| Participants |
General information
Setting: multicentre (41 sites) Country: USA Inclusion criteria: ≥18 years providing informed consent; receiving chronic outpatient in‐centre HD (3 times/week) for kidney failure for at least 12 weeks prior to screening; maintained on IV epoetin alfa therapy for 8 weeks prior to and including screening through screening visit 2; eligibility in the main study and ESA hypo‐responder parallel study is based on the following mean weekly epoetin alfa doses: 1) Main study: mean weekly epoetin alfa dose < 300 U/kg/week for 8 weeks prior to screening visit 2; 2) ESA hypo‐responder parallel study: mean weekly epoetin alfa dose ≥ 300 U/kg/week for 8 weeks prior to screening visit 2; 2 Hb values measured at least 4 days apart between screening visit 1 and screening visit 2 as indicated: 1) Main study: 2 Hb values between 8.5 and 11.0 g/dL; and 2) ESA hypo‐responder parallel study: 2 Hb values between 8.0 and 10.0 g/dL; serum ferritin ≥ 100 ng/mL and TSAT ≥ 20% during screening; folate and vitamin B12 measurements ≥ LLN during screening; HD adequacy as indicated by single‐pool Kt/V urea ≥ 1.2 using the most recent historical measurement within 8 weeks prior to or during screening; understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure Exclusion criteria: anaemia due to a cause other than CKD (e.g. sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, haematologic malignancy, myeloma, haemolytic anaemia, thalassaemia, or PRCA); active bleeding or recent blood loss within 8 weeks prior to randomisation; RBC transfusion within 8 weeks prior to randomisation; anticipated to discontinue HD during the study; judged by the Investigator that the participant is likely to need rescue therapy (ESA administration or RBC transfusion) immediately after enrolment in the study; history of chronic liver disease (e.g. chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver); AST/SGOT, ALT/SGPT, or total bilirubin > 1.5 times ULN during screening; current uncontrolled hypertension as determined by the investigator that would contraindicate the use of epoetin alfa; acute coronary syndrome (hospitalisation for unstable angina or MI), 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, hospitalisation for heart failure or NYHA class IV heart failure, 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; history of DVT or pulmonary embolism within 12 weeks prior to or during screening; history of haemosiderosis or haemochromatosis; history of prior organ transplantation (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 haematopoietic 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 HIF‐PHI or any use of an investigational medication within 30 days or 5 half‐lives of the investigational medication (whichever is longer), prior to randomisation; female participants of non‐childbearing potential: 1) inability to confirm surgical sterility (e.g. hysterectomy, bilateral tubal ligation, bilateral oophorectomy) at least 1 month prior to screening; 2) not considered post‐menopausal; for female participants of childbearing potential: 1) lack of confirmation of the use of acceptable forms of contraception for a minimum of one complete menstrual cycle prior to screening; 2) positive serum pregnancy test at screening visit 2; 3) 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; 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: 1) established use of oral, injected or implanted hormonal methods of contraception; 2) placement of an intrauterine device or intrauterine system; 3) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository Target Hb: 10.0 to 11.0 g/dL CKD stage: 175 patients undergoing HD
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| Outcomes |
Primary outcome
Secondary outcomes
Proportion with Hb values within the target range (10.0 to 11.0 g/dL, inclusive) at the primary evaluation period (weeks 10 to 12) For participants who transitioned to 3 times/week vadadustat dosing, mean change in Hb from weeks 10 to 12 to the secondary evaluation period (weeks 18 to 20) Mean change in Hb between baseline and the secondary evaluation period (weeks 18 to 20) Proportion with Hb values within the target range (10.0 to 11.0 g/dL, inclusive) at the secondary evaluation period (weeks 18 to 20) For who transitioned to 3 times/week vadadustat dosing, proportion of participants with Hb values within the target range (10.0 to 11.0 g/dL, inclusive) at the secondary evaluation period (weeks 18 to 20) Proportion with a mean increase in Hb from baseline to the primary evaluation period ≥ 0.5 g/dL (weeks 10 to 12) Proportion with Hb values within the target range (10.0 to 11.0 g/dL, inclusive) at the primary evaluation period (weeks 10 to 12) Proportion with a mean increase in Hb from baseline to the secondary evaluation period ≥ 0.5 g/dL (weeks 18 to 20) Proportion with Hb values within the target range (10.0 to 11.0 g/dL, inclusive) at the secondary evaluation period (weeks 18 to 20) Number requiring IV iron supplementation (up to 28 weeks) Number requiring ESA rescue (up to 28 weeks) Number requiring RBC transfusion (up to 28 weeks)
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