Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis
Condition: Anemia; End Stage Renal Disease (ESRD)
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Anemia
Intervention: Roxadustat; Epoetin alfa; Darbepoetin alfa; Iron
Intervention description: Participants received initial dose of roxadustat orally as a tablet in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.; Participants received epoetin alfa via intravenous or subcutaneous injection, once a week, twice a week, or three times a week (TIW). Epoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of epoetin alfa was per UK SmPC of Eprex®. Participants received IV iron supplementation according to the standard of care.; Participants received darbepoetin alfa via intravenous or subcutaneous injection, once a week or once every other week. Darbepoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of darbepoetin alfa was per EU SmPC of Aranesp®. Participants received IV iron supplementation according to the standard of care.; Oral iron treatment was recommended for supplementation to support erythropoiesis and as first-line treatment for iron deficiency, unless participant was intolerant to this treatment. For participants receiving roxadustat the recommended daily dose was 200 mg of elemental iron. Participants were advised to take roxadustat at least 1 hour before or 1 hour after oral iron. Intravenous iron supplementation for participants receiving roxadustat was allowed if all of the following criteria were met: The participant's Hb level had not responded adequately to roxadustat following two consecutive dose increases or reached the maximum dose limit, and participant's ferritin was < 100 ng/mL (< 220 pmol/L) or TSAT < 20%, or the participant was intolerant of oral iron therapy. For participants treated with epoetin alfa or darbepoetin alfa, IV iron supplementation was given according to standard of care.
Intervention MeSH terms: Epoetin Alfa; Darbepoetin alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 838.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ASP1517; FG-4592; Anemia; End Stage Renal Disease (ESRD); Erythropoetin Stimulating Agents (ESAs); Chronic Kidney Disease; Hematopoetic Agents; HIF-PH inhibitor; Hemoglobin; Dialysis; roxadustat

Summary:

      This study was conducted to explore a new therapy for anemia in participants with end stage
      renal disease (ESRD) on dialysis. Anemia is a reduced number of red blood cells or
      hemoglobin. Hemoglobin (which contains iron) is important for the transport of oxygen in your
      blood. The purpose of this study was to evaluate if roxadustat is effective and safe in the
      maintenance treatment of anemia in ESRD participants on stable dialysis. Roxadustat was
      compared to epoetin alfa and darbepoetin alfa, commercially available medicines for treatment
      of anemia.
    

Eligibility criteria:

        Inclusion Criteria:

        Main Inclusion:

          -  Participant is on stable hemodialysis (HD), hemodiafiltration (HDF) or peritoneal
             dialysis (PD) treatment with the same mode of dialysis for ≥4 months prior to
             randomization.

          -  Participant is on IV or SC epoetin or IV or SC darbepoetin alfa treatment for ≥8 weeks
             prior to randomization with stable weekly doses (during 4 weeks prior to
             randomization).

          -  Mean of the participant's three most recent Hb values, as measured by central
             laboratory, during the Screening Period.

          -  Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are
             ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN

        Exclusion Criteria:

        Main Exclusion:

          -  Participant has received a red blood cell (RBC) transfusion within 8 weeks prior to
             randomization.

          -  Participant has a known hereditary hematologic disease such as thalassemia or sickle
             cell anemia, pure red cell aplasia, or other known causes for anemia other than
             Chronic Kidney Disease (CKD).

          -  Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure,
             or a thrombotic/thrombo-embolic event (e.g., deep vein thrombosis or pulmonary
             embolism) within 12 weeks prior to randomization.

          -  Participant has had uncontrolled hypertension, in the opinion of the investigator,
             within 2 weeks prior to randomization.

          -  Participant has a history of malignancy, except for the following: cancers determined
             to be cured or in remission for ≥5 years, curatively resected basal cell or squamous
             cell skin cancers, cervical cancer in situ, or resected colonic polyps.

          -  Participant has had any prior organ transplant (that has not been explanted), or
             participant is scheduled for organ transplantation.