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Abstract: TH-PO228

Randomized, Placebo-Controlled Phase 2 Trials of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI), to Treat Anemia of CKD

Session Information

Category: Anemia and Iron Metabolism

  • 202 Anemia and Iron Metabolism: Clinical

Authors

  • Nangaku, Masaomi, University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Khawaja, Zeeshan, Akebia Therapeutics, Inc., Cambridge, Massachusetts, United States
  • Luo, Wenli, Akebia Therapeutics, Inc., Cambridge, Massachusetts, United States
  • Garafola, Svetlana, Akebia Therapeutics, Inc., Cambridge, Massachusetts, United States
  • deGoma, Emil, Akebia Therapeutics, Inc., Cambridge, Massachusetts, United States
  • Komatsu, Yasuhiro, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan
Background

The HIF-PHI vadadustat (VDT) was investigated in two phase 2, randomized, double-blind, placebo-controlled trials in Japanese subjects with anemia due to non-dialysis-dependent (NDD) or dialysis-dependent (DD) CKD.

Methods

Trials consisted of a 6-wk fixed-dose, placebo-controlled, primary efficacy period and a 10-wk dose adjustment period. In each trial, subjects were randomized to VDT 150 mg, 300 mg, 600 mg, or placebo. After 6 wks, subjects randomized to placebo were switched to VDT, and all subjects had their dose adjusted according to Hb response. For the primary efficacy analysis in each study, an ANCOVA model was used in the MITT population to compare mean change in Hb from baseline to Wk 6 between the VDT and placebo groups. Last observation carried forward (LOCF) was used for missing Hb data.

Results

Fifty-one and 60 subjects were randomized in the NDD and DD studies, respectively. Mean changes in Hb from baseline to Wk 6 were statistically significant in all VDT treatment arms compared with placebo (Table). Treatment with VDT 300 mg or 600 mg was associated with statistically significant increases in total iron binding capacity and decreases in ferritin and hepcidin from baseline to Wk 6 compared with placebo (P<0.01). Incidence of AEs during the 6-wk period in the VDT groups (150 mg, 300 mg, 600 mg) and placebo was 33%, 58%, 54%, and 36% (NDD study) and 53%, 73%, 40%, and 40% (DD study). During the 16-wk treatment period and 2-wk follow-up, the most common AEs reported were hypertension and viral upper respiratory infection (NDD study) and nasopharyngitis, diarrhea, and headache (DD study). 13 SAEs in 11 subjects (NDD study) and 10 SAEs in 7 subjects (DD study) were reported. No deaths were reported.

Conclusion

These data support continued development of VDT for patients with renal anemia.

Table. Changes in Hemoglobin (g/dL) Between Baseline and Week 6: Vadadustat vs Placebo
 NDD-CKDDD-CKD
 nMean Change, g/dLP-valuenMean Change, g/dLP-value
VDT 600 mg121.62<0.0001110.41<0.0001
VDT 300 mg121.13<0.0001130.08<0.0001
VDT 150 mg130.430.004513-0.280.0004
Placebo14-0.47-6-1.48-

Funding

  • Commercial Support