Anemia
Conditions
Brief summary
This single arm study will assess the efficacy, safety and tolerability of once-monthly administration of intravenous methoxy polyethylene glycolepoetin beta (Mircera) for the maintenance of hemoglobin levels in hemodialysis participants with chronic renal anemia. Participants currently receiving intravenous epoetin alfa or beta or darbepoetin alfa will receive intravenous Mircera at a starting dose of 120, 200 or 360 micrograms/month (based on the erythropoietin stimulating agent \[ESA\] dose administered on week -1). Subsequent doses will be adjusted to maintain hemoglobin levels within the target range of 10 to12 gram per deciliter (g/dL). The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.
Interventions
Intravenous methoxy polyethylene glycol-epoetin beta (C.E.R.A.) at starting dose of 120, 200, or 360 micrograms every 4 weeks for 24 weeks.
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 intravenous maintenance erythropoietin stimulating agent (ESA) treatment during previous month; * Regular long term hemodialysis therapy with the same mode of dialysis for \>=3 months.
Exclusion criteria
* Transfusion of red blood cells during previous 2 months; * Significant acute or chronic bleeding, such as overt gastrointestinal bleeding; * Active malignant disease (except non-melanoma skin cancer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Mean Hemoglobin Concentration Within Plus or Minus (+/-) 1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range | Week 17 up to Week 24 | Percentage of participants maintaining the mean hemoglobin concentration within +/- 1.0 g/dL of their reference hemoglobin value and within the target range of 10.0 to 12.0 g/dL during the efficacy evaluation period (EEP) was assessed. 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 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 0 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 0) and the value during EEP (Week 17 up to Week 24) was assessed. |
| Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range | 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. |
| Median Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP | Week 17 up to Week 24 | Median time spent by participants with hemoglobin concentration within the target range of 10.0 to 12.0 g/dL during the EEP (Week 17 to Week 24) was assessed. |
| Percentage of Participants Requiring Any Dose Adjustment | Week 1 up to Week 16 and Week 17 up to Week 24 | Percentage of participants requiring any 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. |
| Number of Participants With Red Blood Cell Transfusion During the Study | Week -4 up to Week 52 | Number of participant who underwent red blood cell transfusion during the study was reported. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| C.E.R.A. Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks. | 351 |
| Total | 351 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 15 |
| Overall Study | Blood transfusion | 24 |
| Overall Study | Death | 6 |
| Overall Study | Failure to return | 1 |
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | Other | 5 |
| Overall Study | Protocol Violation | 10 |
| Overall Study | Renal transplantation | 10 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | C.E.R.A. |
|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 13.32 |
| Sex: Female, Male Female | 149 Participants |
| Sex: Female, Male Male | 202 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 351 |
| serious Total, serious adverse events | 98 / 351 |
Outcome results
Primary
Percentage of Participants Maintaining Mean Hemoglobin Concentration Within Plus or Minus (+/-) 1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range
Percentage of participants maintaining the mean hemoglobin concentration within +/- 1.0 g/dL of their reference hemoglobin value and within the target range of 10.0 to 12.0 g/dL during the efficacy evaluation period (EEP) was assessed. 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 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 who received at least 1 dose of C.E.R.A. and for whom data for at least 1 follow-up variable was available with the exception of participants who did not fulfill the protocol specified inclusion criteria for this analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants Maintaining Mean Hemoglobin Concentration Within Plus or Minus (+/-) 1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range | 60.00 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 0) and the value during EEP (Week 17 up to Week 24) was assessed.
Time frame: Week -4 up to Week 0 and Week 17 up to Week 24
Population: PP Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A. | Change in Hemoglobin Concentration Between Reference SVP and EEP | -0.10 g/dL | Standard Deviation 0.98 |
Secondary
Median Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP
Median time spent by participants with hemoglobin concentration within 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: PP population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C.E.R.A. | Median Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP | 44.0 days |
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 52
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Number of Participants With Red Blood Cell Transfusion During the Study | 38 participants |
Secondary
Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range
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: PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range | 73.94 percentage of participants |
Secondary
Percentage of Participants Requiring Any Dose Adjustment
Percentage of participants requiring any 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 up to Week 16 and Week 17 up to Week 24
Population: PP population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A. | Percentage of Participants Requiring Any Dose Adjustment | DTP | 70.3 percentage of participants |
| C.E.R.A. | Percentage of Participants Requiring Any Dose Adjustment | EEP | 50.9 percentage of participants |