Comparative Study of the Efficacy and Safety of BCD-131 and Mircera in Treatment of Anemia in CKD Patients on Dialysis

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

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.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Biological: BCD-131; Biological: Mircera

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus
    • City Clinical Hospital №9
• Russian Federation
  • St. Petersburg, Russian Federation, 194104
    • City Mariin Hospital
  • St.Petersburg, Russian Federation
    • B.Braun Avitum Russland Clinics Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BCD-131 1,05 mcg/kg * conversion ratio; subcutaneously monthly	Biological: BCD-131; subcutaneously monthly; Other Names: pegylated darbepoetin beta
EXPERIMENTAL: BCD-131 1,7 mcg/kg * conversion ratio; subcutaneously monthly	Biological: BCD-131; subcutaneously monthly; Other Names: pegylated darbepoetin beta
EXPERIMENTAL: BCD-131 2,75 mcg/kg * conversion ratio; Subcutaneously monthly	Biological: BCD-131; subcutaneously monthly; Other Names: pegylated darbepoetin beta
ACTIVE_COMPARATOR: Mircera; subcutaneously monthly	Biological: Mircera; subcutaneously monthly; Other Names: Methoxy polyethylene glycol-epoetin beta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 23

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Week 23
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.	Week 9, 23
AUC(0-672 Hour)	Area under the concentration curve from the moment of injection to 672 h [28 days])	3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1
AUC(0-∞)	Area under the concentration curve from the moment of injection to infinity	3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1, weeks 5, 9, 13, 17, 21
Cmax	Maximum serum concentration of the drug product) after the first injection of the test/reference drug	3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1, weeks 5, 9, 13, 17, 21
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	3, 6, 12, 24, 48, 72, 96, 168, 336, 504, 672 h h after injection 1
AC-Emax	Maximum absolute reticulocyte count after the first injection of BCD-131/Mircera®	day 28

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 24, 2017
• Primary Completion (ACTUAL): December 1, 2018
• Study Completion (ACTUAL): December 10, 2018

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (ACTUAL): May 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: BCD-131-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No