A Study of Subcutaneous Mircera for the Maintenance Treatment of Dialysis Patients With Chronic Renal Anemia.

A Randomized, Open Label Study to Compare the Effect of Once Monthly Administration of Subcutaneous Mircera Versus Epoetin Alfa on Maintenance of Hemoglobin Levels, Safety and Tolerability in Dialysis Patients With Chronic Renal Anemia.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00560404

Enrollment

233

Registered

2007-11-19

Start date

2008-04-30

Completion date

2010-12-31

Last updated

2025-09-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anemia

Brief summary

This 2 arm study will compare the efficacy and safety of monthly administration of subcutaneous Mircera versus epoetin alfa for the maintenance of hemoglobin levels in dialysis patients with chronic renal anemia. Patients currently receiving maintenance treatment with epoetin alfa will be randomized to receive either monthly injections of Mircera with a starting dose (120, 200 or 360 micrograms) derived from the dose of epoetin alfa they were receiving in the week preceding study start, or to continue on epoetin alfa treatment. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Interventions

DRUGEpoetin alfa

As prescribed

DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]

120, 200 or 360 micrograms sc monthly (starting dose)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* adult patients, \>=18 years of age; * chronic renal anemia; * regular hemodialysis with the same schedule of dialysis for \>=12 weeks; * maintenance therapy with subcutaneous epoetin alfa at the same administration interval for 4 weeks.

Exclusion criteria

* transfusion of red blood cells during previous 2 months; * poorly controlled hypertension requiring interruption of epoetin alfa in previous 6 months; * acute or chronic bleeding; * active malignant disease (except non-melanoma skin cancer).

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Maintaining Their Mean Hemoglobin Concentration Within Plus or Minus 1 Gram/Deciliter of Their Reference Hemoglobin and Between the Target Range During Efficacy Evaluation Period	EEP (Week 29 to Week 36)	The target hemoglobin (Hb) range was defined as Hb concentration (gram/deciliter \[g/dL\]) between 10.5 and 12.5 g/dL during the efficacy evaluation period (EEP). EEP was from Week 29 to Week 36.

Secondary

Measure	Time frame	Description
Percentage of Participants Maintaining Individual Hemoglobin Concentration Within the Range of 10.5 - 12.5 Gram/Decilitre Throughout the Efficacy Evaluation Period	EEP (Weeks 29 to 36)	Percentage of participants maintaining individual Hb concentration within the Hb range 10.5 - 12.5 g/dL were reported during EEP. The EEP was from Week 29 to Week 36 of the study period.
Mean Time Spent in Hemoglobin Range of 10.5 - 12.5 Gram/Decilitre During the Efficacy Evaluation Period	EEP (Week 29 to Week 36)	Mean time to maintain Hb in the range of 10.5-12.5 g/dL during EEP is presented.
Number of Participants Who Required Dose Adjustments During the Dose Titration Period	DTP (Weeks 0 to 28)	The number of participants who required dose adjustments of C.E.R.A and epoetin alpha were reported during the Dose Titration Period (DTP). The DTP was from Week 0 to Week 28.
Number of Participants Who Required Dose Adjustments During the Efficacy Evaluation Period	EEP (Weeks 29 to 36)	The number of participants who required dose adjustments of C.E.R.A and epoetin alpha were reported during the Efficacy Evaluation Period (EEP). The EEP was from Week 29 to Week 36.
Number of Participants Received Red Blood Cells Transfusions	Up to Week 28	The number of participants who received at least 1 red blood cell (RBC) transfusion (packed RBC or whole blood) during the study was reported. For this study, blood transfusion was reported during the titration period. No transfusion occurred in the EEP.
Mean Values of Hemoglobin Concentration at Baseline and Week 36	Baseline and Week 36	The mean Hb concentration for each participant throughout the study was estimated. Summary data of mean values of Hb concentration at Baseline and Week 36 are presented.
Mean Values of Hematocrit at Baseline and Week 36	Baseline and Week 36	Hematocrit is the volume percentage of red blood cells in blood. The mean hematocrit for each participant was estimated throughout the study. Summary data of mean values of Hb at Baseline and Week 36 are presented.
Mean Values of Mean Corpuscular Volume at Baseline and Week 36	Baseline and Week 36	Mean corpuscular volume (MCV) is the average volume of red cells. The mean MCV concentration for each participant throughout the study was estimated. Summary data of mean values of MCV concentration at Baseline and Week 36 are presented.
Mean Change From Baseline in Hemoglobin Concentration Between Baseline and at the Efficacy Evaluation Period	Baseline (Weeks -4 to 0) and at EEP (Weeks 29 to 36)	The Baseline (Safety Verification Period) was from Week - 4 to Week -1.
Mean Values of Creatinine, Potassium, Phosphate, Parathyroid Hormone , Iron and Total Iron Binding Capacity Parameters at Baseline and Week 36	Baseline and Week 36	Mean values of laboratory parameters: creatinine, potassium, phosphate, parathyroid hormone (PTH), iron and total iron binding capacity (TIBC) for each participant were estimated throughout the study. Summary data of mean values of laboratory parameters are presented at Baseline and Week 36.
Mean Values of Albumin and Transferrin Concentration at Baseline and Week 36	Baseline and Week 36	The mean values of albumin and transferrin concentration for each participant throughout the study was estimated. Summary data of mean values of albumin and transferrin concentration at baseline and week 36 are presented.
Mean Values of Ferritin Concentration at Baseline and Week 36	Baseline and Week 36	Mean values of ferritin concentration for each participant throughout the study was estimated. Summary data of mean values of ferritin concentration at Baseline and Week 36 are presented.
Mean Values of Transferrin Saturation at Baseline and Week 36	Baseline and Week 36	The mean values of transferrin saturation (TS) for each participant were estimated throughout the study. Summary data of mean values of TS at Baseline and Week 36 are presented.
Mean Values of Aspartate Transaminase and Alkaline Phosphatase at Baseline and Week 36	Baseline and Week 36	The mean values of aspartate transaminase (AST) and alkaline phosphatase (ALP) levels in serum for each participant were estimated throughout the study. Summary data of mean values of Potassium and alkaline phosphatase level in serum at Baseline and Week 36 are presented.
Number of Participants With Adverse Events and Serious Adverse Events	Up to Week 40	An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Number of participants with at least one AE and SAE were reported.
Number of Participants With Abnormal Changes in ECG From Baseline to Week 40	From Baseline to Week 40	Twelve-lead ECG was performed.
Number of Participants With Abnormal Changes in Vital Signs From Baseline to Week 40	From Baseline to Week 40	Vital signs included blood pressure, pulse rate and body weight.
Mean Values of Leukocytes and Platelets Count at Baseline and Week 36	Baseline and Week 36	The mean values of laboratory parameters: leukocytes and platelets count for each participant was estimated throughout the study. Summary data of mean values of leukocytes and platelets count at Baseline and Week 36 are presented.

Countries

Brazil

Participant flow

Recruitment details

A total of 457 participants were enrolled across 24 centers in Brazil from period April 02, 2008 to July 02, 2009.

Pre-assignment details

All participants received epoetin alpha during a four-week safety verification period. Of 457 participants, 233 eligible participants entered the treatment period.

Participants by arm

Arm	Count
C.E.R.A. Participants received C.E.R.A. with drug dosage of 120, 200 or 360 microgram subcutaneously, every four weeks, for 36 weeks.	112
Epoetin Alpha Participants received the same total dose of epoetin alpha administrated in the last week of screening period in the study, subcutaneously, three times a week, for 36 weeks.	121
Total	233

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Administrative Reasons	1	1
Overall Study	Adverse Event	2	3
Overall Study	Death	3	3
Overall Study	Failure to return	1	2
Overall Study	Other withdrawal reason	13	5
Overall Study	Protocol Violation	12	7
Overall Study	Withdrew Consent	4	0

Baseline characteristics

Characteristic	C.E.R.A.	Epoetin Alpha	Total
Age, Continuous	54.5 years	53.0 years	54.0 years
Sex: Female, Male Female	43 Participants	53 Participants	96 Participants
Sex: Female, Male Male	69 Participants	68 Participants	137 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	83 / 112	92 / 121
serious Total, serious adverse events	27 / 112	16 / 121

Outcome results

Primary

Percentage of Participants Maintaining Their Mean Hemoglobin Concentration Within Plus or Minus 1 Gram/Deciliter of Their Reference Hemoglobin and Between the Target Range During Efficacy Evaluation Period

The target hemoglobin (Hb) range was defined as Hb concentration (gram/deciliter \[g/dL\]) between 10.5 and 12.5 g/dL during the efficacy evaluation period (EEP). EEP was from Week 29 to Week 36.

Time frame: EEP (Week 29 to Week 36)

Population: Per-protocol population included participants who received at least one dose of C.E.R.A. and had data of at least one follow-up variable excluding those participants who had not adhere the inclusion/exclusion criteria, had less than 3 recorded Hb values, and received any other epoetin alpha and blood transfusion in Weeks 0 to 44.

Arm	Measure	Value (NUMBER)
C.E.R.A.	Percentage of Participants Maintaining Their Mean Hemoglobin Concentration Within Plus or Minus 1 Gram/Deciliter of Their Reference Hemoglobin and Between the Target Range During Efficacy Evaluation Period	50.7 percentage of participants
Epoetin Alpha	Percentage of Participants Maintaining Their Mean Hemoglobin Concentration Within Plus or Minus 1 Gram/Deciliter of Their Reference Hemoglobin and Between the Target Range During Efficacy Evaluation Period	53.0 percentage of participants

95% CI: [-0.25, 0.2]

Secondary

Mean Change From Baseline in Hemoglobin Concentration Between Baseline and at the Efficacy Evaluation Period

The Baseline (Safety Verification Period) was from Week - 4 to Week -1.

Time frame: Baseline (Weeks -4 to 0) and at EEP (Weeks 29 to 36)

Population: The analysis was performed on ITT population.

Arm	Measure	Value (MEAN)	Dispersion
C.E.R.A.	Mean Change From Baseline in Hemoglobin Concentration Between Baseline and at the Efficacy Evaluation Period	-0.02 g/dL	Standard Deviation 1.4
Epoetin Alpha	Mean Change From Baseline in Hemoglobin Concentration Between Baseline and at the Efficacy Evaluation Period	0.05 g/dL	Standard Deviation 1.22

Secondary

Mean Time Spent in Hemoglobin Range of 10.5 - 12.5 Gram/Decilitre During the Efficacy Evaluation Period

Mean time to maintain Hb in the range of 10.5-12.5 g/dL during EEP is presented.

Time frame: EEP (Week 29 to Week 36)

Population: The analysis was performed on ITT population.

Arm	Measure	Value (MEAN)	Dispersion
C.E.R.A.	Mean Time Spent in Hemoglobin Range of 10.5 - 12.5 Gram/Decilitre During the Efficacy Evaluation Period	30.4 days	Standard Deviation 19.5
Epoetin Alpha	Mean Time Spent in Hemoglobin Range of 10.5 - 12.5 Gram/Decilitre During the Efficacy Evaluation Period	33.9 days	Standard Deviation 17

Secondary

Mean Values of Albumin and Transferrin Concentration at Baseline and Week 36

The mean values of albumin and transferrin concentration for each participant throughout the study was estimated. Summary data of mean values of albumin and transferrin concentration at baseline and week 36 are presented.