Anemia
Conditions
Brief summary
This study will assess the efficacy and safety of methoxy polyethylene glycol-epoetin beta (Mircera) in the maintenance of hemoglobin levels in patients who have previously received treatment with epoetin alfa or darbepoetin alfa, and who are transitioning from chronic kidney disease stage 4 through dialysis. Patients will be randomized either to receive Mircera or to remain on their existing therapy; the initial monthly dose of subcutaneous (sc) Mircera (120-360 micrograms) will be based on the average weekly dose of epoetin alfa or darbepoetin alfa administered in the week preceding the switch to Mircera. At the initiation of dialysis, patients in the Mircera group will receive monthly intravenous (iv) Mircera at a starting dose based on their previous (sc) dose, and those in the control group will receive weekly (iv) epoetin alfa. The anticipated time on study treatment is 1-2 years, and the target sample size is 500+ individuals.
Interventions
DRUGmethoxy polyethylene glycol-epoetin beta
Methoxy polyethylene glycol-epoetin beta was provided as a sterile single-use injectable solution in a 1-mL prefilled syringe containing 0.3 mL or 0.6 mL solution. The methoxy polyethylene glycol-epoetin beta injectable solution was formulated in sodium phosphate, sodium sulfate, mannitol, methionine and poloxamer 188, pH 6.2 and did not contain any preservative. Participants received methoxy polyethylene glycol-epoetin beta subcutaneous once a month.
DRUGepoetin alfa
Standard of care as prescribed, per individual participant, subcutaneous once per week. Subcutaneous injections were to be administered in the same part of the body (ie, thigh, abdomen or arm) throughout the study.
DRUGdarbepoetin alfa
Standard of care as prescribed, per individual participant, darbepoetin alfa subcutaneous once every two weeks. Subcutaneous injections were to be administered in the same part of the body (ie, thigh,abdomen or arm) throughout the study.
Sponsors
Hoffmann-La Roche
Study design
Allocation
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 patients, \>=18 years of age; * chronic kidney disease stage IV not requiring dialysis; * expected to initiate dialysis within 18 months; * 15\<=Glomerular Filtration Rate (GFR)\<=29.
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; * immunosuppressive therapy in the 12 weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Able to Maintain Hemoglobin (Hb) Within 10-12 g/dL | 6-7 months post initiation of dialysis | Efficacy analyses were not performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Adjustments | 5 months post-randomization through onset of dialysis, and post-dialysis initiation through study end. | Efficacy analyses were not performed. |
| Number of Participants Assessed for AEs and SAEs | First dose of medication through 15 days post last dose (up to 8 months) | The adverse events are captured in the adverse event and serious adverse event section of this database. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta 120-360 micrograms methoxy polyethylene glycol-epoetin beta subcutaneous (sc) monthly starting dose, for a minimum of 5 months to a maximum of 18 months.
Dosage was adjusted to maintain a hemoglobin target range of ≥10 g/dL to ≤12 g/dL. | 69 |
| Epoetin Alfa Patients randomized to the reference arm continued to receive their standard of care dose and regimen of epoetin alfa subcutaneous once per week for a minimum of 5 months to a maximum of 18 months. Subcutaneous injections were to be administered in the same part of the body (ie, thigh, abdomen or arm) throughout the study.
Dosage was adjusted to maintain a hemoglobin target range of ≥10 g/dL to ≤12 g/dL. | 26 |
| Darbepoetin Alfa Patients randomized to the reference arm continued to receive their standard of care dose and regimen of darbepoetin subcutaneous once every two weeks for a minimum of 5 months and a maximum of 18 months. Subcutaneous injections were to be administered in the same part of the body (ie, thigh, abdomen or arm) throughout the study.
Dosage was adjusted to maintain a hemoglobin target range of ≥10 g/dL to ≤12 g/dL. | 9 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 0 |
| Overall Study | Early termination of study | 62 | 26 | 9 |
| Overall Study | Failure to return | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Refused Treatment | 1 | 1 | 0 |
| Overall Study | Violation of selection criteria at entry | 6 | 0 | 0 |
Baseline characteristics
| Characteristic | Methoxy Polyethylene Glycol-epoetin Beta | Epoetin Alfa | Darbepoetin Alfa | Total |
|---|---|---|---|---|
| Age Continuous | 69.8 years STANDARD_DEVIATION 11.74 | 72.2 years STANDARD_DEVIATION 11.48 | 69.1 years STANDARD_DEVIATION 12.61 | 70.3 years STANDARD_DEVIATION 11.68 |
| Sex: Female, Male Female | 32 Participants | 9 Participants | 5 Participants | 46 Participants |
| Sex: Female, Male Male | 37 Participants | 17 Participants | 4 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 69 | 7 / 26 | 3 / 9 |
| serious Total, serious adverse events | 7 / 69 | 4 / 26 | 1 / 9 |
Outcome results
Primary
Percentage of Patients Able to Maintain Hemoglobin (Hb) Within 10-12 g/dL
Efficacy analyses were not performed.
Time frame: 6-7 months post initiation of dialysis
Secondary
Dose Adjustments
Efficacy analyses were not performed.
Time frame: 5 months post-randomization through onset of dialysis, and post-dialysis initiation through study end.
Secondary
Number of Participants Assessed for AEs and SAEs
The adverse events are captured in the adverse event and serious adverse event section of this database.
Time frame: First dose of medication through 15 days post last dose (up to 8 months)
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-epoetin Beta | Number of Participants Assessed for AEs and SAEs | 69 participants |
| Epoetin Alfa | Number of Participants Assessed for AEs and SAEs | 26 participants |
| Darbepoetin Alfa | Number of Participants Assessed for AEs and SAEs | 9 participants |