Anemia
Conditions
Brief summary
This single arm study will assess the efficacy, safety and tolerability of subcutaneous methoxy polyethylene glycol-epoetin beta (C.E.R.A.) for maintenance of hemoglobin levels in pre-dialysis participants with chronic renal anemia. Participants currently receiving maintenance treatment with subcutaneous darbepoetin alfa will receive monthly subcutaneous injections of C.E.R.A. with the starting dose of 120, 200 or 360 micrograms (mcg) derived from the dose of darbepoetin alfa or epoetin alfa in the week preceding study start.
Interventions
Subcutaneous methoxy polyethylene glycol-epoetin beta (C.E.R.A.) at starting dose of 120, 200, or 360 mcg every 4 weeks for 20 weeks. Further dose adjustments will be performed during the study depending on the participant's blood hemoglobin levels.
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 * Hemoglobin concentration between 10.5 gram per deciliter (g/dL) and 12.5 g/dL * Adequate iron status (serum ferritin greater than \[\>\] 100 nanogram per milliliter and Transferrin Saturation \>20 percent \[%\] or hypochromic red cells less than \[\<\] 10%) * Continuous subcutaneous maintenance darbepoetin alfa therapy with same dosing interval during previous 2 months
Exclusion criteria
* Transfusion of red blood cells during previous 2 months * Poorly controlled hypertension requiring hospitalization or interruption of darbepoetin alfa treatment in previous 6 months * Acute or chronic 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 Their Reference Hemoglobin 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 10.5 to 12.5 g/dL during the efficacy evaluation period (EEP) was reported. The reference hemoglobin value was defined as the mean 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 |
|---|---|---|
| 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 10.5 to 12.5 g/dL during EEP (Week 17 to Week 24) was reported. |
| 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 within the target range of 10.5 to 12.5 g/dL during the EEP (Week 17 to Week 24) was reported. |
| Change in Hemoglobin Concentration Between Reference (SVP) and EEP | Week 17 up to Week 24 | The reference hemoglobin value was defined as the mean of the 5 assessments recorded during the SVP at Weeks -4, -3, -2, -1 and 0. 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 With Red Blood Cell Transfusion During the Study | Week 0 up to Week 24 | Percentage of participant who required red blood cell transfusion during the study was reported. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Week 0 up to Week 24 | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious as well as non-serious AEs. |
| 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. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| C.E.R.A. Participants received subcutaneous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 20 weeks. Further dose adjustments were performed during the study depending on the participant's blood hemoglobin levels. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Renal transplantation | 2 |
Baseline characteristics
| Characteristic | C.E.R.A. |
|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 11.29 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 29 |
| serious Total, serious adverse events | 9 / 29 |
Outcome results
Primary
Percentage of Participants Maintaining Mean Hemoglobin Concentration Within Plus or Minus (+/-) 1 Gram Per Deciliter (g/dL) of Their Reference Hemoglobin 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 10.5 to 12.5 g/dL during the efficacy evaluation period (EEP) was reported. The reference hemoglobin value was defined as the mean 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: The Intention-to-treat (ITT) population included all participants who received at least 1 dose of C.E.R.A. (week 0) and for whom data for at least 1 follow-up variable was available. Data missing at the end of the EEP (that is, the last measured hemoglobin value before Week 24) was handled using the last value carried forward method.
| 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 Their Reference Hemoglobin and Within the Target Range | 51.7 percentage of participants |
Secondary
Change in Hemoglobin Concentration Between Reference (SVP) and EEP
The reference hemoglobin value was defined as the mean of the 5 assessments recorded during the SVP at Weeks -4, -3, -2, -1 and 0. 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 17 up to Week 24
Population: ITT population; data missing at the end of the EEP was handled using the last value carried forward method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A. | Change in Hemoglobin Concentration Between Reference (SVP) and EEP | -0.3 g/dL | Standard Deviation 1.04 |
Secondary
Mean Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP
Mean time spent by participants with hemoglobin concentration within the target range of 10.5 to 12.5 g/dL during the EEP (Week 17 to Week 24) was reported.
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 | 31 days | Standard Deviation 17.2 |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious as well as non-serious AEs.
Time frame: Week 0 up to Week 24
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A. | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 22 participants |
| C.E.R.A. | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 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 10.5 to 12.5 g/dL during EEP (Week 17 to Week 24) was reported.
Time frame: Week 17 up to Week 24
Population: ITT Population; data missing at the end of the EEP was handled using the last value carried forward method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range During EEP | 58.6 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: ITT Population. Here, '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 = 29) | 62 percentage of participants |
| C.E.R.A. | Percentage of Participants Requiring Any Dose Adjustment | EEP (n = 26) | 31 percentage of participants |
Secondary
Percentage of Participants With Red Blood Cell Transfusion During the Study
Percentage of participant who required red blood cell transfusion during the study was reported.
Time frame: Week 0 up to Week 24
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants With Red Blood Cell Transfusion During the Study | 7 percentage of participants |