Vadadustat for anemia in chronic kidney disease patients on peritoneal dialysis: A phase 3 open-label study in Japan

Abstract

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of anemia in patients with chronic kidney disease (CKD). This phase 3, open-label, 24-week single-arm study evaluated the efficacy and safety of vadadustat in 42 Japanese CKD patients with anemia undergoing peritoneal dialysis. Patients received oral vadadustat for 24 weeks, initiated at 300 mg/day and doses were adjusted to achieve the target hemoglobin (Hb) range of 11.0-13.0 g/dL. Least squares mean of average Hb at weeks 20 and 24 was 11.35 g/dL, which was within the target range. The most frequent adverse events were catheter site infections (23.8%), which were not related to vadadustat treatment. Vadadustat was generally well tolerated and effective in controlling Hb levels within the target range, indicating the usefulness of vadadustat for treating anemia in Japanese CKD patients undergoing peritoneal dialysis.

Keywords: anemia; chronic kidney disease; hypoxia-inducible factor prolyl hydroxylase inhibitor; peritoneal dialysis; vadadustat.

Conflict of interest statement

Masaomi Nangaku has received honoraria, advisory fees, or research funding from Akebia, Alexion, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, GSK, JT, Kyowa Kirin, Mitsubishi Tanabe, Ono, Takeda, and Torii. Yasuhiro Komatsu has received honoraria from Baxter, Chugai, and Kyowa Kirin. Kazuoki Kondo, Souichirou Takabe, Kiichiro Ueta, Genki Kaneko, Makiko Otsuka, and Yutaka Kawaguchi are employees of Mitsubishi Tanabe Pharma Corporation. The authors thank the study team and staff for the conduct of this study, their colleagues at Akebia Therapeutics Inc. for editorial input and support with the development of this manuscript, and the patient volunteers for participating in the study.

© 2020 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Figures

FIGURE 1

Study design

FIGURE 2

Patient flow diagram. ESA, erythropoiesis‐stimulating agent; Hb, hemoglobin; ICF, informed consent form

FIGURE 3

Mean (A) hemoglobin and (B) vadadustat dose over 24 weeks (FAS). Symbols represent mean values and bars indicate 95% confidence intervals (CIs). BL, baseline; FAS, full analysis set; Hb, hemoglobin; LOCF, last observation carried forward; n, number of patients

FIGURE 4

Mean hemoglobin and vadadustat dose over 24 weeks in ESA users with screening Hb

FIGURE 5

Mean iron‐related parameters over 24 weeks; (A) serum ferritin, (B) TSAT, (C) TIBC, (D) hepcidin, (E) MCV, (F) MCH, (G) MCHC, (H) RDW, (I) serum iron, and (J) monthly dose of oral iron supplementation over 24 weeks (FAS). Symbols represent mean values and bars indicate 95% confidence intervals. Asterisks indicate significant difference between week 24 LOCF and baseline, except for dose of iron, which is between weeks 20 and 24 and screening (paired t test; *P < .05, **P < .01). BL, baseline; CI, confidence interval; FAS, full analysis set; LOCF, last observation carried forward; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; n, number of patients; RDW, red blood cell distribution width; SCR, screening; TIBC, total iron‐binding capacity; TSAT, transferrin saturation

FIGURE 6

Mean (A) systolic blood pressure and (B) diastolic blood pressure over 24 weeks (FAS). Symbols represent mean values and bars indicate 95% confidence intervals. BL, baseline; BP, blood pressure; FAS, full analysis set; LOCF, last observation carried forward; n, number of patients