Abstract: PO0487
ASCEND-TD: A Randomized, Double-Blind, Active-Controlled Study of Daprodustat Administered Three Times Weekly in Hemodialysis Patients
Session Information
- Anemia: Therapies and Iron Metabolism
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Coyne, Daniel W., Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri, United States
- Singh, Ajay K., Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
- Lopes, Renato D., Duke Clinical Research Institute, Duke Health, Durham, North Carolina, United States
- Bailey, Christine K., GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Dimino, Tara L., GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Huang, Chun, GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Connaire, Jeffrey J., Davita Clinical Research, Minneapolis, Minnesota, United States
- Rastogi, Anjay, Division of Nephrology, Department of Medicine, UCLA, Los Angeles, California, United States
- Kim, Sung gyun, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea (the Republic of)
- Orias, Marcelo, Sanatorio Allende, Córdoba, Argentina
- Shah, Sapna, King’s College Hospital NHS Trust, London, United Kingdom
- Patel, Vickas, GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Cobitz, Alexander Ralph, GlaxoSmithKline, Collegeville, Pennsylvania, United States
- Wanner, Christoph, University of Würzburg, Würzburg, Germany
Background
Daprodustat (dapro) is a hypoxia-inducible factor prolyl hydroxylase inhibitor being investigated for the treatment of anemia of chronic kidney disease (CKD). This study evaluated the efficacy and safety of dapro administered three-times-weekly (TIW) vs recombinant human erythropoietin (rhEPO) for in-center prevalent hemodialysis (HD) patients.
Methods
This double-blind study (NCT03400033) randomized (2:1) HD patients with a baseline hemoglobin (Hb) of 8–11.5 g/dL already on rhEPO to dapro TIW (n=270) or rhEPO (n=137) for 52 weeks. A dosing algorithm aimed to maintain Hb between 10–11g/dL. The primary endpoint was a mean change in Hb in the evaluation period (EP; Weeks 28–52). The principal secondary endpoint was average monthly intravenous (IV) iron dose. Other secondary endpoints included blood pressure (BP) and Hb variability.
Results
Baseline characteristics in 407 randomized patients were balanced between the dapro and rhEPO groups. Dapro TIW was non-inferior to rhEPO for mean change in Hb (model-adjusted mean treatment difference [dapro-rhEPO] -0.05; 95% CI: -0.21, 0.10). In the EP, mean (SD) Hb was 10.45 (0.549) g/dL and 10.51 (0.849) g/dL for dapro and rhEPO groups, respectively. However, 80.0% in the dapro group were responders (mean Hb during EP in the analysis range [10–11.5 g/dL]) vs 63.6% in the rhEPO group, with a difference of 16.5% (one-sided nominal p=0.0007 after adjustment for region). Mean monthly IV iron dose was not statistically significantly lower with dapro vs rhEPO. While fewer BP elevations occurred with dapro vs rhEPO (one-sided nominal p=0.0093), the overall effect of dapro on BP was similar to rhEPO. In general, safety findings were comparable between treatment groups, with the incidence of treatment-emergent adverse events similar between dapro (75%) and rhEPO (79%).
Conclusion
Dapro was non-inferior to rhEPO in Hb response and was well-tolerated. Dapro administered TIW using the protocol employed in this study is a viable alternative to rhEPO in prevalent HD patients with anemia of CKD.
Funding
- Commercial Support –