Effects of Daprodustat on Hemoglobin and Quality of Life in Patients with CKD: Results of the ASCEND-NHQ Randomized, Double-Blind, Placebo-Controlled Trial

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Background: Daprodustat (dapro) is a hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treating anemia of chronic kidney disease (CKD). In a Phase 3 trial in non-dialysis dependent (ND) CKD patients, we evaluated the effect of dapro vs placebo (PBO) on hemoglobin (Hb) and the SF-36 quality of life Vitality score (fatigue) over 28 weeks. Methods: Adults with CKD stage 3-5, Hb 8.5-10.0 g/dL, transferrin saturation ≥15%, ferritin ≥50 ng/ml without recent rhEPO use were randomized 1:1 to dapro or PBO to maintain Hb 11-12 g/dL (NCT03409107). Primary endpoint was mean change in Hb between baseline (BL) and the evaluation period (mean over Wk 24-28). Principal secondary endpoints were 1) proportion with ≥1 g/dL increase in Hb, 2) mean change in SF-36 Vitality (fatigue) between BL and Wk 28. SF-36 Vitality responder (≥6 point increase) and blood pressure (BP) elevations were secondary endpoints. Superiority for all endpoints was tested (1-sided α=0.025). Results: 614 ND-CKD patients were randomized. BL demographic characteristics were balanced; Hb was similar (9.73 g/dL dapro, 9.71 g/dL PBO). The adjusted mean difference (AMD) in change in Hb was 1.40 g/dL (95% CI 1.23, 1.56; P<0.001). A greater proportion on dapro had a ≥1 g/dL increase in Hb from BL (77% vs 18%; P<0.001). Adjusted mean (SE) SF-36 Vitality score increased by 7.3 (1.1) points (dapro) vs 1.9 (1.2) points (PBO); AMD at Wk 28 was 5.4 (95% CI 2.2, 8.6; P<0.001, Figure). 58% on dapro vs 40% on PBO were SF-36 Vitality responders (difference 13%; 95% CI 4%, 22%). While more BP elevations occurred in dapro vs PBO (32% vs 26%, p=0.07), dapro's overall effect on BP was similar to PBO. Rates of adverse events were similar (dapro 69% vs PBO 71%). Conclusions: In patients with ND-CKD, dapro effectively increased Hb, significantly improved the vitality score (fatigue) and was well tolerated. Funding: Commercial Support - GlaxoSmithKline

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