A Phase 3 Study Comparing the Effects of Subcutaneous Epoetin Hospira and Epoetin Alfa [Epogen] (Amgen) in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment. AiME - Anemia Management With Epoetin (AiME - 13)

A Therapeutic-equivalence Study Comparing The Efficacy And Safety Of Subcutaneous Epoetin Hospira And Epoetin Alfa (Amgen) In Patients With Chronic Renal Failure Requiring Hemodialysis And Receiving Epoetin Maintenance Treatment

The purpose of this study is to demonstrate therapeutic equivalence of subcutaneous (SC) Epoetin Hospira compared to SC Epogen (Amgen), based on maintenance of hemoglobin (Hb) levels and study drug dose requirements in patients treated for anemia associated with chronic renal failure and on hemodialysis.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Chronic Renal Failure
• Intervention / Treatment: Biological: Epoetin Hospira; Biological: Epogen Amgen

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute
    • Bakersfield, California, United States, 93309
      • National Institute of Clinical Research
    • Long Beach, California, United States, 90813
      • Long Beach Dialysis Center
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Modesto, California, United States, 95350
      • Long Beach Dialysis Center
    • Northridge, California, United States, 91324
      • Valley Renal Medical Group
    • Northridge, California, United States, 91324
      • Innovative Dialysis Center of Northridge, LLC
    • Paramount, California, United States, 90723
      • Research Management Inc.
    • Pleasanton, California, United States, 94588
      • Pleasanton Dialysis Center
    • Rancho Cordova, California, United States, 95670
      • Sunset Dialysis Center
    • Sacramento, California, United States, 95825
      • Capital Nephrology Medical Group
    • San Leandro, California, United States, 94578
      • Chabot Nephrology Medical Group
    • San Leandro, California, United States, 94578
      • San Leandro Dialysis
    • Santa Clarita, California, United States, 91387
      • Renal Consultants Medical Group
    • Whittier, California, United States, 90603
      • American Institute of Research
    • Whittier, California, United States, 90602
      • intercommunity Dialysis Center
    • Whittier, California, United States, 90603
      • Whittier Kidney Dialysis Center
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Western Nephrology and Metabolic Bone Disease, PC
    • Westminster, Colorado, United States, 80031
      • Kidney Center of westminster, LLC
    • Westminster, Colorado, United States, 80031
      • Western Nephrology and Metabolic Bone Disease, PC
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research Inc.
  • Georgia
    • Albany, Georgia, United States, 31701-2057
      • Dialysis Clinic, Inc. - Albany
    • Augusta, Georgia, United States, 30909
      • Kidney Care Associates
    • Dublin, Georgia, United States, 31021
      • Renal Physicians of Georgia, PC
  • Illinois
    • Chicago, Illinois, United States, 60636
      • Neomedica Marquette Park
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design, LLC
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Kansas Nephrology Physicians, PA
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Research Nurse Specialists, LLc
    • Lafayette, Louisiana, United States, 70506
      • New York Harbor Health Care System
    • Marrero, Louisiana, United States, 70072
      • Westbank Nephrology Associates
    • Opelousas, Louisiana, United States, 70570
      • FMC Opelousas
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Michigan
    • Kalamazoo, Michigan, United States, 49001
      • Fresenius Medical Care-Kalamazoo East
    • Kalamazoo, Michigan, United States, 49007
      • Fresenius Medical Care-Kalamazoo
    • Kalamazoo, Michigan, United States, 49007
      • Nephrology Center DBA Paragon Health PC
    • Kalamazoo, Michigan, United States, 49009
      • Fresenius Medical Care-Oshtemo
    • Kalamazoo, Michigan, United States, 49048
      • Fresenius Medical Care-Gull Road
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
    • Kansas City, Missouri, United States, 64111
      • Kansas City Renal Center
    • Kansas City, Missouri, United States, 64131
      • Renal Advantage, Inc.
    • Saint Louis, Missouri, United States, 63136
      • Metro Hypertension and Kidney Center
  • New Jersey
    • North Brunswick, New Jersey, United States, 08902
      • University of Cincinnati College of Medicine.
    • Voorhees, New Jersey, United States, 08043
      • Nephrology & Hypertension Associates of NJ
  • New York
    • Astoria, New York, United States, 11102
      • Newtown Dialysis Center
    • Flushing, New York, United States, 11355
      • New York Hospital Medical Center Queens Institutional Review Board
    • New Hyde Park, New York, United States, 11040
      • Parker Jewish Institute for Health Care and Rehabilitation
    • New York, New York, United States, 10010
      • New York Harbor Health Care System
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Wake Nephrology Associates, PA
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati College of Medicine
    • Toledo, Ohio, United States, 43606
      • Private Practice of Kenneth Lempert
  • Pennsylvania
    • Meadville, Pennsylvania, United States, 16335
      • Northwest Physicians Associates, PC
  • South Carolina
    • Aiken, South Carolina, United States, 29801
      • CSRA Renal Services, LLC
    • Columbia, South Carolina, United States, 29201
      • Fresenius Medical Care Midtown JV
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, PA
    • Irmo, South Carolina, United States, 29063
      • Fresenius Medical Care Irmo JV
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology and Hypertension Center, Inc.
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center, PLLC
  • Texas
    • Austin, Texas, United States, 78758
      • Fresenius Medical Care - Austin North Dialysis
    • Austin, Texas, United States, 78758
      • Research Management, Inc.
    • Austin, Texas, United States, 78758
      • Research Management, Inc
    • Dallas, Texas, United States, 75216
      • Dallas Veterans Affairs Medical Center
    • Grand Prairie, Texas, United States, 75051
      • Grand Prairie Dialysis Center
    • Houston, Texas, United States, 77054
      • Research Across America
    • Houston, Texas, United States, 77077
      • Westminster Dialysis
    • Houston, Texas, United States, 77083
      • Mission Bend Dialysis
    • Houston, Texas, United States, 77099
      • Southwest Houston Research, Ltd.
    • Lufkin, Texas, United States, 75904
      • East Texas Nephrology Associates
    • San Antonio, Texas, United States, 78229
      • San Antonio Kidney Disease Center
  • Virginia
    • Arlington, Virginia, United States, 22206
      • Renal Care Partners of Pentagon City
    • Fairfax, Virginia, United States, 22030
      • Clinical Research and Consulting Center, LLC
    • Fairfax, Virginia, United States, 22030
      • Renal Care Partners of Fairfax
    • Mechanicsville, Virginia, United States, 23116
      • Nephrology Specialists, PC
  • Washington
    • Olympia, Washington, United States, 98502
      • Western Institutional Review Board

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is able to provide written informed consent after risks and benefits of the study have been explained prior to any study related activities

2. Hemodialysis patients with chronic renal failure and renal anemia currently on stable Epogen (Amgen) dose administered IV or SC, 1 to 3 times per week for whom the following apply:

   • A change in Epogen dosing of no more than 10% from the mean
   • Mean hemoglobin between 9.0 and 11.0 g/dL
   • No more than one hemoglobin result outside of range from 9.0-11.0 g/dL
   • No hemoglobin result more than ±1 g/dL from the mean hemoglobin level
3. Patients on stable, adequate dialysis for at least 12 weeks prior to randomization, defined as no clinically relevant changes of dialysis regimen and/or dialyzer
4. Patients with adequate iron stores, defined as plasma ferritin > 100 μg/L and TSAT >20%, prior to randomization
5. Male or female patients aged 18 to 80 years (both inclusive)

6. If female, patient must be postmenopausal for at least one year prior to randomization, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following methods of birth control:

   • hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to randomization
   • intrauterine device (IUD)
   • double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)

If hormonal contraceptives are used, the specific contraceptive must have been used for at least 3 months prior to randomization. If the patient is currently using a hormonal contraceptive, she should also use a barrier method during this study and for at least 30 days following the administration of the patient's last dose

Exclusion Criteria:

1. Maintenance epoetin dosage >600 U/kg per week (1-3 times per week)
2. Treatment with long-acting epoetin analogues such as Aranesp ® within 12 weeks prior to randomization

3. Any of the following within 3 months prior to randomization:

   • Myocardial infarction
   • Stroke (cerebrovascular accident)/cerebrovascular insult (minor stroke) or transient ischemic attack/intracerebral bleeding/cerebral infarction
   • Severe/unstable angina
   • Coronary angioplasty, bypass surgery, or peripheral artery bypass graft
   • Decompensated congestive heart failure (New York Heart Association [NYHA] class IV)
   • Pulmonary embolism
   • Deep vein thrombosis or other thromboembolic event
   • Received live or attenuated vaccination (except flu vaccination)
4. Uncontrolled hypertension within the 4 weeks prior to randomization defined as more than 10% of post-dialysis blood pressures >170 mmHg systolic and/or >110 mmHg diastolic, based on blood pressure readings obtained when the patient's post-dialysis body weight was not more than 0.5 kg above their listed dry weight
5. Known, clinically manifested deficiency of folic acid and/or vitamin B12 (irrespective of whether currently treated or not)
6. A patient with any active, uncontrolled systemic, inflammatory or malignant disease that in the Investigator's opinion may be significant to exclude participation in the study, including but not limited to demyelinating diseases such as multiple sclerosis, microbial, viral or fungal infection or mental disease
7. Contraindication for the test drug or have been previously treated with Epoetin Hospira
8. Relative or absolute iron deficiency prior to randomization into the Maintenance Period
9. Platelet count below 100 x 10^9/L
10. Clinically relevant increase of CRP (>10 mg/dL) for at least 2 weeks
11. Significant drug sensitivity or a significant allergic reaction to any drug, as well as known hypersensitivity or idiosyncratic reaction to epoetin (or its excipients, including albumin) or any other related drugs that in the judgment of the Investigator is exclusionary for the study participation

12. History of any of the following:

    • Detectable anti-rhEPO antibodies
    • Clinically relevant malnutrition
    • Confirmed aluminum intoxication
    • Myelodysplastic syndrome
    • Known bone marrow fibrosis (osteitis fibrosa cystica)
    • Known seizure disorder
    • Liver cirrhosis with clinical evidence of complications (portal hypertension, splenomegaly, ascites)
13. A female patient who is pregnant, lactating or planning a pregnancy during the study
14. History of drug abuse or alcohol abuse within 2 years prior to randomization as determined by the Investigator
15. Current participation or participation in a drug or other investigational research study within 30 days prior to randomization
16. May not be able to comply with the requirements of this clinical study, communicate effectively with study personnel, or is considered by the Investigator, for any reason, to be an unsuitable candidate for the study
17. Donated or lost >475 mL (i.e., 1 pint) blood volume (including plasmapheresis) or had a transfusion of any blood product within 3 months prior to randomization
18. A patient who in the Investigator's opinion, has any clinically significant abnormal laboratory evaluations, including liver function taken at Screening Visit
19. Positive laboratory test for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epoetin Hospira	Biological: Epoetin Hospira; Variable dose
Active Comparator: Epogen (Amgen)	Biological: Epogen Amgen; Variable dose; Other Names: Epoetin Alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Weekly Hemoglobin Level From Week 30 to Week 34: Maintenance Period	Week 30 up to Week 34
Mean Weekly Dosage of Study Medication From Week 30 to Week 34: Maintenance Period	Week 30 up to Week 34

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Weekly Hemoglobin Level From Week 19 to Week 34: Maintenance Period		Week 19 up to Week 34
Mean Weekly Dosage of Study Medication From Week 19 to Week 34: Maintenance Period		Week 19 up to Week 34
Total Dose of Study Medication Administered: Maintenance Period	In this outcome measure mean of total dose of study medication administered in maintenance period was reported.	Week 19 up to Week 34
Percentage of Participants With Mean Weekly Hemoglobin Level Within the Target Range: Maintenance Period	Percentage of participants who had hemoglobin level within the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 26, 34
Percentage of Participants Who Required Permanent Dose Changes: Maintenance Period		Week 19 up to Week 34
Percentage of Participants Who Required Temporary Dose Changes: Maintenance Period		Week 19 up to Week 34
Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 1.0 Gram Per Deciliter (g/dL): Maintenance Period		Week 19 up to Week 34
Percentage of Participants With Mean Weekly Hemoglobin Level Outside the Target Range: Maintenance Period	Percentage of participants who had hemoglobin level outside the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 26, 34
Percentage of Participants Who Qualified as Optimally Titrated and Stable: Titration Period		Week 1 up to Week 18
Percentage of Participants Who Received Blood Transfusions: Maintenance Period		Week 19 up to Week 34
Number of Participants With Change in Mean Dose of Study Medication Based on Hemoglobin Level: Maintenance Period	In this outcome measure number of participants with change (increase and decrease) in mean dose of Epoetin Hospira and Epogen were categorized and reported according to their mean hemoglobin levels. Hemoglobin levels were divided in following classes: >11.0 g/dL, from 9.0 to 11.0 g/dL and <9.0 g/dL	Week 19 up to Week 34
Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 2.0 Gram Per Deciliter (g/dL) in Hemoglobin Level: Maintenance Period		Week 19 up to Week 34

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL): Maintenance Period		Week 19 up to Week 34
Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL): Maintenance Period		Week 19 up to Week 34
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Number of Participants With Treatment-Emergent Adverse Events by Severity	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. An AE was assessed according to severity; mild (AE was transient and easily tolerated by the participant), moderate (caused problem that did not interfere significantly with usual activities) and severe (caused problem that interferes significantly with usual activities and might be incapacitating or life-threatening).	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Number of Participants With Treatment Related Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Number of Participants That Discontinued Treatment Due to a Treatment Emergent Adverse Event	In this outcome measure number of participants discontinued from study drug (Epoetin Hospira, Epogen) due to any AE were reported.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters	Laboratory parameters: Hematology (hematocrit, hemoglobin, red blood cell count, reticulocytes, white blood cell count, neutrophils, bands, lymphocytes, monocytes, basophils, eosinophils, platelet count, mean corpuscular volume); coagulation panel (prothrombin time, international normalized ratio, activated partial thromboplastin time); clinical chemistry (blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, gamma-glutamyl transpeptidase, alkaline phosphatase, sodium, potassium, calcium, magnesium, phosphorus, uric acid, total protein, glucose, albumin, C-reactive protein, plasma ferritin, transferrin saturation). Participants with clinically significant change from baseline in laboratory parameters were as determined by the investigator.	Titration Period: Baseline (Pre-dose on Week 1) up to Week 18 and Maintenance Period: Baseline (Pre-dose on Week 19) up to Week 38
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Vital sign parameters: temperature (oral, tympanic, or other), blood pressure (diastolic and systolic), heart rate (in a seated position) and dry weight (post-dialysis). Participants with clinically significant change from baseline in vital signs were as determined by the investigator.	Titration Period: Baseline (Pre-dose on Week 1) up to Week 18 and Maintenance Period: Baseline (Pre-dose on Week 19) up to Week 38
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)	ECG parameters: PR interval, QRS complex, QT interval and QTC interval. Participants with clinically significant change from baseline in ECG were as determined by the investigator.	Titration Period: Baseline (Pre-dose on Week 1) up to Week 18 and Maintenance Period: Baseline (Pre-dose on Week 19) up to Week 38
Number of Participants With Clinically Significant Change From Baseline in Physical Examination	Physical examination included examination of the following: skin, eyes, ears, throat, cardiac, respiratory, gastrointestinal, genitourinary and musculoskeletal systems. Participants with clinically significant change from baseline in physical examination were as determined by the investigator.	Titration Period: Baseline (Pre-dose on Week 1) up to Week 18 and Maintenance Period: Baseline (Pre-dose on Week 19) up to Week 38
Percentage of Participants With Anti-Recombinant Human Erythropoietin (Anti-rhEPO) Antibodies	Percentage of participants with presence of anti-rhEPO antibodies were reported in this outcome measure. Radioimmunoprecipitation assay method was used to determine the presence of anti-rhEPO antibodies.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Percentage of Participants With General Tolerability	General tolerability was classified as: 1) excellent tolerability = no reaction, 2) good tolerability = minimal reaction, 3) mild intolerability = reaction above that normally observed with any kind of subcutaneous product, 4) moderate intolerability = marked reaction, but no need for discontinuation of treatment and 5) severe intolerability = treatment discontinued due to intolerability.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Percentage of Participants With Local Tolerability	Local tolerability was classified as: 1) excellent tolerability = no reaction at site of injection, 2) good tolerability = minimal reaction at site of injection normally observed with any kind of subcutaneous product, 3) mild intolerability = reaction at site of injection above that normally observed with any kind of subcutaneous product, 4) moderate intolerability = marked reaction, but no need for discontinuation of treatment and 5) severe intolerability = treatment discontinued due to intolerability.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer

Publications and helpful links

General Publications

• Wish JB, Rocha MG, Martin NE, Reyes CRD, Fishbane S, Smith MT, Nassar G. Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies. Kidney Med. 2019 Aug 28;1(5):271-280. doi: 10.1016/j.xkme.2019.06.009. eCollection 2019 Sep-Oct.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2012
• Primary Completion (Actual): February 28, 2014
• Study Completion (Actual): February 28, 2014

Study Registration Dates

• First Submitted: November 2, 2011
• First Submitted That Met QC Criteria: November 16, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Actual): August 9, 2018
• Last Update Submitted That Met QC Criteria: July 12, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Hematinics; Epoetin Alfa
• Other Study ID Numbers: EPOE-10-13; C3461003 (Other Identifier: Alias Study Number)