Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis in China

Dose ranging study with three consecutive dose escalation cohorts. The study objectives are to demonstrate that FG-4592 is effective in maintaining hemoglobin (Hb) levels when converting from epoetin alfa and to establish optimum starting doses and dose adjustment regimens for Hb maintenance.

Inclusion criteria

• Subject has voluntarily signed and dated an informed consent form
• Age 18 to 75 years
• End-stage renal disease (ESRD) and receiving maintenance hemodialysis TIW for ≥4 months prior to Day 1
• Hemoglobin (Hb) values in 4 screening visits and the mean Hb must be between 9.0 and 12.0 g/dL (inclusive), and the difference between them must be ≤1.5 g/dL.
• Stable doses of IV or Subcutaneous injection of epoetin alfa, defined as follows:

• Epoetin alfa dose range for 6 weeks prior to Day -7:

3000 to 20,000 IU/week

• Stable doses of epoetin alfa (i.e., the maximum epoetin alfa dose does not exceed 130% of the lowest dose of epoetin alfa taken in this period)
• Complete Blood Count (CBC), Hematology, liver function blood tests within acceptable limits
• Serum folate and vitamin B12 levels above the lower limit of normal (LLN)
• Body weight: 40 to 100 kg (dry weight) inclusive
• Body mass index (BMI): 16 to 38 kg/m2 inclusive
• HD subjects: dialysis vascular access via native arteriovenous fistula or synthetic graft (not via catheter)

Exclusion criteria

• Anticipated change in hemodialysis prescription or access during the screening or dosing period of the study
• Any clinically significant infection or evidence of an underlying infection such as a white blood cell count (WBC) > ULN during screening on two separate occasions,
• Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); 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 other than glomerulonephritis that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
• Active or chronic gastrointestinal bleeding, or a known coagulation disorder
• Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.)
• Hematological disorders, including myelodysplastic syndrome, multiple myeloma, or pure red cell aplasia
• 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 (PTH>600ng/L)
• Any prior organ transplantation
• Drug-treated gastroparesis, short-bowel syndrome, or any other gastrointestinal condition that may lead to reduced absorption of study drug
• History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the subject
• Prior treatment with FG-4592
• Use of traditional Chinese medicines (TCM) during the screening visit to Day 1 or plans to use TCM during the study unless approved in advance by the Medical Monitor