH deficiency (GHD). Design and methods: Thirty children (age >= 6 and <= 12 years, weight >= 16 kg) were randomised to NNC126-0083 or daily GH treatment. The subjects discontinued their daily GH treatment 7-9 days before receiving NNC126-0083 at 0.01, 0.02, 0.04 or 0.06 mg protein/kg (n = 22) or seven once-daily doses of GH at 0.035 mg protein/kg (n = 8). Results: NNC126-0083 was well tolerated, and no short-term safety or local tolerability issues were identified. After NNC126-0083 treatment, dose-dependent IGF1 increases were evident for maximum concentration (C-max), but not area under the curve (AUC(0-168 h)). Mean values for IGF1 AUC(0-168h)/168 h and C-max were higher for GH than for NNC126-0083, although the difference was not statistically significant for cohort's 0.06 mg protein/kg. At 0.06 mg protein/kg, the resulting IGF1 response began subsiding at similar to 3 days post-dose. Conclusion: Single doses of long-acting NNC126-0083 were safe and well tolerated in children with GHD. Increased IGF1 levels were observed in all NNC126-0083 dose groups; however, a satisfactory once-weekly IGF1 profile was not reached within the NNC126-0083 dose levels administered.