Back to resultsComparative Study of the Efficacy and Safety of BCD-131 and Mircera in Treatment of Anemia in CKD Patients on Dialysis
Primary Purpose
Anemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BCD-131
Mircera
Sponsored by
About this trial
This is an interventional treatment trial for Anemia
Eligibility Criteria
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.
Sites / Locations
- City Clinical Hospital №9
- City Mariin Hospital
- B.Braun Avitum Russland Clinics Ltd.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
BCD-131 1,05 mcg/kg * conversion ratio
BCD-131 1,7 mcg/kg * conversion ratio
BCD-131 2,75 mcg/kg * conversion ratio
Mircera
Arm Description
subcutaneously monthly
subcutaneously monthly
Subcutaneously monthly
subcutaneously monthly
Outcomes
Primary Outcome Measures
Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period
The baseline hemoglobin will be calculated as the arithmetic mean of hemoglobin values obtained at screening and at Visit 1. The final hemoglobin value during the evaluation period will be calculated as the arithmetic mean of hemoglobin values obtained at Week 21 and Week 23.
Secondary Outcome Measures
The Proportion of Patients Who Developed AEs/SAEs That, in the Investigator's Opinion, Are Related to BCD-131
The proportion of patients, in each group, who developed СТСАЕ v. 4.03 Grade 3-4 AEs that, in the Investigator's opinion, are related to BCD-131
- the proportion of patients, in each group, who discontinued the study due to AEs/SAEs
The Proportion of BAb- and NAb-positive Patients
Blood sampling for immunogenicity assessment (BAbs and NAbs) will be performed in all the patients included in the study before the first injection and then at Week 9 and Week 23.
The immunogenicity endpoints will be analyzed after the completion of all periods of the study.
AUC(0-672 Hour)
Area under the concentration curve from the moment of injection to 672 h [28 days])
AUC(0-∞)
Area under the concentration curve from the moment of injection to infinity
Cmax
Maximum serum concentration of the drug product) after the first injection of the test/reference drug
AUEC(0-672 Hour)
Area under the effect curve from the drug injection to 672 h [28 days]) based on the change in the absolute reticulocyte count after the first injection of the test/reference drug
AC-Emax
Maximum absolute reticulocyte count after the first injection of BCD-131/Mircera®
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03519243
Brief Title
Comparative Study of the Efficacy and Safety of BCD-131 and Mircera in Treatment of Anemia in CKD Patients on Dialysis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
October 24, 2017 (Actual)
Primary Completion Date
December 1, 2018 (Actual)
Study Completion Date
December 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocad
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BCD-131 1,05 mcg/kg * conversion ratio
Arm Type
Experimental
Arm Description
subcutaneously monthly
Arm Title
BCD-131 1,7 mcg/kg * conversion ratio
Arm Type
Experimental
Arm Description
subcutaneously monthly
Arm Title
BCD-131 2,75 mcg/kg * conversion ratio
Arm Type
Experimental
Arm Description
Subcutaneously monthly
Arm Title
Mircera
Arm Type
Active Comparator
Arm Description
subcutaneously monthly
Intervention Type
Biological
Intervention Name(s)
BCD-131
Other Intervention Name(s)
pegylated darbepoetin beta
Intervention Description
subcutaneously monthly
Intervention Type
Biological
Intervention Name(s)
Mircera
Other Intervention Name(s)
Methoxy polyethylene glycol-epoetin beta
Intervention Description
subcutaneously monthly
Primary Outcome Measure Information:
Title
Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period
Description
The baseline hemoglobin will be calculated as the arithmetic mean of hemoglobin values obtained at screening and at Visit 1. The final hemoglobin value during the evaluation period will be calculated as the arithmetic mean of hemoglobin values obtained at Week 21 and Week 23.
Time Frame
Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 23
Secondary Outcome Measure Information:
Title
The Proportion of Patients Who Developed AEs/SAEs That, in the Investigator's Opinion, Are Related to BCD-131
Description
The proportion of patients, in each group, who developed СТСАЕ v. 4.03 Grade 3-4 AEs that, in the Investigator's opinion, are related to BCD-131
- the proportion of patients, in each group, who discontinued the study due to AEs/SAEs
Time Frame
Week 23
Title
The Proportion of BAb- and NAb-positive Patients
Description
Blood sampling for immunogenicity assessment (BAbs and NAbs) will be performed in all the patients included in the study before the first injection and then at Week 9 and Week 23.
The immunogenicity endpoints will be analyzed after the completion of all periods of the study.
Time Frame
Week 9, 23
Title
AUC(0-672 Hour)
Description
Area under the concentration curve from the moment of injection to 672 h [28 days])
Time Frame
3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1
Title
AUC(0-∞)
Description
Area under the concentration curve from the moment of injection to infinity
Time Frame
3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1, weeks 5, 9, 13, 17, 21
Title
Cmax
Description
Maximum serum concentration of the drug product) after the first injection of the test/reference drug
Time Frame
3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1, weeks 5, 9, 13, 17, 21
Title
AUEC(0-672 Hour)
Description
Area under the effect curve from the drug injection to 672 h [28 days]) based on the change in the absolute reticulocyte count after the first injection of the test/reference drug
Time Frame
3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1
Title
AC-Emax
Description
Maximum absolute reticulocyte count after the first injection of BCD-131/Mircera®
Time Frame
day 28
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:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roman Ivanov, PhD
Organizational Affiliation
JCS BIOCAD
Official's Role
Study Chair
Facility Information:
Facility Name
City Clinical Hospital №9
City
Minsk
Country
Belarus
Facility Name
City Mariin Hospital
City
St. Petersburg
ZIP/Postal Code
194104
Country
Russian Federation
Facility Name
B.Braun Avitum Russland Clinics Ltd.
City
St.Petersburg
Country
Russian Federation
12. IPD Sharing Statement
Learn more about this trial
Comparative Study of the Efficacy and Safety of BCD-131 and Mircera in Treatment of Anemia in CKD Patients on Dialysis
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