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

• Sponsor: Biocad (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02506868
• Collaborator: (none)
• Enrollment: 196
• Locations: 30
• Arms: 2
• Actual Duration (Months): 28.5
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease; End Stage Renal Failure on Dialysis; Anemia	Drug: Darbepoetin alfa	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 196 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 8, 2015
• Actual Primary Completion Date: Jan 8, 2017
• Actual Study Completion Date: Dec 21, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Number or Percentage of Patients Who Have Target Hemoglobin Concentration During Evaluation Period [Weeks 21 to 24]

   Hb concentration between 100 and 120 g/l will be considered as target

2. Mean Darbepoetin Alfa Dose During Evaluation Period [Week 21 to Week 24]

   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)

3. Number or Percentage of Patients With Need for Blood Transfusions [Weeks 1 to 24]

4. Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study [Weeks 1 to 20]

5. Mean Hemoglobin Level During Evaluation Period [Week 24]

   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)

6. Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l [Weeks 21 to 24]

7. Hemoglobin Level Dynamics [Weeks 1 to 24]

8. Mean Darbepoetin Alfa Dose During the Whole Study [Week 24]

   The outcome includes the mean Darbepoetin Alfa Dose During the Whole Study

9. Mean Hemoglobin Level During the Whole Study (24 Week) [Week 24]

   The outcome includes the measuere of Mean Hemoglobin Level During the Whole Study (during the study period from week 1 to week 24 week)

10. Mean Hematocrit Level During the Whole Study [Week 24]

11. Number of Patients With AE/SAE (AE/SAE Incidence) [Weeks 1 to 52]

12. Number of Participants With Grade 3-4 AE/SAE [Weeks 1 to 52]

13. Number of Participants Who Withdrew From Study Due to AE/SAE [Weeks 1 to 52]

14. Number of Participants With Arterial and Venous Thrombotic Events [Weeks 1 to 52]

15. Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa [Weeks 1 to 52]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Josaphat Belgorod Regional Clinical Hospital	Belgorod		Russian Federation
2	Alyans Biomedical - Ural'skaya gruppa	Izhevsk		Russian Federation
3	Kaluga Region Hospital	Kaluga		Russian Federation
4	Kazan State Medical University	Kazan		Russian Federation
5	Fresenius Medical Care Kuban	Krasnodar		Russian Federation
6	NEFROS Ltd, Medical Centre	Krasnodar		Russian Federation
7	Centr Dializa Ltd	Moscow		Russian Federation
8	City Clinical Hospital #24	Moscow		Russian Federation
9	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
10	N.I.Pirogov City Clinical Hospital #1	Moscow		Russian Federation
11	Scientific Clinical Centre, JSC Russian Railways	Moscow		Russian Federation
12	Nefrolayn-Novosibirsk Ltd	Novosibirsk		Russian Federation
13	Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation, Urology and Interventional Radiology Research Institute	Obninsk		Russian Federation	249036
14	A.N. Kabanov City Clinical Hospital #1	Omsk		Russian Federation
15	Omsk Regional Clinical Hospital	Omsk		Russian Federation
16	V.A. Baranov Republican Hospital of Ministry of Health republic Karelia	Petrozavodsk		Russian Federation	185000
17	Regional Clinical Hospital, Saratov	Saratov		Russian Federation
18	Smolensk Regional Clinical Hospital	Smolensk		Russian Federation
19	City Mariin Hospital	St. Petersburg		Russian Federation	194104
20	City Hospital #40, Kurortny district	St. Petersburg		Russian Federation
21	Nikolaevskaya Hospital	St. Petersburg		Russian Federation
22	B.Braun Avitum Russland Clinics Ltd.	St.Petersburg		Russian Federation
23	Centr Dializa Sankt-Peterburg Ltd	St.Petersburg		Russian Federation
24	City Hospital #15	St.Petersburg		Russian Federation
25	North-Western State Medical University named after I.I Mechnikov under the Ministry of Public Health of the Russian Federation	St.Petersburg		Russian Federation
26	St.Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine	St.Petersburg		Russian Federation
27	State Healthcare Institution Holy Great Martyr Elizabeth City Hospital #2	St.Petersburg		Russian Federation
28	Tula Regional Hospital	Tula		Russian Federation	300053
29	Fresenius Nephrocare Ltd - Dialysis Centre #2, Ul'yanovsk	Ul'yanovsk		Russian Federation
30	State Healthcare Institution Volgograd Region Uronephrology Centre	Volgograd		Russian Federation

Sponsors and Collaborators

• Biocad

Investigators

• Study Director: Andrey Biryulin, MD, Biocad

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biocad
• ClinicalTrials.gov Identifier: NCT02506868
• Other Study ID Numbers: BCD-066-2
• First Posted: Jul 23, 2015
• Last Update Posted: May 7, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Biocad: darbepoetin alfa
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Anemia; Darbepoetin alfa

Study Results

Participant Flow

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Period Title: Main Period of Study (24 Weeks)
STARTED	98	98
mITT Population	98	97
Per Protocol Population	86	90
COMPLETED	86	90
NOT COMPLETED	12	8
Period Title: Main Period of Study (24 Weeks)
STARTED	86	90
COMPLETED	83	85
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	BCD-066	Aranesp	Total
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: weekly sc administration of darbepoetin alfa	Total of all reporting groups
Overall Participants	98	97	195
Age (years) [Median (Inter-Quartile Range) ]
mITT population	58	56	57
Per protocol	57.5	56	56.5
Sex: Female, Male (Count of Participants)
Female	56 57.1%	43 44.3%	99 50.8%
Male	42 42.9%	54 55.7%	96 49.2%
Female	47 48%	40 41.2%	87 44.6%
Male	39 39.8%	50 51.5%	89 45.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 3.1%	1 1%	4 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	95 96.9%	96 99%	191 97.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 3.1%	1 1%	4 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	83 84.7%	89 91.8%	172 88.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period
Time Frame	Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Geometric Mean (Standard Deviation) [gram per liter]	4.695 (10.941)	4.641 (8.987)

2. Secondary Outcome

Title	Number or Percentage of Patients Who Have Target Hemoglobin Concentration During Evaluation Period
Description	Hb concentration between 100 and 120 g/l will be considered as target
Time Frame	Weeks 21 to 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Count of Participants [Participants]	61 62.2%	61 62.9%

3. Secondary Outcome

Title	Mean Darbepoetin Alfa Dose During Evaluation Period
Description	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)
Time Frame	Week 21 to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Mean (Standard Deviation) [micrograms]	20.779 (10.858)	20.982 (10.970)

4. Secondary Outcome

Title	Number or Percentage of Patients With Need for Blood Transfusions
Time Frame	Weeks 1 to 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Count of Participants [Participants]	0 0%	0 0%

5. Secondary Outcome

Title	Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study
Time Frame	Weeks 1 to 20

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Count of Participants [Participants]	31 31.6%	24 24.7%

6. Secondary Outcome

Title	Mean Hemoglobin Level During Evaluation Period
Description	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)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Mean (Standard Deviation) [gram per liter]	114.054 (9.222)	115.277 (7.966)

7. Secondary Outcome

Title	Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l
Time Frame	Weeks 21 to 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Count of Participants [Participants]	1 1%	1 1%

8. Secondary Outcome

Title	Hemoglobin Level Dynamics
Time Frame	Weeks 1 to 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Week 1	111.155 (8.713)	112.68 (8.827)
Week 2	111.831 (9.332)	113.619 (9.85)
Week 3	113.802 (8.962)	115.378 (9.541)
Week 4	114.686 (9.416)	116.533 (10.276)
Week 8	116.279 (10.327)	116.846 (9.589)
Week 12	117.520 (10.317)	116.878 (10.488)
Week 16	117.326 (11.646)	115.322 (9.419)
Week 20	113.80 (10.61)	116.528 (9.05)
Week 21	114.593 (10.951)	115.966 (9.598)
Week 22	114.372 (10.619)	115.467 (8.656)
Week 23	114.247 (9.645)	114.582 (9.143)
Week 24	113.174 (9.604)	115.444 (8.8)

9. Secondary Outcome

Title	Mean Darbepoetin Alfa Dose During the Whole Study
Description	The outcome includes the mean Darbepoetin Alfa Dose During the Whole Study
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Mean (Standard Deviation) [micrograms]	22.625 (10.637)	22.449 (11.541)

10. Secondary Outcome

Title	Mean Hemoglobin Level During the Whole Study (24 Week)
Description	The outcome includes the measuere of Mean Hemoglobin Level During the Whole Study (during the study period from week 1 to week 24 week)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Mean (Standard Deviation) [gram per liter]	114.394 (6.376)	115.434 (6.213)

11. Secondary Outcome

Title	Mean Hematocrit Level During the Whole Study
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	86	90
Mean (Standard Deviation) [percentage of hematocrit (%)]	35.119 (2.194)	35.173 (2.502)

12. Secondary Outcome

Title	Number of Patients With AE/SAE (AE/SAE Incidence)
Time Frame	Weeks 1 to 52

Outcome Measure Data

Analysis Population Description

The analysis included all patients who received at least one injection of BCD-066 or Aranesp - mITT population. One patient from Aranesp group was excluded prior to the first administration.

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) or 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	98	97
Count of Participants [Participants]	79 80.6%	76 78.4%

13. Secondary Outcome

Title	Number of Participants With Grade 3-4 AE/SAE
Time Frame	Weeks 1 to 52

Outcome Measure Data

Analysis Population Description

The analysis included all patients who received at least one injection of BCD-066 or Aranesp - mITT population. One patient from Aranesp group was excluded prior to the first administration.

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) or 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	98	97
Count of Participants [Participants]	60 61.2%	51 52.6%

14. Secondary Outcome

Title	Number of Participants Who Withdrew From Study Due to AE/SAE
Time Frame	Weeks 1 to 52

Outcome Measure Data

Analysis Population Description

The analysis included all patients who received at least one injection of BCD-066 or Aranesp - mITT population. One patient from Aranesp group was excluded prior to the first administration.

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) or 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	98	97
Count of Participants [Participants]	6 6.1%	4 4.1%

15. Secondary Outcome

Title	Number of Participants With Arterial and Venous Thrombotic Events
Time Frame	Weeks 1 to 52

Outcome Measure Data

Analysis Population Description

The analysis included all patients who received at least one injection of BCD-066 or Aranesp - mITT population. One patient from Aranesp group was excluded prior to the first administration.

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) or 24 weeks of main period and 28 week of additional period Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	98	97
Count of Participants [Participants]	4 4.1%	5 5.2%

16. Secondary Outcome

Title	Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa
Time Frame	Weeks 1 to 52

Outcome Measure Data

Analysis Population Description

The analysis included all patients who received at least one injection of BCD-066 or Aranesp - mITT population. One patient from Aranesp group was excluded prior to the first administration.

Arm/Group Title	BCD-066	Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa	Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
Measure Participants	98	97
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study)
Adverse Event Reporting Description	The analysis included all patients who received at least one injection of BCD-066 or Aranesp - mITT population. One patient from Aranesp group was excluded prior to the first administration.
Arm/Group Title	BCD-066		Aranesp
Arm/Group Description	Patients in this arm received weekly subcutaneous injections of BCD-066 (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa		Patients in this arm received weekly subcutaneous injections of Aranesp (darbepoetin alfa) with dose level titration to maintain target hemoglobin level (100 - 120 g/l) for 52 weeks Darbepoetin alfa: Weekly sc administration of darbepoetin alfa
All Cause Mortality
	BCD-066		Aranesp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/98 (5.1%)		4/97 (4.1%)
Serious Adverse Events
	BCD-066		Aranesp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/98 (19.4%)		13/97 (13.4%)
Cardiac disorders
Sudden cardiac death	2/98 (2%)		2/97 (2.1%)
Paroxysmal atrial fibrillation	1/98 (1%)		1/97 (1%)
Acute myocardial infarction. Relapse of myocardial infarction	1/98 (1%)		0/97 (0%)
Eye disorders
cataract	1/98 (1%)		0/97 (0%)
Gastrointestinal disorders
peptic ulcer aggaravation	1/98 (1%)		0/97 (0%)
acute gastoentrocolitis	1/98 (1%)		0/97 (0%)
peritonitis	0/98 (0%)		1/97 (1%)
chronic pancreatitis aggravation	0/98 (0%)		1/97 (1%)
General disorders
Prepatellar hematoma of the left knee	0/98 (0%)		1/97 (1%)
Hepatobiliary disorders
acute gangrenous cholecystitis	1/98 (1%)		0/97 (0%)
chronic cholecystitis aggravation	1/98 (1%)		0/97 (0%)
Infections and infestations
sepsis	1/98 (1%)		0/97 (0%)
Injury, poisoning and procedural complications
Vascular access site thrombosis	3/98 (3.1%)		3/97 (3.1%)
Metabolism and nutrition disorders
diabetic foot	0/98 (0%)		1/97 (1%)
Nervous system disorders
cerebrovascular accident	0/98 (0%)		1/97 (1%)
Dyscirculatory encephalopathy	0/98 (0%)		1/97 (1%)
Reproductive system and breast disorders
breast cancer	1/98 (1%)		0/97 (0%)
Respiratory, thoracic and mediastinal disorders
pneumonia	1/98 (1%)		0/97 (0%)
pneumothorax	1/98 (1%)		0/97 (0%)
Vascular disorders
Chronic circulatory failure	1/98 (1%)		0/97 (0%)
Increased blood pressure	1/98 (1%)		1/97 (1%)
Paget-Schroetter syndrome	1/98 (1%)		0/97 (0%)
steal syndrome	0/98 (0%)		1/97 (1%)
pulmonary thromboembolism	0/98 (0%)		1/97 (1%)
Other (Not Including Serious) Adverse Events
	BCD-066		Aranesp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/98 (85.7%)		84/97 (86.6%)
Blood and lymphatic system disorders
lymphopenia	11/98 (11.2%)		12/97 (12.4%)
neutropenia	5/98 (5.1%)		5/97 (5.2%)
leukopenia	5/98 (5.1%)		4/97 (4.1%)
Investigations
C-reactive protein increased	8/98 (8.2%)		4/97 (4.1%)
Metabolism and nutrition disorders
hyperkalemia	51/98 (52%)		47/97 (48.5%)
hyperglycemia	8/98 (8.2%)		9/97 (9.3%)
Respiratory, thoracic and mediastinal disorders
acute respiratory infection	6/98 (6.1%)		5/97 (5.2%)
Vascular disorders
Increased blood pressure	42/98 (42.9%)		36/97 (37.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.