Evaluation of Efficacy and Safety of Roxadustat in the Treatment of Anemia in Stable Dialysis Subjects

This study will consist of three study periods as follows:

1. Screening Period of up to 6 weeks (8 weeks if on Mircera)

2. Treatment Period: a minimum of 52 weeks, a maximum of up to 3 years.

3. A Follow-up period of 4 weeks.

A total of up to 820 patients will be randomized in a 1:1 ratio to receive either roxadustat
or Epoetin alfa (Active Control) in an open-label manner.

Under Amendment 1, approximately 150 incident dialysis subjects will be randomized to either
roxadustat or epoetin alfa (active control) in a 1:1 ratio

Inclusion Criteria:

- Subject age ≥ 18 years

- Subject receiving adequate dialysis using the same modality of dialysis for end-stage
renal disease for ≥ 3 months prior to and during screening.

Amendment 1 Only: Incident dialysis subjects receiving dialysis for native kidney ESRD for
≥ 2 weeks but ≤ 4 months at the time of randomization

- Subject is receiving IV or SC ESA for ≥ 8 weeks prior to screening and on a stable ESA
(≤30% change) dose during 4 weeks ( 8 weeks if on Mircera) prior to randomization.

Amendment 1 Only: Incident dialysis subjects must be on ESA for ≥ 4 weeks prior to
screening

- Mean of subject's 3 most recent Hb values must be ≥ 9.0 g/dL and ≤ 12.0 g/dL; with an
absolute difference of ≤ 1.3 g/dL between the highest and the lowest value.

Amendment 1 Only: For Incident dialysis subjects, mean of the three most recent central lab
Hb values during the Screening Period must be ≥ 8.5 g/dL and ≤12.0 g/dL

- Subject has a ferritin level of ≥ 100 ng/mL at screening

- Subject has a transferrin saturation (TSAT) level be ≥ 20% at screening

- Subject has a serum folate level ≥ lower limit of normal (LLN), Vitamin B12 level ≥
LLN

- Subject's ALT and AST are ≤ 3x the upper limit of normal (ULN), and TBL is ≤ 1.5x ULN
at screening

- Subject's body weight 45 kg to 160 kg.

Exclusion Criteria:

- Subject received an RBC transfusion within 8 weeks prior to randomization

- Subject has known history of myelodysplastic syndrome or multiple myeloma

- Subject has known inherited disease such as thalassemia or sickle cell anemia or other
known causes for anemia other than chronic kidney disease.

- Subject has known hemosiderosis, hemochromatosis, coagulation disorder,or
hypercoagulable condition

- Subject has known chronic inflammatory disease that could cause anemia

- Subject has anticipated surgery that is expected to cause blood loss

- Subject has known gastrointestinal bleeding

- Subject has history of chronic liver disease (eg,chronic infectious hepatitis,chronic
auto-immune liver disease,cirrhosis, or fibrosis of the liver)

- Subject has congestive heart failure (NYHA Class III or IV)

- Subject has had a heart attack, stroke, seizure, or a thrombotic/thromboembolic event
(eg, DVT or pulmonary embolism) within 12 weeks prior to participating in the study

- Subject has uncontrolled high blood pressure within 2 weeks prior to participating in
the study

- Subject has a history of malignancy, except for the following: cancers determined to
be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell
skin cancers, cervical cancer in situ, or resected colonic polyps.)

- Subject is positive for human immunodeficiency virus (HIV), Hepatitis B surface
antigen, or anti-hepatitis C virus antibody

- Subject has had any prior organ transplant (that has not been explanted)

- Subject has any of the following known untreated conditions; proliferative diabetic
retinopathy,diabetic macular edema,macular degeneration or retinal vein occlusion.