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

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

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.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease; End Stage Renal Failure on Dialysis
• Intervention / Treatment: Drug: Darbepoetin alfa

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).

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Belgorod, Russian Federation
    • St. Josaphat Belgorod Regional Clinical Hospital
  • Izhevsk, Russian Federation
    • Alyans Biomedical - Ural'skaya gruppa
  • Kaluga, Russian Federation
    • Kaluga Region Hospital
  • Kazan, Russian Federation
    • Kazan State Medical University
  • Krasnodar, Russian Federation
    • Fresenius Medical Care Kuban
  • Krasnodar, Russian Federation
    • NEFROS Ltd, Medical Centre
  • Moscow, Russian Federation
    • Centr Dializa Ltd
  • Moscow, Russian Federation
    • City Clinical Hospital #24
  • Moscow, 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
    • N.I.Pirogov City Clinical Hospital #1
  • Moscow, Russian Federation
    • Scientific Clinical Centre, JSC Russian Railways
  • Novosibirsk, Russian Federation
    • Nefrolayn-Novosibirsk Ltd
  • Obninsk, Russian Federation, 249036
    • Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation, Urology and Interventional Radiology Research Institute
  • Omsk, Russian Federation
    • Omsk Regional Clinical Hospital
  • Omsk, Russian Federation
    • A.N. Kabanov City Clinical Hospital #1
  • Petrozavodsk, Russian Federation, 185000
    • V.A. Baranov Republican Hospital of Ministry of Health republic Karelia
  • Saratov, Russian Federation
    • Regional Clinical Hospital, Saratov
  • Smolensk, Russian Federation
    • Smolensk Regional Clinical Hospital
  • St. Petersburg, Russian Federation, 194104
    • City Mariin Hospital
  • St. Petersburg, Russian Federation
    • City Hospital #40, Kurortny district
  • St. Petersburg, Russian Federation
    • Nikolaevskaya Hospital
  • St.Petersburg, Russian Federation
    • B.Braun Avitum Russland Clinics Ltd.
  • St.Petersburg, Russian Federation
    • Centr Dializa Sankt-Peterburg Ltd
  • St.Petersburg, Russian Federation
    • City Hospital #15
  • 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
    • St.Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine
  • St.Petersburg, Russian Federation
    • State Healthcare Institution Holy Great Martyr Elizabeth City Hospital #2
  • Tula, Russian Federation, 300053
    • Tula Regional Hospital
  • Ul'yanovsk, Russian Federation
    • Fresenius Nephrocare Ltd - Dialysis Centre #2, Ul'yanovsk
  • Volgograd, Russian Federation
    • State Healthcare Institution Volgograd Region Uronephrology Centre

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCD-066; 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; Weekly sc administration of darbepoetin alfa; Other Names: Aranesp; BCD-066
Active Comparator: Aranesp; 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; Weekly sc administration of darbepoetin alfa; Other Names: Aranesp; BCD-066

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Study Director: Andrey Biryulin, MD, Biocad

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2015
• Primary Completion (Actual): January 8, 2017
• Study Completion (Actual): December 21, 2017

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: April 21, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: darbepoetin alfa
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: BCD-066-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED