Comparative Study of the Efficacy and Safety of BCD-131 and Mircera in Treatment of Anemia in CKD Patients on Dialysis

Randomized Open-Label Comparative Study of the Efficacy and Safety of BCD-131 (JSC BIOCAD, Russia) and Mircera (F. Hoffmann-La Roche Ltd, Switzerland) in Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis

BCD-131 is pegylated darbepoetin beta. BCD-131-2 is International Multicenter Randomized Open-Label Comparative Study (Phase II) of the Efficacy and Safety of BCD-131 and Mircera in Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis.

The hypothesis of the study is that the efficacy of BCD-131 is equivalent to that of Mircera® based on the analysis of the primary endpoint (changes in the Hb level over the period of evaluation as compared to the baseline Hb level ) during the 21-week period of treatment.

This study is a study of the maintenance treatment of anemia. The study will include up to 100 dialysis patients with stage 5D chronic kidney disease, established efficacy of dialysis and renal anemia without other causes of anemia, receiving erythropoiesis-stimulating agents (ESA) and reaching target hemoglobin levels.

Inclusion Criteria:

• Signed written informed consent.
• Men and women aged from 18 to 75 years (inclusive) on the day of signing informed consent;
• End-stage kidney disease.
• Need for dialysis for at least 3 months before signing informed consent.
• Need for at least 12 hours on standard dialysis procedure weekly.
• rHuEpo (epoetin alpha, epoetin beta, darbepoetin alpha) administration for at least 3 months before signing informed consent.
• Regular rHuEpo (epoetin alfa, epoetin beta, darbepoetin alfa) administration 1, 2 or 3 times a week (stable dose, stable frequency) before signing informed consent.
• Target hemoglobin level (100-120 g/l) for at least 3 months before signing informed consent.
• Effective dialysis dose index (Kt/v) ≥1.2 for patients receiving hemodialysis and (Kt/v) ≥1.7 for patients receiving peritoneal dialysis.
• 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

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.
• Scheduled kidney transplant during study participation period.
• Hypersensitivity to darbepoetin alfa or of any components of study drugs, or to Fe (III)-hydroxide-sucrose complex.
• Vaccination less than 8 weeks before signing informed consent.
• Liver cirrhosis with portal hypertension and/or splenomegaly and/or ascitis.
• HIV infection, active HBV, HCV.
• ALT, AST level above 3x ULN.
• Congestive heart failure (Grade IV NYHA)
• Resistant arterial hypertension.
• Unstable angina.
• Hemoglobinopathy, MDS, hematologic malignancy, PRCA.
• Severe secondary hyperparathyroidism.
• Gastrointestinal bleeding history.
• Thrombotic events history (myocardial infarction, stroke, TIA, DVT, PATE) less than 6 months before signing informed consent.
• Seizures, including epilepsy.
• Major surgery in less than 1 month before signing informed consent
• Blood transfusions in less than 3 months before signing informed consent.
• Acute inflammatory diseases or exacerbations of chronic inflammation.
• Severe psychiatric disorders and suicidal ideation and suicidal behavior.
• History of malignancy, excluding appropriately treated basal cell carcinoma or cervical carcinoma in situ.
• Alcohol or drug abuse.
• Simultaneous participation in other trials or in less than 3 months before signing informed consent
• Pregnancy of breast-feeding.