Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Dialysis-dependent Chronic Kidney Disease (DD-CKD)
Condition: Anemia; Dialysis-Dependent Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia
Intervention: Vadadustat; Darbepoetin alfa
Intervention description: Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.; Subcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
Intervention MeSH terms: Darbepoetin alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: Sponsor was blinded during the study
Enrollment: 3554.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: AKB-6548; Chronic kidney disease; anemia; CKD; chronic renal insufficiency; renal impairment; erythropoietin; kidney; renal; oral anemia treatment; hemoglobin; hypoxia-inducible factor; HIF; hypoxia-inducible factor prolyl-hydroxylase inhibitor; HIF-PHI; efficacy; safety; Phase 3; cardiovascular; DD-CKD

Summary:

      A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance
      treatment of anemia in participants with dialysis-dependent chronic kidney disease (DD-CKD)
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥18 years of age

          -  Receiving chronic maintenance dialysis (either peritoneal or hemodialysis) for
             end-stage kidney disease for at least 12 weeks prior to Screening

          -  Currently maintained on erythropoiesis-stimulating agent therapy, with a dose received
             within 6 weeks prior to or during Screening

          -  Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive)
             in the US and between 9.0 and 12.0 g/dL (inclusive) outside of the US

          -  Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT)
             ≥20% during Screening

        Exclusion Criteria:

          -  Anemia due to a cause other than chronic kidney disease or participants with active
             bleeding or recent blood loss

          -  Uncontrolled hypertension

          -  Red blood cell transfusion within 8 weeks prior to randomization

          -  Anticipated to recover adequate kidney function to no longer require dialysis

          -  Severe heart failure at Screening (New York Heart Association Class IV)

          -  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, or stroke within 12 weeks prior to or during Screening

          -  Hypersensitivity to Vadadustat, Darbepoetin alfa, or any of their excipients