Clinical trial NCT01147666 (phase 2, status: completed)
Conditions: end stage renal disease, anemia
ICD codes: N18.6, I12.0, I13.11, I13.2, D53.2, D64.9, D46.4, D53.0, D53.9, D61.3, D61.9
Drugs: fg-4592, epoetin alfa, fg-4592, epoetin alfa
SMILES: CC1=NC(C(=O)NCC(O)=O)=C(O)C2=CC=C(OC3=CC=CC=C3)C=C12, OC(=O)CNC(=O)C1C(=O)N(C2CCCCC2)C(=O)N(C2CCCCC2)C1=O, CC1=NC(C(=O)NCC(O)=O)=C(O)C2=CC=C(OC3=CC=CC=C3)C=C12, OC(=O)CNC(=O)C1C(=O)N(C2CCCCC2)C(=O)N(C2CCCCC2)C1=O
Eligibility criteria:

        Key Inclusion Criteria:

          1. Age 18 to 75 years

          2. End-stage renal disease (ESRD) and receiving maintenance hemodialysis

          3. Two most recent hemoglobin values obtained during screening period must be within the
             ranges set below:

               -  Croup A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization
                  within 9.0 to 13.5 g/dL

               -  Group B. Hyporesponder Criteria: Hb range in the 8 weeks prior to randomization
                  within 8.5 to 13.5 g/dL

          4. Epoetin alfa, dose requirements:

               -  Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa
                  dose at baseline (i.e., no more than a 30% fluctuation in the weekly dose) during
                  the 4 weeks prior to study Day -3

                    -  Cohorts A-1 to A-4: Current and previous (past 4 weeks) epoetin alfa dose
                       range 25 to 85 IU/kg/dose, three times a week (TIW); weekly dose between 75
                       and 255 IU/kg/week

                    -  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 335
                       IU/kg/week

                    -  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

                    -  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

                    -  Cohorts A-10 to A-12: Optional cohorts TBD, dosing frequency and dose range
                       to be determined by sponsor

               -  Group B. Hyporesponder Criteria:

                    -  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

                    -  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

          5. Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and
             vitamin B12 within acceptable limits

          6. Absence of active or chronic gastrointestinal bleeding

          7. hsCRP <60 mg/L for normoresponders Cohorts A-8 through A-12 enrolled under Amendment
             3; no hsCRP criteria for hyporesponders

          8. Body weight: 40 to 140 kg (dry weight)

          9. Body mass index (BMI): 18 to 45 kg/m2

         10. 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:

          1. Anticipated change in hemodialysis prescription

          2. Any clinically significant infection or evidence of an underlying infection

          3. Positive for any of the following: Human immunodeficiency virus (HIV); hepatitis B
             surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab)

          4. History of chronic liver disease

          5. New York Heart Association Class III or IV congestive heart failure

          6. Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus
             erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in
             remission

          7. History of myelodysplastic syndrome

          8. History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric

          9. Active hemolysis or diagnosis of hemolytic syndrome

         10. Known bone marrow fibrosis

         11. Uncontrolled or symptomatic secondary hyperparathyroidism

         12. Any prior organ transplantation

         13. Drug-treated gastroparesis or short-bowel syndrome

         14. History of alcohol or drug abuse; or a positive drug screen for a substance that has
             not been prescribed for the subject

         15. Prior treatment with FG-4592

         16. Diagnosis or suspicion of renal cell carcinoma

         17. RBC transfusion within 12 weeks prior to Day 1, or anticipated need for RBC
             transfusion during the dosing period

         18. IV iron supplement within 2 weeks prior to Day 1 and/or unwilling to withhold IV iron
             during the dosing/Treatment period