A Phase 3b Study of Erythropoietin Drugs Using a Specified Dosing Algorithm in Patients With Chronic Kidney Disease on Hemodialysis

Study Overview
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Brief Summary
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A phase 3b study for subjects receiving Epogen to compare a dosing algorithm between Hospira Epoetin and Standard of Care Epogen.

Detailed Description
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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.

Official Title
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The Pieda Study: A Phase 3b Investigation Of Erythropoietin Drugs Using A Specified Dosing Algorithm: A Randomized Open Label Dosing Study In Adult Chronic Kidney Disease Subjects On Hemodialysis

Conditions
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Chronic Kidney Disease (CKD)

Intervention / Treatment
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* Biological: Epoetin Hospira Arm
* Other: Standard of Care Arm
* Drug: IV Iron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects eligible to be entered into the study will meet all of the following criteria: Adult female or male subjects; age ≥ 18 years. End stage renal disease subjects treated in-center with the modality of hemodialysis for ≥ 120 days. Diagnosed with anemia. 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. Currently using the IV Epogen version of the ESA dosing algorithm cMAB 5 (inclusive of versions 5.0, 5.1, …) for anemia management. 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: Subjects unable to provide a signed and dated informed consent for this clinical research study. As determined by the Investigator, female subjects of child bearing potential who do not agree to use a highly effective method of contraception. 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. Female subjects who are known to be or found to be, pregnant or lactating. 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. Treatment with any investigational drug within 30 days prior to randomization and throughout this clinical trial. 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. 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. Subjects currently receiving a long acting ESA, or who have received a long acting ESA in the 16 weeks prior to study randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Epoetin Hospira<br>Epoetin Hospira Arm | Biological: Epoetin Hospira Arm<br>* 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.<br>Drug: IV Iron<br>* Subjects will also receive IV iron per the FMCNA protocol that is standard of care at FMCNA clinics.<br>|
| Other: Standard of Care<br>Standard of care arm | Other: Standard of Care Arm<br>* 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.<br>Drug: IV Iron<br>* Subjects will also receive IV iron per the FMCNA protocol that is standard of care at FMCNA clinics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 |