Phase 3, randomized, open-label, active-controlled study evaluating the efficacy and safety of oral vadadustat for the maintenance treatment of anemia in subjects with non-dialysis-dependent chronic kidney disease (ndd-ckd) (pro2tect - conversion)

Inclusion Criteria:

• ≥18 years of age

• Diagnosis of CKD with an eGFR ≤60 mL/min/1.73 m2 using the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation at Screening and not expected to start dialysis within 6 months of Screening

• Currently maintained on ESA therapy, with the last dose received within 8 weeks prior to Screening

• Mean Screening HGB between 8.0 and 11.0 g/dL (inclusive) in the US and between 9.0 and 12.0 g/dL (inclusive) outside of the US, as determined by the average of 2 HGB values measured by the central laboratory during Screening

• Serum ferritin ≥100 ng/mL and transferrin saturation (TSAT) ≥20% at Screening

• Folate and vitamin B12 measurements ≥lower limit of normal at Screening

• Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.

Exclusion Criteria:**

• Anemia due to a cause other than CKD or subjects with active bleeding or recent blood loss
• Subjects with sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia
• Red blood cell (RBC) transfusion within 4 weeks prior to or during Screening
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), or total bilirubin >2.0 x upper limit of normal (ULN) at Screening. Subjects with a history of Gilbert’s syndrome are not excluded.
• Uncontrolled hypertension (confirmed diastolic blood pressure >110 mmHg or systolic blood pressure >180 mmHg) at Screening
• Severe heart failure at Screening (New York Heart Association Class IV)
• Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), urgent coronary revascularization, hospitalization for CHF, or stroke within 12 weeks prior to Screening
• History of active malignancy within 2 years prior to Screening, except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or resected benign colonic polyps
• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring active treatment within 8 weeks prior to Screening
• History of hemosiderosis or hemochromatosis
• History of prior organ transplantation or scheduled organ transplant (subjects on kidney transplant wait-list are not excluded), or prior stem cell or bone marrow transplant (corneal transplants are not excluded)
• Use of an investigational medication or participation in an investigational study within 30 days or 5 half-lives of the investigational medication (whichever is longer), prior to the Screening visit
• Previous participation in this study, receipt of vadadustat in another study, or previous participation in a study with another hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI)
• Females who are pregnant or breast-feeding. Women of childbearing potential who are unable or unwilling to use an acceptable method of contraception
• Non-vasectomized male subjects who are unable or unwilling to use an acceptable method of contraception
• Any other reason that in the opinion of the Investigator would make the subject not suitable for participation in the study.inion of the Investigator would make the subject not suitable for participation in the study.</li></ul>