Study of Vadadustat in Hemodialysis Participants With Anemia Switching From Epoetin Alfa

Inclusion Criteria

• ≥18 years of age, providing informed consent
• Receiving chronic, outpatient in-center hemodialysis (TIW) for end-stage renal disease for at least 12 weeks prior to Screening
• Maintained on intravenous Epoetin Alfa therapy for 8 weeks prior to and including Screening through Screening Visit 2 (SV2)
• Eligibility in the Main study and erythropoiesis-stimulating agent (ESA) hyporesponder parallel study is based on the following mean weekly Epoetin Alfa doses:
• Main study: Mean weekly Epoetin Alfa dose 1.5 x upper limit of normal (ULN) during Screening. Participants with a history of Gilbert's syndrome are not excluded.
• Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of Epoetin Alfa
• Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening
• History of new or recurrent malignancy within 2 years prior to and during Screening or currently receiving treatment or suppressive therapy for cancer. Participants with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ are not excluded.
• History of deep vein thrombosis or pulmonary embolism within 12 weeks prior to or during Screening
• History of hemosiderosis or hemochromatosis
• History of prior organ transplantation (participants with a history of failed kidney transplant or corneal transplants are not excluded)
• Scheduled organ transplant from a living donor and participants on the kidney transplant wait-list who are expected to receive a transplant within 6 months
• History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded)
• Known hypersensitivity to Vadadustat, Epoetin Alfa, or any of their excipients
• Any prior use of a hypoxia-inducible factor prolyl-hydroxylase (HIF-PH) inhibitor or any use of an investigational medication within 30 days or 5 half-lives of the investigational medication (whichever is longer), prior to randomization
• For female participants of non-childbearing potential:
• inability to confirm surgical sterility (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy) at least 1 month prior to Screening;
• not considered post-menopausal (no menses for >1 year with follicle stimulating hormone >40 U/Liter at Screening)
• For female participants of childbearing potential:
• lack of confirmation of the use of acceptable forms of contraception* for a minimum of one complete menstrual cycle prior to Screening;
• positive serum pregnancy test at SV2;
• unwilling to use two acceptable forms of contraception* (at least one of which must be a barrier method) starting Baseline/Day 1, throughout the Treatment Period and for 30 days after the final study drug administration
• Breastfeeding during Screening or throughout the Treatment Period and for 30 days after the final study drug administration
• Donation of ova starting at Screening, throughout the Treatment Period, and for 30 days after the final study drug administration
• Male participants who have not had a vasectomy and do not agree to the following: use of an acceptable form of contraception* during the study and for 30 days after the last dose of the study drug; to not donate semen during the study and for at least 30 days after the last dose of Vadadustat
• Participants with bilateral native nephrectomy
• Any other reason, which in the opinion of the Investigator, would make the participant not suitable for participation in the study
• Acceptable forms of contraception include:
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