Study of Roxadustat (FG-4592) in Participants With End-Stage Renal Disease Receiving Maintenance Hemodialysis
Condition: End Stage Renal Disease; Anemia
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Anemia
Intervention: Roxadustat; Epoetin Alfa; Placebo
Intervention description: Roxadustat will be administered per dose and schedule specified in the arms.; Epoetin Alfa will be administered per dose and schedule specified in the arms.; Placebo matching to roxadustat will be administered per schedule specified in the arm.
Intervention MeSH terms: Epoetin Alfa
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 161.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Kidney; End Stage Renal Disease; ESRD; Chronic Kidney Disease; CKD; Renal; Anemia; Oral anemia treatment; Hemoglobin levels; Blood count; Erythropoietin; Hemodialysis; Normoresponder; Hyporesponder

Summary:

      The primary objective of this study is to evaluate the efficacy and safety of roxadustat in
      participants with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) therapy,
      previously treated with intravenous (IV) epoetin alfa.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  ESRD and receiving maintenance HD TIW for ≥4 months prior to Day 1

          -  Two most recent Hb values obtained during screening period must be within the ranges
             set below:

             i) Group A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization
             within 9.0 to 13.5 g/dL ii) Group B. Hyporesponder Criteria: Hb range in the 8 weeks
             prior to randomization within 8.5 to 13.5 g/dL

          -  Epoetin alfa, dose requirements:

             i) Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa dose
             at baseline (that is, no more than a 30% fluctuation in the weekly dose) during the 4
             weeks prior to study Day -3

               1. Cohorts A-1 to A-4: Current and previous (past 4 weeks) epoetin alfa dose range
                  25 to 85 IU/kg/dose, TIW; weekly dose between 75 and 255 IU/kg/week

               2. Cohort A-5: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to
                  115 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week

               3. Cohort A-9: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to
                  150 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week

               4. Cohorts A-6 to A-8: Current and previous (past 4 weeks) epoetin alfa dose range
                  25 to 115 IU/kg/dose, TIW, and two times a week (BIW); total weekly dose between
                  75 and 345 IU/kg/week

               5. Cohorts A-10 to A-12: Optional cohorts to be decided (TBD), dosing frequency and
                  dose range to be determined by sponsor ii) Group B. Hyporesponder Criteria:

               1. Cohort B-1 (completed): Current and previous (past 4 weeks) epoetin alfa dose
                  range 125 to 400 IU/kg/dose, TIW; weekly dose between 375 and 1200 IU/kg/week

               2. Cohort B-2 to B-4: Current and previous (past 4 weeks) epoetin alfa dose range
                  >115 IU/kg/dose, TIW; total weekly dose >345 IU/kg/week no requirement for
                  stability of epoetin alfa doses

          -  Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and
             vitamin B12 within acceptable limits

          -  Absence of active or chronic gastrointestinal bleeding

          -  High sensitivity C-reactive protein (hsCRP) <60 mg/liter for normoresponders Cohorts
             A-8 through A-12 enrolled under Amendment 3; no hsCRP criteria for hyporesponders

          -  Body weight: 40 to 140 kg (dry weight)

          -  Body mass index (BMI): 18 to 45 kg/meter square (m^2)

          -  Dialysis vascular access via native arteriovenous fistula or synthetic graft, or
             permanent (tunneled) catheter (not via temporary catheter); permanent and temporary
             catheters, however, are still prohibited in Cohort A-5

        Key Exclusion Criteria:

          -  Anticipated change in HD prescription

          -  Any clinically significant infection or evidence of an underlying infection

          -  Positive for any of the following: Human immunodeficiency virus (HIV); hepatitis B
             surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab)

          -  History of chronic liver disease

          -  New York Heart Association Class III or IV congestive heart failure

          -  Chronic inflammatory disease that could impact erythropoiesis (for example, systemic
             lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in
             remission

          -  History of myelodysplastic syndrome

          -  History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric

          -  Active hemolysis or diagnosis of hemolytic syndrome

          -  Known bone marrow fibrosis

          -  Uncontrolled or symptomatic secondary hyperparathyroidism

          -  Any prior organ transplantation

          -  Drug-treated gastroparesis or short-bowel syndrome

          -  History of alcohol or drug abuse; or a positive drug screen for a substance that has
             not been prescribed for the participant

          -  Prior treatment with roxadustat

          -  Diagnosis or suspicion of renal cell carcinoma

          -  Red blood cell (RBC) transfusion within 12 weeks prior to Day 1, or anticipated need
             for RBC transfusion during the dosing period

          -  IV iron supplement within 2 weeks prior to Day 1 and/or unwilling to withhold IV iron
             during the dosing/treatment period