ESPE Abstracts (2016) 86 RFC8.7

Safety and Tolerability of Once-Weekly Administration of CTP-Modified Human Growth Hormone (MOD-4023): 24-month Complete Dataset Results of a Phase 2 Study in Children with Growth Hormone Deficiency

Nataliya Zelinskaa, Julia Skorodokb, Oleg Malievskyc, Ron G. Rosenfeldd, Zvi Zadike, Ronit Korenf, Shelly Vanderf, Gili Hartf & Klaudziya Radziukg

aUkrainian Children Specialized Clinical Hospital, Kyev, Ukraine; bSt. Petersburg State Pediatric Medical Academy, St. Petersburg, Russia; cBashkir State Medical University, Ufa, Russia; dOregon Health & Science University, Oregon, USA; eKaplan Medical Center, Rehovot, Israel; fOPKO Biologics, Nes Ziona, Israel; g2nd Children City Clinic, Minsk, Belarus

Background: Daily injections are currently required for growth hormone (GH) replacement therapy, which may cause poor compliance, inconvenience and distress for patients. MOD-4023 is a CTP-modified human GH (hGH) developed for once-weekly administration in growth hormone deficient (GHD) adults and children.

Objective and hypotheses: In the present Phase 2 study, the safety and tolerability of once-weekly subcutaneous (SC) administration of MOD-4023 were assessed in children with GHD over a period of 24 months.

Method: A randomized, controlled Phase 2 study was conducted in prepubertal GHD children receiving SC injections of one of three MOD-4023 doses in a once-weekly regimen (0.25, 0.48, and 0.66 mg/kg per week), or daily hGH (34 μg/kg per day) as control for 24 months. Safety assessments included monitoring of adverse events (AEs), injection site reactions, vital signs and physical condition. Laboratory assessments were also performed and included glucose and lipid metabolism, blood biochemistry, and immunogenicity.

Results: No severe AEs were reported during MOD-4023 treatment. A similar rate of adverse events was reported by patients treated with MOD-4023 and by patient in the daily arm. No injection site-related reactions such as local discomfort, swelling, erythema or lipoatrophy were observed. Laboratory findings supported the tolerability of MOD-4023 treatment, and no significant overall changes were observed in glucose levels, insulin, HbA1c, or vital signs.

Conclusion: MOD-4023 demonstrated excellent safety and tolerability during treatment for up to 24 months in a dose range of 0.25–0.66 mg/kg per week. No unexpected AEs were considered as MOD-4023-related. This supports the ongoing clinical development of MOD-4023 for once-weekly treatment of GHD children. Based on the above, a pivotal Phase 3 study will be initiated shortly at a dose of 0.66 mg/kg per week, and patients receiving the lower MOD-4023 doses will be switched to 0.66 mg/kg per week for long-term assessment.