Anemia
Conditions
Brief summary
This study assessed the long-term efficacy, safety, and tolerability of intravenous (iv) or subcutaneous (sc) methoxy polyethylene glycol-epoetin beta in chronic kidney disease patients with renal anemia. Eligible patients were those who were receiving stable maintenance therapy with methoxy polyethylene glycol-epoetin beta or erythropoiesis stimulating agents (ESAs) in Phase II or III clinical studies. They continued to receive methoxy polyethylene glycol-epoetin beta or comparator ESAs at the same weekly dose and by the same route of administration (sc or iv) as in the qualifying studies.
Interventions
DRUGMethoxy Polyethylene Glycol-Epoetin Beta
Methoxy polyethylene glycol-epoetin beta was provided as a sterile single-use injectable solution in 2-mL glass vials containing 1 mL solution or in single-use sterile pre-filled syringes (PFSs) containing 0.3 mL or 0.6 mL injectable solution. The injectable solution was available in vials with the following strengths: 50, 100, 200, 400, and 1000 μg/mL. The injectable solution was available in PFSs with the following strengths: 30, 40, 50, 60, 75, 100, 120, 150, 200, and 250 μg/0.3 mL; and 360 and 400 μg/0.6 mL.
DRUGEpoetin alfa
Epoetin alfa was provided with commercial packaging in English with country-specific labels (10,000 IU, 20,000 IU).
DRUGEpoetin beta
Epoetin beta was provided with commercial packaging in English with country-specific labels (50,000 IU, 100,000 IU).
DRUGDarbepoetin alfa
Darbepoetin alfa was provided with commercial packaging in English with country-specific labels (vials and PFSs in various strengths).
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
* Written informed consent * Adult patients (≥ 18 years old) with chronic renal anemia * Maintenance erythropoietic therapy with methoxy polyethylene glycol-epoetin beta or a protocol-specified reference medication (epoetin alfa formulated with human albumin, epoetin beta or darbepoetin alfa) in one of the following studies: BA16528\[NCT00048048\], BA16285\[NCT00048035\], BA16286\[NCT00364832\], BA16736\[NCT00077597\], BA16738\[NCT00081471\], BA16739\[NCT00077610\], BA16740\[NCT00077623\], BA17283\[NCT00077766\] and BA17284\[NCT00081484\] * Hemoglobin (Hb) concentration between 10.5 and 13.0 g/dL * Adequate iron status defined as serum ferritin ≥ 100 ng/mL or Transferrin Saturation (TSAT)≥ 20% or percentage of hypochromic red blood cells (RBCs) \< 10%
Exclusion criteria
* Poorly controlled hypertension * History of epileptic seizure * Pure red cell aplasia * Chronic congestive heart failure \[New York Heart Association (NYHA) IV\] * High likelihood of early withdrawal or interruption of the study * Active malignant disease (except non-melanoma skin cancer) * Life expectancy less than 12 months * Pregnancy or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin Concentration to the Last Month of Study Participation | Baseline to the end of the study (Up to 49 Months) | Blood samples were collected at each study visit, that is, every 4 weeks for the first 12 weeks, every 12 weeks until week 105 of the first study period, every 3 months thereafter, and at the end of study or the last visit if the patient discontinued the study prematurely. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Had at Least 1 Adverse Event | From first dose of study drug to date of last contact or 30 days after last drug dose (Up to 49 months) | See the adverse events section of the results for more information. |
Countries
Australia, Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Mexico, Netherlands, Norway, Panama, Poland, Portugal, Puerto Rico, Russia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in one of the following Phase II or Phase III studies: BA16528\[NCT00048048\], BA16285\[NCT00048035\], BA16286\[NCT00364832\], BA16736\[NCT00077597\], BA16738\[NCT00081471\], BA16739\[NCT00077610\], BA16740\[NCT00077623\], BA17283\[NCT00077766\] or BA17284\[NCT00081484\]
Participants by arm
| Arm | Count |
|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta Patients received the same weekly dose of methoxy polyethylene glycol-epoetin beta via the same route of administration (iv or sc) as they received in the Phase II or Phase III study that qualified the patient for participation in this study. Methoxy polyethylene glycol-epoetin beta was administered every 2 or every 4 weeks in the initial 104-week treatment period. Patients on a 4-week dosing interval were switched to once-monthly administration in the 24-month extension phase. The dose of methoxy polyethylene glycol-epoetin beta was adjusted to maintain the patient's hemoglobin (Hb) within a target range of 11 to 13 g/dL. | 748 |
| Comparator ESA Patients received the same comparator ESA \[epoetin alfa, epoetin beta, or darbepoetin alfa\] at the same weekly dose and dosing interval via the same route of administration (iv or sc) as they received in the Phase III study that qualified the patient for participation in this study. The dose of the comparator drug was adjusted to maintain the patient's Hb within a target range of 11 to 13 g/dL. Of the 480 patients in the comparator drug group, 170 received darbepoetin alfa, 134 received epoetin alfa, and 176 received epoetin beta. | 480 |
| Total | 1,228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extended Treatment Period | Adverse Event | 11 | 0 |
| Extended Treatment Period | Death | 58 | 30 |
| Extended Treatment Period | Lack of Efficacy | 1 | 0 |
| Extended Treatment Period | Lost to Follow-up | 3 | 1 |
| Extended Treatment Period | Mircera Commercialization | 188 | 93 |
| Extended Treatment Period | Other Unrelated to Safety and Efficacy | 65 | 43 |
| Extended Treatment Period | Refused Treatment | 18 | 12 |
| Extended Treatment Period | Renal Transplant | 15 | 12 |
| First Treatment Period | Adverse Event | 20 | 8 |
| First Treatment Period | Death | 88 | 62 |
| First Treatment Period | Lack of Efficacy | 2 | 1 |
| First Treatment Period | Lost to Follow-up | 4 | 4 |
| First Treatment Period | Mircera Commercialization | 1 | 0 |
| First Treatment Period | Other Unrelated to Safety and Efficacy | 39 | 28 |
| First Treatment Period | Refused Treatment | 32 | 25 |
| First Treatment Period | Renal Transplant | 70 | 50 |
Baseline characteristics
| Characteristic | Methoxy Polyethylene Glycol-Epoetin Beta | Comparator ESA | Total |
|---|---|---|---|
| Age Continuous | 61.2 years STANDARD_DEVIATION 14.8 | 61.9 years STANDARD_DEVIATION 14.42 | 61.5 years STANDARD_DEVIATION 14.65 |
| Sex: Female, Male Female | 327 Participants | 223 Participants | 550 Participants |
| Sex: Female, Male Male | 421 Participants | 257 Participants | 678 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 624 / 748 | 390 / 480 |
| serious Total, serious adverse events | 499 / 748 | 316 / 480 |
Outcome results
Primary
Change From Baseline in Hemoglobin Concentration to the Last Month of Study Participation
Blood samples were collected at each study visit, that is, every 4 weeks for the first 12 weeks, every 12 weeks until week 105 of the first study period, every 3 months thereafter, and at the end of study or the last visit if the patient discontinued the study prematurely.
Time frame: Baseline to the end of the study (Up to 49 Months)
Population: Analysis includes participants from the Intent-to-treat population (all patients who received at least 1 dose of methoxy polyethylene glycol-epoetin beta or a comparator ESA) who had hemoglobin values available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Change From Baseline in Hemoglobin Concentration to the Last Month of Study Participation | -0.55 g/dL | Standard Deviation 1.832 |
| Comparator ESA | Change From Baseline in Hemoglobin Concentration to the Last Month of Study Participation | -0.38 g/dL | Standard Deviation 1.614 |
Secondary
Percentage of Patients Who Had at Least 1 Adverse Event
See the adverse events section of the results for more information.
Time frame: From first dose of study drug to date of last contact or 30 days after last drug dose (Up to 49 months)
Population: Intent-to-treat population: All patients who received at least 1 dose of methoxy polyethylene glycol-epoetin beta or a comparator ESA.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methoxy Polyethylene Glycol-Epoetin Beta | Percentage of Patients Who Had at Least 1 Adverse Event | 94.3 Percentage of participants |
| Comparator ESA | Percentage of Patients Who Had at Least 1 Adverse Event | 93.3 Percentage of participants |