FC037: A Study to Ascertain the Optimum Starting Dose of Subcutaneous (SC) C.E.R.A. for Maintenance Treatment of Anemia in Pediatric Patients with Chronic Kidney Disease (CKD) on Dialysis or not yet on Dialysis

Abstract

Abstract BACKGROUND AND AIMS The Phase II study DOLPHIN (NH19707; NCT00717366) demonstrated that pediatric patients with chronic kidney disease (CKD) on hemodialysis can be safely and effectively switched from maintenance treatment with epoetin alfa/beta or darbepoetin alfa to intravenous continuous erythropoietin receptor activator (C.E.R.A.)—methoxy polyethylene glycol-epoetin beta, using defined conversion factors [1]. This study (NH19708; NCT03552393; SKIPPER) was conducted to ascertain the optimum starting dose of C.E.R.A. administered subcutaneously for maintenance treatment of anemia in pediatric patients with CKD on dialysis, or those not yet on dialysis, using the same conversion factors. Methods This Phase II, open-label, single-arm, multicentre study included a 3-week screening period, 16-week dose-titration period, 4-week evaluation period and 24-week optional safety extension (for patients who completed the 20 weeks of treatment with hemoglobin [Hb] within ± 1 g/dL of their baseline Hb and within the target range of 10–12 g/dL). Patients aged 3 months to 17 years with stable chronic renal anemia and a baseline Hb concentration of 10.0–12.0 g/dL were switched from epoetin alfa/beta or darbepoetin to subcutaneous (SC) C.E.R.A. every 4 weeks using the previously determined conversion factors. The primary endpoint was change in Hb concentration (g/dL) between baseline and the evaluation period. Secondary endpoints included the number of patients with a mean Hb concentration within a target range of 10.0–12.0 g/dL and/or ± 1 g/dL of baseline during the evaluation period and change in C.E.R.A. SC dose over time. Safety/tolerability and the pharmacokinetics/pharmacodynamics profile of C.E.R.A. SC were also assessed. RESULTS Forty patients were enrolled, with 38 completing the core study period and 25 entering the safety extension period. Six patients withdrew from the study, mainly due to kidney transplantation (5/6; 83.3%). The mean age of patients was 10 years; 12 (30%) aged <5 years, 11 (27.5%) aged 5–11 years and 17 (42.5%) aged 12–17 years. Eighteen patients (45.0%) were on peritoneal dialysis, 5 (12.5%) were on hemodialysis and 17 (42.5%) were not on dialysis. The mean Hb level at baseline was 11.02 g/dL (range: 10.1–12.2 g/dL). Mean change in Hb between baseline and the evaluation period was 0.48 g/dL (standard deviation: 1.03; 90% confidence interval 0.20–0.76). Results were consistent based on sub-analyses by age groups (<5, 5–11, 12–17 years), dialysis status (no dialysis, hemodialysis or peritoneal dialysis) and previous type of erythropoiesis-stimulating agent treatment. Mean Hb concentration levels were maintained within 10–12 g/dL and within ± 1 g/dL of baseline throughout the entire core period and safety extension period. During the evaluation period, 24/38 patients (63.2%) maintained Hb within 10–12 g/dL, 19 (50%) maintained Hb within 1 g/dL of baseline and 18 (47.4%) fulfilled both criteria. The median ratio of C.E.R.A. dose between Week 1 (median dose of 75 μg) and Week 17 (50 μg) was 1.44, indicating a decrease relative to the initial dose. Safety results were consistent with the known safety profile for C.E.R.A. in adults and pediatric patients aged 6–17 years on hemodialysis and IV administration of C.E.R.A [1], with no unexpected safety signals detected. CONCLUSION In this study, the primary endpoint was met and provided evidence that pediatric patients with CKD on dialysis, or those not yet on dialysis, can be safely and effectively switched from previous treatment with epoetin alfa/beta or darbepoetin to C.E.R.A. SC every 4 weeks for maintenance treatment of anemia.