Anemia
Conditions
Brief summary
This two arm study will compare the efficacy and safety of subcutaneous Mircera versus darbepoetin alfa for the maintenance of hemoglobin levels in kidney transplant recipients with chronic renal anemia. Patients currently receiving maintenance treatment with darbepoetin alfa will be randomized either to receive 4-weekly injections of Mircera with a starting dose (120, 200 or 360 micrograms subcutaneously) derived from the dose of darbepoetin alfa they were receiving in the 2 weeks preceding study start, or to stay on 2-weekly darbepoetin alfa therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGDarbepoetin alfa
As prescribed
DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]
120, 200 or 360 micrograms sc 4-weekly (starting dose)
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, \> or = 18 years of age; * kidney transplant recipients with stage 3 or stage 4 chronic kidney disease; * functioning graft of \> 6 months and \< 10 years after kidney transplantation, with no signs of acute rejection; * stable maintenance subcutaneous darbepoetin alfa therapy every 2 weeks.
Exclusion criteria
* transfusion of red blood cells during previous 2 months; * poorly controlled hypertension; * significant acute or chronic bleeding; * need for dialysis therapy expected in next 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Maintaining Average Haemoglobin (Hb) Concentration During the Efficacy Evaluation Period (EEP) Within the Target Range | Weeks 16-28 | Key outcomes will be assessed during the first 12 weeks following the 16 weeks dose titration period, i.e. during the Efficacy Evaluation Period (EEP). Assessments performed every four weeks, beginning at week 16 up to week 28. The reference haemoglobin is defined as the mean of the two assessments recorded during the SVP (weeks -4 and -2). For the purposes of efficacy assessment the target haemoglobin concentration range will be defined as ± 1 g/dL of the reference haemoglobin concentration AND within the range 10 - 12 g/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hb Concentration From Baseline to Efficacy Evaluation Period (EEP) | Baseline to 28 weeks | Reference haemoglobin at baseline is defined as the mean of the two assessments recorded at weeks -4 and -2. Additional assessments were then performed every 4 weeks at week 0 through week 28. Mean change was calculated as value at 28 weeks minus baseline. |
| Percentage of Participants Maintaining Hb Concentration in 10-12 g/dL Range Throughout the Efficacy Evaluation Period (EEP) | Weeks 16-28 | — |
| Mean Time Spent in 10-12g/dL Range During the Efficacy Evaluation Period (EEP) | Weeks 16-28 | Efficacy Evaluation Period was the 12 weeks following 16 weeks of treatment in the Dose Titration Period. |
| Percentage of Participants Needing Dose Adjustments | Up to 28 weeks | Assessment of the Dose Titration Period of 16 weeks of treatment and following 12 weeks, known as the Efficacy Evaluation Period (EEP). |
| Incidence of RBC Transfusions | Up to 28 weeks | Assessment of the Dose Titration Period of 16 weeks of treatment and following 12 weeks, known as the Efficacy Evaluation Period (EEP). |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CERA Treatment Once Monthly CERA 120, 200 or 360 micrograms subcutaneously | 46 |
| Darbepoetin Alfa Once Biweekly Darbepoetin Alfa as prescribed | 25 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | CERA Treatment Once Monthly | Darbepoetin Alfa Once Biweekly | Total |
|---|---|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 11.04 | 56.7 years STANDARD_DEVIATION 10.49 | 55.3 years STANDARD_DEVIATION 10.82 |
| Region of Enrollment Spain | 46 participants | 25 participants | 71 participants |
| Sex: Female, Male Female | 27 Participants | 8 Participants | 35 Participants |
| Sex: Female, Male Male | 19 Participants | 17 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 46 | 16 / 25 |
| serious Total, serious adverse events | 9 / 46 | 3 / 25 |
Outcome results
Primary
The Percentage of Participants Maintaining Average Haemoglobin (Hb) Concentration During the Efficacy Evaluation Period (EEP) Within the Target Range
Key outcomes will be assessed during the first 12 weeks following the 16 weeks dose titration period, i.e. during the Efficacy Evaluation Period (EEP). Assessments performed every four weeks, beginning at week 16 up to week 28. The reference haemoglobin is defined as the mean of the two assessments recorded during the SVP (weeks -4 and -2). For the purposes of efficacy assessment the target haemoglobin concentration range will be defined as ± 1 g/dL of the reference haemoglobin concentration AND within the range 10 - 12 g/dL.
Time frame: Weeks 16-28
Population: Analysis was performed in the per protocol (PP) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CERA Treatment Once Monthly | The Percentage of Participants Maintaining Average Haemoglobin (Hb) Concentration During the Efficacy Evaluation Period (EEP) Within the Target Range | 64.29 percentage of participants |
| Darbepoetin Alfa Once Biweekly | The Percentage of Participants Maintaining Average Haemoglobin (Hb) Concentration During the Efficacy Evaluation Period (EEP) Within the Target Range | 57.14 percentage of participants |
p-value: 0.5947Fisher Exact
Secondary
Incidence of RBC Transfusions
Assessment of the Dose Titration Period of 16 weeks of treatment and following 12 weeks, known as the Efficacy Evaluation Period (EEP).
Time frame: Up to 28 weeks
Population: Analysis performed with the intent to treat (ITT) population, which includes all participants receiving at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CERA Treatment Once Monthly | Incidence of RBC Transfusions | 1 participants |
| Darbepoetin Alfa Once Biweekly | Incidence of RBC Transfusions | 2 participants |
Secondary
Mean Change in Hb Concentration From Baseline to Efficacy Evaluation Period (EEP)
Reference haemoglobin at baseline is defined as the mean of the two assessments recorded at weeks -4 and -2. Additional assessments were then performed every 4 weeks at week 0 through week 28. Mean change was calculated as value at 28 weeks minus baseline.
Time frame: Baseline to 28 weeks
Population: Analysis performed in the Intent toTreat (ITT) population, which includes all participants receiving at least one dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CERA Treatment Once Monthly | Mean Change in Hb Concentration From Baseline to Efficacy Evaluation Period (EEP) | 0.08 g/dL | Standard Deviation 0.85 |
| Darbepoetin Alfa Once Biweekly | Mean Change in Hb Concentration From Baseline to Efficacy Evaluation Period (EEP) | 0.05 g/dL | Standard Deviation 1.06 |
Secondary
Mean Time Spent in 10-12g/dL Range During the Efficacy Evaluation Period (EEP)
Efficacy Evaluation Period was the 12 weeks following 16 weeks of treatment in the Dose Titration Period.
Time frame: Weeks 16-28
Population: Analysis was performed using the intent to treat (ITT) population, which includes all participants receiving at least one dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CERA Treatment Once Monthly | Mean Time Spent in 10-12g/dL Range During the Efficacy Evaluation Period (EEP) | 57.0 days | Standard Deviation 23.98 |
| Darbepoetin Alfa Once Biweekly | Mean Time Spent in 10-12g/dL Range During the Efficacy Evaluation Period (EEP) | 50.5 days | Standard Deviation 27.7 |
Secondary
Percentage of Participants Maintaining Hb Concentration in 10-12 g/dL Range Throughout the Efficacy Evaluation Period (EEP)
Time frame: Weeks 16-28
Population: Analysis performed with intent to treat (ITT) population, which includes all participants receiving at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CERA Treatment Once Monthly | Percentage of Participants Maintaining Hb Concentration in 10-12 g/dL Range Throughout the Efficacy Evaluation Period (EEP) | 71.7 percentage of participants |
| Darbepoetin Alfa Once Biweekly | Percentage of Participants Maintaining Hb Concentration in 10-12 g/dL Range Throughout the Efficacy Evaluation Period (EEP) | 64.0 percentage of participants |
Secondary
Percentage of Participants Needing Dose Adjustments
Assessment of the Dose Titration Period of 16 weeks of treatment and following 12 weeks, known as the Efficacy Evaluation Period (EEP).
Time frame: Up to 28 weeks
Population: Analysis was performed on the safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CERA Treatment Once Monthly | Percentage of Participants Needing Dose Adjustments | Dose Titration Period | 73.9 percentage of participants |
| CERA Treatment Once Monthly | Percentage of Participants Needing Dose Adjustments | Efficacy Evaluation Period (n=45,23) | 33.3 percentage of participants |
| Darbepoetin Alfa Once Biweekly | Percentage of Participants Needing Dose Adjustments | Dose Titration Period | 56.0 percentage of participants |
| Darbepoetin Alfa Once Biweekly | Percentage of Participants Needing Dose Adjustments | Efficacy Evaluation Period (n=45,23) | 20.8 percentage of participants |