Study of FG-4592 in Subjects With Chronic Kidney Disease in China

Dose ranging study with two consecutive dose escalation cohorts. The study objective is to demonstrate that FG-4592 is effective in the correction of anemia in chronic kidney disease patients.

Inclusion criteria

• Age 18 to 75 years
• Subject has voluntarily signed and dated an informed consent form
• Chronic Kidney Disease, not receiving dialysis
• Hemoglobin (Hb) values in 4 screening visits and the mean Hb must be <10g/dL
• Aminotransferase levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) and total bilirubin must be ≤ upper limit of normal (ULN) during the screening period
• Serum alkaline phosphatase (ALP) ≤2x ULN during screening period. Subjects with serum ALP values between 1 x and 2 x ULN may be included only if bone-specific ALP (BSAP) is also elevated > ULN
• Total bilirubin values must be ≤ULN during screening period
• 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

Exclusion criteria

• Received any erythropoiesis-stimulating agent (ESA) other than epoetin alfa within 12 weeks prior to Day 1
• 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
• Serum albumin <3 g/dL
• 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 an investigational medication or treatment, or carryover effect of an investigational treatment expected, during the screening visit, treatment and follow-up period.
• 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