Anemia
Conditions
Brief summary
This single arm study will assess the efficacy, safety and tolerability of once-monthly administration of intravenous Mircera for the maintenance of hemoglobin levels in dialysis participants with chronic renal anemia. Participants will receive monthly intravenous injections of Mircera, at a starting dose of 120, 200 or 360 micrograms, according to the dose of epoetin administered in the week preceding first study drug administration. 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 [Mircera]
120, 200 or 360 micrograms iv monthly (starting dose)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic renal anemia; * Continuous stable intravenous maintenance epoetin therapy during previous month; * Regular long-term hemodialysis therapy with the same mode of dialysis for previous 3 months.
Exclusion criteria
* Transfusion of red blood cells during previous 2 months; * Poorly controlled hypertension, that is, sitting blood pressure exceeding 170/100 millimeter of mercury (mmHg) despite medication; * Significant acute or chronic bleeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Average Hemoglobin Concentration Within +/-1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range | Week 17 up to Week 24 | Percentage of participants maintaining their mean hemoglobin concentration in g/dL within plus or minus (+/-) 1 g/dL of their reference hemoglobin value, and between the target range of 10.0 and 12.0 g/dL during the efficacy evaluation period (EEP). The reference hemoglobin value was defined on the basis of the 5 assessments recorded during the Stability Verification Period (SVP) at Weeks -4, -3, -2, -1 and 0. The mean hemoglobin concentration for each individual participant during the EEP (Week 17 up to Week 24) was estimated as a time adjusted average. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin Concentration Between Reference (SVP) and EEP | Week -4 up to Week -1 and Week 17 up to Week 24 | The mean change of the time adjusted average of hemoglobin from reference value obtained during the SVP (Week -4 up to Week -1) and the value during EEP (Week 17 up to Week 24) was assessed. |
| Mean Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP | Week 17 up to Week 24 | Mean time spent by participants with hemoglobin concentration in the target range of 10.0 to 12.0 g/dL during the EEP (Week 17 to Week 24) was assessed. |
| Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range During EEP | Week 17 up to Week 24 | Percentage of participants maintaining hemoglobin concentration within the target range of 10.0 to 12.0 g/dL during EEP (Week 17 to Week 24) was assessed. |
| Number of Participants With Red Blood Cell Transfusion During the Study | Week -4 up to Week 28 | Number of participant who underwent red blood cell transfusion during the study was reported. |
| Number of Participants With Anti-epoetin Antibody | Week -4 and at early withdrawal or Week 28 | — |
| Percentage of Participants Requiring Any Dose Adjustment | Week 1 to Week 16 and Week 17 to Week 24 | Percentage of participants requiring adjustment in the dose of study drug during the dose titration period (DTP: Week 1 to Week 16) and EEP (Week 17 to Week 24) was reported. |
Countries
Czechia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| C.E.R.A. Adult participants with chronic renal disease and who had received intravenous epoetin maintenance treatment, received intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks. | 188 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Blood transfusion | 6 |
| Overall Study | Death | 7 |
| Overall Study | Kidney transplantation | 8 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Other reasons | 7 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | C.E.R.A. |
|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 11.56 |
| Sex: Female, Male Female | 84 Participants |
| Sex: Female, Male Male | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / 188 |
| serious Total, serious adverse events | 41 / 188 |
Outcome results
Primary
Percentage of Participants Maintaining Average Hemoglobin Concentration Within +/-1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range
Percentage of participants maintaining their mean hemoglobin concentration in g/dL within plus or minus (+/-) 1 g/dL of their reference hemoglobin value, and between the target range of 10.0 and 12.0 g/dL during the efficacy evaluation period (EEP). The reference hemoglobin value was defined on the basis of the 5 assessments recorded during the Stability Verification Period (SVP) at Weeks -4, -3, -2, -1 and 0. The mean hemoglobin concentration for each individual participant during the EEP (Week 17 up to Week 24) was estimated as a time adjusted average.
Time frame: Week 17 up to Week 24
Population: Per protocol (PP) population included all participants in the safety population with the exception of participants with less than 3 recorded hemoglobin values, missing administrations of C.E.R.A., withdrawal, inadequate iron status in Weeks 16-24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants Maintaining Average Hemoglobin Concentration Within +/-1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range | 53.3 percentage of participants |
Secondary
Change in Hemoglobin Concentration Between Reference (SVP) and EEP
The mean change of the time adjusted average of hemoglobin from reference value obtained during the SVP (Week -4 up to Week -1) and the value during EEP (Week 17 up to Week 24) was assessed.
Time frame: Week -4 up to Week -1 and Week 17 up to Week 24
Population: The Intention-to-treat (ITT) population included all participants who had received at least 1 dose of C.E.R.A. (Week 0) and for whom data for at least 1 follow-up variable had been available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A. | Change in Hemoglobin Concentration Between Reference (SVP) and EEP | 0.0 g/dL | Standard Deviation 1.21 |
Secondary
Mean Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP
Mean time spent by participants with hemoglobin concentration in the target range of 10.0 to 12.0 g/dL during the EEP (Week 17 to Week 24) was assessed.
Time frame: Week 17 up to Week 24
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A. | Mean Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP | 32 days | Standard Deviation 18.4 |
Secondary
Number of Participants With Anti-epoetin Antibody
Time frame: Week -4 and at early withdrawal or Week 28
Population: ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A. | Number of Participants With Anti-epoetin Antibody | Week -4 | 0 participants |
| C.E.R.A. | Number of Participants With Anti-epoetin Antibody | Early Withdrawal or Week 28 | 0 participants |
Secondary
Number of Participants With Red Blood Cell Transfusion During the Study
Number of participant who underwent red blood cell transfusion during the study was reported.
Time frame: Week -4 up to Week 28
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Number of Participants With Red Blood Cell Transfusion During the Study | 9 participants |
Secondary
Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range During EEP
Percentage of participants maintaining hemoglobin concentration within the target range of 10.0 to 12.0 g/dL during EEP (Week 17 to Week 24) was assessed.
Time frame: Week 17 up to Week 24
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range During EEP | 57.0 percentage of participants |
Secondary
Percentage of Participants Requiring Any Dose Adjustment
Percentage of participants requiring adjustment in the dose of study drug during the dose titration period (DTP: Week 1 to Week 16) and EEP (Week 17 to Week 24) was reported.
Time frame: Week 1 to Week 16 and Week 17 to Week 24
Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A. | Percentage of Participants Requiring Any Dose Adjustment | DTP (n = 186) | 75.0 percentage of participants |
| C.E.R.A. | Percentage of Participants Requiring Any Dose Adjustment | EEP (n = 165) | 32.0 percentage of participants |