Back to resultsSafety and Efficacy Study of BCD-066 Compared to Aranesp® for Anemia Treatment in Chronic Kidney Disease Patients
Primary Purpose
Chronic Kidney Disease, End Stage Renal Failure on Dialysis, Anemia
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Darbepoetin alfa
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Disease focused on measuring darbepoetin alfa
Eligibility Criteria
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
Sites / Locations
- St. Josaphat Belgorod Regional Clinical Hospital
- Alyans Biomedical - Ural'skaya gruppa
- Kaluga Region Hospital
- Kazan State Medical University
- Fresenius Medical Care Kuban
- NEFROS Ltd, Medical Centre
- Centr Dializa Ltd
- City Clinical Hospital #24
- Federal State Budgetary Institution "Academician V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation
- N.I.Pirogov City Clinical Hospital #1
- Scientific Clinical Centre, JSC Russian Railways
- Nefrolayn-Novosibirsk Ltd
- Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation, Urology and Interventional Radiology Research Institute
- A.N. Kabanov City Clinical Hospital #1
- Omsk Regional Clinical Hospital
- V.A. Baranov Republican Hospital of Ministry of Health republic Karelia
- Regional Clinical Hospital, Saratov
- Smolensk Regional Clinical Hospital
- City Mariin Hospital
- City Hospital #40, Kurortny district
- Nikolaevskaya Hospital
- B.Braun Avitum Russland Clinics Ltd.
- Centr Dializa Sankt-Peterburg Ltd
- City Hospital #15
- North-Western State Medical University named after I.I Mechnikov under the Ministry of Public Health of the Russian Federation
- St.Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine
- State Healthcare Institution Holy Great Martyr Elizabeth City Hospital #2
- Tula Regional Hospital
- Fresenius Nephrocare Ltd - Dialysis Centre #2, Ul'yanovsk
- State Healthcare Institution Volgograd Region Uronephrology Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
BCD-066
Aranesp
Arm Description
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
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
Outcomes
Primary Outcome Measures
Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period
Secondary Outcome Measures
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
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)
Number or Percentage of Patients With Need for Blood Transfusions
Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study
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)
Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l
Hemoglobin Level Dynamics
Mean Darbepoetin Alfa Dose During the Whole Study
The outcome includes the mean Darbepoetin Alfa Dose During the Whole Study
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)
Mean Hematocrit Level During the Whole Study
Number of Patients With AE/SAE (AE/SAE Incidence)
Number of Participants With Grade 3-4 AE/SAE
Number of Participants Who Withdrew From Study Due to AE/SAE
Number of Participants With Arterial and Venous Thrombotic Events
Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02506868
Brief Title
Safety and Efficacy Study of BCD-066 Compared to Aranesp® for Anemia Treatment in Chronic Kidney Disease Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
August 8, 2015 (Actual)
Primary Completion Date
January 8, 2017 (Actual)
Study Completion Date
December 21, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocad
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease, End Stage Renal Failure on Dialysis, Anemia
Keywords
darbepoetin alfa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
196 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BCD-066
Arm Type
Experimental
Arm Description
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
Arm Title
Aranesp
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Darbepoetin alfa
Other Intervention Name(s)
Aranesp, BCD-066
Intervention Description
Weekly sc administration of darbepoetin alfa
Primary Outcome Measure Information:
Title
Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period
Time Frame
Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 24
Secondary Outcome Measure Information:
Title
Number or Percentage of Patients Who Have Target Hemoglobin Concentration During Evaluation Period
Description
Hb concentration between 100 and 120 g/l will be considered as target
Time Frame
Weeks 21 to 24
Title
Mean Darbepoetin Alfa Dose During Evaluation Period
Description
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)
Time Frame
Week 21 to Week 24
Title
Number or Percentage of Patients With Need for Blood Transfusions
Time Frame
Weeks 1 to 24
Title
Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study
Time Frame
Weeks 1 to 20
Title
Mean Hemoglobin Level During Evaluation Period
Description
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)
Time Frame
Week 24
Title
Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l
Time Frame
Weeks 21 to 24
Title
Hemoglobin Level Dynamics
Time Frame
Weeks 1 to 24
Title
Mean Darbepoetin Alfa Dose During the Whole Study
Description
The outcome includes the mean Darbepoetin Alfa Dose During the Whole Study
Time Frame
Week 24
Title
Mean Hemoglobin Level During the Whole Study (24 Week)
Description
The outcome includes the measuere of Mean Hemoglobin Level During the Whole Study (during the study period from week 1 to week 24 week)
Time Frame
Week 24
Title
Mean Hematocrit Level During the Whole Study
Time Frame
Week 24
Title
Number of Patients With AE/SAE (AE/SAE Incidence)
Time Frame
Weeks 1 to 52
Title
Number of Participants With Grade 3-4 AE/SAE
Time Frame
Weeks 1 to 52
Title
Number of Participants Who Withdrew From Study Due to AE/SAE
Time Frame
Weeks 1 to 52
Title
Number of Participants With Arterial and Venous Thrombotic Events
Time Frame
Weeks 1 to 52
Title
Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa
Time Frame
Weeks 1 to 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrey Biryulin, MD
Organizational Affiliation
Biocad
Official's Role
Study Director
Facility Information:
Facility Name
St. Josaphat Belgorod Regional Clinical Hospital
City
Belgorod
Country
Russian Federation
Facility Name
Alyans Biomedical - Ural'skaya gruppa
City
Izhevsk
Country
Russian Federation
Facility Name
Kaluga Region Hospital
City
Kaluga
Country
Russian Federation
Facility Name
Kazan State Medical University
City
Kazan
Country
Russian Federation
Facility Name
Fresenius Medical Care Kuban
City
Krasnodar
Country
Russian Federation
Facility Name
NEFROS Ltd, Medical Centre
City
Krasnodar
Country
Russian Federation
Facility Name
Centr Dializa Ltd
City
Moscow
Country
Russian Federation
Facility Name
City Clinical Hospital #24
City
Moscow
Country
Russian Federation
Facility Name
Federal State Budgetary Institution "Academician V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation
City
Moscow
Country
Russian Federation
Facility Name
N.I.Pirogov City Clinical Hospital #1
City
Moscow
Country
Russian Federation
Facility Name
Scientific Clinical Centre, JSC Russian Railways
City
Moscow
Country
Russian Federation
Facility Name
Nefrolayn-Novosibirsk Ltd
City
Novosibirsk
Country
Russian Federation
Facility Name
Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation, Urology and Interventional Radiology Research Institute
City
Obninsk
ZIP/Postal Code
249036
Country
Russian Federation
Facility Name
A.N. Kabanov City Clinical Hospital #1
City
Omsk
Country
Russian Federation
Facility Name
Omsk Regional Clinical Hospital
City
Omsk
Country
Russian Federation
Facility Name
V.A. Baranov Republican Hospital of Ministry of Health republic Karelia
City
Petrozavodsk
ZIP/Postal Code
185000
Country
Russian Federation
Facility Name
Regional Clinical Hospital, Saratov
City
Saratov
Country
Russian Federation
Facility Name
Smolensk Regional Clinical Hospital
City
Smolensk
Country
Russian Federation
Facility Name
City Mariin Hospital
City
St. Petersburg
ZIP/Postal Code
194104
Country
Russian Federation
Facility Name
City Hospital #40, Kurortny district
City
St. Petersburg
Country
Russian Federation
Facility Name
Nikolaevskaya Hospital
City
St. Petersburg
Country
Russian Federation
Facility Name
B.Braun Avitum Russland Clinics Ltd.
City
St.Petersburg
Country
Russian Federation
Facility Name
Centr Dializa Sankt-Peterburg Ltd
City
St.Petersburg
Country
Russian Federation
Facility Name
City Hospital #15
City
St.Petersburg
Country
Russian Federation
Facility Name
North-Western State Medical University named after I.I Mechnikov under the Ministry of Public Health of the Russian Federation
City
St.Petersburg
Country
Russian Federation
Facility Name
St.Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine
City
St.Petersburg
Country
Russian Federation
Facility Name
State Healthcare Institution Holy Great Martyr Elizabeth City Hospital #2
City
St.Petersburg
Country
Russian Federation
Facility Name
Tula Regional Hospital
City
Tula
ZIP/Postal Code
300053
Country
Russian Federation
Facility Name
Fresenius Nephrocare Ltd - Dialysis Centre #2, Ul'yanovsk
City
Ul'yanovsk
Country
Russian Federation
Facility Name
State Healthcare Institution Volgograd Region Uronephrology Centre
City
Volgograd
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Safety and Efficacy Study of BCD-066 Compared to Aranesp® for Anemia Treatment in Chronic Kidney Disease Patients
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