Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan

Background

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in China for dialysis-dependent CKD anemia.


Methods

This phase 3, 24-week, double-blind, double-dummy study evaluated roxadustat’s noninferiority to darbepoetin alfa for hemodialysis-dependent CKD anemia. We randomly assigned Japanese patients to oral roxadustat three times weekly or to darbepoetin alfa injections once weekly, titrating doses to maintain hemoglobin between 10–12 g/dl. The primary end point was change of average hemoglobin from baseline to weeks 18–24 (Hb18–24). Secondary end points were average hemoglobin and proportion of patients with hemoglobin between 10–12 g/dl (maintenance rate) at weeks 18–24, and iron parameters. Safety assessments included treatment-emergent adverse events and adjudicated ophthalmologic findings.


Results

We randomly assigned 303 patients to roxadustat (n=151) or darbepoetin alfa (n=152). The difference between roxadustat and darbepoetin alfa in Hb18–24 was –0.02 g/dl (95% confidence interval, –0.18 to 0.15), confirming roxadustat’s noninferiority to darbepoetin alfa. Average hemoglobin at weeks 18–24 with roxadustat was 10.99 g/dl (95% confidence interval: 10.88 to 11.10), confirming its efficacy. Among patients with one or more hemoglobin value during weeks 18–24, the maintenance rate was 95.2% with roxadustat and 91.3% with darbepoetin alfa. Serum iron, ferritin, and transferrin saturation remained clinically stable with roxadustat; transferrin and total iron binding capacity increased through week 4 before stabilizing. Common treatment-emergent adverse events were nasopharyngitis, shunt stenosis, diarrhea, contusion, and vomiting. The proportion of patients with new or worsening retinal hemorrhage was 32.4% with roxadustat and 36.6% with darbepoetin alfa. We observed no clinically meaningful changes in retinal thickness groups.


Conclusions

Roxadustat maintained hemoglobin within 10–12 g/dl in patients on hemodialysis and was noninferior to darbepoetin alfa. Treatment-emergent adverse events were consistent with previous reports.


Clinical Trial registry name and registration number

A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients with Anemia, NCT02952092 (ClinicalTrials.gov)