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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Chronic Kidney Disease, End Stage Renal Failure on Dialysis, Anemia

Intervention / Treatment
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* Drug: Darbepoetin alfa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-066<br>Patients in this arm will receive weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks | Drug: Darbepoetin alfa<br>* Weekly sc administration of darbepoetin alfa<br>* Other names: BCD-066;|
| Active Comparator: Aranesp<br>Patients in this arm will receive weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks | Drug: Darbepoetin alfa<br>* Weekly sc administration of darbepoetin alfa<br>* Other names: BCD-066;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period |  | Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number or Percentage of Patients Who Have Target Hemoglobin Concentration During Evaluation Period | Hb concentration between 100 and 120 g/l will be considered as target | Weeks 21 to 24 | 
| Mean Darbepoetin Alfa Dose During Evaluation Period | The outcome includes the mean weekly dose of Darbepoetin Alfa which was administered to the patients during the period from week 21 to week 24 (last 4 weeks of the main period of the study) | Week 21 to Week 24 | 
| Number or Percentage of Patients With Need for Blood Transfusions |  | Weeks 1 to 24 | 
| Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study |  | Weeks 1 to 20 | 
| Mean Hemoglobin Level During Evaluation Period | The outcome includes the mean hemoglobin level which was registered in the patients during the last 4 weeks of the main period of the study (period from week 21 to week 24) | Week 24 | 
| Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l |  | Weeks 21 to 24 | 
| Hemoglobin Level Dynamics |  | Weeks 1 to 24 | 
| Mean Darbepoetin Alfa Dose During the Whole Study | The outcome includes the mean Darbepoetin Alfa Dose During the Whole Study | Week 24 | 
| Mean Hemoglobin Level During the Whole Study (24 Week) | The outcome includes the measuere of Mean Hemoglobin Level During the Whole Study (during the study period from week 1 to week 24 week) | Week 24 | 
| Mean Hematocrit Level During the Whole Study |  | Week 24 | 
| Number of Patients With AE/SAE (AE/SAE Incidence) |  | Weeks 1 to 52 | 
| Number of Participants With Grade 3-4 AE/SAE |  | Weeks 1 to 52 | 
| Number of Participants Who Withdrew From Study Due to AE/SAE |  | Weeks 1 to 52 | 
| Number of Participants With Arterial and Venous Thrombotic Events |  | Weeks 1 to 52 | 
| Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa |  | Weeks 1 to 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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darbepoetin alfa