Anemia
Conditions
Brief summary
This 2 arm study will evaluate the efficacy of intravenous Mircera treatment for the correction of anemia in patients with chronic kidney disease who are on dialysis. Patients will be randomized to receive either Mircera 0.6 micrograms/kg i.v. every 2 weeks, or epoetin 3 times per week i.v. according to approved treatment recommendations. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGmethoxy polyethylene glycol-epoetin beta [RO0503821, Mircera]
0.6 micrograms/kg every 2 weeks
DRUGEpoetin
As prescribed, iv, 3 times weekly
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * chronic renal anemia; * maintenance hemodialysis or peritoneal dialysis for \>=2 weeks before screening, and during screening period.
Exclusion criteria
* previous therapy with epoetin within 8 weeks prior to screening; * overt gastrointestinal bleeding within 8 weeks before screening or during screening period; * RBC transfusions within 8 weeks before screening or during screening period; * active malignant disease except non-melanoma skin cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Hemoglobin Response up to Week 24 | Up to Week 24 | Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL compared with baseline and Hb\>/=11 g/dL without red blood cell transfusion during 24-week correction phase. The average baseline value was estimated by the mean of all values recorded between the day of first study dose and the previous 20 days. The percentage of participants who achieved Hb response is presented |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time in Which Hemoglobin Value Was Maintained Within Target Range of >/= 11g/dL up to Week 24 | Up to Week 24 | Median time during the correction period in which Hb value was maintained within target range of \>/= 11.0 g/dL and an increase in hemoglobin from baseline \>/= 1.0 g/dL was reported. |
| Number of Participants Who Received Red Blood Cells Transfusions up to Week 49 | Up to Week 49 | The number of participants who received at least 1 red blood cell transfusion during the study is presented. RBC transfusions was given in case of medical need, i.e., in severely anemic participants with recognized symptoms or signs of anemia (e.g., in participants with acute blood loss, with severe angina, or whose Hb decreases to critical levels) |
| Number of Participants With Any Adverse Events and Serious Adverse Events | Up to Week 49 | 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. |
| Mean Change From Baseline in Hemoglobin Concentration at Week 24 | From Baseline (Day 1) to Week 24 | Mean hemoglobin levels and their changes in correction phase from baseline were presented. Baseline is defined as Day 1 visit. The mean Hb concentration from Baseline at week 24 was calculated by subtracting the baseline Hb concentration value from the week 24 value |
| Mean Change From Baseline in Vital Sign: Heart Rate Measurements up to Week 24 | From Baseline (Day 1) to Week 24 | Heart rate was measured before blood sampling for all participants and before the dialysis session. Baseline is defined as Day 1. One participant from CERA group and two participants from Epoetin Beta group did not receive any study medication and were excluded from the safety analysis. |
| Number of Participants With Abnormal Changes in Electrocardiogram up to Week 24 | Up to Week 24 | Twelve-lead ECG was recorded before or after the dialysis session. Number of participants with abnormal changes in electrocardiogram observed at any time point was reported. One participant from CERA group and two participants from Epoetin Beta group did not receive any study medication and were excluded from the safety analysis. |
| Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | From Baseline (Day 1) to Week 24 | Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline and end of correction phase (Week 24) is presented. SBP and DBP were determined both before and after the dialysis session for participants. Baseline is defined as Day 1 visit. One participant from CERA group and two participants from Epoetin Beta group did not receive any study medication and were excluded from the safety analysis. |
Countries
South Korea
Participant flow
Recruitment details
A total of 80 participants were enrolled in this study conducted from 05 November 2007 to 23 December 2009 at 7 centers in Korea.
Participants by arm
| Arm | Count |
|---|---|
| Correction Phase: CERA Eligible participants were administered CERA IV once every 2 weeks at the starting dose of 0.6 μg/kg for 24 weeks. | 39 |
| Correction Phase: Epoetin Beta Eligible participants were administered Epoetin beta IV three times per week at the starting dose of 40 IU/kg for 24 weeks. | 41 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Correction Phase (CERA or Epoetin Beta) | Kidney transplantation | 2 | 0 | 0 |
| Correction Phase (CERA or Epoetin Beta) | Lack of Efficacy | 1 | 0 | 0 |
| Correction Phase (CERA or Epoetin Beta) | Lost to Follow-up | 1 | 1 | 0 |
| Correction Phase (CERA or Epoetin Beta) | Protocol Violation | 1 | 0 | 0 |
| Correction Phase (CERA or Epoetin Beta) | RBC transfusion | 0 | 1 | 0 |
| Correction Phase (CERA or Epoetin Beta) | Withdrawal by Subject | 1 | 3 | 0 |
| Maintenance Phase (CERA) | Kidney transplantation | 0 | 0 | 1 |
| Maintenance Phase (CERA) | Other Reason | 0 | 0 | 1 |
| Maintenance Phase (CERA) | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Correction Phase: CERA | Correction Phase: Epoetin Beta | Total |
|---|---|---|---|
| Age, Continuous | 55 Years STANDARD_DEVIATION 15.3 | 54.3 Years STANDARD_DEVIATION 12.8 | 54.7 Years STANDARD_DEVIATION 14 |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Male | 21 Participants | 23 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 34 / 38 | 39 / 39 | 51 / 54 |
| serious Total, serious adverse events | 10 / 38 | 6 / 39 | 8 / 54 |
Outcome results
Primary
Percentage of Participants Who Achieved Hemoglobin Response up to Week 24
Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL compared with baseline and Hb\>/=11 g/dL without red blood cell transfusion during 24-week correction phase. The average baseline value was estimated by the mean of all values recorded between the day of first study dose and the previous 20 days. The percentage of participants who achieved Hb response is presented
Time frame: Up to Week 24
Population: The Intent-to-Treat population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Correction Phase: CERA | Percentage of Participants Who Achieved Hemoglobin Response up to Week 24 | 79.5 Percentage of participants |
| Correction Phase: Epoetin Beta | Percentage of Participants Who Achieved Hemoglobin Response up to Week 24 | 87.8 Percentage of participants |
Secondary
Mean Change From Baseline in Hemoglobin Concentration at Week 24
Mean hemoglobin levels and their changes in correction phase from baseline were presented. Baseline is defined as Day 1 visit. The mean Hb concentration from Baseline at week 24 was calculated by subtracting the baseline Hb concentration value from the week 24 value
Time frame: From Baseline (Day 1) to Week 24
Population: The Intent-to-Treat population included all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Correction Phase: CERA | Mean Change From Baseline in Hemoglobin Concentration at Week 24 | 2.00 Grams per deciliter (g/dL) | Standard Deviation 1.51 |
| Correction Phase: Epoetin Beta | Mean Change From Baseline in Hemoglobin Concentration at Week 24 | 2.03 Grams per deciliter (g/dL) | Standard Deviation 1.37 |
Secondary
Mean Change From Baseline in Vital Sign: Heart Rate Measurements up to Week 24
Heart rate was measured before blood sampling for all participants and before the dialysis session. Baseline is defined as Day 1. One participant from CERA group and two participants from Epoetin Beta group did not receive any study medication and were excluded from the safety analysis.
Time frame: From Baseline (Day 1) to Week 24
Population: All participants who received at least one dose of the study medication and had a safety follow-up, whether withdrawn prematurely or not, included in the Safety Population. Only participants available at the time of assessment were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Correction Phase: CERA | Mean Change From Baseline in Vital Sign: Heart Rate Measurements up to Week 24 | -5.39 Beats per minute for heart rate | Standard Deviation 13.5 |
| Correction Phase: Epoetin Beta | Mean Change From Baseline in Vital Sign: Heart Rate Measurements up to Week 24 | -1.79 Beats per minute for heart rate | Standard Deviation 10.1 |
Secondary
Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24
Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline and end of correction phase (Week 24) is presented. SBP and DBP were determined both before and after the dialysis session for participants. Baseline is defined as Day 1 visit. One participant from CERA group and two participants from Epoetin Beta group did not receive any study medication and were excluded from the safety analysis.
Time frame: From Baseline (Day 1) to Week 24
Population: All participants who received at least one dose of the study medication and had a safety follow-up, whether withdrawn prematurely or not, included in the Safety Population. Only participants available at the time of assessment were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Correction Phase: CERA | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Pre-dialysis: SBP | 2.74 millimeters of mercury | Standard Deviation 22.5 |
| Correction Phase: CERA | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Post-dialysis: SBP | 5.26 millimeters of mercury | Standard Deviation 22.3 |
| Correction Phase: CERA | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Post-dialysis: DBP | 0.84 millimeters of mercury | Standard Deviation 13.7 |
| Correction Phase: CERA | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Pre-dialysis: DBP | -1.74 millimeters of mercury | Standard Deviation 13.3 |
| Correction Phase: Epoetin Beta | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Post-dialysis: DBP | 3.28 millimeters of mercury | Standard Deviation 11.7 |
| Correction Phase: Epoetin Beta | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Pre-dialysis: SBP | 2.72 millimeters of mercury | Standard Deviation 19.2 |
| Correction Phase: Epoetin Beta | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Pre-dialysis: DBP | 3.87 millimeters of mercury | Standard Deviation 11.5 |
| Correction Phase: Epoetin Beta | Mean Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure up to Week 24 | Post-dialysis: SBP | 2.59 millimeters of mercury | Standard Deviation 23 |
Secondary
Median Time in Which Hemoglobin Value Was Maintained Within Target Range of >/= 11g/dL up to Week 24
Median time during the correction period in which Hb value was maintained within target range of \>/= 11.0 g/dL and an increase in hemoglobin from baseline \>/= 1.0 g/dL was reported.
Time frame: Up to Week 24
Population: The Intent-to-Treat population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Correction Phase: CERA | Median Time in Which Hemoglobin Value Was Maintained Within Target Range of >/= 11g/dL up to Week 24 | 84 Days |
| Correction Phase: Epoetin Beta | Median Time in Which Hemoglobin Value Was Maintained Within Target Range of >/= 11g/dL up to Week 24 | 72 Days |
Secondary
Number of Participants Who Received Red Blood Cells Transfusions up to Week 49
The number of participants who received at least 1 red blood cell transfusion during the study is presented. RBC transfusions was given in case of medical need, i.e., in severely anemic participants with recognized symptoms or signs of anemia (e.g., in participants with acute blood loss, with severe angina, or whose Hb decreases to critical levels)
Time frame: Up to Week 49
Population: The Intent-to-Treat Population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Correction Phase: CERA | Number of Participants Who Received Red Blood Cells Transfusions up to Week 49 | 8 Number of participants |
| Correction Phase: Epoetin Beta | Number of Participants Who Received Red Blood Cells Transfusions up to Week 49 | 2 Number of participants |
| Maintenance Phase: CERA | Number of Participants Who Received Red Blood Cells Transfusions up to Week 49 | 1 Number of participants |
Secondary
Number of Participants With Abnormal Changes in Electrocardiogram up to Week 24
Twelve-lead ECG was recorded before or after the dialysis session. Number of participants with abnormal changes in electrocardiogram observed at any time point was reported. One participant from CERA group and two participants from Epoetin Beta group did not receive any study medication and were excluded from the safety analysis.
Time frame: Up to Week 24
Population: All participants who received at least one dose of the study medication and had a safety follow-up, whether withdrawn prematurely or not, included in the Safety Population. Only participants available at the time of assessment were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Correction Phase: CERA | Number of Participants With Abnormal Changes in Electrocardiogram up to Week 24 | 3 Number of participants |
| Correction Phase: Epoetin Beta | Number of Participants With Abnormal Changes in Electrocardiogram up to Week 24 | 3 Number of participants |
Secondary
Number of Participants With Any Adverse Events and Serious Adverse Events
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.
Time frame: Up to Week 49
Population: All participants who received at least one dose of the study medication and had a safety follow-up, whether withdrawn prematurely or not, included in the Safety Population. One participant from CERA group and two participants from Epoetin Beta group did not receive any study medication and were excluded from the safety analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Correction Phase: CERA | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any AE | 34 Number of participants |
| Correction Phase: CERA | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any SAE | 10 Number of participants |
| Correction Phase: Epoetin Beta | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any AE | 39 Number of participants |
| Correction Phase: Epoetin Beta | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any SAE | 6 Number of participants |
| Maintenance Phase: CERA | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any SAE | 8 Number of participants |
| Maintenance Phase: CERA | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any AE | 51 Number of participants |