Summary
Objective
To evaluate the safety, local tolerability, pharmacodynamics and pharmacokinetics of escalating single doses of once-weekly somapacitan, a reversible, albumin-binding GH derivative, versus once-daily GH in children with GH deficiency (GHD).
Design
Phase 1, randomized, open-label, active-controlled, dose-escalation trial (NCT01973244).
Patients: Thirty-two pre-pubertal GH-treated children with GHD were sequentially randomized 3:1 within each of four cohorts to a single dose of somapacitan (0.02, 0.04, 0.08 and 0.16 mg/kg) (n = 6 each), or once-daily Norditropin® SimpleXx® (0.03 mg/kg) (n = 2 each) for 7 days.
Measurements
Pharmacokinetic and pharmacodynamic profiles were assessed.
Results
Adverse events were all mild and there were no apparent treatment-dependent patterns in type or frequency. Four mild transient injection site reactions were reported in three of 24 children treated with somapacitan. No anti-somapacitan/anti-human growth hormone (hGH) antibodies were detected. Mean serum concentrations of somapacitan increased in a dose-dependent but non-linear manner: maximum concentration ranged from 21.8 ng/mL (0.02 mg/kg dose) to 458.4 ng/mL (0.16 mg/kg dose). IGF-I and IGFBP-3, and change from baseline in IGF-I standard deviation score (SDS) and IGFBP-3 SDS, increased dose-dependently; greatest changes in SDS values were seen for 0.16 mg/kg. IGF-I SDS values were between –2 and +2 SDS, except for peak IGF-I SDS with 0.08 mg/kg somapacitan. Post-dosing, IGF-I SDS remained above baseline levels for at least 1 week.
Conclusions
Single doses of once-weekly somapacitan (0.02–0.16 mg/kg) were well tolerated in children with GHD, with IGF-I profiles supporting a once-weekly treatment profile. No clinically significant safety/tolerability signals or immunogenicity concerns were identified.
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