Safety and Efficacy Study of BCD-066 Compared to Aranesp® for Anemia Treatment in Chronic Kidney Disease Patients

Multicenter Double-blind Randomized Parallel Comparative Study of Efficacy and Safety of BCD-066 (CJSC BIOCAD, Russia) and Aranesp (Amgen Europe B.V., Netherlands) in Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis

The purpose of the study is to prove equivalence of efficacy and safety of BCD-066 and Aranesp® in treatment of anemia in end-stage chronic kidney disease patients on dialysis.

In this study CKD patients on dialysis previously treated by short-acting epoetins will switch to one of darbepoetin alfa products - BCD-066 (experimental arm) or Aranesp (active comparator) to maintain previously achieved target level of hemoglobin (100-120 g/l).

Patients will be treated for 52 weeks. IV iron supplementation will be provided to maintain serum ferritin level above 500 µg/l according to KDIGO Anemia Guidelines (2012).

Inclusion Criteria:

• Written informed consent
• Age between 18 and 75 years
• End-stage kidney disease
• Need for dialysis for at least 3 months before enrollment
• Need for at least 12 hours on standard dialysis procedure weekly
• Regular rHuEpo (epoetin alfa, epoetin beta, darbepoetin alfa) administration 1, 2 or 3 times a week (stable dose, stable frequency) for at least 3 months before enrollment
• Target hemoglobin level (100-120 g/l) for at least 3 months before enrollment
• Effective dialysis (Kt/v≥1,2)
• TSAT ≥20%, Serum ferritin >200 ng/ml
• Patients and their sexual partners with childbearing potential must implement reliable contraceptive measures during all the study treatment, starting 4 weeks prior to the administration of the first dose of investigational product until 4 weeks after the last dose of investigational product. This requirement does not apply to participants who have undergone surgical sterilization. Reliable contraceptive measures include two methods of contraception, including one barrier method
• Patients should be able to follow the Protocol procedures (according to Investigator's assessment)

Exclusion Criteria:

• Any other causes of anemia except for renal anemia, including folate and B12 deficiency, chronic blood loss, aluminium intoxication, sickle-cell anemia, chronic disease anemia (CRP above 20 mg/l), refractory anemia with blast cells in peripheral blood
• Lupus nephritis of kidney disease due to systemic vasculitis
• Platelet count below 100х10^9 cells/l
• Hemoglobin above 120 g/l or below 100 g/l
• Scheduled kidney transplant during study participation period
• Binding/neutralizing antibodies against erythropoetin/darbepoetin
• History of severe allergic reactions
• Vaccination less than 8 weeks before enrollment
• Liver cirrhosis with portal hypertension and/or splenomegaly and/or ascitis
• HIV infection, active HBV, HCV
• ALT, AST level above 3x ULN
• Bone marrow fibrosis
• Congestive heart failure (Grade IV NYHA)
• Resistant arterial hypertension
• Unstable angina
• Hemoglobinopathy, MDS, hematologic malignancy
• PRCA
• Severe secondary hyperparathyroidism (PTH > 9x ULN)
• GI bleeding history
• Thrombotic events history (myocardial infarction, stroke, TIA, DVT, PATE) less than 6 months before enrollment
• Acute hemolysis history
• Seizures, including epilepsy
• Major surgery in less than 1 month before enrollment
• Blood transfusions in less than 3 months before enrollment
• Acute inflammatory diseases or exacerbations of chronic inflammation including septic of aseptic inflammation foci
• Severe psychiatric disorders
• History of malignancy, excluding appropriately treated basal cell carcinoma or cervical carcinoma in situ
• Alcohol or drug abuse
• Hypersensitivity to darbepoetin alfa of any components of study drugs
• Simultaneous participation in other trials or in less than 3 months before enrollment
• Pregnancy of breast-feeding