Reversible albumin-binding GH possesses a potential once-weekly treatment profile in adult growth hormone deficiency

CONTEXT: NNC0195-0092 is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration.

OBJECTIVES: Evaluate safety, local tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of multiple once-weekly doses of NNC0195-0092, compared with daily GH.

DESIGN AND SETTING: Phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial.

PATIENTS: Thirty-four GH-treated adult subjects (male, n=25) with GH deficiency (GHD).

INTERVENTIONS AND MAIN OUTCOME MEASURES: Subjects were sequentially assigned into four cohorts of eight subjects, randomized within each cohort (3:1) to once-weekly NNC0195-0092 (n=6) for 4 weeks (0.02, 0.04, 0.08, and 0.12 mg/kg) or daily injections of Norditropin NordiFlex(®) (n=2) for 4 weeks with a dose replicating the pre-trial dose of somatropin. A safety assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before trial start. Blood samples were drawn for assessment of safety, PK, PD (IGF-I and IGFBP-3) profiles, and immunogenicity studies.

RESULTS: Numbers of adverse events (AEs) were similar at the 0.02, 0.04, and 0.08 mg/kg NNC0195-0092 dose levels versus daily injections of Norditropin NordiFlex(®), whereas the number of AEs was greater at the highest dose level of NNC0195-0092 (0.12 mg/kg). NNC0195-0092 (AUC(0-168h)) and Cmax) increased in a dose-dependent manner, and a dose-dependent increase in IGF-I levels was observed. IGF-I profiles were elevated for at least one week, and for the 0.02 mg/kg and 0.04 mg/kg NNC0195-0092 doses, the observed IGF-I levels were similar to the levels for the active control group.

CONCLUSION: Four once-weekly doses of NNC0195-0092 (dose range 0.02-0.12 mg/kg) administered to adult patients with GHD were well tolerated and IGF-I profiles were consistent with a once-weekly treatment profile. No clinically significant safety and tolerability signals causally related to NNC0195-0092 were identified, nor were any immunogenicity concerns revealed.