Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
Condition: Anemia; Non-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: 1725.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Vadadustat; 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; NDD-CKD

Summary:

      A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance
      treatment of anemia in participants with Non-dialysis-dependent Chronic Kidney Disease
      (NDD-CKD)
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥18 years of age

          -  Diagnosis of chronic kidney disease (CKD) with an estimated glomerular filtration rate
             ≤60 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) at Screening and
             not expected to start dialysis within 6 months of Screening

          -  Currently maintained on erythropoiesis-stimulating agents 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 United States (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 CKD or participant with active bleeding or recent
             blood loss

          -  Red blood cell transfusion within 8 weeks prior to randomization

          -  Uncontrolled hypertension

          -  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 Darbepoetin or Vadadustat or to any of their excipients