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

• Anemia and Iron Metabolism: Clinical Research
  November 07, 2019 | Location: 150, Walter E. Washington Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

Category: Anemia and Iron Metabolism

• 202 Anemia and Iron Metabolism: Clinical

Authors

• Nangaku, Masaomi, The University of Tokyo School of Medicine, Tokyo, Japan

Masaomi Nangaku, MD, PhD



Masaomi Nangaku is a vice dean and a professor and head of the division of nephrology and endocrinology, the University of Tokyo. He is the president of the Asian Pacific Society of Nephrology. He is also a co-chair of the research committee of the International Society of Nephrology, a vice president of the Japanese Society of Nephrology, and a member of Continuous Professional Development Committee of the ASN. He has published more than 280 original articles and 90 reviews articles in international journals, and has given 100 invited talks at international academic meetings. He served as a member of the Scientific Program Committee of American Society of Nephrology (ASN) meetings, a chair of the Scientific Program Committee of APCN 2016, and a chair of the program committee of the World Congress of Nephrology in 2019. He is a member of the editorial board of many prestigious journals, and is currently serving his second term as an associate editor of Kidney International.

• Kondo, Kazuoki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan

Kazuoki Kondo,

• Ueta, Kiichiro, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan

Kiichiro Ueta,

• Kokado, Yoshimasa, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan

Yoshimasa Kokado,

• Kaneko, Genki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan

Genki Kaneko,

• Matsuda, Hiroki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan

Hiroki Matsuda,

• Kawaguchi, Yutaka, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan

Yutaka Kawaguchi,

• Komatsu, Yasuhiro, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan

Yasuhiro Komatsu,

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 –