Anemia
Conditions
Brief summary
This single arm study will assess the efficacy and safety of subcutaneous Mircera for correction of anemia in participants with chronic kidney disease who are not treated with erythropoiesis stimulating agent (ESA) and not on dialysis. Eligible participants will receive Mircera by monthly subcutaneous injections. The initial dose, based on body weight, will be 1.2 micrograms/kilogram (mcg/kg). The anticipated time on study treatment is 9-11 months, and the target sample size is 100-500 individuals.
Interventions
DRUGMethoxy polyethylene glycol-epoetin beta
Methoxy polyethylene glycol-epoetin beta will be administered subcutaneously once a month. The starting dose will be 1.2 mcg/kg of body weight. Further dose adjustments will be performed during the study depending on the hemoglobin value. Total duration of treatment will be 9 months for all participants in the study and up to 11 months for participants who will be shifted to the dialysis.
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 value less than or equal to (\<=) 10.5 grams/deciliter (g/dL).
Exclusion criteria
* prior ESA therapy during previous 3 months; * acute or chronic bleeding requiring therapy during previous 2 months; * transfusion of red blood cells during previous 2 months; * active malignant disease (except non-melanoma skin cancer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-12 Grams Per Deciliter (g/dL) | Evaluation phase (Months 8 and 9) | Participants with both hemoglobin values of the evaluation phase (Months 8 and 9, i.e., Study Days 200-260, values were at least 21 days apart) in the range of 11-12 g/dL were classified as responder. Participants who received transfusion of erythrocytes between Study Day 139 and 260, or with at least one value missing or outside the range were classified as non-responder for the hemoglobin-range concerned. |
| Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-13 g/dL | Evaluation phase (Months 8 and 9) | Participants with both hemoglobin values of the evaluation phase (Months 8 and 9, i.e., Study Days 200-260, values were at least 21 days apart) in the range of 11-13 g/dL were classified as responder. Participants who received transfusion of erythrocytes between Study Day 139 and 260, or with at least one value missing or outside the range were classified as non-responder for the hemoglobin-range concerned. |
| Change From Baseline in Hemoglobin Value to the Evaluation Phase | Baseline, evaluation phase (Months 8 and 9) | The change from the baseline hemoglobin value to the mean hemoglobin value of the evaluation phase was only calculated if both the baseline value and the mean of the evaluation phase (mean of Months 8 and 9) were available. In case of only one available hemoglobin value within the evaluation phase, that single value replaced the mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Dose Adjustments | Baseline until Month 8 | A dose adjustment was defined as a change versus the preceding dose. It included dose increase, dose reduction and dose interruption. An interruption (no dose given) was always counted as a dose adjustment, regardless of whether or not at the previous time point a dose had been administered. After an interruption a change in the dose relative to the dose given before the interruption was counted as a dose adjustment. |
| Duration of Hemoglobin Values in the Range of 11-12 g/dL | Baseline to Month 9 | The duration of hemoglobin values staying within the range of 11-12 g/dL was defined as the number of (not necessarily consecutive) months with all corresponding hemoglobin values in the respective range. All months with missing hemoglobin values were counted as months where the hemoglobin value did not stay within the respective range. |
| Total Number of Red Blood Cell (RBC) Transfusions | Baseline to Month 9 | RBC transfusions could be given during the study, if medically necessary, i.e., in participants with severe anemia with distinct symptoms or signs of anemia (such as in participants with acute blood loss, with severe angina, or whose hemoglobin decreased to critical levels). |
| Duration of Hemoglobin Values in the Range of 11-13 g/dL | Baseline to Month 9 | The duration of hemoglobin values staying within the range of 11-13 g/dL was defined as the number of (not necessarily consecutive) months with all corresponding hemoglobin values in the respective range. All months with missing hemoglobin values were counted as months where the hemoglobin value did not stay within the respective range. |
| Time to Increase of Hemoglobin Value to Over 11 g/dL | Baseline to Month 9 | The duration (number of months) until the hemoglobin value exceeded 11 g/dL for the first time was summarized for participants for whom at least one measured hemoglobin value exceeded 11 g/dL. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta Methoxy polyethylene glycol-epoetin beta was administered subcutaneously once a month. The starting dose was 1.2 mcg/kg of body weight. Further dose adjustments were performed during the study depending on the hemoglobin value. Total duration of treatment was 9 months for all participants in the study and up to 11 months if participants were shifted to dialysis. | 184 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 22 |
| Overall Study | Change of center | 1 |
| Overall Study | Change of home | 1 |
| Overall Study | Delayed administration of C.E.R.A | 1 |
| Overall Study | Failure to return | 6 |
| Overall Study | Inclusion or exclusion criteria violated | 2 |
| Overall Study | Insufficient response | 3 |
| Overall Study | Participation in another study | 1 |
| Overall Study | Protocol Violation | 6 |
| Overall Study | Started requiring dialysis after month 7 | 2 |
| Overall Study | Suspected lung cancer | 1 |
| Overall Study | Withdrawal by Subject | 4 |
| Overall Study | Withdrawal criteria fulfilled | 4 |
Baseline characteristics
| Characteristic | Methoxy Polyethylene Glycol-epoetin Beta |
|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 15.77 |
| Sex: Female, Male Female | 91 Participants |
| Sex: Female, Male Male | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 109 / 184 |
| serious Total, serious adverse events | 88 / 184 |
Outcome results
Primary
Change From Baseline in Hemoglobin Value to the Evaluation Phase
The change from the baseline hemoglobin value to the mean hemoglobin value of the evaluation phase was only calculated if both the baseline value and the mean of the evaluation phase (mean of Months 8 and 9) were available. In case of only one available hemoglobin value within the evaluation phase, that single value replaced the mean.
Time frame: Baseline, evaluation phase (Months 8 and 9)
Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Change From Baseline in Hemoglobin Value to the Evaluation Phase | 1.6 g/dL | Standard Deviation 1.1 |
Primary
Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-12 Grams Per Deciliter (g/dL)
Participants with both hemoglobin values of the evaluation phase (Months 8 and 9, i.e., Study Days 200-260, values were at least 21 days apart) in the range of 11-12 g/dL were classified as responder. Participants who received transfusion of erythrocytes between Study Day 139 and 260, or with at least one value missing or outside the range were classified as non-responder for the hemoglobin-range concerned.
Time frame: Evaluation phase (Months 8 and 9)
Population: Intent to treat (ITT) population included all participants who received at least one dose of study medication with at least one hemoglobin value measured during treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-12 Grams Per Deciliter (g/dL) | 10.67 percentage of participants |
Primary
Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-13 g/dL
Participants with both hemoglobin values of the evaluation phase (Months 8 and 9, i.e., Study Days 200-260, values were at least 21 days apart) in the range of 11-13 g/dL were classified as responder. Participants who received transfusion of erythrocytes between Study Day 139 and 260, or with at least one value missing or outside the range were classified as non-responder for the hemoglobin-range concerned.
Time frame: Evaluation phase (Months 8 and 9)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Percentage of Participants With Both Hemoglobin Values of the Evaluation Phase in the Range of 11-13 g/dL | 29.21 percentage of participants |
Secondary
Duration of Hemoglobin Values in the Range of 11-12 g/dL
The duration of hemoglobin values staying within the range of 11-12 g/dL was defined as the number of (not necessarily consecutive) months with all corresponding hemoglobin values in the respective range. All months with missing hemoglobin values were counted as months where the hemoglobin value did not stay within the respective range.
Time frame: Baseline to Month 9
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Duration of Hemoglobin Values in the Range of 11-12 g/dL | 2.40 months | Standard Deviation 1.796 |
Secondary
Duration of Hemoglobin Values in the Range of 11-13 g/dL
The duration of hemoglobin values staying within the range of 11-13 g/dL was defined as the number of (not necessarily consecutive) months with all corresponding hemoglobin values in the respective range. All months with missing hemoglobin values were counted as months where the hemoglobin value did not stay within the respective range.
Time frame: Baseline to Month 9
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Duration of Hemoglobin Values in the Range of 11-13 g/dL | 3.62 months | Standard Deviation 2.45 |
Secondary
Time to Increase of Hemoglobin Value to Over 11 g/dL
The duration (number of months) until the hemoglobin value exceeded 11 g/dL for the first time was summarized for participants for whom at least one measured hemoglobin value exceeded 11 g/dL.
Time frame: Baseline to Month 9
Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Time to Increase of Hemoglobin Value to Over 11 g/dL | 2.28 months | Standard Deviation 1.649 |
Secondary
Total Number of Dose Adjustments
A dose adjustment was defined as a change versus the preceding dose. It included dose increase, dose reduction and dose interruption. An interruption (no dose given) was always counted as a dose adjustment, regardless of whether or not at the previous time point a dose had been administered. After an interruption a change in the dose relative to the dose given before the interruption was counted as a dose adjustment.
Time frame: Baseline until Month 8
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Total Number of Dose Adjustments | Total number of dose adjustments | 595 dose adjustments |
| Methoxy Polyethylene Glycol-epoetin Beta | Total Number of Dose Adjustments | Total number of dose increases | 249 dose adjustments |
| Methoxy Polyethylene Glycol-epoetin Beta | Total Number of Dose Adjustments | Total number of dose reductions | 210 dose adjustments |
| Methoxy Polyethylene Glycol-epoetin Beta | Total Number of Dose Adjustments | Total number of dose interruptions | 136 dose adjustments |
Secondary
Total Number of Red Blood Cell (RBC) Transfusions
RBC transfusions could be given during the study, if medically necessary, i.e., in participants with severe anemia with distinct symptoms or signs of anemia (such as in participants with acute blood loss, with severe angina, or whose hemoglobin decreased to critical levels).
Time frame: Baseline to Month 9
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Total Number of Red Blood Cell (RBC) Transfusions | 39 number of transfusions |