Anemia, Chronic Kidney Disease, Chronic Renal Failure
Conditions
Keywords
anemia, chronic kidney disease, CKD, chronic renal failure, CRF, erythropoietin, EPO, erythropoiesis stimulating agent, ESA, Hematide™, hemoglobin, Hb, Hgb, Omontys, peginesatide, red blood cell, red blood cell production
Brief summary
The purpose of this study is to evaluate the safety and efficacy of peginesatide for the treatment of anemia in participants with chronic kidney disease who are on dialysis and are not taking any treatment to increase their red blood cell production.
Detailed description
Anemia associated with chronic kidney disease is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The presence and severity of anemia are related to the duration and extent of kidney failure. Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function, and increased left ventricular hypertrophy and heart failure. Erythropoiesis stimulating agents (ESAs) have been established as a treatment for anemia in chronic renal failure subjects, and have improved the management of anemia over alternatives such as transfusion. Peginesatide is a parenteral formulation developed for the treatment of anemia in patients with chronic kidney disease. Peginesatide binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents. Eligible participants were randomized in equal proportions to two peginesatide treatment regimens, in which participants received peginesatide once every 4 weeks, and one control, epoetin alfa, treatment regimen, in which participants received epoetin alfa three times per week. Total commitment time of this study was a 4 week screening period followed by a minimum of 7 months of treatment.
Interventions
DRUGpeginesatide
Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).
DRUGEpoetin Alfa
Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Sponsors
Takeda
Affymax
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
1. On hemodialysis for chronic renal failure for at least 2 weeks prior to randomization. 2. Two consecutive hemoglobin values of ≥ 8.0 g/dL and \< 11.0 g/dL within the 4 weeks prior to randomization.
Exclusion criteria
1. Females who are pregnant or breast-feeding. 2. Prior treatment with an erythropoiesis stimulating agent (ESA) in the 12 weeks prior to randomization. 3. Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule. 4. Known bleeding or coagulation disorder. 5. Known hematologic disease or cause for anemia other than renal disease 6. Poorly controlled hypertension. 7. Evidence of active malignancy within one year. 8. A scheduled kidney transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Baseline and Weeks 21-28 | The baseline hemoglobin value is defined as the mean of the two most recent hemoglobin values taken prior to the day of randomization plus the value obtained on the day of randomization prior to Dose 1. The mean hemoglobin during the Evaluation period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 21 through 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods | Weeks 1 to 28 | — |
| Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods | Weeks 1 to 28 | A hemoglobin response is defined as a hemoglobin increase of ≥ 1.0 g/dL above baseline and a hemoglobin ≥ 11.0 g/dL without RBC or whole blood transfusion during the previous 8 weeks. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Peginesatide 0.04 mg/kg Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL). | 39 |
| Peginesatide 0.08 mg/kg Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL. | 37 |
| Epoetin Alfa Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL. | 38 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Patient Not Compliant With Study Reqs. | 0 | 1 | 0 |
| Overall Study | Renal Transplant | 1 | 0 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Peginesatide 0.04 mg/kg | Peginesatide 0.08 mg/kg | Epoetin Alfa | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 6 Participants | 8 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 31 Participants | 30 Participants | 98 Participants |
| Age Continuous | 48.8 years STANDARD_DEVIATION 11.71 | 48.8 years STANDARD_DEVIATION 13.55 | 51.4 years STANDARD_DEVIATION 14.16 | 49.7 years STANDARD_DEVIATION 13.1 |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 19 Participants | 45 Participants |
| Sex: Female, Male Male | 27 Participants | 23 Participants | 19 Participants | 69 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 | 21 / 39 | 26 / 37 | 27 / 38 |
| serious Total, serious adverse events | 6 / 39 | 8 / 37 | 4 / 38 |
Outcome results
Primary
Mean Change in Hemoglobin Between Baseline and the Evaluation Period
The baseline hemoglobin value is defined as the mean of the two most recent hemoglobin values taken prior to the day of randomization plus the value obtained on the day of randomization prior to Dose 1. The mean hemoglobin during the Evaluation period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 21 through 28.
Time frame: Baseline and Weeks 21-28
Population: Full Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peginesatide 0.04 mg/kg | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Evaluation Period [N=37, 37, 36] | 11.45 g/dL | Standard Deviation 1.101 |
| Peginesatide 0.04 mg/kg | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Change from Baseline [N=37, 37, 36] | 2.15 g/dL | Standard Deviation 1.038 |
| Peginesatide 0.04 mg/kg | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Baseline [N=39, 37, 38] | 9.34 g/dL | Standard Deviation 0.738 |
| Peginesatide 0.08 mg/kg | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Change from Baseline [N=37, 37, 36] | 2.39 g/dL | Standard Deviation 0.974 |
| Peginesatide 0.08 mg/kg | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Baseline [N=39, 37, 38] | 9.20 g/dL | Standard Deviation 0.701 |
| Peginesatide 0.08 mg/kg | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Evaluation Period [N=37, 37, 36] | 11.59 g/dL | Standard Deviation 0.943 |
| Epoetin Alfa | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Evaluation Period [N=37, 37, 36] | 11.49 g/dL | Standard Deviation 0.775 |
| Epoetin Alfa | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Baseline [N=39, 37, 38] | 9.07 g/dL | Standard Deviation 0.739 |
| Epoetin Alfa | Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Change from Baseline [N=37, 37, 36] | 2.41 g/dL | Standard Deviation 0.991 |
97.5% CI: [-0.79, 0.29]ANOVA
97.5% CI: [-0.56, 0.52]ANOVA
Secondary
Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods
A hemoglobin response is defined as a hemoglobin increase of ≥ 1.0 g/dL above baseline and a hemoglobin ≥ 11.0 g/dL without RBC or whole blood transfusion during the previous 8 weeks.
Time frame: Weeks 1 to 28
Population: Full Analysis Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginesatide 0.04 mg/kg | Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods | 0.923 percentage of participants |
| Peginesatide 0.08 mg/kg | Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods | 0.973 percentage of participants |
| Epoetin Alfa | Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods | 1.0 percentage of participants |
95% CI: [0.84, 1.01]Cochran-Mantel-Haenszel
95% CI: [0.92, 1.03]Cochran-Mantel-Haenszel
Secondary
Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods
Time frame: Weeks 1 to 28
Population: Full Analysis Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginesatide 0.04 mg/kg | Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods | 0.026 percentage of participants |
| Peginesatide 0.08 mg/kg | Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods | 0.0 percentage of participants |
| Epoetin Alfa | Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods | 0.0 percentage of participants |