Study of the Efficacy and Safety of BCD-131 and Mircera® in the Treatment of Anemia in Patients With Chronic Kidney Disease on Dialysis

This study is designed to test the hypothesis that BCD-131 is non-inferior to Mircera for the treatment of anemia in patients with end-stage renal disease on dialysis, with the primary assessment occurring at Weeks 28-32 of treatment. Eligible subjects will have Stage 5 Chronic Kidney Disease (CKD) and will have been receiving dialysis (a minimum frequency of 3 sessions per week and at least 12 hours per week of standard hemodialysis, with a stable dialysis prescription) for at least 90 days prior to informed consent form (ICF) signature. Subjects must have anemia of renal origin with no other identifiable causes of anemia (including anemia of chronic disease, vitamin B12 deficiency, folic acid deficiency, or iron deficiency, etc.).

This study evaluates the efficacy of BCD-131 as maintenance therapy. Eligible patients must have received stable doses of erythropoiesis-stimulating agents (erythropoietin alfa, erythropoietin beta, or darbepoetin alfa) for at least 3 months prior to ICF signature and throughout the screening period, with target hemoglobin levels (100-120 g/L) maintained for at least 2 weeks prior to and at the time of screening.

The study comprises the following periods:

• Screening period (up to 28 days).
• Main treatment period (Weeks 0-32).
• Extension period (Weeks 33-84) for long-term safety and efficacy assessment. • Follow-up period (28 days after last investigational product dose at Week 84).

Inclusion criteria

• The patient signed a written ICF for participation in the study.
• Men and women aged 18 to 75 years inclusive at the time of signing the ICF.
• End stage kidney disease (documented).
• The need for dialysis sessions within at least the last 90 days prior to signing the ICF.
• For patients on hemodialysis - hemodialysis procedures should be at least 3 times a week, for a total duration of at least 12 hours a week.
• Documented use of recombinant erythropoietin (epoetin alfa, epoetin beta or darbepoetin alfa) for at least 90 days prior to signing the ICF.
• The dose of recombinant erythropoietins (epoetin alfa or epoetin beta received 1, 2 or 3 times a week, or darbepoetin alfa received once a week/once every 2 weeks) should be stable for at least 90 days prior to signing the ICF and the entire screening period (documented).
• Target hemoglobin level (100-120 g/L inclusive) based on the results of screening examination (two measurements).
• The efficacy of dialysis established at screening or not more than 14 days before signing the ICF (dialysis dose index (Kt/v) ≥1.2 in patients on long-term hemodialysis, and weekly Kt/v ≥1.7 for patients on peritoneal dialysis).
• Transferrin saturation ≥20%, ferritin level >100 ng/mL at screening.
• Cyancobalamine (vitamin B12) and folic acid levels within the laboratory reference values at screening.
• Willingness of patients of both sexes and their sexual partners of childbearing potential to use methods of contraception in accordance with the protocol, starting from signing the informed consent form, throughout the study and for up to 90 days after receiving the last dose of the drug in the clinical study, as well as to refrain from donation of eggs for female subjects or sperm for male subjects during this period.
• The ability of the patient to comply with the Protocol requirements, in the Investigator's opinion.

Exclusion criteria

• Any other diagnosed forms of anemia, except for anemia of renal disease, including anemia in chronic diseases (C-reactive protein level >20 mg/L at screening).
• Diagnosed lupus nephritis or chronic kidney disease due to systemic vasculitis.
• Platelet count <100×10^9/L based on the results of screening examination.
• A high probability of early withdrawal from the study, in particular a planned (i.e., available information about a planned date and/or a suitable donor) kidney transplant surgery during the estimated period of participation in the study.
• A history of severe allergic reactions (anaphylactic shock or multiple drug allergy) according to the patient, and hypersensitivity to recombinant erythropoietins, polyethylene glycol or any components of the study drugs, or to iron (III) hydroxide sucrose complex.
• Vaccination less than 8 weeks before signing the ICF (according to the patient).
• Diagnosed liver cirrhosis.
• HIV infection.
• ALT, AST >3хULN at screening.
• Decompensated heart disease (NYHA Class IV CHF).
• Resistant hypertension.
• Unstable angina.
• History of acute hemolysis episodes.
• Documented hemoglobinopathy, myelodysplastic syndrome, hematological malignancy, pure red cell aplasia.
• Severe secondary hyperparathyroidism (intact PTH>1000 pg/mL at screening) or biopsy-confirmed bone marrow fibrosis (myelofibrosis).
• Documented episodes of gastrointestinal or other bleeding within less than 90 days prior to signing the ICF.
• Documented history of episodes of thrombosis (acute myocardial infarction, stroke, transient ischemic attacks, deep vein thrombosis, pulmonary thromboembolism within less than 6 months before the signing of the ICF, as well as long-term vascular access thrombosis within 30 days before the signing of the ICF.
• Seizure syndrome, including a history of or epilepsy during the screening period.
• Documented major surgery less than 30 days before signing the ICF.
• Documented blood transfusion within less than 90 days prior to signing the ICF.
• Any acute or chronic infections in the stage of exacerbation, as well as other chronic diseases that at the time of signing the informed consent, may adversely affect the patient's safety while using the study therapy in the opinion of the investigator.
• A history of severe depression, suicidal ideation, or attempted suicide.
• Documented malignancies other than cured basal-cell carcinoma and/or cervical carcinoma in situ with a remission duration of more than 5 years at the time of signing the ICF.
• Known alcohol or drug addiction, or current signs of alcohol/drug addiction, which, according to the investigator, is contraindication for the treatment with the test drug/reference drug or limits the treatment adherence.
• Participation in other clinical studies of medicinal products within less than 90 calendar days prior to signing the informed consent form for participation in this study.
• Pregnancy or breastfeeding.