Efficacy, safety, and dose selection of efepoetin alfa in anemic patients on maintenance dialysis: a phase 2, randomized, multicenter, active-controlled trial

초록

Background Efepoetin alfa (GC1113, GX-E2) is a long-acting recombinant human erythropoietin fused to a hybrid fragment crystallizable (hyFc) that prolongs systemic exposure via neonatal Fc receptor-mediated recycling. This active-controlled phase 2 trial evaluated efepoetin alfa and informed phase 3 starting dose selection for chronic kidney disease-related anemia in dialysis patients. Methods In this multicenter, open-label, active-controlled trial, adults on hemodialysis (HD) or peritoneal dialysis (PD) with hemoglobin (Hb) levels <10 g/dL were randomized after erythropoiesis-stimulating agent discontinuation. Over 12 weeks, HD patients received intravenous efepoetin alfa (5 or 8 & micro;g/kg once weekly [Q1W], 8 & micro;g/kg every 2 weeks [Q2W]) or darbepoetin alfa (30 & micro;g Q1W). PD patients received subcutaneous efepoetin alfa (5 or 8 & micro;g/kg Q2W) or methoxy polyethylene glycol-epoetin beta (0.6 & micro;g/kg Q2W). The primary endpoint was the mean Hb change from baseline after 12 weeks of treatment, and an exploratory dose-conversion ratio (DCR) analysis was performed in the PD cohort to inform phase 3 dosing. Results Efepoetin alfa showed dose-dependent Hb increases. In the HD cohort, mean Hb increases were 3.19 g/dL for efepoetin alfa 5 and 8 & micro;g/kg Q1W and 2.52 g/dL for darbepoetin alfa. In the PD cohort, mean Hb increases were 2.69 g/dL and 3.48 g/dL for efepoetin alfa 5 and 8 & micro;g/kg Q2W, respectively, and 2.01 g/dL for the control group. Exploratory DCR analysis supported 4 & micro;g/kg Q2W efepoetin alfa as the phase 3 starting dose. Conclusion Efepoetin alfa demonstrated dose-dependent erythropoietic efficacy and an acceptable safety profile in dialysis patients, supporting dose-range characterization and phase 3 starting dose selection.

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