ESPE Abstracts (2014) 82 FCLB1

Top Line Results of Once-Weekly, CTP-Modified Human GH (MOD-4023): Phase 2 Dose Finding Study in Children with GH Deficiency

Zvi Zadika, Ron Rosenfeldb, Klaudziya Radziukd, Nataliya Zelinskae, Oleg Malievskyf, Violeta Iotovac, Julia Skorodokf, Ronit Korenb, Leanne Amitzib, Gili Hartb, Oren Herskovitzb & Eyal Fimab

aKaplan Medical Center, Rehovot, Israel; bOPKO BIOLOGICS, Nes Ziona, Israel; cUMHAT ‘Sv. Marina’, Varna, Bulgaria; d2nd Children City Clinic, Minsk, Belarus; eUkrainian Children Specialized Clinical, Kyev, Ukraine; fSt Petersburg State Pediatric Medical Academy, St Petersburg, Russia; gBashkir State Medical Universit, Ufa, Russia

Objective: GH replacement therapy currently requires daily injections, which may cause poor compliance, inconvenience and distress for patients. CTP-modified hGH (MOD-4023) has been developed for once-weekly administration in GH deficient (GHD) adults and children. Pharmacokinetics (PK), pharmacodynamics, (PD) efficacy and safety analysis of weekly treatment with MOD-4023 in GHD naïve children was performed and compared to daily hGH.

Design and methods: A randomized, controlled Phase 2 study was conducted in up to 56 pre-pubertal, naïve GHD children receiving S.C. injections of one of MOD-4023 doses as a once-weekly regimen (range: 0.25–0.66 mg/kg per week) or daily hGH (34 μg/kg per day) as a control arm. MOD-4023 and IGF1 levels were monitored throughout the study. Annualized Height Velocity (HV) assessment was evaluated at 6, 9 and 12 months.

Results: The baseline characteristics were comparable between all groups. PK/PD profile following administration of MOD-4023 demonstrated a significantly extended half-life as reflected by a 12- and 50-fold increase in T1/2 and AUC respectively. A dose dependent PK/PD (IGF1) response was observed between MOD-4023 dose cohorts, reaching steady state with no accumulation or excessive levels. All cohorts demonstrated expected ‘catch-up’ growth, in line with reported age- and GHD severity-matched data. All cohorts demonstrated 6 m annualized HV above 12 cm/year, correlated with the PK/PD profile in those patients. No unexpected adverse events were observed.

Conclusions: This is the first report describing PK, PD, efficacy and safety results of extended treatment with MOD-4023 in pediatric patients with GHD. MOD-4023 administration to GHD children further confirmed its long acting properties. This study further affirmed that a single weekly injection of MOD-4023 has the potential to replace seven consecutive daily injections of currently marketed hGH in pediatric GHD patients and provided data for dose selection for the company’s upcoming Phase 3 trial.