Clinical trial NCT02506868: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
End Stage Renal Failure on Dialysis
Anemia
Keywords: darbepoetin alfa
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2015-07-23
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period
timeFrame: Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 24
Secondary outcomes:
measure: Number or Percentage of Patients Who Have Target Hemoglobin Concentration During Evaluation Period
timeFrame: Weeks 21 to 24
measure: Mean Darbepoetin Alfa Dose During Evaluation Period
timeFrame: Week 21 to Week 24
measure: Number or Percentage of Patients With Need for Blood Transfusions
timeFrame: Weeks 1 to 24
measure: Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study
timeFrame: Weeks 1 to 20
measure: Mean Hemoglobin Level During Evaluation Period
timeFrame: Week 24
measure: Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l
timeFrame: Weeks 21 to 24
measure: Hemoglobin Level Dynamics
timeFrame: Weeks 1 to 24
measure: Mean Darbepoetin Alfa Dose During the Whole Study
timeFrame: Week 24
measure: Mean Hemoglobin Level During the Whole Study (24 Week)
timeFrame: Week 24
measure: Mean Hematocrit Level During the Whole Study
timeFrame: Week 24
measure: Number of Patients With AE/SAE (AE/SAE Incidence)
timeFrame: Weeks 1 to 52
measure: Number of Participants With Grade 3-4 AE/SAE
timeFrame: Weeks 1 to 52
measure: Number of Participants Who Withdrew From Study Due to AE/SAE
timeFrame: Weeks 1 to 52
measure: Number of Participants With Arterial and Venous Thrombotic Events
timeFrame: Weeks 1 to 52
measure: Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa
timeFrame: Weeks 1 to 52
Other outcomes:
Locations:
city: Belgorod
country: Russian Federation
facility: St. Josaphat Belgorod Regional Clinical Hospital
city: Izhevsk
country: Russian Federation
facility: Alyans Biomedical - Ural'skaya gruppa
city: Kaluga
country: Russian Federation
facility: Kaluga Region Hospital
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Krasnodar
country: Russian Federation
facility: Fresenius Medical Care Kuban
city: Krasnodar
country: Russian Federation
facility: NEFROS Ltd, Medical Centre
city: Moscow
country: Russian Federation
facility: Centr Dializa Ltd
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #24
city: Moscow
country: Russian Federation
facility: 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: N.I.Pirogov City Clinical Hospital #1
city: Moscow
country: Russian Federation
facility: Scientific Clinical Centre, JSC Russian Railways
city: Novosibirsk
country: Russian Federation
facility: Nefrolayn-Novosibirsk Ltd
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation, Urology and Interventional Radiology Research Institute
city: Omsk
country: Russian Federation
facility: A.N. Kabanov City Clinical Hospital #1
city: Omsk
country: Russian Federation
facility: Omsk Regional Clinical Hospital
city: Petrozavodsk
country: Russian Federation
facility: V.A. Baranov Republican Hospital of Ministry of Health republic Karelia
city: Saratov
country: Russian Federation
facility: Regional Clinical Hospital, Saratov
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: City Mariin Hospital
city: St. Petersburg
country: Russian Federation
facility: City Hospital #40, Kurortny district
city: St. Petersburg
country: Russian Federation
facility: Nikolaevskaya Hospital
city: St.Petersburg
country: Russian Federation
facility: B.Braun Avitum Russland Clinics Ltd.
city: St.Petersburg
country: Russian Federation
facility: Centr Dializa Sankt-Peterburg Ltd
city: St.Petersburg
country: Russian Federation
facility: City Hospital #15
city: St.Petersburg
country: Russian Federation
facility: 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: St.Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine
city: St.Petersburg
country: Russian Federation
facility: State Healthcare Institution Holy Great Martyr Elizabeth City Hospital #2
city: Tula
country: Russian Federation
facility: Tula Regional Hospital
city: Ul'yanovsk
country: Russian Federation
facility: Fresenius Nephrocare Ltd - Dialysis Centre #2, Ul'yanovsk
city: Volgograd
country: Russian Federation
facility: State Healthcare Institution Volgograd Region Uronephrology Centre
Study officials:
affiliation: Biocad
name: Andrey Biryulin, MD
role: STUDY_DIRECTOR
References: