ESPE Abstracts (2015) 84 FC7.5

ESPE2015 Free Communications Growth-promoting therapies (6 abstracts)

12-Month Safety and Efficacy of a Weekly Long-Acting GH (MOD-4023) Compared to Daily Recombinant Human GH Therapy in Pre-Pubertal GH-Deficient Children; Phase 2 Study: Study CP-4-004 Summary

Zvi Zadik b , Ron Rosenfeld c , Klaudziya Radziuk d , Nataliya Zelinska e , Oleg Malievsky f , Violeta Iotova g , Julia Skorodok h , Ronit Koren a , Leanne Amitzi a , Oren Hershkovitz a & Gili Hart a


aOpko Biologics Ltd, Nes Ziona, Israel; bKaplan Medical Center, Rehovot, Israel; cDepartment of Pediatrics, OHSU, Portland, Oregon, USA; d2nd Children City Clinic, Department of Endocrinology, Minsk, Belarus; eEndocrinology Department, Ukrainian Children Specialized Clinical Hospital, Kyev, Ukraine; fDepartment of Pediatrics, Bashkir State Medical University, Ufa, Russia; gUMHAT, Sv. Marina’ Multiprofile Specialised Pediatrics Clinic, Varna, Bulgaria; hPediatrics and Endocrinology, St Petersburg State Pediadric Medical Academy, St Petersburg, Russia

Objective and hypotheses: To compare the PK/PD, safety, efficacy, and tolerability of three doses of once-weekly MOD-4023 to that of a daily recombinant human GH (rhGH) formulation in pre-pubertal children with growth failure due to GH deficiency (GHD).

Method: The randomised, controlled phase 2 study was conducted in 53 pre-pubertal, hGH-naïve GHD children randomised to receive one of three MOD-4023 doses as a once-weekly s.c. injection (0.25, 0.48, and 0.66 mg/kg per week) or daily rhGH (34 μg/kg per day) as a control arm. Annual height velocity (HV) was evaluated at 12 months, accompanied by assessment of safety, including metabolic profiles.

Results: Last subject, last visit is anticipated in June 2015. Data on 49/52 subjects who completed 12 months treatment indicated that baseline demographic and auxological characteristics were comparable among all groups. Twelve months PK/PD profile following administration of MOD-4023 in these subjects demonstrated a significantly extended half-life compared to daily rhGH. A dose-dependent PK/PD (IGF1) response was observed among MOD-4023 dose cohorts, reaching steady state with no accumulation or excessive levels by 10 weeks. All cohorts demonstrated expected ‘catch-up’ growth, with subjects on the two highest doses of MOD-4023, demonstrating HV comparable to those in the hGH arm and ranging from 10 to 12 cm/year. Sub-analysis of HV response based on baseline characteristics confirmed a comparable response in all sub-populations. The 12-month safety analysis indicates a safety profile comparable to daily rhGH, while IGF1 and metabolic parameters remained within the normal range.

Conclusion: Available data on the PK/PD, efficacy, and safety analysis of MOD-4023 administration to GHD children confirmed its long acting properties and affirmed that a single weekly injection of MOD-4023 has the potential to replace seven consecutive daily injections of rhGH in pediatric GHD patients. Further, final study data, anticipated in June 2015, will provide the basis for dose selection for phase 3.

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