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Kidney Week

Abstract: TH-OR024

Randomized, Double-Blinded, Active-Controlled (Darbepoetin Alfa), Phase 3 Study of Vadadustat in CKD Patients with Anemia on Hemodialysis in Japan

Session Information

Category: Anemia and Iron Metabolism

  • 202 Anemia and Iron Metabolism: Clinical

Authors

  • Nangaku, Masaomi, The University of Tokyo School of Medicine, Tokyo, Japan
  • Kondo, Kazuoki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
  • Ueta, Kiichiro, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
  • Kokado, Yoshimasa, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
  • Kaneko, Genki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
  • Matsuda, Hiroki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
  • Kawaguchi, Yutaka, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
  • Komatsu, Yasuhiro, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan
Background

Vadadustat (VDT) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being assessed in Japan and Global Phase 3 studies. This is the first result of phase 3 study (NCT03439137), evaluates the efficacy and safety of VDT for 52 weeks in 323 Japanese hemodialysis-dependent (HD) chronic kidney disease (CKD) subjects with anemia receiving erythropoiesis stimulating agents (ESA). Prespecified primary analysis results up to week 24 are presented here.

Methods

Subjects on maintenance hemodialysis receiving ESA were randomized to VDT (n=162) or darbepoetin alfa (DA) group (n=161). After the initial VDT dose of 300 mg daily, doses were adjusted to achieve a Hb target of 10–12 g/dL, within 150–600 mg. Primary endpoint was average Hb at weeks 20 and 24. Iron parameters were measured. Safety was assessed up to 24 weeks.

Results

The baseline Hb of both groups was 10.74 g/dL. The LSMean of average Hb at weeks 20 and 24 was 10.61 (95%CI: 10.45, 10.76) and 10.65 g/dL (10.50, 10.80) in the VDT and DA groups, respectively; 95% CI of both groups were within the target range of 10−12 g/dL. Difference in LSMean between the groups was −0.05 g/dL (−0.26, 0.17); the 95% CI lower limit was above the predefined noninferiority margin of −0.75 g/dL, confirming the noninferiority of VDT to DA. At week 24, 104 (75.4%) and 115 (75.7%) subjects in the VDT and DA groups, respectively, had Hb within the target range. VDT regimen was associated with significant increases in total iron-binding capacity and decreases in hepcidin from baseline to week 24, not found in the DA group. At least one adverse event (AE) was seen in 89.5% (VDT group) and 88.2% (DA group) subjects. The most common AEs in the VDT group were nasopharyngitis (VDT: 19.8%, DA: 28.6%), diarrhea (VDT: 10.5%, DA: 9.9%), and shunt stenosis (VDT: 8.0%, DA: 12.4%). The incidence rates of serious AEs (SAEs) were 13.0% (VDT group) and 10.6% (DA group). No SAE related to the study drug was considered.

Conclusion

VDT was generally well tolerated and effective as DA in maintaining Hb levels within the target range, indicating the usefulness of VDT for treating anemia in Japanese HD CKD patients converting from ESA.

Funding

  • Commercial Support