Anemia
Conditions
Keywords
Anemia, Chronic Kidney disease, Kidney disease, Epoetin alfa, Procrit
Brief summary
The purpose of this study is to demonstrate that once weekly and once every-2-weeks treatment with epoetin alfa, in patients with anemia associated with chronic kidney disease, is not less effective than the approved treatment with epoetin alfa that is given 3 times weekly with respect to changes in hemoglobin.
Detailed description
This is a open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), multicenter study designed to show that 2 alternative dosing regimens, once weekly and once every-2-weeks (given at doses equivalent to 50 IU/kg 3 times a week) are not inferior to the 3-times-weekly dosing regimen. Approximately 375 patients with anemia will be enrolled in this study. Patients will be randomly assigned to receive epoetin alfa by subcutaneous (SC) injection according to one of the following 3 regimens: 3 times weekly (Group 1), once weekly (Group 2), or once every 2 weeks (Group 3) for 22 weeks. Thereafter, patients in Group 1 will be switched to the once-weekly dosing regimen for an additional 22 weeks, and patients in Groups 2 and 3 will continue their current treatment for an additional 22 weeks. The total duration of the open-label treatment phase is 44 weeks which will include initiation and maintenance treatment periods (with the goal of increasing, then maintaining, the hemoglobin level between 11.0 and 11.9 g/dL inclusive) and a safety period (to assess longer exposure to epoetin alfa treatment and any period of hemoglobin instability during the transition from 3-times-weekly to once-weekly dosing). Starting doses of epoetin alfa in the 3-times-weekly, once-weekly, and every-2-weeks groups will be 50 IU/kg, 10,000 IU, and 20,000 IU, respectively; thereafter adjusted according to weekly hemoglobin concentrations. Safety evaluations will include assessment of adverse events, laboratory tests, physical examinations, and vital signs.
Interventions
DRUGEpoetin alfa 3 times weekly /once weekly
Epoetin alfa will be administered as a SC injections at initial dose of 50 IU/kg (3 times weekly for 22 weeks) and at initial dose of 10000 IU (once weekly for 22 weeks)
DRUGEpoetin alfa once weekly
Epoetin alfa will be administered as a SC injection at initial dose of 10000 IU (once weekly for 44 weeks).
DRUGEpoetin alfa once every two weeks
Epoetin alfa will be administered as a SC injection at initial dose of 20000 IU (once every 2 weeks for 44 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) more than or equal to 15 mL/min per 1.73 m2 and less than 60 mL/min per 1.73 m2 (Stages 3 and 4) as calculated by the central laboratory * Require support of an erythropoietin receptor agonist
Exclusion criteria
* Uncontrolled hypertension * Serum ferritin level less than 50 ng/mL * Serum iron overload * Severe congestive heart failure * Active infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hb Concentration (g/dL) From Baseline to the Average of the Last 8 Weeks of Treatment Through Week 22 | From baseline through Week 22 | The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included in calculating the average Hb during the last 8 weeks of treatment through Week 22. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With an Increase of ≥1 g/dL in Hb Concentration From Baseline by Week 9 | From baseline to Week 9 | The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Hb increase is defined as the post-baseline Hb level minus the baseline Hb level. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Met or Exceeded Hb Rate of Rise >=1.0 g/dL/2 Weeks During First 22 Weeks of Treatment | From baseline to Week 22 | Change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Participants who met or exceeded a Hb Rate of Rise (RR) of 1.0 g/dL/2 weeks at least once were included in the numerator of the percentage calculation. |
| Participants Who Exceeded a Hb Concentration of 11.9 g/dL During First 22 Weeks of Treatment | From baseline to Week 22 | The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. participants who exceed a Hb value of 11.9 g/dL at least once were included in the numerator of the percentage calculation. |
| Particpants Who Met or Exceeded Hb Rate of Rise >=2.0 g/dL/2 Weeks During First 22 Weeks of Treatment | From baseline to Week 22 | Change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Participants who met or exceeded a Hb Rate of Rise (RR) of 2.0 g/dL/2 weeks at least once were included in the numerator of the percentage calculation. |
| Participants Who Met or Exceeded Hb Rate of Rise >=1.5 g/dL/2 Weeks During First 22 Weeks of Treatment | From baseline to Week 22 | Change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Participants who met or exceeded a Hb Rate of Rise (RR) of 1.5 g/dL/2 weeks at least once were included in the numerator of the percentage calculation. |
| Maximum Hb Concentration (g/dL) During First 22 Weeks of Treatment | From baseline to Week 22 | The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. A maximum Hb observation was identified for each participant during the first 22 weeks of treatment. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The study was initiated 29 August 2006 and completed on 21 February 2008. Subjects were screened for eligibility at 64 investigative sites within the U.S. Three hundred seventy-five subjects (intent to treat) were randomly assigned to a treatment group by 52 investigators from 56 sites. Safety population consisted of 373 subjects.
Participants by arm
| Arm | Count |
|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) Epoetin alfa 3 times weekly for 22 weeks (initial subcutaneous (SC) dose 50 IU/kg), then once weekly, for 22 weeks (initial SC dose 10,000 IU) | 123 |
| Epoetin Alfa:Once Weekly (QW) Epoetin alfa once weekly for 44 weeks (initial subcutaneous dose 10,000 IU) | 125 |
| Epoetin Alfa:Once Every Two Weeks (Q2W) Epoetin alfa once every 2 weeks for 44 weeks (initial subcutaneous dose 20,000 IU) | 125 |
| Total | 373 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 5 |
| Overall Study | Began Dialysis | 4 | 1 | 4 |
| Overall Study | Death | 2 | 6 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 | 6 |
| Overall Study | Patient had surgery | 1 | 0 | 0 |
| Overall Study | Patient moved | 1 | 2 | 1 |
| Overall Study | Patient transferred to nursing home | 0 | 1 | 0 |
| Overall Study | Principal Investigator decision | 0 | 3 | 1 |
| Overall Study | Principal Investigator's office closed | 3 | 6 | 4 |
| Overall Study | Withdrawal by Subject | 10 | 5 | 11 |
Baseline characteristics
| Characteristic | Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Epoetin Alfa:Once Weekly (QW) | Epoetin Alfa:Once Every Two Weeks (Q2W) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 90 Participants | 82 Participants | 81 Participants | 253 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants | 43 Participants | 44 Participants | 120 Participants |
| Age, Continuous | 71.1 years STANDARD_DEVIATION 13.02 | 68.9 years STANDARD_DEVIATION 11.86 | 68.9 years STANDARD_DEVIATION 13.02 | 69.6 years STANDARD_DEVIATION 12.65 |
| Sex: Female, Male Female | 77 Participants | 80 Participants | 85 Participants | 242 Participants |
| Sex: Female, Male Male | 46 Participants | 45 Participants | 40 Participants | 131 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 | 93 / 123 | 85 / 125 | 102 / 125 |
| serious Total, serious adverse events | 36 / 123 | 41 / 125 | 42 / 125 |
Outcome results
Primary
Change in Hb Concentration (g/dL) From Baseline to the Average of the Last 8 Weeks of Treatment Through Week 22
The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included in calculating the average Hb during the last 8 weeks of treatment through Week 22.
Time frame: From baseline through Week 22
Population: Modified Intent-To-Treat (mITT) population. The mITT population was defined as all participants who were randomized and had at least 1 postrandomization hemoglobin concentration measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Change in Hb Concentration (g/dL) From Baseline to the Average of the Last 8 Weeks of Treatment Through Week 22 | 1.81 g/dL | Standard Deviation 0.91 |
| Epoetin Alfa:Once Weekly (QW) | Change in Hb Concentration (g/dL) From Baseline to the Average of the Last 8 Weeks of Treatment Through Week 22 | 1.59 g/dL | Standard Deviation 0.997 |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Change in Hb Concentration (g/dL) From Baseline to the Average of the Last 8 Weeks of Treatment Through Week 22 | 1.27 g/dL | Standard Deviation 0.906 |
Comparison: The null hypothesis is the mean change in Hb concentration from baseline to the average of the last 8 weeks of treatment (tX) through Week 22 in the QW group is not lower than that of the TIW group by more than 1 g/dL.95% CI: [-0.38, 0.037]
Comparison: The null hypothesis is the mean change in Hb concentration from baseline to the average of the last 8 weeks of treatment through Week 22 in the Q2W group is not lower than that of the TIW group by more than 1 g/dL.95% CI: [-0.641, -0.221]
Secondary
Participants With an Increase of ≥1 g/dL in Hb Concentration From Baseline by Week 9
The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Hb increase is defined as the post-baseline Hb level minus the baseline Hb level.
Time frame: From baseline to Week 9
Population: Modified Intent-To-Treat (mITT) population. The mITT population was defined as all participants who were randomized and had at least 1 postrandomization Hb concentration measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Participants With an Increase of ≥1 g/dL in Hb Concentration From Baseline by Week 9 | 116 participants |
| Epoetin Alfa:Once Weekly (QW) | Participants With an Increase of ≥1 g/dL in Hb Concentration From Baseline by Week 9 | 108 participants |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Participants With an Increase of ≥1 g/dL in Hb Concentration From Baseline by Week 9 | 106 participants |
95% CI: [-16, -1.9]
95% CI: [-18, -3.2]
Other Pre-specified
Maximum Hb Concentration (g/dL) During First 22 Weeks of Treatment
The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. A maximum Hb observation was identified for each participant during the first 22 weeks of treatment.
Time frame: From baseline to Week 22
Population: Safety population. The safety population was defined as all participants who received at least 1 injection of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Maximum Hb Concentration (g/dL) During First 22 Weeks of Treatment | 12.87 g/dL | Standard Deviation 1.176 |
| Epoetin Alfa:Once Weekly (QW) | Maximum Hb Concentration (g/dL) During First 22 Weeks of Treatment | 12.61 g/dL | Standard Deviation 1.158 |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Maximum Hb Concentration (g/dL) During First 22 Weeks of Treatment | 12.42 g/dL | Standard Deviation 1.31 |
95% CI: [-0.564, 0.043]ANOVA
95% CI: [-0.755, -0.147]ANOVA
Post Hoc
Maximum (Max) Hb Rate (g/dL/2 Weeks) of Rise During First 22 Weeks of Treatment
Change is calculated as mean hemoglobin (Hb) over last 8 wks subtracts baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Max Hb RR observation was identified for each participant during the 1st 22 wks of treatment. This was the max RR in hemoglobin over any 2-wk period per participant.
Time frame: From baseline to Week 22
Population: Safety population. The safety population was defined as all participants who received at least 1 injection of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Maximum (Max) Hb Rate (g/dL/2 Weeks) of Rise During First 22 Weeks of Treatment | 1.99 g/dL/2 weeks | Standard Deviation 0.839 |
| Epoetin Alfa:Once Weekly (QW) | Maximum (Max) Hb Rate (g/dL/2 Weeks) of Rise During First 22 Weeks of Treatment | 2.02 g/dL/2 weeks | Standard Deviation 1.008 |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Maximum (Max) Hb Rate (g/dL/2 Weeks) of Rise During First 22 Weeks of Treatment | 1.92 g/dL/2 weeks | Standard Deviation 1.027 |
95% CI: [-0.21, 0.27]ANOVA
95% CI: [-0.315, 0.166]ANOVA
Other Pre-specified
Participants Who Exceeded a Hb Concentration of 11.9 g/dL During First 22 Weeks of Treatment
The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. participants who exceed a Hb value of 11.9 g/dL at least once were included in the numerator of the percentage calculation.
Time frame: From baseline to Week 22
Population: Safety population. The safety population was defined as all participants who received at least 1 injection of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Participants Who Exceeded a Hb Concentration of 11.9 g/dL During First 22 Weeks of Treatment | 106 participants |
| Epoetin Alfa:Once Weekly (QW) | Participants Who Exceeded a Hb Concentration of 11.9 g/dL During First 22 Weeks of Treatment | 98 participants |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Participants Who Exceeded a Hb Concentration of 11.9 g/dL During First 22 Weeks of Treatment | 89 participants |
95% CI: [-17.2, 1.7]
95% CI: [-25, -5]
Other Pre-specified
Participants Who Met or Exceeded Hb Rate of Rise >=1.0 g/dL/2 Weeks During First 22 Weeks of Treatment
Change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Participants who met or exceeded a Hb Rate of Rise (RR) of 1.0 g/dL/2 weeks at least once were included in the numerator of the percentage calculation.
Time frame: From baseline to Week 22
Population: Safety population. The safety population was defined as all subjects who received at least 1 injection of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Participants Who Met or Exceeded Hb Rate of Rise >=1.0 g/dL/2 Weeks During First 22 Weeks of Treatment | 119 participants |
| Epoetin Alfa:Once Weekly (QW) | Participants Who Met or Exceeded Hb Rate of Rise >=1.0 g/dL/2 Weeks During First 22 Weeks of Treatment | 116 participants |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Participants Who Met or Exceeded Hb Rate of Rise >=1.0 g/dL/2 Weeks During First 22 Weeks of Treatment | 114 participants |
95% CI: [-9.5, 1.6]
95% CI: [-11.4, 0.3]
Other Pre-specified
Participants Who Met or Exceeded Hb Rate of Rise >=1.5 g/dL/2 Weeks During First 22 Weeks of Treatment
Change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Participants who met or exceeded a Hb Rate of Rise (RR) of 1.5 g/dL/2 weeks at least once were included in the numerator of the percentage calculation.
Time frame: From baseline to Week 22
Population: Safety population. The safety population was defined as all participants who received at least 1 injection of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Participants Who Met or Exceeded Hb Rate of Rise >=1.5 g/dL/2 Weeks During First 22 Weeks of Treatment | 87 participants |
| Epoetin Alfa:Once Weekly (QW) | Participants Who Met or Exceeded Hb Rate of Rise >=1.5 g/dL/2 Weeks During First 22 Weeks of Treatment | 85 participants |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Participants Who Met or Exceeded Hb Rate of Rise >=1.5 g/dL/2 Weeks During First 22 Weeks of Treatment | 76 participants |
95% CI: [-14.2, 8.7]
95% CI: [-21.7, 1.8]
Other Pre-specified
Particpants Who Met or Exceeded Hb Rate of Rise >=2.0 g/dL/2 Weeks During First 22 Weeks of Treatment
Change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Participants who met or exceeded a Hb Rate of Rise (RR) of 2.0 g/dL/2 weeks at least once were included in the numerator of the percentage calculation.
Time frame: From baseline to Week 22
Population: Safety population. The safety population was defined as all participants who received at least 1 injection of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Alfa:Three Injections Weekly (TIW)/Once Weekly (QW) | Particpants Who Met or Exceeded Hb Rate of Rise >=2.0 g/dL/2 Weeks During First 22 Weeks of Treatment | 47 participants |
| Epoetin Alfa:Once Weekly (QW) | Particpants Who Met or Exceeded Hb Rate of Rise >=2.0 g/dL/2 Weeks During First 22 Weeks of Treatment | 51 participants |
| Epoetin Alfa:Once Every Two Weeks (Q2W) | Particpants Who Met or Exceeded Hb Rate of Rise >=2.0 g/dL/2 Weeks During First 22 Weeks of Treatment | 44 participants |
95% CI: [-9.6, 14.8]
95% CI: [-15, 9]