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

Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02506868
• Other study ID #: BCD-066-2
• Status: Completed
• Phase: Phase 3
• Start date: August 8, 2015
• Est. completion date: December 21, 2017

Study information

• Verified date: April 2020
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: December 21, 2017
• Est. primary completion date: January 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 100?10^9 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

Related Conditions & MeSH terms

• Anemia
• Chronic Kidney Disease
• End Stage Renal Failure on Dialysis
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Drug:
• Darbepoetin alfa
Weekly sc administration of darbepoetin alfa

Locations

Country	Name	City	State
Russian Federation	St. Josaphat Belgorod Regional Clinical Hospital	Belgorod
Russian Federation	Alyans Biomedical - Ural'skaya gruppa	Izhevsk
Russian Federation	Kaluga Region Hospital	Kaluga
Russian Federation	Kazan State Medical University	Kazan
Russian Federation	Fresenius Medical Care Kuban	Krasnodar
Russian Federation	NEFROS Ltd, Medical Centre	Krasnodar
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	Moscow
Russian Federation	Nefrolayn-Novosibirsk Ltd	Novosibirsk
Russian Federation	Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation, Urology and Interventional Radiology Research Institute	Obninsk
Russian Federation	A.N. Kabanov City Clinical Hospital #1	Omsk
Russian Federation	Omsk Regional Clinical Hospital	Omsk
Russian Federation	V.A. Baranov Republican Hospital of Ministry of Health republic Karelia	Petrozavodsk
Russian Federation	Regional Clinical Hospital, Saratov	Saratov
Russian Federation	Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	City Hospital #40, Kurortny district	St. Petersburg
Russian Federation	City Mariin Hospital	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	St.Petersburg
Russian Federation	Tula Regional Hospital	Tula
Russian Federation	Fresenius Nephrocare Ltd - Dialysis Centre #2, Ul'yanovsk	Ul'yanovsk
Russian Federation	State Healthcare Institution Volgograd Region Uronephrology Centre	Volgograd

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Number or Percentage of Patients With Need for Blood Transfusions		Weeks 1 to 24
Secondary	Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study		Weeks 1 to 20
Secondary	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
Secondary	Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l		Weeks 21 to 24
Secondary	Hemoglobin Level Dynamics		Weeks 1 to 24
Secondary	Mean Darbepoetin Alfa Dose During the Whole Study	The outcome includes the mean Darbepoetin Alfa Dose During the Whole Study	Week 24
Secondary	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
Secondary	Mean Hematocrit Level During the Whole Study		Week 24
Secondary	Number of Patients With AE/SAE (AE/SAE Incidence)		Weeks 1 to 52
Secondary	Number of Participants With Grade 3-4 AE/SAE		Weeks 1 to 52
Secondary	Number of Participants Who Withdrew From Study Due to AE/SAE		Weeks 1 to 52
Secondary	Number of Participants With Arterial and Venous Thrombotic Events		Weeks 1 to 52
Secondary	Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa		Weeks 1 to 52