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

A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis (HD)

The purpose of this study is to evaluate the efficacy and safety of FG-4592 in maintaining and/or correcting hemoglobin (Hb) given to subjects with End Stage Renal Disease (ESRD) on maintenance hemodialysis and receiving epoetin alfa.

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:

1. Subject has voluntarily signed and dated an informed consent form

2. Age 18 to 75 years

3. End-stage renal disease (ESRD) and receiving maintenance hemodialysis TIW for ≥4 months prior to Day 1

4. 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.

5. 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)

6. Complete Blood Count (CBC), Hematology, liver function blood tests within acceptable limits

7. Serum folate and vitamin B12 levels above the lower limit of normal (LLN)

8. Body weight: 40 to 100 kg (dry weight) inclusive

9. Body mass index (BMI): 16 to 38 kg/m2 inclusive

10. HD subjects: dialysis vascular access via native arteriovenous fistula or synthetic graft (not via catheter)

Exclusion Criteria:

1. Anticipated change in hemodialysis prescription or access during the screening or dosing period of the study
2. 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,
3. Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); 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 other than glomerulonephritis that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
7. Active or chronic gastrointestinal bleeding, or a known coagulation disorder
8. Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.)
9. Hematological disorders, including myelodysplastic syndrome, multiple myeloma, or pure red cell aplasia
10. History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
11. Active hemolysis or diagnosis of hemolytic syndrome
12. Known bone marrow fibrosis
13. Uncontrolled or symptomatic secondary hyperparathyroidism (PTH>600ng/L)
14. Any prior organ transplantation
15. Drug-treated gastroparesis, short-bowel syndrome, or any other gastrointestinal condition that may lead to reduced absorption of study drug
16. History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the subject
17. Prior treatment with FG-4592
18. 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