Efficacy and Safety Study to Evaluate Vadadustat for the Correction or Maintenance Treatment of Anemia in Participants With Incident 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: 369.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Vadadustat; AKB-6548; anemia; chronic kidney disease; CKD; chronic renal insufficiency; renal impairment; erythropoietin; kidney; renal; oral anemia treatment; hemoglobin; hypoxia-inducible factor; HIF; efficacy; safety; phase 3; cardiovascular

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

Eligibility criteria:

        Inclusion Criteria:

          -  ≥18 years of age

          -  Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for
             end-stage kidney disease within 16 weeks prior to Screening

          -  Mean Screening hemoglobin between 8.0 and <11.0 grams per deciliter (g/dL) (inclusive)

          -  Serum ferritin ≥100 nanograms per deciliter (ng/mL) and 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

          -  Red blood cells transfusion within 8 weeks prior to randomization

          -  Anticipated to recover adequate kidney function to no longer require dialysis

          -  Uncontrolled hypertension

          -  Severe heart failure at Screening (New York Heart Association Class IV)

          -  Acute coronary syndrome (hospitalization for unstable angina, 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
             congestive heart failure; or stroke within 12 weeks prior to or during Screening.

          -  Participants meeting the criteria of erythropoiesis-stimulating agent resistance
             within 8 weeks prior to or during Screening defined as follows

               1. epoetin: > 7700 units/dose three times per week or >23,000 units per week

               2. Darbepoetin alfa: >100 micrograms per week (mcg/week)

               3. methoxy polyethylene glycol-epoetin beta: >100 micrograms (mcg) every other week
                  or >200 mcg/month

          -  Hypersensitivity to Vadadustat, Darbepoetin alfa or any of their excipients