Background: GH administration restores normal growth in children with GH deficiency (GHD). However, current daily s.c. injection treatment regimens may be inconvenient leading to impaired adherence and subsequently suboptimal treatment outcomes. NNC0195-0092 is a novel, reversible albumin-binding GH developed for once-weekly administration.
Objective and hypotheses: This was a randomised, open-label, active-controlled, dose-escalation trial (NCT01973244) investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single dose of NNC0195-0092 compared with once-daily GH for 7 days.
Method: Four cohorts of eight prepubertal children (≥6 and <13 years) with GHD on GH therapy (≥3 months) were investigated (n=32). Within each cohort, children were randomised to receive either a single s.c. dose of NNC0195-0092 (0.02, 0.04, 0.08, or 0.16 mg/kg; n=6) or once-daily GH for 7 days (0.03 mg/kg; n=2). Each child was allocated to one dose level only. Current GH therapy was discontinued 710 days before randomisation. At each dose-level, the pharmacokinetics and pharmacodynamics (IGF1 and IGFBP3) were evaluated.
Results: All doses of NNC0195-0092 were well tolerated, with no safety or local tolerability issues identified. Dose-dependent increases in IGF1 and IGFBP3 were observed for AUC(0168 h) and Cmax after adjustment for baseline. IGF1 responses following 0.04 and 0.08 mg/kg NNC0195-0092 and daily GH were similar. Mean changes in IGF1 and IGFBP3 were within reference ranges, except for a peak in IGF1 SDS in the 0.08 mg/kg NNC0195-0092 dose-group that was slightly above the reference range (days 13).
Conclusion: All doses of NNC0195-0092 were well tolerated in children with GHD with no clinically relevant short-term safety or local tolerability issues observed. A dose-dependent IGF1 response, similar to the IGF1 response observed after daily GH, was found. The present data indicate that NNC0195-0092 may potentially serve as a well-tolerated once-weekly treatment for children with GHD.
Declaration of interest: N Zuckerman-Levin and Z Gucev, consultants (Novo Nordisk and Spring). M H Rasmussen and M B Olsen, employees Novo Nordisk. L Sävendahl, consultant (Ferring, Novo Nordisk, Merck Serono, Pfizer, and Sandoz); grants (Merck Serono, Novo Nordisk, and Pfizer). T Battelino, board member (Novo Nordisk, Sanofi, and Eli Lilly). Consultation fees from Ferring, Novo Nordisk, and Pfizer.
Funding: This study was sponsored by Novo Nordisk A/S, Denmark. Dr J de Schepper.
01 Oct 2015 - 03 Oct 2015