Anemia
Conditions
Brief summary
This single arm study will assess the long term maintenance of hemoglobin (Hb) levels, safety and tolerability of once monthly subcutaneous methoxy polyethylene glycol-epoetin beta (CERA) in predialysis participants with chronic renal anemia. Participants currently receiving subcutaneous darbopoetin alfa maintenance treatment will receive subcutaneous methoxy polyethylene glycol-epoetin beta for a maximum of 32 weeks at a starting dose of 120, 200 or 360 micrograms every 4 weeks according to the dose of darbopoetin alfa administered in Week -1. Subsequent doses will be adjusted to maintain hemoglobin levels within the target range of 10 to 12 grams per deciliter (g/dL).
Interventions
DRUGMethoxy Polyethylene Glycol-Epoetin Beta
120, 200 or 360 micrograms every 4 weeks by subcutaneous injection.
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 subcutaneous maintenance darbopoetin alfa treatment during previous month; * Hb concentration between 10 and 12 g/dL; * Adequate iron status.
Exclusion criteria
* Transfusion of red blood cells during previous 2 months; * Significant acute or chronic bleeding, such as overt gastrointestinal bleeding; * Poorly controlled hypertension requiring hospitalization or interruption of darbopoetin alfa treatment in the previous 6 months; * Active malignant disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Their Mean Hb Concentration Within Plus/Minus (±) 1 Grams Per Deciliter (g/dL) of the Reference Range and Between 10.0 and 12.0 g/dL During Efficacy Evaluation Period (EEP) | EEP: Weeks 17 to 28 | The reference Hb was defined as the average Hb concentration calculated on the basis of all Hb assessments taken at Weeks -4, -2, and 0 (before the first dose administration). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hb Concentrations Between EEP and Stability Verification Period (SVP) | SVP: Week -4 to Week 0; EEP: Weeks 17 to 28 | Hb concentrations during SVP were the reference Hb concentrations. For each assessment period (SVP and EEP) the average Hb concentration was calculated on the basis of all Hb assessments taken during the assessment period. Change in average Hb concentration from reference range (SVP) was calculated. |
| Percentage of Participants Maintaining Hb Concentrations Within the Range of 10.0 to 12.0 g/dL Throughout EEP | EEP: Weeks 17 to 28 | — |
| Median Time Spent in the Hb Range of 10.0 to 12.0 g/dL During the EEP | EEP: Weeks 17 to 28 | — |
| Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP | DTP: Weeks 1 to 16; EEP: Weeks 17 to 28 | The methoxy polyethylene glycol-epoetin beta dose adjustment (dose increase or decrease) was required: if a single Hb concentration was either greater than or equal to (≥) 13 g/dL or less than or equal to (≤) 9 g/dL; if the difference of 2 consecutive Hb concentrations was ≥2 g/dL; when the values of scheduled Hb assessments on the days of drug administration and on the previous study visit were both out of range of 10.5 to 11.5 g/dL and the difference between the reference value (average Hb concentration calculated on the basis of all Hb assessments taken at Weeks -4, -2, and 0) and the most recent value was \>1 g/dL; and when the values of scheduled Hb assessments on the days of drug administration and on the previous study visit were both out of range of 10 to 12 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted. |
| Percentage of Participants Who Required Red Blood Cell Transfusions | Weeks 1 to 28 | — |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta Participants received methoxy polyethylene glycol-epoetin beta once monthly by SC injection, for 28 weeks. The initial dose of methoxy polyethylene glycol-epoetin beta was 120 or 200 or 360 µg if the last weekly dose of previous ESA (darbepoetin alfa) was \<40 µg or 40-80 µg or \>80 µg, respectively. The doses were adjusted according to individual participant's Hb value. | 111 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Failure to Return | 2 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Other | 8 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Screen Failure | 17 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Methoxy Polyethylene Glycol-Epoetin Beta |
|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 13.49 |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 111 |
| serious Total, serious adverse events | 10 / 111 |
Outcome results
Primary
Percentage of Participants Maintaining Their Mean Hb Concentration Within Plus/Minus (±) 1 Grams Per Deciliter (g/dL) of the Reference Range and Between 10.0 and 12.0 g/dL During Efficacy Evaluation Period (EEP)
The reference Hb was defined as the average Hb concentration calculated on the basis of all Hb assessments taken at Weeks -4, -2, and 0 (before the first dose administration).
Time frame: EEP: Weeks 17 to 28
Population: Per protocol population included all participants who received at least one dose of methoxy polyethylene glycol-epoetin beta and for whom the data for at least one follow-up variable were available and were without any major protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Maintaining Their Mean Hb Concentration Within Plus/Minus (±) 1 Grams Per Deciliter (g/dL) of the Reference Range and Between 10.0 and 12.0 g/dL During Efficacy Evaluation Period (EEP) | 65.85 percentage of participants |
Secondary
Change in Hb Concentrations Between EEP and Stability Verification Period (SVP)
Hb concentrations during SVP were the reference Hb concentrations. For each assessment period (SVP and EEP) the average Hb concentration was calculated on the basis of all Hb assessments taken during the assessment period. Change in average Hb concentration from reference range (SVP) was calculated.
Time frame: SVP: Week -4 to Week 0; EEP: Weeks 17 to 28
Population: Per protocol population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Change in Hb Concentrations Between EEP and Stability Verification Period (SVP) | 0.27 g/dL | Standard Deviation 0.73 |
Secondary
Median Time Spent in the Hb Range of 10.0 to 12.0 g/dL During the EEP
Time frame: EEP: Weeks 17 to 28
Population: Per protocol population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Median Time Spent in the Hb Range of 10.0 to 12.0 g/dL During the EEP | 57.0 days |
Secondary
Percentage of Participants Maintaining Hb Concentrations Within the Range of 10.0 to 12.0 g/dL Throughout EEP
Time frame: EEP: Weeks 17 to 28
Population: Per protocol population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Maintaining Hb Concentrations Within the Range of 10.0 to 12.0 g/dL Throughout EEP | 73.17 percentage of participants |
Secondary
Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP
The methoxy polyethylene glycol-epoetin beta dose adjustment (dose increase or decrease) was required: if a single Hb concentration was either greater than or equal to (≥) 13 g/dL or less than or equal to (≤) 9 g/dL; if the difference of 2 consecutive Hb concentrations was ≥2 g/dL; when the values of scheduled Hb assessments on the days of drug administration and on the previous study visit were both out of range of 10.5 to 11.5 g/dL and the difference between the reference value (average Hb concentration calculated on the basis of all Hb assessments taken at Weeks -4, -2, and 0) and the most recent value was \>1 g/dL; and when the values of scheduled Hb assessments on the days of drug administration and on the previous study visit were both out of range of 10 to 12 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted.
Time frame: DTP: Weeks 1 to 16; EEP: Weeks 17 to 28
Population: Per protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP | DTP: Dose Increase Only | 17.1 percentage of participants |
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP | DTP: Dose Decrease Only | 39.0 percentage of participants |
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP | DTP: Both Dose Increase and Decrease | 22.0 percentage of participants |
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP | EEP: Dose Increase Only | 31.7 percentage of participants |
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP | EEP: Dose Decrease Only | 9.8 percentage of participants |
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Requiring Any Dose Adjustment During Dose Titration Period (DTP) and EEP | EEP: Both Dose Increase and Decrease | 9.8 percentage of participants |
Secondary
Percentage of Participants Who Required Red Blood Cell Transfusions
Time frame: Weeks 1 to 28
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Participants Who Required Red Blood Cell Transfusions | 0.9 percentage of participants |