Anemia, Kidney Disease, Chronic
Conditions
Brief summary
This comparative, open-label, multicenter, parallel-group study evaluated the effect of altitude on the dose requirements of Mircera (methoxy polyethylene glycol-epoetin beta) to achieve a target hemoglobin concentration of 11-12 grams per deciliter (g/dL) in participants with chronic renal anemia in pre-dialysis and dialysis. Four groups of participants, at sea level (below 50 meters) or an altitude above 1800 meters, and pre-dialysis or dialysis, received 50-250 micrograms (mcg) Mircera subcutaneously (SC), according to the local prescribing label.
Interventions
DRUGMethoxy polyethylene glycol-epoetin beta
Participants received 50-250 mcg SC according to local label
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants, \>/= 18 years of age * Chronic kidney disease stage III-IV or V * Probable start of dialysis within 18 months (pre-dialysis group) * Hemodialysis or peritoneal dialysis in a stable regimen for at least 3 months (dialysis group) * Adequate iron status * Females of childbearing potential must agree to use two effective methods of contraception during the study and for at least 2 months following the last dose of study drug
Exclusion criteria
* Failing renal allograft in place * Acute or chronic bleeding within 8 weeks prior to screening * Transfusion of red blood cells within 8 weeks prior to screening * Poorly controlled hypertension, defined as hypertension that needs hospitalization to obtain control * History of seizures, hemoglobinopathies and/or severe liver disease * Active malignant disease, except for non-melanoma skin cancer * Immunosuppressive therapy in the 12 weeks prior to screening * Treatment with any other investigational agent or participation in a clinical trial within 28 days prior to enrolment * Known hypersensitivity to Mircera (methoxy polyethylene glycol-epoetin beta) or any of its excipients * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Dose Required to Achieve Target Hemoglobin of 11-12 g/dL | Up to approximately 20 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin Concentration | From baseline to 6 months | — |
| Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 3 and 6 months | — |
| Percentage of Participants With Adverse Events | Up to approximately 20 months | An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. |
| Percentage of Participants Requiring Dose Adjustments | Up to approximately 20 months | This outcome measure was not assessed. |
| Incidence of Red Blood Cell Transfusions | Up to approximately 20 months | This outcome measure was not assessed. |
Countries
Mexico
Participant flow
Pre-assignment details
87 participants were enrolled in the study. One participant did not receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| Pre-dialysis, Sea Level Participants received 50-250 mcg SC according to local label. | 19 |
| Dialysis, Sea Level Participants received 50-250 mcg SC according to local label. | 10 |
| Pre-dialysis, >1800 Meters Participants received 50-250 mcg SC according to local label. | 15 |
| Dialysis, >1800 Meters Participants received 50-250 mcg SC according to local label. | 42 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 |
| Overall Study | Blood Transfusion | 0 | 1 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 1 |
| Overall Study | Development of Anemia | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 3 | 2 |
| Overall Study | Peritoneal Dialysis Needed | 0 | 1 | 0 | 0 |
| Overall Study | Poor Response | 1 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Pre-dialysis, Sea Level | Dialysis, Sea Level | Pre-dialysis, >1800 Meters | Dialysis, >1800 Meters | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 15.1 | 38.5 years STANDARD_DEVIATION 18.8 | 61.7 years STANDARD_DEVIATION 15.6 | 56.5 years STANDARD_DEVIATION 17.4 | 56.2 years STANDARD_DEVIATION 17.8 |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 8 Participants | 23 Participants | 48 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 7 Participants | 19 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 19 | 9 / 10 | 10 / 15 | 36 / 42 |
| serious Total, serious adverse events | 1 / 19 | 3 / 10 | 2 / 15 | 6 / 42 |
Outcome results
Primary
Mean Dose Required to Achieve Target Hemoglobin of 11-12 g/dL
Time frame: Up to approximately 20 months
Population: The intent-to treat (ITT) population included all enrolled participants who received at least one dose of study drug and had baseline and post-baseline measurements of the primary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-dialysis, Sea Level | Mean Dose Required to Achieve Target Hemoglobin of 11-12 g/dL | 150.3 micrograms (mcg) | Standard Deviation 69 |
| Dialysis, Sea Level | Mean Dose Required to Achieve Target Hemoglobin of 11-12 g/dL | 194.7 micrograms (mcg) | Standard Deviation 214.2 |
| Pre-dialysis, >1800 Meters | Mean Dose Required to Achieve Target Hemoglobin of 11-12 g/dL | 98.7 micrograms (mcg) | Standard Deviation 22.5 |
| Dialysis, >1800 Meters | Mean Dose Required to Achieve Target Hemoglobin of 11-12 g/dL | 66.6 micrograms (mcg) | Standard Deviation 33.6 |
Secondary
Change in Hemoglobin Concentration
Time frame: From baseline to 6 months
Population: The intent-to treat (ITT) population included all enrolled participants who received at least one dose of study drug and had baseline and post-baseline measurements of the primary outcome measure. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-dialysis, Sea Level | Change in Hemoglobin Concentration | 1.4 grams per deciliter (g/dL) | Standard Deviation 0.8 |
| Dialysis, Sea Level | Change in Hemoglobin Concentration | 2.5 grams per deciliter (g/dL) | Standard Deviation 1.5 |
| Pre-dialysis, >1800 Meters | Change in Hemoglobin Concentration | 2.0 grams per deciliter (g/dL) | Standard Deviation 0.8 |
| Dialysis, >1800 Meters | Change in Hemoglobin Concentration | 2.4 grams per deciliter (g/dL) | Standard Deviation 1.4 |
Secondary
Incidence of Red Blood Cell Transfusions
This outcome measure was not assessed.
Time frame: Up to approximately 20 months
Population: Data were not collected.
Secondary
Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment
Time frame: 3 and 6 months
Population: The intent-to treat (ITT) population included all enrolled participants who received at least one dose of study drug and had baseline and post-baseline measurements of the primary outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pre-dialysis, Sea Level | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 3 months | 36.8 percentage of participants |
| Pre-dialysis, Sea Level | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 6 months | 52.6 percentage of participants |
| Dialysis, Sea Level | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 6 months | 0.0 percentage of participants |
| Dialysis, Sea Level | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 3 months | 10.0 percentage of participants |
| Pre-dialysis, >1800 Meters | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 3 months | 0.0 percentage of participants |
| Pre-dialysis, >1800 Meters | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 6 months | 13.3 percentage of participants |
| Dialysis, >1800 Meters | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 3 months | 28.6 percentage of participants |
| Dialysis, >1800 Meters | Percentage of Participants Achieving Target Hemoglobin Concentration 11-12 g/dL After 3 and 6 Months of Treatment | 6 months | 19.0 percentage of participants |
Secondary
Percentage of Participants Requiring Dose Adjustments
This outcome measure was not assessed.
Time frame: Up to approximately 20 months
Population: Data were not collected.
Secondary
Percentage of Participants With Adverse Events
An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.
Time frame: Up to approximately 20 months
Population: The safety population included all enrolled participants who received at least one dose of study drug and had a subsequent safety evaluation dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-dialysis, Sea Level | Percentage of Participants With Adverse Events | 84.2 percentage of participants |
| Dialysis, Sea Level | Percentage of Participants With Adverse Events | 90.0 percentage of participants |
| Pre-dialysis, >1800 Meters | Percentage of Participants With Adverse Events | 66.7 percentage of participants |
| Dialysis, >1800 Meters | Percentage of Participants With Adverse Events | 85.7 percentage of participants |