Chronic Kidney Disease (CKD)
Conditions
Brief summary
A phase 3b study for subjects receiving Epogen to compare a dosing algorithm between Hospira Epoetin and Standard of Care Epogen.
Detailed description
Primary Objective: To evaluate switching from Epogen to Epoetin Hospira for maintenance of hemoglobin levels in anemic chronic kidney disease (CKD) subjects on hemodialysis using a specified algorithm for the dosing of erythropoietin stimulating agents (ESA). Secondary Objective: To evaluate switching from Epogen to Epoetin Hospira on the dosing of ESA in anemic CKD subjects on hemodialysis using a specified algorithm for the dosing of ESA. Exploratory Objectives: To generate hypotheses regarding maintenance of hemoglobin levels, dosing of ESA, intravenous (IV) iron dosing requirements, transferrin saturation (TSAT) levels and ferritin levels associated with the switch from Epogen to Epoetin Hospira in anemic CKD subjects on hemodialysis using specified algorithms for the dosing of ESA and for the dosing of IV iron, that are standard of care.
Interventions
BIOLOGICALEpoetin Hospira Arm
Epoetin Hospira Arm: Epoetin Hospira will be administered intravenously (IV) per the analogous version of the Fresenius Medical Care North America (FMCNA) cMAB 1 (inclusive of version 1.0, 1.1,...)erythropoietin stimulating agents (ESA) dosing algorithm for Epoetin Hospira for 24 weeks. Subjects will have Epoetin Hospira initiated using the same ESA dose level and frequency of administration for Epogen prior to randomization into the trial. Subjects will also receive IV iron per the FMCNA protocol that is standard of care at FMCNA clinics.
OTHERStandard of Care Arm
Standard of care arm: No interventions will be performed in this arm for the clinical study; and subjects will receive ongoing standard of care, which includes Epogen administered IV per the FMCNA cMAB 5 (inclusive of versions 5.0, 5.1,....) ESA dosing algorithm and IV iron per the FMCNA protocol that is standard of care, at FMCNA clinics during the contemporaneous 24 week period.
DRUGIV Iron
Subjects will also receive IV iron per the FMCNA protocol that is standard of care at FMCNA clinics.
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects eligible to be entered into the study will meet all of the following criteria: 1. Adult female or male subjects; age ≥ 18 years. 2. End stage renal disease subjects treated in-center with the modality of hemodialysis for ≥ 120 days. 3. Diagnosed with anemia. 4. Administered routine Epogen therapy for at least 16 weeks by an IV route for treatment of anemia using an Epogen version of an FMCNA dosing algorithm for ESA, and did not miss more than 3 prescribed doses of Epogen within 12 weeks prior to randomization. 5. Currently using the IV Epogen version of the ESA dosing algorithm cMAB 5 (inclusive of versions 5.0, 5.1, …) for anemia management. 6. Receiving hemodialysis at a clinic using the FMCNA dosing algorithm for IV iron that is the FMCNA standard of care treatment for iron replacement.
Exclusion criteria
Subjects that meet any of the following criteria will be ineligible to be entered into the interventional cohort: 1. Subjects unable to provide a signed and dated informed consent for this clinical research study. 2. As determined by the Investigator, female subjects of child bearing potential who do not agree to use a highly effective method of contraception. 3. Any condition as determined by the investigator that would place a subject at an increased risk, or preclude subject's full compliance with the study procedures and visits. 4. Female subjects who are known to be or found to be, pregnant or lactating. 5. Subjects that are not a candidate for ESA therapies per the label warnings listed in the package insert for Epogen and/or contraindications to Epoetin Hospira listed in the Investigators' Brochure; or have had a known positive test for anti-rhEPO antibodies. 6. Treatment with any investigational drug within 30 days prior to randomization and throughout this clinical trial. 7. Diagnosed with any concurrent condition that could lead to greater-than-normal loss of blood, including but not limited to: * Menorrhagia, peptic ulcer disease, gastrointestinal bleeding, blood dyscrasia, hemoglobinopathy * Use of anticoagulation therapy, including warfarin with a target international normalized ratio (INR) of 2 or greater Anti-platelet therapy (e.g. aspirin or clopidogrel) is permitted, as is heparin given during hemodialysis. Low-dose warfarin is permitted and defined as the presence of at least two INR values less than or equal to 1.5 during the 120 days prior to enrollment and no values exceeding 1.5 at any time after 120 days prior to enrollment. Subjects started on warfarin with a known INR goal of 2.0 or greater are to receive no further treatment with the study drugs, but follow up visits can continue. Subjects on warfarin who meet criteria to enter the study are terminated if an INR \> 2.0 is discovered or if no INR is available for 60 days. 8. History of transfusion of any blood product in the past 3 months, or 2 or more transfusions in the past 1 year; or donated or lost \> 475 mL blood volume (including plasmapheresis) in the past 3 months. 9. Subjects currently receiving a long acting ESA, or who have received a long acting ESA in the 16 weeks prior to study randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Time When Participants Had Hemoglobin Levels Between 9 to 11 Gram Per Deciliter (g/dL) | Week 17 up to Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Weekly Mean Study Medication Dose Over Final 8 Weeks of Study Treatment | Baseline (8 Weeks prior to randomization), Week 17 up to Week 24 |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
In this study, 432 participants were enrolled, however, only 418 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| Epoetin Hospira Participants received intravenous (IV) injection of Epoetin Hospira as per the analogous version of Fresenius Medical Care North America (FMCNA) Erythropoietin Stimulating Agent (ESA) dosing algorithm Corporate Medical Advisory board (cMAB algorithm 1) along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26. | 212 |
| Epogen Participants received their ongoing standard of care which included IV injection of Epogen, as per the current version of the FMCNA ESA dosing algorithm cMAB 5 along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26. | 206 |
| Total | 418 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 12 |
| Overall Study | Lost to Follow-up | 6 | 7 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Protocol Violation | 27 | 26 |
| Overall Study | Withdrawal by Subject | 7 | 1 |
Baseline characteristics
| Characteristic | Epoetin Hospira | Epogen | Total |
|---|---|---|---|
| Age, Continuous | 60.5 Years STANDARD_DEVIATION 13.96 | 59.3 Years STANDARD_DEVIATION 14.23 | 59.9 Years STANDARD_DEVIATION 14.09 |
| Sex: Female, Male Female | 82 Participants | 102 Participants | 184 Participants |
| Sex: Female, Male Male | 130 Participants | 104 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 212 | 21 / 206 |
| serious Total, serious adverse events | 66 / 212 | 64 / 206 |
Outcome results
Primary
Percentage of Time When Participants Had Hemoglobin Levels Between 9 to 11 Gram Per Deciliter (g/dL)
Time frame: Week 17 up to Week 24
Population: FAS included all participants who received at least 1 dose of study medication after randomization into the study. Here, Number of participants analyzed (N) signifies those number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Hospira | Percentage of Time When Participants Had Hemoglobin Levels Between 9 to 11 Gram Per Deciliter (g/dL) | 61.9330 Percentage of Weeks |
| Epogen | Percentage of Time When Participants Had Hemoglobin Levels Between 9 to 11 Gram Per Deciliter (g/dL) | 63.3305 Percentage of Weeks |
Comparison: Clustered binomial analysis using logistic regression method was performed and generalized estimating equation method was used to construct 95 percent (%) two-sided confidence intervals (CIs).95% CI: [-7.6503, 4.8553]
Secondary
Change From Baseline in Weekly Mean Study Medication Dose Over Final 8 Weeks of Study Treatment
Time frame: Baseline (8 Weeks prior to randomization), Week 17 up to Week 24
Population: FAS included all participants who received at least 1 dose of study medication after randomization in to the study. Here, N signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Hospira | Change From Baseline in Weekly Mean Study Medication Dose Over Final 8 Weeks of Study Treatment | -1861.8 Units per week | Standard Error 563.5 |
| Epogen | Change From Baseline in Weekly Mean Study Medication Dose Over Final 8 Weeks of Study Treatment | -799.8 Units per week | Standard Error 573.14 |
Comparison: P-value was calculated using analysis of covariance (ANCOVA) model with treatment as factor and baseline ESA dose as covariate.p-value: 0.187495% CI: [-2643.2, 519.2]ANCOVA