Anemia
Conditions
Brief summary
This open-label single-arm study will evaluate the efficacy, safety and tolerability of methoxy polyethylene glycol epoetin beta on long-term maintenance of haemoglobin levels in patients with chronic renal anaemia. Patients will receive methoxy polyethylene glycol-epoetin beta intravenously once monthly at initial doses of either 120 micrograms or 200 micrograms or 360 micrograms in the titration phase of 16 weeks with a potential dose adjustment in the evaluation phase of 8 weeks. The anticipated time on study treatment is 24 weeks. The target sample size is 50-100 patients.
Interventions
DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]
initial doses of either 120 micrograms or 200 micrograms or 360 micrograms, once monthly
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 \>/=18 years of age * Chronic renal anaemia * Haemoglobin concentration between 10 and 12 g/dL at screening * Adequate iron status * Continuous intravenous maintenance short-acting therapy with same dosing interval for 8 weeks prior to screening * Regular long-term haemodialysis therapy for at least 12 weeks prior to screening
Exclusion criteria
* Change in haemoglobin concentration \>/=2 g/dL during screening * Transfusion of red blood cells less than 8 weeks prior to screening * Poorly controlled hypertension * Relevant acute or chronic bleeding requiring treatment less than 8 weeks prior to screening * Active malignant disease * Haemolysis * Haemoglobinopathies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Maintaining Average Haemoglobin During the Efficacy Evaluation Period Within the Target Range (10-12 g/dl) | Up to Week 24 | The proportion of participants with their mean haemoglobin (Hb) concentration (g/dL) within the target range during the efficacy evaluation period was assessed. The target range is the reference Hb not \>12 g/dL and not \< 10 g/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Haemoglobin Concentration From Screening Period and Efficacy Evaluation Period | Up to Week 24 | The mean haemoglobin (Hb) concentration (g/dL) change from the baseline (Week 0) till efficacy evaluation period (EEP) was assessed and reported. |
| Proportion of Participants Maintaining Haemoglobin Concentration Within the Haemoglobin Range 10-12g/dL Throughout the Efficacy Evaluation Period | Up to Week 24 | The proportion of participants maintaining haemoglobin concentration within the haemoglobin range 10-12g/dL throughout the efficacy evaluation period (EEP) was assessed and reported. |
| Mean Time Spent by Participants in the Haemoglobin Range of 10 - 12 g/dL During the Efficacy Evaluation Period | Up to Week 24 | Mean time spent in the haemoglobin range 10 - 12 g/dL during the efficacy evaluation period (EEP) was assessed and reported. |
| Number of Participants With Adverse Events and Serious Adverse Events | Up to Week 28 | An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. The AEs were assessed from baseline to every visit throughout the treatment, post study drug discontinuation, and follow up period. |
| Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods | Baseline, Week 4, Week 8, Week 12, Week 16, and Week 20 | Mean monthly dose of methoxy polyethylene glycol-epoetin beta during the dose titration and evaluation periods was assessed and reported. |
| Number of Participants With Marked Laboratory Abnormalities | Up to Week 28 | A marked laboratory abnormality is defined as above and/or below the normal range of a laboratory parameter which was considered to be potentially clinically relevant. The number of participants with marked laboratory abnormality are presented. Marked laboratory abnormalities were analyzed according to the Roche specified limits for the following reference range: Haemoglobin (Hb) (11.7-17.3 g/dL), Haematocrit (Hct) (35-47%), White blood cells (WBC) (3.6-11.0 10\^3/µL), Red blood cells (RBC) (3.8- 5.9 10\^6/µL), MCV (80-100 fL) Platelets (150-440 10\^3/µL), Iron (37-158 µg/dL), Ferritin (10-365 ng/mL), Transferrin (170-340 mg/dL), TIBC (250-450 µg/dL), TSAT (15-50%), Albumin (3.4-4.8 g/dL), hs-CRP (\<= 10.000 mg/dL), Potassium (3.5-5.1 mmol/L), and Phosphorus (2.7-4.5 mg/dL). |
| Mean Number of Months Per Participant Requiring Dose Adjustment During the Dose Titration and Evaluation Periods | Up to Week 24 | Mean number of months per participant requiring dose adjustment during the dose titration and evaluation periods was assessed and reported. |
Countries
Indonesia
Participant flow
Recruitment details
The study was conducted at 10 sites in the Indonesia and the study period was from 05 October 2009 to 12 September 2011.
Pre-assignment details
Of the 85 screened participants 52 were screening failure due to abnormal haemoglobin concentration and 33 were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Mircera Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 3 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Mircera |
|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 13.4 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 33 |
| serious Total, serious adverse events | 4 / 33 |
Outcome results
Primary
Proportion of Participants Maintaining Average Haemoglobin During the Efficacy Evaluation Period Within the Target Range (10-12 g/dl)
The proportion of participants with their mean haemoglobin (Hb) concentration (g/dL) within the target range during the efficacy evaluation period was assessed. The target range is the reference Hb not \>12 g/dL and not \< 10 g/dL.
Time frame: Up to Week 24
Population: Intent to treat (ITT) population was defined as all participants who entered study and took at least one dose of study drug. The ITT and safety population were identical. At Week 24, data of 24 participants were included whereas 9 participants were excluded from the analysis as they discontinued the study before analysis of this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera | Proportion of Participants Maintaining Average Haemoglobin During the Efficacy Evaluation Period Within the Target Range (10-12 g/dl) | 45.8 Percentage of participants |
Secondary
Mean Change in Haemoglobin Concentration From Screening Period and Efficacy Evaluation Period
The mean haemoglobin (Hb) concentration (g/dL) change from the baseline (Week 0) till efficacy evaluation period (EEP) was assessed and reported.
Time frame: Up to Week 24
Population: ITT population was defined as all participants who entered study and took at least one dose of study drug. The ITT and safety population were identical. At Week 24, data of 24 participants were included whereas 9 participants were excluded from the analysis as they discontinued the study before analysis of this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Change in Haemoglobin Concentration From Screening Period and Efficacy Evaluation Period | Mean change at EEP | 0.04 g/dL | Standard Deviation 1.23 |
| Mircera | Mean Change in Haemoglobin Concentration From Screening Period and Efficacy Evaluation Period | At baseline | 10.89 g/dL | Standard Deviation 0.48 |
Secondary
Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods
Mean monthly dose of methoxy polyethylene glycol-epoetin beta during the dose titration and evaluation periods was assessed and reported.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16, and Week 20
Population: ITT population was defined as all participants who entered into study and took at least one dose of study drug. The ITT and safety population were identical. Data of maximum number of participants (24 participants) available at the time of analysis were analysed and 9 participants discontinued the study before this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods | At Baseline | 97.9 μg/month | Standard Deviation 14.6 |
| Mircera | Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods | At Week 4 | 103.1 μg/month | Standard Deviation 19.9 |
| Mircera | Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods | At Week 8 | 107.3 μg/month | Standard Deviation 37.9 |
| Mircera | Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods | At Week 12 | 119 μg/month | Standard Deviation 43.8 |
| Mircera | Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods | At Week 16 | 114.6 μg/month | Standard Deviation 53.6 |
| Mircera | Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods | At Week 20 | 120.8 μg/month | Standard Deviation 73.2 |
Secondary
Mean Number of Months Per Participant Requiring Dose Adjustment During the Dose Titration and Evaluation Periods
Mean number of months per participant requiring dose adjustment during the dose titration and evaluation periods was assessed and reported.
Time frame: Up to Week 24
Population: ITT population was defined as all participants who entered study and took at least one dose of study drug. The ITT and safety population were identical. At Week 24, data of 24 participants were included whereas 9 participants were excluded from the analysis as they discontinued the study before analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera | Mean Number of Months Per Participant Requiring Dose Adjustment During the Dose Titration and Evaluation Periods | 1 Months | Standard Deviation 3.5 |
Secondary
Mean Time Spent by Participants in the Haemoglobin Range of 10 - 12 g/dL During the Efficacy Evaluation Period
Mean time spent in the haemoglobin range 10 - 12 g/dL during the efficacy evaluation period (EEP) was assessed and reported.
Time frame: Up to Week 24
Population: ITT population was defined as all participants who entered study and took at least one dose of study drug. The ITT and safety population were identical. At Week 24, data of 24 participants were included whereas 9 participants were excluded from the analysis as they discontinued the study before analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera | Mean Time Spent by Participants in the Haemoglobin Range of 10 - 12 g/dL During the Efficacy Evaluation Period | 3.92 Weeks | Standard Deviation 2.39 |
Secondary
Number of Participants With Adverse Events and Serious Adverse Events
An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. The AEs were assessed from baseline to every visit throughout the treatment, post study drug discontinuation, and follow up period.
Time frame: Up to Week 28
Population: Safety population included all participants who entered into the study and took at least one dose of study drug.The ITT and safety population were identical. Data of maximum number of participants (33 participants) available at the time of analysis were analysed and reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera | Number of Participants With Adverse Events and Serious Adverse Events | Number of participants serious AE | 4 Participants |
| Mircera | Number of Participants With Adverse Events and Serious Adverse Events | Total number of participants with at least one AE | 15 Participants |
Secondary
Number of Participants With Marked Laboratory Abnormalities
A marked laboratory abnormality is defined as above and/or below the normal range of a laboratory parameter which was considered to be potentially clinically relevant. The number of participants with marked laboratory abnormality are presented. Marked laboratory abnormalities were analyzed according to the Roche specified limits for the following reference range: Haemoglobin (Hb) (11.7-17.3 g/dL), Haematocrit (Hct) (35-47%), White blood cells (WBC) (3.6-11.0 10\^3/µL), Red blood cells (RBC) (3.8- 5.9 10\^6/µL), MCV (80-100 fL) Platelets (150-440 10\^3/µL), Iron (37-158 µg/dL), Ferritin (10-365 ng/mL), Transferrin (170-340 mg/dL), TIBC (250-450 µg/dL), TSAT (15-50%), Albumin (3.4-4.8 g/dL), hs-CRP (\<= 10.000 mg/dL), Potassium (3.5-5.1 mmol/L), and Phosphorus (2.7-4.5 mg/dL).
Time frame: Up to Week 28
Population: Safety population included all participants who entered into the study and took at least one dose of study drug.The ITT and safety population were identical. Data of maximum number of participants (33 participants) available at the time of analysis were analysed and reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Hb-Low | 30 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Hct-Low | 28 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, WBC-Low | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, WBC-High | 2 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, MCV-Low | 3 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, MCV- High | 4 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, RBC-Low | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, RBC -High | 2 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Platelets-Low | 7 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Iron-Low | 10 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Iron-High | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Feritin-High | 25 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Transferin-Low | 9 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, TIBC-Low | 24 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, TSAT-Low | 8 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, TSAT-High | 8 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Albumin-Low | 3 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, hs-CRP-High | 2 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Potassium-High | 9 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Baseline, Phosphorus-High | 19 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Hb-Low | 22 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Hct-Low | 22 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, WBC-High | 3 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, MCV-Low | 5 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, RBC -High | 25 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Platelets-Low | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Platelets-High | 21 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Iron-Low | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Iron-High | 22 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Feritin-High | 6 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, Transferin-Low | 6 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 8, TIBC-Low | 24 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Hb-Low | 18 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Hct-Low | 14 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, WBC-High | 2 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, RBC -High | 4 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Platelets-Low | 4 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Platelets-High | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Iron-Low | 4 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Iron-High | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Feritin-High | 8 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Transferin-Low | 6 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Transferin-High | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, TIBC-Low | 12 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, TSAT-Low | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, TSAT-High | 3 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Albumin-High | 1 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, hs-CRP-High | 2 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24,Potassium-Low | 2 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Potassium-High | 3 Participants |
| Mircera | Number of Participants With Marked Laboratory Abnormalities | At Week 24, Phosphorus-High | 11 Participants |
Secondary
Proportion of Participants Maintaining Haemoglobin Concentration Within the Haemoglobin Range 10-12g/dL Throughout the Efficacy Evaluation Period
The proportion of participants maintaining haemoglobin concentration within the haemoglobin range 10-12g/dL throughout the efficacy evaluation period (EEP) was assessed and reported.
Time frame: Up to Week 24
Population: ITT population was defined as all participants who entered study and took at least one dose of study drug. The ITT and safety population were identical. At Week 24, data of 24 participants were included whereas 9 participants were excluded from the analysis as they discontinued the study before analysis of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera | Proportion of Participants Maintaining Haemoglobin Concentration Within the Haemoglobin Range 10-12g/dL Throughout the Efficacy Evaluation Period | Participants maintaining Hb >10 g/dl | 62.5 Percentage of participants |
| Mircera | Proportion of Participants Maintaining Haemoglobin Concentration Within the Haemoglobin Range 10-12g/dL Throughout the Efficacy Evaluation Period | Participants maintaining Hb within 10-12 g/dl | 16.7 Percentage of participants |