A Phase 3 Study of Efepoetin Alfa for Treatment of Anemia in Patients With Chronic Kidney Disease on Dialysis

Inclusion Criteria:

1. Adult males and females ≥ 18 years old.

2. Patient (or patient's legally acceptable representative) has voluntarily signed anddated an informed consent form (ICF), approved by an Ethics Committee (EC) orinstitutional review board (IRB), after the nature of the study has been explainedand the patient has had the opportunity to ask questions.

3. Patient with stage 5 CKD defined by estimated GFR (eGFR, ≤15 mL/min/1.73m2) onadequate HD for a minimum of 12 weeks prior to Day 1. *CKD staging will be based onthe five-stage system for classification of CKD based on KDIGO guidelines.

4. Hemodialysis patients with single-pool Kt/V ≥ 1.2 or urea reduction ratio ≥ 65%.

*Single-pool Kt/V or urea reduction ratio will be based on results measured within 4weeks prior to screening or during the screening period.

5. Patients must be on stable doses of IV injections of ESA (including biosimilars) forat least 6 weeks prior to Day 1. Minimum ESA dose;

• Epoetin alfa, epoetin beta, and epoetin kappa: ≥1,500 U/week

• Darbepoetin alfa: ≥20 µg/week

• Mircera®: ≥30 µg/2 weeks

6. Mean of the 2 most recent local laboratory Hb screening values obtained at least 6days apart, must be 9.0 g/dL to 12.0 g/dL, inclusive, with a difference of ≤1.5 g/dLbetween the highest and the lowest value.

7. Patients with serum ferritin ≥100 ng/mL at screening.

8. Patients with transferrin saturation (TSAT) ≥20% at screening.

9. Serum folate concentrations ≥lower limit of normal (LLN) at screening.

10. Serum total vitamin B12 concentrations ≥LLN at screening.

Exclusion Criteria:

1. Active acute or chronic infection, or uncontrolled or symptomatic inflammatorydisease other than glomerulonephritis that could impact erythropoiesis (e.g.,systemic lupus erythematosus, rheumatoid arthritis, celiac disease), or a C reactiveprotein level 40> mg/L (high sensitive C-reactive protein level > 10 mg/L).

2. By history or current clinical evidence, patients with active acute hepatitis Bvirus (HBV) or hepatitis C virus (HCV) infection should be excluded. Routinescreening for HBV, HCV, and human immunodeficiency virus (HIV) infection is notrequired in this protocol. Chronic HBV/HCV infection with liver function tests (LFT) >3 times of normal are excluded. Known HIV positive patients are excluded.

3. History or clinical evidence of cardiovascular, hematologic, hepatic, or anyphysical conditions that, in the opinion of the Investigator, would compromiseparticipation in the study.

4. Any of the following laboratory abnormalities at screening visit;

• Alanine transaminase (ALT) >3 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) >3 x ULN

• Total bilirubin >1.5 x ULN

5. Chronic congestive heart failure (New York Heart Association class III or IV).

6. High risk for early withdrawal or interruption of the study (due to myocardialinfarction, severe or unstable coronary artery disease, stroke, or severe liverdisease) within the 12 weeks before Screening or during Screening.

7. Uncontrolled hypertension defined as a sitting systolic blood pressure ≥170 mmHgand/or diastolic blood pressure ≥100 mmHg.

8. History of active malignancy except for cancers determined to be cured or inremission for ≥5 years, curatively resected basal cell or squamous cell skincancers, or in situ cancer at any site.

9. Patients with a history of overt gastrointestinal bleeding or any other bleedingepisode associated with a fall in Hb of ≥1 g/dL within the last 8 weeks prior toScreening.

10. Known history of myelodysplastic syndrome, multiple myeloma, hereditary hematologicdisease such as thalassemia, sickle cell anemia, pure red cell aplasia, or otherknown causes for anemia other than CKD, hemosiderosis, hemochromatosis, knowncoagulation disorder, or hypercoagulable condition.

11. Any prior functioning organ transplant or a scheduled organ transplantation, oranephric state (one or both kidneys).

12. Planned elective surgery that could lead to significant blood loss during the studyperiod.

13. Hypoalbuminemia (Serum albumin <2.5 g/dL) at Screening Visit.

14. Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior toDay 1.

15. Life expectancy of <12 months.

16. Cognitive or psychiatric condition rendering the patient unable to be cooperativewith and complete study requirements.

17. Hypersensitivity to any one of the investigational drugs or its excipients.

18. Received a blood transfusion (including RBC transfusion) within the 12 weeks priorto Screening, or blood transfusion is anticipated during the study period (excludingtemporary blood transfusion given in case of blood loss due to accident or surgery).

19. Immunosuppressive therapy (tacrolimus/cyclosporine, and other than corticosteroidsfor a chronic condition) within 12 weeks prior to Day 1.

20. History of alcohol or drug abuse within the past 2 years and inability to avoidconsumption of more than >3 alcoholic beverages per day.

21. Use of an investigational medication or treatment, participation in aninvestigational interventional study, or carryover effect of an investigationaltreatment expected during the study.

22. Females of childbearing potential or males who are unable/unwilling to take adequatecontraceptive precautions defined by the protocol for the duration of the study andfor at least 4 months for male subjects and 7 months for female patients after theend of the study. Females with a positive pregnancy test result within 24 hoursprior to study entry, are otherwise known to be pregnant, plan to become pregnant inthe next 12 months or are currently breastfeeding.

23. Patients who are investigational site staff members directly involved in the conductof the trial and their family members, site staff members otherwise supervised bythe Investigator, or patients who are Sponsor or clinical research organization (CRO) employees directly involved in the conduct of the study.

24. Patients with very limited functional capacity for which a target Hb value of 12g/dL may have a lower benefit/risk ratio.

25. Any medical condition (patients weighing over 150 kg) that, in the opinion of theInvestigator, may pose a safety risk to a patient in this study, may confoundefficacy or safety assessment, or may interfere with study participation