Denali, a phase 3B multicenter, open-label single-arm study of roxadustat: Operational learnings within us dialysis organizations

Background: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that promotes erythropoiesis and improves iron availability in patients with anemia of chronic kidney disease (CKD). This trial aims to provide practical data on roxadustat use in dialysis patients with anemia via a semi-pragmatic evaluation of introduction into providers' practices (Fresenius Medical Care). Methods: This open-label, single-arm study assesses the efficacy and safety of roxadustat in correcting/maintaining hemoglobin (Hb) in patients with CKD-related anemia receiving in-center/home dialysis at nine US sites (NCT04410198). Initial roxadustat dose is weight-based (erythropoiesis-stimulating agent [ESA]-naive patients) or guided by an ESA dose-conversion algorithm (ESA patients), in this trial targeting Hb=11±1 g/dL. Roxadustat dose is titrated every 4 weeks based on Hb level or rate of change, with 24-week treatment duration and up to 1-year extension. Efficacy is assessed by change from baseline in Hb and proportion of patients achieving mean Hb ≥10 g/dL averaged over weeks 16-24. Exploratory endpoints include time to first red blood cell transfusion, proportion of patients achieving mean Hb ≥10 g/dL in first 8 weeks, intravenous iron use, and dosing adherence. Safety endpoints include treatment-emergent adverse events (AE), with COVID-19 positivity an AE of special interest. Results: This ongoing trial was successfully initiated and enrolled (n=203) during the COVID-19 pandemic, with modifications for home dialysis. Baseline characteristics appear representative of the US dialysis population (Table). Conclusions: This trial adds to phase 3 studies of roxadustat by evaluating its use in treating anemia of CKD in home/in-center dialysis patients during the COVID-19 pandemic, while providing a view into operationalization and ease of real-world use. Full study results will be presented. (Table Presented) .