Anemia, Chronic Kidney Disease
Conditions
Keywords
Anemia, Chronic Renal Failure, CRF, Chronic Kidney Disease, CKD, Erythropoietin, Hematide, Peginesatide, Hemoglobin, Hgb, Red Blood Cell, Red Blood Cell Production, Dialysis
Brief summary
The purpose of this study is to understand the effects of a dialysis center switching its dialysis patients from using Epoetin alfa to peginesatide injection on hemoglobin levels and other parameters.
Detailed description
Monthly Erythropoiesis-Stimulating Agents (ESA) dosing, compared with the longstanding practice of dosing three times per week, represents a significant change in anemia treatment for dialysis patients. Because of the differences in the processes needed to support monthly dosing versus thrice weekly dosing, there is a need to prospectively identify and evaluate factors in the dialysis environment during center-level transition of patients from one ESA to another. AFX01-18 is a Phase 3b open-label, single-arm conversion study that was conducted at 5 hemodialysis sites in the United States, and enrolled Chronic Kidney Disease (CKD) patients receiving outpatient, in-center hemodialysis. The study treatment period was approximately 12 months in duration. Participants received peginesatide injection for approximately six months.
Interventions
DRUGEpoetin
Commercially available epoetin alfa administered weekly, twice weekly, or thrice weekly at an initial starting dose, frequency of administration, and mode of administration (intravenous \[IV\] or subcutaneous \[SC\]) individually determined for each participant using the site's usual standard of care. Subsequent dose adjustments or dose holds may have been made in order to maintain a hemoglobin concentration of \<11 g/dL.
DRUGPeginesatide
Administered as a once monthly intravenous (IV) or subcutaneous (SC) injection. The initial dose of peginesatide injection was based on the final weekly dose of epoetin administered in the SCP; subsequent doses may have been adjusted in order to maintain hemoglobin concentrations at \<11 g/dL.
Sponsors
Affymax
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have provided written informed consent in accordance with institutional, local, and national guidelines * Are ≥18 years of age at the start of screening * Have been on in-center hemodialysis for ≥12 weeks at the start of screening * Are currently maintained on Epoetin at the start of screening * If sexually active and a female of childbearing potential, are willing to use highly effective method of birth control ≥4 weeks before study enrollment and through the study * If a female of childbearing potential, have a negative pregnancy test during screening
Exclusion criteria
* Are scheduled for a renal transplantation during study (Note: patients awaiting transplantation with no date scheduled may enroll.) * Have an active malignancy or malignancy treated within one year prior to the start of screening for curative or palliative intent (Note: patients with non-melanoma skin cancers may enroll.) * Have known intolerance to any ESA or PEGylated molecule * Have been exposed to any investigational agent during the four weeks prior to the start of screening or are anticipated to receive such agents during the study * Have any significant medical or psychiatric condition judged by the investigator to prevent informed consent or study compliance * Are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Undergoing Conversion to Peginesatide Injection | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peginesatide Dosing | Month 6 - 12 | The starting dose, mean dose throughout the study, and mean dose during the last week of treatment of peginesatide. |
| Peginesatide Dose Deviations | Months 6 - 12 | Data collected by sponsor of study (Affymax), and sponsor did not provide aggregate summary data. |
| Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Months 1, 2, 3, 4, 5 and 6 of each treatment period | Percentage of participants with hemoglobin values within the hemoglobin range of 10-11 g/dL. |
| Percentage of Participants Who Received at Least One Intravenous Iron Dose | 12 months | Participants received iron supplementation during the study to prevent iron deficiency and to maintain iron stores. |
| Percentage of Participants Who Received a Whole Blood or Red Blood Cell Transfusion | 12 months | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 5 investigative sites in the United States from 11 October 2011 to 08 February 2013.
Pre-assignment details
Participants with chronic kidney disease and on dialysis continued to receive their standard of care epoetin treatment for 6 months and then transitioned to receive peginesatide injection for 6 months.
Participants by arm
| Arm | Count |
|---|---|
| Peginesatide Injection In the first 6 months participants received Standard of Care treatment with epoetin (the Standard of Care Period \[SCP\]), followed by a 1 -week erythropoiesis-stimulating agent (ESA)-free period, followed by a transition to once monthly peginesatide injection for 6 months (the Peginesatide Treatment Period \[PTP\]). | 178 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Peginesatide Treatment Period | Adverse Event | 1 |
| Peginesatide Treatment Period | Death | 4 |
| Peginesatide Treatment Period | Lost to Follow-up | 4 |
| Peginesatide Treatment Period | Other | 4 |
| Peginesatide Treatment Period | Withdrawal by Subject | 1 |
| Standard of Care Period | Adverse Event | 1 |
| Standard of Care Period | Death | 8 |
| Standard of Care Period | Lost to Follow-up | 9 |
| Standard of Care Period | Other | 4 |
| Standard of Care Period | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Peginesatide Injection |
|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 15.33 |
| Age, Customized 65 - 74 years | 44 participants |
| Age, Customized < 65 years | 103 participants |
| Age, Customized ≥ 75 years | 31 participants |
| Baseline hemoglobin | 10.9 g/dL STANDARD_DEVIATION 0.96 |
| Current dialysis frequency 2 times a week | 3 participants |
| Current dialysis frequency 3 times a week | 169 participants |
| Current dialysis frequency 4 times a week | 4 participants |
| Current dialysis frequency 5 times a week | 1 participants |
| Current dialysis frequency 6 times a week | 1 participants |
| Ferritin | 1068.7 ng/mL STANDARD_DEVIATION 513.1 |
| Kidney transplant recipient No | 161 participants |
| Kidney transplant recipient Yes | 17 participants |
| Nephrotic syndrome history No | 148 participants |
| Nephrotic syndrome history Yes | 30 participants |
| Primary cause of chronic kidney disease Congenital | 1 participants |
| Primary cause of chronic kidney disease Cystic renal disease | 6 participants |
| Primary cause of chronic kidney disease Diabetes | 97 participants |
| Primary cause of chronic kidney disease Glomerulonephritis | 15 participants |
| Primary cause of chronic kidney disease Hypertension | 37 participants |
| Primary cause of chronic kidney disease Immunoglobulin (Ig) A nephropathy | 3 participants |
| Primary cause of chronic kidney disease Interstitial nephritis | 2 participants |
| Primary cause of chronic kidney disease Other | 10 participants |
| Primary cause of chronic kidney disease Unknown | 3 participants |
| Primary cause of chronic kidney disease Urological | 4 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants |
| Race/Ethnicity, Customized Asian | 10 participants |
| Race/Ethnicity, Customized Black | 43 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 76 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 5 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 102 participants |
| Race/Ethnicity, Customized White | 119 participants |
| Region of Enrollment United States | 178 participants 3.71 |
| Sex: Female, Male Female | 84 Participants |
| Sex: Female, Male Male | 94 Participants |
| Time on dialysis | 4.2 years STANDARD_DEVIATION 3.71 |
| Transferrin saturation | 35.2 percent saturation STANDARD_DEVIATION 13.85 |
| Weight | 83.8 kg STANDARD_DEVIATION 22.93 |
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 | 74 / 178 | 7 / 160 | 70 / 157 |
| serious Total, serious adverse events | 64 / 178 | 2 / 160 | 54 / 157 |
Outcome results
Primary
Percentage of Participants Undergoing Conversion to Peginesatide Injection
Time frame: 6 months
Population: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginesatide Injection | Percentage of Participants Undergoing Conversion to Peginesatide Injection | 88 percentage of participants |
Secondary
Peginesatide Dose Deviations
Data collected by sponsor of study (Affymax), and sponsor did not provide aggregate summary data.
Time frame: Months 6 - 12
Secondary
Peginesatide Dosing
The starting dose, mean dose throughout the study, and mean dose during the last week of treatment of peginesatide.
Time frame: Month 6 - 12
Population: Participants who received at least 1 dose of study treatment during the Peginesatide Treatment Period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peginesatide Injection | Peginesatide Dosing | Starting Dose | 5.1 mg | Standard Deviation 2.82 |
| Peginesatide Injection | Peginesatide Dosing | Average Dose During Treatment Period | 4.9 mg | Standard Deviation 2.97 |
| Peginesatide Injection | Peginesatide Dosing | Last Weekly Average Dose | 5.2 mg | Standard Deviation 3.68 |
Secondary
Percentage of Participants Who Received at Least One Intravenous Iron Dose
Participants received iron supplementation during the study to prevent iron deficiency and to maintain iron stores.
Time frame: 12 months
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginesatide Injection | Percentage of Participants Who Received at Least One Intravenous Iron Dose | 85.4 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants Who Received at Least One Intravenous Iron Dose | 73.2 percentage of participants |
Secondary
Percentage of Participants Who Received a Whole Blood or Red Blood Cell Transfusion
Time frame: 12 months
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginesatide Injection | Percentage of Participants Who Received a Whole Blood or Red Blood Cell Transfusion | 10.7 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants Who Received a Whole Blood or Red Blood Cell Transfusion | 8.3 percentage of participants |
Secondary
Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL
Percentage of participants with hemoglobin values within the hemoglobin range of 10-11 g/dL.
Time frame: Months 1, 2, 3, 4, 5 and 6 of each treatment period
Population: Full Analysis Population included all enrolled participants who received at least 1 dose of study treatment during the Peginesatide Treatment Period. n indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginesatide Injection | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 1 (n=156, 155) | 39.1 percentage of participants |
| Peginesatide Injection | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 2 (n=157, 155) | 40.8 percentage of participants |
| Peginesatide Injection | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 3 (n=156, 155) | 41.0 percentage of participants |
| Peginesatide Injection | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 4 (n=156, 151) | 44.9 percentage of participants |
| Peginesatide Injection | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 5 (n=157, 147) | 42.7 percentage of participants |
| Peginesatide Injection | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month6 (n=157, 146) | 58.0 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 5 (n=157, 147) | 44.9 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 1 (n=156, 155) | 44.5 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 4 (n=156, 151) | 49.0 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 2 (n=157, 155) | 46.5 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month6 (n=157, 146) | 39.0 percentage of participants |
| Peginesatide Treatment Period | Percentage of Participants With Hemoglobin Levels Greater Than 10 and Less Than or Equal to 11 g/dL | Month 3 (n=156, 155) | 45.2 percentage of participants |