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

Phase 3

Completed

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

Interventions: Drug: Darbepoetin alfa

Registration Number: NCT02506868

Lead Sponsor: Biocad

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 196

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BCD-066	Darbepoetin alfa	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
Aranesp	Darbepoetin alfa	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Number or Percentage of Patients Who Have Target Hemoglobin Concentration During Evaluation Period	Weeks 21 to 24	Hb concentration between 100 and 120 g/l will be considered as target
Hemoglobin Level Dynamics	Weeks 1 to 24
Number of Participants With Grade 3-4 AE/SAE	Weeks 1 to 52
Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l	Weeks 21 to 24
Mean Darbepoetin Alfa Dose During Evaluation Period	Week 21 to Week 24	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)
Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study	Weeks 1 to 20
Mean Darbepoetin Alfa Dose During the Whole Study	Week 24	The outcome includes the mean Darbepoetin Alfa Dose During the Whole Study
Number of Patients With AE/SAE (AE/SAE Incidence)	Weeks 1 to 52
Number or Percentage of Patients With Need for Blood Transfusions	Weeks 1 to 24
Mean Hemoglobin Level During Evaluation Period	Week 24	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)
Mean Hemoglobin Level During the Whole Study (24 Week)	Week 24	The outcome includes the measuere of Mean Hemoglobin Level During the Whole Study (during the study period from week 1 to week 24 week)
Number of Participants Who Withdrew From Study Due to AE/SAE	Weeks 1 to 52
Mean Hematocrit Level During the Whole Study	Week 24
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

Trial Locations

Locations (30): NEFROS Ltd, Medical Centre
🇷🇺
Krasnodar, Russian Federation
N.I.Pirogov City Clinical Hospital #1
🇷🇺
Moscow, Russian Federation
Alyans Biomedical - Ural'skaya gruppa
🇷🇺
Izhevsk, Russian Federation
City Hospital #40, Kurortny district
🇷🇺
St. Petersburg, Russian Federation
City Clinical Hospital #24
🇷🇺
Moscow, Russian Federation
St. Josaphat Belgorod Regional Clinical Hospital
🇷🇺
Belgorod, Russian Federation
Smolensk Regional Clinical Hospital
🇷🇺
Smolensk, Russian Federation
Centr Dializa Sankt-Peterburg Ltd
🇷🇺
St.Petersburg, Russian Federation
City Hospital #15
🇷🇺
St.Petersburg, Russian Federation
Kazan State Medical University
🇷🇺
Kazan, Russian Federation
Fresenius Medical Care Kuban
🇷🇺
Krasnodar, Russian Federation
Federal State Budgetary Institution "Academician V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation
🇷🇺
Moscow, Russian Federation
City Mariin Hospital
🇷🇺
St. Petersburg, Russian Federation
St.Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine
🇷🇺
St.Petersburg, Russian Federation
State Healthcare Institution Holy Great Martyr Elizabeth City Hospital #2
🇷🇺
St.Petersburg, Russian Federation
Tula Regional Hospital
🇷🇺
Tula, Russian Federation
Fresenius Nephrocare Ltd - Dialysis Centre #2, Ul'yanovsk
🇷🇺
Ul'yanovsk, Russian Federation
Kaluga Region Hospital
🇷🇺
Kaluga, Russian Federation
Centr Dializa Ltd
🇷🇺
Moscow, Russian Federation
Nefrolayn-Novosibirsk Ltd
🇷🇺
Novosibirsk, Russian Federation
Scientific Clinical Centre, JSC Russian Railways
🇷🇺
Moscow, Russian Federation
A.N. Kabanov City Clinical Hospital #1
🇷🇺
Omsk, Russian Federation
Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation, Urology and Interventional Radiology Research Institute
🇷🇺
Obninsk, Russian Federation
Omsk Regional Clinical Hospital
🇷🇺
Omsk, Russian Federation
V.A. Baranov Republican Hospital of Ministry of Health republic Karelia
🇷🇺
Petrozavodsk, Russian Federation
Regional Clinical Hospital, Saratov
🇷🇺
Saratov, Russian Federation
Nikolaevskaya Hospital
🇷🇺
St. Petersburg, Russian Federation
B.Braun Avitum Russland Clinics Ltd.
🇷🇺
St.Petersburg, Russian Federation
North-Western State Medical University named after I.I Mechnikov under the Ministry of Public Health of the Russian Federation
🇷🇺
St.Petersburg, Russian Federation
State Healthcare Institution Volgograd Region Uronephrology Centre
🇷🇺
Volgograd, Russian Federation