Trial Outcomes & Findings for Safety and Efficacy Study of BCD-066 Compared to Aranesp® for Anemia Treatment in Chronic Kidney Disease Patients (NCT NCT02506868)

NCT ID: NCT02506868

Last Updated: 2020-05-07

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

196 participants

Primary outcome timeframe

Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 24

Results posted on

2020-05-07

Participant Flow

Participant milestones

Participant milestones
Measure	BCD-066 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	Aranesp 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
Main Period of Study (24 Weeks) STARTED	98	98
Main Period of Study (24 Weeks) mITT Population	98	97
Main Period of Study (24 Weeks) Per Protocol Population	86	90
Main Period of Study (24 Weeks) COMPLETED	86	90
Main Period of Study (24 Weeks) NOT COMPLETED	12	8
Additional Period of Study (Until 52W) STARTED	86	90
Additional Period of Study (Until 52W) COMPLETED	83	85
Additional Period of Study (Until 52W) NOT COMPLETED	3	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

two population: mITT and Per protocol

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline - measurements on Screening (weeks -4 - 0) and on day 1; Evaluation period - weekly measures on weeks 21 to 24

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period	4.695 gram per liter Standard Deviation 10.941	4.641 gram per liter Standard Deviation 8.987

SECONDARY outcome

Timeframe: Weeks 21 to 24

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

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Number or Percentage of Patients Who Have Target Hemoglobin Concentration During Evaluation Period	61 Participants	61 Participants

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Mean Darbepoetin Alfa Dose During Evaluation Period	20.779 micrograms Standard Deviation 10.858	20.982 micrograms Standard Deviation 10.970

SECONDARY outcome

Timeframe: Weeks 1 to 24

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Number or Percentage of Patients With Need for Blood Transfusions	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 1 to 20

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Number or Percentage of Patients With Need for 'Dose Titration' at the Beginning of the Study	31 Participants	24 Participants

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Mean Hemoglobin Level During Evaluation Period	114.054 gram per liter Standard Deviation 9.222	115.277 gram per liter Standard Deviation 7.966

SECONDARY outcome

Timeframe: Weeks 21 to 24

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Number or Percentage of Patients With Hemoglobin Level Between 90 and 100 g/l	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Weeks 1 to 24

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Hemoglobin Level Dynamics Week 1	111.155 gram per liter Standard Deviation 8.713	112.68 gram per liter Standard Deviation 8.827
Hemoglobin Level Dynamics Week 2	111.831 gram per liter Standard Deviation 9.332	113.619 gram per liter Standard Deviation 9.85
Hemoglobin Level Dynamics Week 3	113.802 gram per liter Standard Deviation 8.962	115.378 gram per liter Standard Deviation 9.541
Hemoglobin Level Dynamics Week 4	114.686 gram per liter Standard Deviation 9.416	116.533 gram per liter Standard Deviation 10.276
Hemoglobin Level Dynamics Week 8	116.279 gram per liter Standard Deviation 10.327	116.846 gram per liter Standard Deviation 9.589
Hemoglobin Level Dynamics Week 12	117.520 gram per liter Standard Deviation 10.317	116.878 gram per liter Standard Deviation 10.488
Hemoglobin Level Dynamics Week 16	117.326 gram per liter Standard Deviation 11.646	115.322 gram per liter Standard Deviation 9.419
Hemoglobin Level Dynamics Week 20	113.80 gram per liter Standard Deviation 10.61	116.528 gram per liter Standard Deviation 9.05
Hemoglobin Level Dynamics Week 21	114.593 gram per liter Standard Deviation 10.951	115.966 gram per liter Standard Deviation 9.598
Hemoglobin Level Dynamics Week 22	114.372 gram per liter Standard Deviation 10.619	115.467 gram per liter Standard Deviation 8.656
Hemoglobin Level Dynamics Week 23	114.247 gram per liter Standard Deviation 9.645	114.582 gram per liter Standard Deviation 9.143
Hemoglobin Level Dynamics Week 24	113.174 gram per liter Standard Deviation 9.604	115.444 gram per liter Standard Deviation 8.8

SECONDARY outcome

Timeframe: Week 24

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

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Mean Darbepoetin Alfa Dose During the Whole Study	22.625 micrograms Standard Deviation 10.637	22.449 micrograms Standard Deviation 11.541

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Mean Hemoglobin Level During the Whole Study (24 Week)	114.394 gram per liter Standard Deviation 6.376	115.434 gram per liter Standard Deviation 6.213

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	BCD-066 n=86 Participants 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	Aranesp n=90 Participants 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
Mean Hematocrit Level During the Whole Study	35.119 percentage of hematocrit (%) Standard Deviation 2.194	35.173 percentage of hematocrit (%) Standard Deviation 2.502

SECONDARY outcome

Timeframe: Weeks 1 to 52

Population: 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.

Outcome measures

Outcome measures
Measure	BCD-066 n=98 Participants 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	Aranesp n=97 Participants 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
Number of Patients With AE/SAE (AE/SAE Incidence)	79 Participants	76 Participants

SECONDARY outcome

Timeframe: Weeks 1 to 52

Outcome measures

Outcome measures
Measure	BCD-066 n=98 Participants 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	Aranesp n=97 Participants 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
Number of Participants With Grade 3-4 AE/SAE	60 Participants	51 Participants

SECONDARY outcome

Timeframe: Weeks 1 to 52

Outcome measures

Outcome measures
Measure	BCD-066 n=98 Participants 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	Aranesp n=97 Participants 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
Number of Participants Who Withdrew From Study Due to AE/SAE	6 Participants	4 Participants

SECONDARY outcome

Timeframe: Weeks 1 to 52

Outcome measures

Outcome measures
Measure	BCD-066 n=98 Participants 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	Aranesp n=97 Participants 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
Number of Participants With Arterial and Venous Thrombotic Events	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Weeks 1 to 52

Outcome measures

Outcome measures
Measure	BCD-066 n=98 Participants 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	Aranesp n=97 Participants 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
Number or Percentage of Patients With Binding and/or Neutralizing Antibodies Against Darbepoetin Alfa	0 Participants	0 Participants

Adverse Events

BCD-066

Serious events: 19 serious events

Other events: 84 other events

Deaths: 5 deaths

Aranesp

Serious events: 13 serious events

Other events: 84 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	BCD-066 n=98 participants at risk 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	Aranesp n=97 participants at risk 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
Metabolism and nutrition disorders hyperkalemia	52.0% 51/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	48.5% 47/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Blood and lymphatic system disorders lymphopenia	11.2% 11/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	12.4% 12/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Vascular disorders Increased blood pressure	42.9% 42/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	37.1% 36/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Investigations C-reactive protein increased	8.2% 8/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	4.1% 4/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Respiratory, thoracic and mediastinal disorders acute respiratory infection	6.1% 6/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	5.2% 5/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Metabolism and nutrition disorders hyperglycemia	8.2% 8/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	9.3% 9/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Blood and lymphatic system disorders neutropenia	5.1% 5/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	5.2% 5/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Blood and lymphatic system disorders leukopenia	5.1% 5/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	4.1% 4/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.

Additional Information

Yulia Linkova Medical Director

Biocad

Phone: +7 (495) 992 66 28

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	BCD-066 n=98 Participants 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	Aranesp n=97 Participants 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 n=195 Participants Total of all reporting groups
Age, Continuous mITT population	58 years n=98 Participants • two population: mITT and Per protocol	56 years n=97 Participants • two population: mITT and Per protocol	57 years n=195 Participants • two population: mITT and Per protocol
Age, Continuous Per protocol	57.5 years n=86 Participants • two population: mITT and Per protocol	56 years n=90 Participants • two population: mITT and Per protocol	56.5 years n=176 Participants • two population: mITT and Per protocol
Sex: Female, Male mITT · Female	56 Participants n=98 Participants • Two population: mITT and Per Protocol	43 Participants n=97 Participants • Two population: mITT and Per Protocol	99 Participants n=195 Participants • Two population: mITT and Per Protocol
Sex: Female, Male mITT · Male	42 Participants n=98 Participants • Two population: mITT and Per Protocol	54 Participants n=97 Participants • Two population: mITT and Per Protocol	96 Participants n=195 Participants • Two population: mITT and Per Protocol
Sex: Female, Male Per protocol · Female	47 Participants n=86 Participants • Two population: mITT and Per Protocol	40 Participants n=90 Participants • Two population: mITT and Per Protocol	87 Participants n=176 Participants • Two population: mITT and Per Protocol
Sex: Female, Male Per protocol · Male	39 Participants n=86 Participants • Two population: mITT and Per Protocol	50 Participants n=90 Participants • Two population: mITT and Per Protocol	89 Participants n=176 Participants • Two population: mITT and Per Protocol
Race (NIH/OMB) mITT · American Indian or Alaska Native	0 Participants n=98 Participants • Two population: mITT and Per protocol	0 Participants n=97 Participants • Two population: mITT and Per protocol	0 Participants n=195 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) mITT · Asian	3 Participants n=98 Participants • Two population: mITT and Per protocol	1 Participants n=97 Participants • Two population: mITT and Per protocol	4 Participants n=195 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) mITT · Native Hawaiian or Other Pacific Islander	0 Participants n=98 Participants • Two population: mITT and Per protocol	0 Participants n=97 Participants • Two population: mITT and Per protocol	0 Participants n=195 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) mITT · Black or African American	0 Participants n=98 Participants • Two population: mITT and Per protocol	0 Participants n=97 Participants • Two population: mITT and Per protocol	0 Participants n=195 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) mITT · White	95 Participants n=98 Participants • Two population: mITT and Per protocol	96 Participants n=97 Participants • Two population: mITT and Per protocol	191 Participants n=195 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) mITT · More than one race	0 Participants n=98 Participants • Two population: mITT and Per protocol	0 Participants n=97 Participants • Two population: mITT and Per protocol	0 Participants n=195 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) mITT · Unknown or Not Reported	0 Participants n=98 Participants • Two population: mITT and Per protocol	0 Participants n=97 Participants • Two population: mITT and Per protocol	0 Participants n=195 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) Per protocol · American Indian or Alaska Native	0 Participants n=86 Participants • Two population: mITT and Per protocol	0 Participants n=90 Participants • Two population: mITT and Per protocol	0 Participants n=176 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) Per protocol · Asian	3 Participants n=86 Participants • Two population: mITT and Per protocol	1 Participants n=90 Participants • Two population: mITT and Per protocol	4 Participants n=176 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) Per protocol · Native Hawaiian or Other Pacific Islander	0 Participants n=86 Participants • Two population: mITT and Per protocol	0 Participants n=90 Participants • Two population: mITT and Per protocol	0 Participants n=176 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) Per protocol · Black or African American	0 Participants n=86 Participants • Two population: mITT and Per protocol	0 Participants n=90 Participants • Two population: mITT and Per protocol	0 Participants n=176 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) Per protocol · White	83 Participants n=86 Participants • Two population: mITT and Per protocol	89 Participants n=90 Participants • Two population: mITT and Per protocol	172 Participants n=176 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) Per protocol · More than one race	0 Participants n=86 Participants • Two population: mITT and Per protocol	0 Participants n=90 Participants • Two population: mITT and Per protocol	0 Participants n=176 Participants • Two population: mITT and Per protocol
Race (NIH/OMB) Per protocol · Unknown or Not Reported	0 Participants n=86 Participants • Two population: mITT and Per protocol	0 Participants n=90 Participants • Two population: mITT and Per protocol	0 Participants n=176 Participants • Two population: mITT and Per protocol

Measure	BCD-066 n=98 participants at risk 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	Aranesp n=97 participants at risk 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
Respiratory, thoracic and mediastinal disorders pneumonia	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Hepatobiliary disorders acute gangrenous cholecystitis	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Vascular disorders Chronic circulatory failure	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Cardiac disorders Sudden cardiac death	2.0% 2/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	2.1% 2/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Cardiac disorders Paroxysmal atrial fibrillation	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Vascular disorders Increased blood pressure	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Infections and infestations sepsis	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Injury, poisoning and procedural complications Vascular access site thrombosis	3.1% 3/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	3.1% 3/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Cardiac disorders Acute myocardial infarction. Relapse of myocardial infarction	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Gastrointestinal disorders peptic ulcer aggaravation	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Reproductive system and breast disorders breast cancer	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Hepatobiliary disorders chronic cholecystitis aggravation	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Eye disorders cataract	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Vascular disorders Paget-Schroetter syndrome	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Respiratory, thoracic and mediastinal disorders pneumothorax	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Gastrointestinal disorders acute gastoentrocolitis	1.0% 1/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	0.00% 0/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
General disorders Prepatellar hematoma of the left knee	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Nervous system disorders cerebrovascular accident	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Gastrointestinal disorders peritonitis	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Vascular disorders steal syndrome	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Gastrointestinal disorders chronic pancreatitis aggravation	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Metabolism and nutrition disorders diabetic foot	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Vascular disorders pulmonary thromboembolism	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.
Nervous system disorders Dyscirculatory encephalopathy	0.00% 0/98 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.	1.0% 1/97 • adverse event were collected during 1 year (24 weeks of main and 28 weeks of additional periods of study) 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.