Anemia
Conditions
Brief summary
This single-arm study will assess the efficacy and safety of monthly administration of intravenous methoxy polyethylene glycol-epoetin beta (CERA/Mircera) for the maintenance of hemoglobin (Hb) levels in participants on dialysis with chronic renal anemia in routine clinical practice in Hungary. Participants currently receiving maintenance treatment with intravenous epoetin or darbepoetin will receive monthly injections of Mircera, with the starting dose derived from the erythropoiesis-stimulating agent (ESA) dose they had been receiving.
Interventions
DRUGMethoxy polyethylene glycol-epoetin beta
Participants will receive intravenous CERA/Mircera every month, with starting dose based on previous ESA therapy. Treatment will continue for 52 weeks.
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 * Continuous stable intravenous or subcutaneous maintenance epoetin or darbepoetin therapy during previous month * Regular long-term hemodialysis therapy with the same mode of dialysis for the previous 3 months
Exclusion criteria
* Transfusion of red blood cells during previous 2 months * Poorly controlled hypertension * Significant acute or chronic bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb and Within Target Range During the Efficacy Evaluation Period (EEP) | Weeks -4, -3, -2, and -1; pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to -1). During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. 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 target range of 10.0 to 12.0 g/dL 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 |
|---|---|---|
| Percentage of Participants Whose Hb Remained Within Target Range Throughout the EEP | Pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. The percentage of participants who maintained each single Hb measurement in the target range of 10.0 to 12.0 g/dL was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds. |
| Mean Time Spent in the Target Range for Hb During the EEP | Pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. Time spent in the target range of 10.0 to 12.0 g/dL 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. |
| Mean Dose of Mircera/CERA During the Dose Titration Period (DTP) and EEP | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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 EEP (Weeks 18 to 24) 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 EEP and expressed in mcg. |
| Mean Change in Time-Adjusted Hb From Baseline to EEP | At Weeks -4, -3, -2, and -1; pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to -1). During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. 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. |
| Number of Participants Receiving Blood Transfusion During the DTP and EEP | Continuously and at every visit from Week 0 (every week until Week 2, thereafter every 2 weeks) through Week 24 | The number of participants who received blood transfusion during the DTP (Weeks 0 and 16) and EEP (Weeks 18 to 24) was reported. |
| Number of Blood Transfusions During the DTP and EEP | Continuously and at every visit from Week 0 (every week until Week 2, thereafter every 2 weeks) through Week 24 | The number of blood transfusion during the DTP (Weeks 0 and 16) and EEP (Weeks 18 to 24) was reported. |
| Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the DTP and EEP | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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 EEP (Weeks 18 to 24) on the basis of Hb levels or other modification criteria. The percentage of participants who required a dose adjustment for any reason was calculated during the DTP and EEP. |
Countries
Hungary
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 in the week preceding the switch to Mircera/CERA, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.0 and 12.0 g/dL. | 114 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Blood Transfusion | 5 |
| Overall Study | Death | 8 |
| Overall Study | Missed Pregnancy Test | 1 |
| Overall Study | Other Screening Failure | 9 |
| Overall Study | Renal Transplantation | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Mircera in Renal Anemia |
|---|---|
| Age, Continuous | 63.5 years |
| Sex: Female, Male Female | 66 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 114 |
| serious Total, serious adverse events | 45 / 114 |
Outcome results
Primary
Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb and 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 -1). During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. 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 target range of 10.0 to 12.0 g/dL 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: Weeks -4, -3, -2, and -1; pre-dose (0 hours) during Weeks 18, 20, 22, and 24
Population: Per Protocol (PP) Population: All participants from the ITT Population who fulfill inclusion/exclusion 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 and Within Target Range During the Efficacy Evaluation Period (EEP) | 72.7 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 -1). During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. 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, and -1; pre-dose (0 hours) during Weeks 18, 20, 22, and 24
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera in Renal Anemia | Mean Change in Time-Adjusted Hb From Baseline to EEP | -0.06 g/dL | Standard Deviation 1.04 |
Secondary
Mean Dose of Mircera/CERA During the Dose Titration Period (DTP) and EEP
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 EEP (Weeks 18 to 24) 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 EEP and expressed in mcg.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; the number (n) of participants who received at least one dose during the specific period was used for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera in Renal Anemia | Mean Dose of Mircera/CERA During the Dose Titration Period (DTP) and EEP | EEP (n=110) | 100.3 mcg | Standard Deviation 69.43 |
| Mircera in Renal Anemia | Mean Dose of Mircera/CERA During the Dose Titration Period (DTP) and EEP | DTP (n=114) | 113 mcg | Standard Deviation 39.4 |
Secondary
Mean Time Spent in the Target Range for Hb During the EEP
During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. Time spent in the target range of 10.0 to 12.0 g/dL 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) during Weeks 18, 20, 22, and 24
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera in Renal Anemia | Mean Time Spent in the Target Range for Hb During the EEP | 43.5 days | Standard Deviation 15.64 |
Secondary
Number of Blood Transfusions During the DTP and EEP
The number of blood transfusion during the DTP (Weeks 0 and 16) and EEP (Weeks 18 to 24) was reported.
Time frame: Continuously and at every visit from Week 0 (every week until Week 2, thereafter every 2 weeks) through Week 24
Population: ITT Population; the number (n) of participants who received at least one dose during the specific period was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera in Renal Anemia | Number of Blood Transfusions During the DTP and EEP | DTP (n=114) | 4 blood transfusions |
| Mircera in Renal Anemia | Number of Blood Transfusions During the DTP and EEP | EEP (n=110) | 0 blood transfusions |
Secondary
Number of Participants Receiving Blood Transfusion During the DTP and EEP
The number of participants who received blood transfusion during the DTP (Weeks 0 and 16) and EEP (Weeks 18 to 24) was reported.
Time frame: Continuously and at every visit from Week 0 (every week until Week 2, thereafter every 2 weeks) through Week 24
Population: ITT Population; the number (n) of participants who received at least one dose during the specific period was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera in Renal Anemia | Number of Participants Receiving Blood Transfusion During the DTP and EEP | DTP (n=114) | 3 participants |
| Mircera in Renal Anemia | Number of Participants Receiving Blood Transfusion During the DTP and EEP | EEP (n=110) | 0 participants |
Secondary
Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the DTP and EEP
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 EEP (Weeks 18 to 24) on the basis of Hb levels or other modification criteria. The percentage of participants who required a dose adjustment for any reason was calculated during the DTP and EEP.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; the number (n) of participants who received at least one dose during the specific period was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the DTP and EEP | DTP (n=114) | 79.8 percentage of participants |
| Mircera in Renal Anemia | Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the DTP and EEP | EEP (n=110) | 48.2 percentage of participants |
Secondary
Percentage of Participants Whose Hb Remained Within Target Range Throughout the EEP
During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. The percentage of participants who maintained each single Hb measurement in the target range of 10.0 to 12.0 g/dL was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds.
Time frame: Pre-dose (0 hours) during Weeks 18, 20, 22, and 24
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Whose Hb Remained Within Target Range Throughout the EEP | 79.0 percentage of participants |