Researchers in Japan recently conducted a randomized, double-blind, active-controlled, phase 3 study of vadadustat in patients with chronic kidney disease (CKD) with anemia. Results were reported by Masaomi Nangaku, MD, PhD, at Kidney Week 2019 in a presentation titled Randomized, Double-Blinded, Active Controlled (Darbepoetin Alfa), Phase 3 Study of Vadadustat in CKD Patients with Anemia on Hemodialysis in Japan.
Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being tested in Japan. The results reported at Kidney Week 2019 included prespecified primary analysis of the efficacy and safety of vadadustat for up to 24 weeks. The study cohort included 323 Japanese hemodialysis-dependent CKD patients with anemia receiving erythropoiesis stimulating agents (ESAs).
The 323 patients were randomized to vadadustat (n=162) or darbepoetin alfa (DA; n=161). Following an initial dose of vadadustat 300 mg daily, doses were adjusted within 150 to 600 mg as necessary to achieve a hemoglobin target of 10 to 12 g/dL. The primary end point of interest was average hemoglobin at weeks 20 and 24. Iron parameters were also measured; safety was assessed up to 24 weeks.
At baseline, hemoglobin for both groups was 10.74 g/dL. The least squares mean of average hemoglobin at weeks 20 and 24 was 10.61 (95% confidence interval [CI], 10.45-10.76) in the vadadustat group and 10.65 g/dL (95% CI, 10.50-10.80) in the DA group; 95% CI of both groups were within the target range of 10 to 12 g/dL. The difference in least squares mean between the groups was -0.05 g/dL (95% CI, -0.26 to 0.17); the 95% CI lower limit was above the predefined noninferiority margin of –0.75 g/dL, confirming the noninferiority of vadadustat to DA.
At week 24, 75.4% of patients in the vadadustat group (n=104) were in the hemoglobin target range compared with 75.7% (n=115) of patients in the DA group. There was an association between a vadadustat regimen and significant increases in total iron-binding capacity and decreases in hepcidin from baseline to week 24; the association was not seen in patients in the DA group.
In the vadadustat group, 89.5% of participants had at least one adverse event; in the DA group, 88.2% of participants had at lease on adverse event. In the vadadustat group, the most common adverse events were nasopharyngitis (19.8% vs 28.6% in the DA group), diarrhea (10.5% vs 9.9% in the DA group), and shunt stenosis (8.0% vs 12.4% in the DA group). The rates of serious adverse events were 13.0% in the vadadustat group and 10.6% in the DA group. No serious adverse event related to the study drug was considered.
“Vadadustat was generally well tolerated and effective as DA in maintaining hemoglobin levels within the target range, indicating the usefulness of vadadustat for treating anemia in Japanese hemodialysis-dependent CKD patient converting from ESA,” the researchers said.
Source: Nangaku M, Kondo K, Ueta K, et al. Randomized, double-blinded, active-controlled (darbepoetin alfa), phase 3 study of vadadustat in CKD patients with anemia on hemodialysis in Japan. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2019 (Abstract TH-OR024), November 7, 2019, Washington DC.