Anemia, Renal Diseases
Conditions
Keywords
Anemia, Reduction in the number of erythrocytes, Hemoglobin low level, Red blood cell deficiency, Procrit, Epoetin alfa, Chronic kidney disease
Brief summary
The purpose of this study is to demonstrate that once every-2-weeks and once every-4-weeks treatment with epoetin alfa, a drug that increases red blood cell production, in patients with anemia associated with chronic kidney disease, is not less effective than treatment with epoetin alfa that is given once a week
Detailed description
A consequence of chronic kidney disease is anemia due to decreased production of erythropoietin. Anemia is associated with decreased oxygen delivery and utilization, and can result in fatigue, lethargy, decreased cognition and mental acuity, and cardiac complications.This study was designed to compare 2 dosing regimens, once every-2-weeks and once every-4-weeks with the once-weekly dosing regimen. Men and women who are diagnosed with anemia associated with chronic kidney disease will participate in this study. Approximately 400 patients will be included. This is a randomized (patients are assigned different treatments based on chance), open-label, multicenter study of epoetin alfa in patients who are not on dialysis and who are already maintaining anemia with epoetin alfa administered once weekly. The study is 40 to 42 weeks in duration. All eligible patients will be treated with epoetin alfa according to one of the following 3 regimens: once-a-week injection (Group 1), or once every-2-weeks injection (Group 2), or once every-4-weeks injection (Group 3). The maximum volume per injection will not be more than 1 mL, therefore some patients may receive more than one injection per dose. The study treatment includes a period to convert to the new dosing regimen, and a subsequent stable maintenance treatment period. After the initial dose, hemoglobin will be measured on a weekly basis and used to determine adjustments in dose for each patient. The primary hypothesis is that the average change in hemoglobin level in the groups that received epoetin alfa once every 2 weeks or once every 4 weeks is not lower than the change in hemoglobin level in the group that received epoetin alfa only once a week. Adverse events will be monitored throughout the study. Clinical laboratory examinations, vital signs, and physical examinations will be conducted routinely to ensure patient safety. Approximately 1 mL of epoetin alfa will be injected under the skin either once a week, once every 2 weeks, or once every 4 weeks (maximum doses of 20,000 IU once a week, 40, 000 IU every 2 weeks, or 80,000 IU every 4 weeks, respectively) for up to 36 weeks of treatment.
Interventions
DRUGepoetin alfa
Continue pre-study once weekly dose of epoetin alfa for 36 weeks
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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
* Meet the diagnostic criteria for chronic kidney disease, defined as a glomerular filtration rate (GFR) \>=15 mL/min per 1.73 m2 and \<60 mL/min per 1.73 m2 (Stages 3 and 4) as calculated by the central laboratory * Hemoglobin level between 10.0 and 11.9 g/dL during the 4 weeks before randomization * History of increase in hemoglobin after the initial dose * Stable dose of epoetin alfa given once-weekly before randomization.
Exclusion criteria
* Uncontrolled hypertension * Iron deficiency * iron overload * severe congestive heart failure * Active infection * Recent heart attack, Stroke or blood clot.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Hemoglobin Concentration in Grams Per Deciliter (g/dL) From Baseline to the Average of the Last 12 Weeks of Treatment | from baseline (Week 1) to the last 12 weeks of treatment |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Weeks Per Patient With Hemoglobin Concentration Between 10.0 and 11.9 Grams Per Deciliter (g/dL) | Weeks 13-37 |
Other
| Measure | Time frame |
|---|---|
| Participants Who Met or Exceeded 1.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 36 weeks of treatment |
| Participants Who Met or Exceeded 1.5 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 36 weeks of treatment |
| Participants Who Exceeded a Hemoglobin Concentration of 11.9 Grams Per Deciliter (g/dL) | 36 weeks of treatment |
| Maximum Hemoglobin Rate of Rise in Grams Per Deciliter (g/dL/2 Weeks) | 36 weeks of treatment |
| Number of Participants Who Died | 36 weeks of treatment |
| Participants Who Met or Exceeded 2.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 36 weeks of treatment |
| Maximum Hemoglobin Concentration in Grams Per Deciliter (g/dL) | 36 weeks of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Epoetin Alfa QW Continue pre-study once weekly dose of epoetin alfa for 36 weeks | 108 |
| Epoetin Alfa Q2W Double the pre-study once weekly dose of epoetin alfa every 2 weeks for 36 wks | 107 |
| Epoetin Alfa Q4W Quadruple the pre-study once weekly dose of epoetin alfa every 4 weeks for 36 wk | 215 |
| Total | 430 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 11 |
| Overall Study | Began Dialysis | 0 | 0 | 1 |
| Overall Study | Death | 3 | 2 | 9 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 |
| Overall Study | Met Hemoglobin Withdrawal Criteria | 0 | 4 | 4 |
| Overall Study | Physician Decision | 2 | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 9 |
Baseline characteristics
| Characteristic | Total | Epoetin Alfa QW | Epoetin Alfa Q2W | Epoetin Alfa Q4W |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 314 Participants | 75 Participants | 81 Participants | 158 Participants |
| Age, Categorical Between 18 and 65 years | 116 Participants | 33 Participants | 26 Participants | 57 Participants |
| Age, Continuous | 71 years STANDARD_DEVIATION 12.18 | 70.3 years STANDARD_DEVIATION 13.04 | 71.7 years STANDARD_DEVIATION 10.63 | 71.1 years STANDARD_DEVIATION 12.48 |
| Sex: Female, Male Female | 267 Participants | 68 Participants | 73 Participants | 126 Participants |
| Sex: Female, Male Male | 163 Participants | 40 Participants | 34 Participants | 89 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 | 59 / 108 | 59 / 107 | 116 / 215 |
| serious Total, serious adverse events | 24 / 108 | 28 / 107 | 56 / 215 |
Outcome results
Primary
Change in Hemoglobin Concentration in Grams Per Deciliter (g/dL) From Baseline to the Average of the Last 12 Weeks of Treatment
Time frame: from baseline (Week 1) to the last 12 weeks of treatment
Population: Modified Intent-To-Treat (mITT) population defined as all participants who were randomly assigned to treatment with epoetin alfa and had at least 1 post-randomization hemoglobin assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa QW | Change in Hemoglobin Concentration in Grams Per Deciliter (g/dL) From Baseline to the Average of the Last 12 Weeks of Treatment | -0.02 g/dL | Standard Deviation 0.728 |
| Epoetin Alfa Q2W | Change in Hemoglobin Concentration in Grams Per Deciliter (g/dL) From Baseline to the Average of the Last 12 Weeks of Treatment | -0.10 g/dL | Standard Deviation 0.774 |
| Epoetin Alfa Q4W | Change in Hemoglobin Concentration in Grams Per Deciliter (g/dL) From Baseline to the Average of the Last 12 Weeks of Treatment | -0.19 g/dL | Standard Deviation 0.738 |
Comparison: The null hypothesis was that the lower limit of the 95% confidence interval (CI) for the difference in mean change in hemoglobin from baseline to the average of the last 12 weeks of treatment between the every-2-weeks (Q2W) and once-weekly (QW) groups would be lower than -1 g/dL.95% CI: [-0.208, 0.153]ANCOVA
Comparison: The null hypothesis was that the lower limit of the 95% confidence interval (CI) for the difference in mean change in hemoglobin from baseline to the average of the last 12 weeks of treatment between the every-4-weeks (Q4W) and once-weekly (QW) groups would be lower than -1 g/dL.95% CI: [-0.249, 0.063]ANCOVA
Secondary
Proportion of Weeks Per Patient With Hemoglobin Concentration Between 10.0 and 11.9 Grams Per Deciliter (g/dL)
Time frame: Weeks 13-37
Population: Modified Intent-To-Treat (mITT) population defined as all participants who were randomly assigned to treatment with epoetin alfa and had at least 1 post-randomization hemoglobin assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoetin Alfa QW | Proportion of Weeks Per Patient With Hemoglobin Concentration Between 10.0 and 11.9 Grams Per Deciliter (g/dL) | 0.87 Proportion |
| Epoetin Alfa Q2W | Proportion of Weeks Per Patient With Hemoglobin Concentration Between 10.0 and 11.9 Grams Per Deciliter (g/dL) | 0.88 Proportion |
| Epoetin Alfa Q4W | Proportion of Weeks Per Patient With Hemoglobin Concentration Between 10.0 and 11.9 Grams Per Deciliter (g/dL) | 0.83 Proportion |
Other Pre-specified
Maximum Hemoglobin Concentration in Grams Per Deciliter (g/dL)
Time frame: 36 weeks of treatment
Population: Safety population defined as all participants who received at least 1 injection of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa QW | Maximum Hemoglobin Concentration in Grams Per Deciliter (g/dL) | 12.35 g/dL | Standard Deviation 0.828 |
| Epoetin Alfa Q2W | Maximum Hemoglobin Concentration in Grams Per Deciliter (g/dL) | 12.48 g/dL | Standard Deviation 0.76 |
| Epoetin Alfa Q4W | Maximum Hemoglobin Concentration in Grams Per Deciliter (g/dL) | 12.46 g/dL | Standard Deviation 0.988 |
95% CI: [-0.113, 0.372]ANOVA
95% CI: [-0.098, 0.32]ANOVA
Other Pre-specified
Maximum Hemoglobin Rate of Rise in Grams Per Deciliter (g/dL/2 Weeks)
Time frame: 36 weeks of treatment
Population: Safety population defined as all participants who received at least 1 injection of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa QW | Maximum Hemoglobin Rate of Rise in Grams Per Deciliter (g/dL/2 Weeks) | 1.77 g/dL/2 weeks | Standard Deviation 1.068 |
| Epoetin Alfa Q2W | Maximum Hemoglobin Rate of Rise in Grams Per Deciliter (g/dL/2 Weeks) | 1.69 g/dL/2 weeks | Standard Deviation 0.79 |
| Epoetin Alfa Q4W | Maximum Hemoglobin Rate of Rise in Grams Per Deciliter (g/dL/2 Weeks) | 1.81 g/dL/2 weeks | Standard Deviation 1.173 |
95% CI: [-0.367, 0.208]ANOVA
95% CI: [-0.206, 0.289]ANOVA
Other Pre-specified
Number of Participants Who Died
Time frame: 36 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa QW | Number of Participants Who Died | 4 Participants |
| Epoetin Alfa Q2W | Number of Participants Who Died | 3 Participants |
| Epoetin Alfa Q4W | Number of Participants Who Died | 9 Participants |
Other Pre-specified
Participants Who Exceeded a Hemoglobin Concentration of 11.9 Grams Per Deciliter (g/dL)
Time frame: 36 weeks of treatment
Population: Safety population defined as all participants who received at least 1 injection of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa QW | Participants Who Exceeded a Hemoglobin Concentration of 11.9 Grams Per Deciliter (g/dL) | 79 Participants |
| Epoetin Alfa Q2W | Participants Who Exceeded a Hemoglobin Concentration of 11.9 Grams Per Deciliter (g/dL) | 89 Participants |
| Epoetin Alfa Q4W | Participants Who Exceeded a Hemoglobin Concentration of 11.9 Grams Per Deciliter (g/dL) | 161 Participants |
95% CI: [0.1, 21.7]95% Confidence Interval
95% CI: [-9.1, 11.2]95% of Confidence Interval
Other Pre-specified
Participants Who Met or Exceeded 1.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise
Time frame: 36 weeks of treatment
Population: Safety population defined as all participants who received at least 1 injection of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa QW | Participants Who Met or Exceeded 1.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 84 Particpants |
| Epoetin Alfa Q2W | Participants Who Met or Exceeded 1.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 91 Particpants |
| Epoetin Alfa Q4W | Participants Who Met or Exceeded 1.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 191 Particpants |
95% CI: [-2, 18.3]95% of Confidence Interval
95% CI: [1.5, 19.2]95% of Confidence Interval
Other Pre-specified
Participants Who Met or Exceeded 1.5 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise
Time frame: 36 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa QW | Participants Who Met or Exceeded 1.5 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 52 Participants |
| Epoetin Alfa Q2W | Participants Who Met or Exceeded 1.5 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 57 Participants |
| Epoetin Alfa Q4W | Participants Who Met or Exceeded 1.5 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 124 Participants |
95% CI: [-7.7, 19.1]95% of Confidence Interval
95% CI: [-2.5, 20.6]95% of Confidence Interval
Other Pre-specified
Participants Who Met or Exceeded 2.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise
Time frame: 36 weeks of treatment
Population: Safety population defined as all participants who received at least 1 injection of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa QW | Participants Who Met or Exceeded 2.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 37 Participants |
| Epoetin Alfa Q2W | Participants Who Met or Exceeded 2.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 33 Participants |
| Epoetin Alfa Q4W | Participants Who Met or Exceeded 2.0 Grams Per Deciliter Per 2 Weeks (g/dL/2 Weeks) Hemoglobin Rates of Rise | 68 Participants |
95% CI: [-15.8, 9.5]95% of Confidence Interval
95% CI: [-13.9, 8]95% of Confidence Interval