Anemia
Conditions
Brief summary
This single-arm study will assess the long-term maintenance of hemoglobin levels, safety, and tolerability of once-monthly intravenous administration of Mircera in hemodialysis participants with chronic renal anemia. Those currently receiving darbepoetin alfa, epoetin alfa, or epoetin beta maintenance treatment will receive intravenous Mircera at a starting dose of 120, 200, or 360 micrograms (mcg) per month (based on the erythropoiesis stimulating agent \[ESA\] dose administered on Week -1). Subsequent doses will be adjusted to maintain hemoglobin levels within the country-specific target range (11 to 13 grams per deciliter \[g/dL\] for Switzerland and 10 to 12 g/dL for Austria).
Interventions
DRUGMethoxy polyethylene glycol-epoetin beta
Mircera will be administered intravenously every 4 weeks for a total of 52 weeks. The first dose of 120, 200, or 360 mcg will be determined by the dose of ESA received prior to administration of study treatment, while subsequent doses will be adjusted to maintain hemoglobin within a country-specific target range.
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
* Adults greater than or equal to (≥) 18 years of age * Chronic renal anemia * Hemoglobin concentration in country-specific target range (Switzerland: 11 to 13 g/dL; Austria: 10 to 12 g/dL) * Regular long-term hemodialysis therapy with the same mode of dialysis for ≥3 months * Continuous intravenous or subcutaneous maintenance ESA treatment during previous 2 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 Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb or Within Target Range During the Efficacy Evaluation Period (EEP) | At Weeks -4, -3, -2, -1, 0; pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24 | Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The average Hb during the EEP was calculated per participant and assessed against the reference value. The percentage of participants who had average Hb during the EEP in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) and within ±1 g/dL of their individual reference Hb was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time Spent in the Target Range for Hb During the Long-Term Safety Period (LTSP) | Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48 | During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Time spent in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) was defined as time from first on-target Hb to time of last known on-target Hb, as collected during the EEP. Time spent in the target range was averaged among all participants and expressed in days. |
| Percentage of Participants Who Maintained Average Hb Within Target Range Throughout the EEP | Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24 | During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The percentage of participants who had average Hb during the EEP in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds. |
| Percentage of Hb Values Above or Below the Target Range During the LTSP | Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48 | During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The percentage of all Hb values outside of the country-specific target range was determined and reported separately as Hb values above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and Hb values below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria). |
| Mean Time Spent Above or Below the Target Range for Hb During the LTSP | Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48 | During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Time spent outside the country-specific target range was defined as time from each off-target Hb to time of next on-target Hb, as collected during the LTSP. Time spent outside the target range was averaged among all participants and expressed in days, reported separately as time spent above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and time spent below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria). |
| Mean Change in Time-Adjusted Hb From Baseline to EEP | At Weeks -4, -3, -2, -1, 0; pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24 | Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The average Hb during the EEP was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., Baseline) Hb and the EEP average Hb was calculated and expressed in g/dL. |
| Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP | Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 | Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the LTSP (Weeks 18 to 52) on the basis of Hb levels or other modification criteria. The mean number of months required for dose adjustment for any reason was calculated and averaged among all participants during the DTP and LTSP. |
| Mean Dose of Mircera/CERA During the DTP and LTSP | Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 | Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the LTSP (Weeks 18 to 52) on the basis of Hb levels or other modification criteria. The dose received at each administration visit was averaged among all participants during the DTP and LTSP and expressed in mcg. |
| Percentage of Participants Who Received Blood Transfusions During the DTP and LTSP | From Week 0 (every week until Week 2, every 2 weeks until Week 48) through the final visit at Week 52 | The number of participants who received blood transfusion during the DTP (Weeks 0 and 16) and LTSP (Weeks 18 to 52) was reported. |
| Mean Excursions Above or Below Target Range for Hb During the LTSP | Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48 | During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Deviation from the country-specific target range was calculated as \[Hb value minus country-specific upper bound\] for deviations above the target range and \[Hb value minus country-specific lower bound\] for deviations below the target range. Deviations were averaged among all Hb values from all participants and expressed in g/dL, reported separately as mean deviation above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and mean deviation below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria). |
Countries
Austria, Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mircera in Renal Anemia Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 52 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted during a 16-week DTP to maintain Hb concentrations within a country-specific target: 11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria. | 91 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative Reasons | 1 |
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 5 |
| Overall Study | Early Termination of Study | 24 |
| Overall Study | Kidney Transplantation | 3 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Refused Treatment | 1 |
| Overall Study | Screen Failure | 16 |
| Overall Study | Transfusion | 12 |
Baseline characteristics
| Characteristic | Mircera in Renal Anemia |
|---|---|
| Age, Continuous | 67.9 Years STANDARD_DEVIATION 13.34 |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 62 / 91 |
| serious Total, serious adverse events | 43 / 91 |
Outcome results
Primary
Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb or Within Target Range During the Efficacy Evaluation Period (EEP)
Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The average Hb during the EEP was calculated per participant and assessed against the reference value. The percentage of participants who had average Hb during the EEP in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) and within ±1 g/dL of their individual reference Hb was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.
Time frame: At Weeks -4, -3, -2, -1, 0; pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24
Population: Per Protocol (PP) Population: All participants from the Intent-to-Treat (ITT) Population who fulfill select criteria per study protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb or Within Target Range During the Efficacy Evaluation Period (EEP) | 75.6 percentage of participants |
Secondary
Mean Change in Time-Adjusted Hb From Baseline to EEP
Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The average Hb during the EEP was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., Baseline) Hb and the EEP average Hb was calculated and expressed in g/dL.
Time frame: At Weeks -4, -3, -2, -1, 0; pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera in Renal Anemia | Mean Change in Time-Adjusted Hb From Baseline to EEP | -0.4 g/dL | Standard Deviation 1.09 |
Secondary
Mean Dose of Mircera/CERA During the DTP and LTSP
Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the LTSP (Weeks 18 to 52) on the basis of Hb levels or other modification criteria. The dose received at each administration visit was averaged among all participants during the DTP and LTSP and expressed in mcg.
Time frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Population: Safety Population; only those participants (n = number) who provided evaluable data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera in Renal Anemia | Mean Dose of Mircera/CERA During the DTP and LTSP | DTP (n=91) | 140 mcg | Standard Deviation 48.6 |
| Mircera in Renal Anemia | Mean Dose of Mircera/CERA During the DTP and LTSP | LTSP (n=72) | 133.8 mcg | Standard Deviation 70.7 |
Secondary
Mean Excursions Above or Below Target Range for Hb During the LTSP
During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Deviation from the country-specific target range was calculated as \[Hb value minus country-specific upper bound\] for deviations above the target range and \[Hb value minus country-specific lower bound\] for deviations below the target range. Deviations were averaged among all Hb values from all participants and expressed in g/dL, reported separately as mean deviation above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and mean deviation below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria).
Time frame: Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Population: ITT Population; only those participants (n = number) who entered the LTSP and had at least one Hb excursion during the LTSP were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera in Renal Anemia | Mean Excursions Above or Below Target Range for Hb During the LTSP | Above (n=32) | 0.5 g/dL | Standard Deviation 0.42 |
| Mircera in Renal Anemia | Mean Excursions Above or Below Target Range for Hb During the LTSP | Below (n=51) | -0.7 g/dL | Standard Deviation 0.61 |
Secondary
Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP
Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the LTSP (Weeks 18 to 52) on the basis of Hb levels or other modification criteria. The mean number of months required for dose adjustment for any reason was calculated and averaged among all participants during the DTP and LTSP.
Time frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Population: Safety Population: All participants who received at least one dose of trial medication and at least one safety follow-up assessment, whether prematurely withdrawn or not; only those participants (n = number) who provided evaluable data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera in Renal Anemia | Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP | DTP: Any Dose Change (n=90) | 1.1 months | Standard Deviation 1.11 |
| Mircera in Renal Anemia | Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP | DTP: Dose Increase (n=90) | 0.4 months | Standard Deviation 0.75 |
| Mircera in Renal Anemia | Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP | DTP: Dose Decrease (n=90) | 0.6 months | Standard Deviation 0.87 |
| Mircera in Renal Anemia | Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP | LTSP: Any Dose Change (n=67) | 1.5 months | Standard Deviation 1.32 |
| Mircera in Renal Anemia | Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP | LTSP: Dose Increase (n=67) | 0.7 months | Standard Deviation 0.99 |
| Mircera in Renal Anemia | Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP | LTSP: Dose Decrease (n=67) | 0.8 months | Standard Deviation 0.93 |
Secondary
Mean Time Spent Above or Below the Target Range for Hb During the LTSP
During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Time spent outside the country-specific target range was defined as time from each off-target Hb to time of next on-target Hb, as collected during the LTSP. Time spent outside the target range was averaged among all participants and expressed in days, reported separately as time spent above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and time spent below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria).
Time frame: Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Population: ITT Population; only those participants (n = number) who entered the LTSP and had at least one Hb excursion during the LTSP or at the last DTP visit were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera in Renal Anemia | Mean Time Spent Above or Below the Target Range for Hb During the LTSP | Above (n=35) | 43 days | Standard Deviation 45.3 |
| Mircera in Renal Anemia | Mean Time Spent Above or Below the Target Range for Hb During the LTSP | Below (n=51) | 48 days | Standard Deviation 41.2 |
Secondary
Mean Time Spent in the Target Range for Hb During the Long-Term Safety Period (LTSP)
During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Time spent in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) was defined as time from first on-target Hb to time of last known on-target Hb, as collected during the EEP. Time spent in the target range was averaged among all participants and expressed in days.
Time frame: Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Population: ITT Population; only participants who entered the LTSP were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera in Renal Anemia | Mean Time Spent in the Target Range for Hb During the Long-Term Safety Period (LTSP) | 130 days | Standard Deviation 67.5 |
Secondary
Percentage of Hb Values Above or Below the Target Range During the LTSP
During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The percentage of all Hb values outside of the country-specific target range was determined and reported separately as Hb values above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and Hb values below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria).
Time frame: Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Population: ITT Population; only those participants (n = number) who entered the LTSP and had at least one Hb excursion during the LTSP were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera in Renal Anemia | Percentage of Hb Values Above or Below the Target Range During the LTSP | Above (n=32) | 22 percentage of Hb values |
| Mircera in Renal Anemia | Percentage of Hb Values Above or Below the Target Range During the LTSP | Below (n=51) | 38 percentage of Hb values |
Secondary
Percentage of Participants Who Maintained Average Hb Within Target Range Throughout the EEP
During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The percentage of participants who had average Hb during the EEP in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds.
Time frame: Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Who Maintained Average Hb Within Target Range Throughout the EEP | 48.4 percentage of participants |
Secondary
Percentage of Participants Who Received Blood Transfusions During the DTP and LTSP
The number of participants who received blood transfusion during the DTP (Weeks 0 and 16) and LTSP (Weeks 18 to 52) was reported.
Time frame: From Week 0 (every week until Week 2, every 2 weeks until Week 48) through the final visit at Week 52
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Who Received Blood Transfusions During the DTP and LTSP | 15.4 percentage of participants |