A Phase 3 Study Comparing the Effects of Intravenous 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 - 01)

A Therapeutic-equivalence Study Comparing The Efficacy And Safety Of Intravenous 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 IV Epoetin Hospira compared to IV Epogen (Amgen), based on maintenance of 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): 612
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Consolidated Medical Plaza
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36106
      • Montgomery Kidney Specialists
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Southwest Clinical Research Institute, LLC
  • California
    • Alhambra, California, United States, 91801
      • Lakhi M. Sakhrani, MD A Medical Coporation
    • Azusa, California, United States, 91702
      • North America Research Institute
    • Bakersfield, California, United States, 93309
      • DaVita Dialysis Center-Bakersfield Dialysis Center
    • Fairfield, California, United States, 94533
      • Ong, Rubin, Shahmir A Medical Corp DBA: Solano Kidney Care
    • Glendale, California, United States, 91204
      • A Medical Corporation
    • Granada Hills, California, United States, 91344
      • Renal Consultants Medical Group
    • La Puente, California, United States, 91744
      • La Puente Dialysis Center
    • Lakewood, California, United States, 90712
      • Advanced Medical Research, LLC
    • Long Beach, California, United States, 90807
      • DaVita Bixby Knolls Dialysis
    • Long Beach, California, United States, 90813
      • Bayview Nephrology, Inc
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Modesto, California, United States, 95350
      • Desert Nephrology Medical Group
    • National City, California, United States, 91950
      • La Jolla Clinical Research, Inc.
    • Northridge, California, United States, 91324
      • Valley Renal Medical Group
    • Ontario, California, United States, 91762
      • Ontario Dialysis Inc
    • Porterville, California, United States, 93257
      • Discovery Medical Research Group, Inc.
    • Tarzana, California, United States, 91356
      • Nephrology Educational Services and Research, Inc
    • West Covina, California, United States, 91790
      • Queen Dialysis Center
    • Whittier, California, United States, 90603
      • American Institute of Research
    • Whittier, California, United States, 90606
      • Mark C. Lee, Inc. Santa Fe Springs Dialysis
    • Yuba City, California, United States, 95991
      • North Valley Nephrology
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Nephrology and Hypertension Associates
  • Florida
    • Coral Springs, Florida, United States, 33071
      • South Florida Nephrology, Inc.
    • Lauderdale Lakes, Florida, United States, 33313
      • South Florida Research Institute
    • Miami, Florida, United States, 33173
      • Nephrology Associates of South Miami
    • Miami, Florida, United States, 33015
      • San Marcus research Clinic, Inc
    • Naples, Florida, United States, 34112-6703
      • ARA Naples South Dialysis Center
    • Naples, Florida, United States, 34119
      • ARA- Naples Dialysis Center, LLC
    • North Miami Beah, Florida, United States, 33169
      • Innovative Medical Research of South Florida, Inc.
    • Ocala, Florida, United States, 34471
      • Discovery Medical Research Group, Inc.
    • Orlando, Florida, United States, 32801-3621
      • Central Florida Kidney Centers
  • Georgia
    • Dublin, Georgia, United States, 31021
      • Renal Physicians of Georgia, PC
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Boise Kidney & Hypertension Institute, PLLC
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design, LLC
    • Gurnee, Illinois, United States, 60031
      • North Suburban Nephrology, LLC
  • Indiana
    • Merrillville, Indiana, United States, 46410
      • Nephrology Specialists, PC
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Westbank Nephrology Associates
    • New Orleans, Louisiana, United States, 70115
      • Internal Medicine Specialists
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • DaVita Dialysis Centers
    • Detroit, Michigan, United States, 48236
      • St. Clair Specialty Physicians, P.C.
  • Mississippi
    • Gulfport, Mississippi, United States, 39501
      • South Mississippi Medical Research, PLLC
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Chromalloy American Kidney Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Kidney Specialists of Southern Nevada
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Hypertension & Nephrology Associates
  • New York
    • Brooklyn, New York, United States, 11212
      • Brookdale Physician Dialysis Associates
    • New York, New York, United States, 10016
      • Lower Manhattan Dialysis Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates, PA
    • Greenville, North Carolina, United States, 27834
      • East Carolina University, ECU School of Medicine, Department of Internal Medicine
    • New Bern, North Carolina, United States, 28562
      • Eastern Nephrology Associates, PLLC
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Cincinnati VA Medical Center
    • Columbus, Ohio, United States, 43215
      • HNC Dialysis Ltd.
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Bayview Nephrology, Inc
    • Erie, Pennsylvania, United States, 16507
      • DaVita-Erie Dialysis Center
    • Erie, Pennsylvania, United States, 16507
      • UPMC Hamot Clinical Trials Department
    • Philadelphia, Pennsylvania, United States, 19106
      • Franklin Dialysis Center
    • Philadelphia, Pennsylvania, United States, 19118
      • Delaware Valley Nephrology and Hypertension Associates, PC
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Nephrology and Internal Medicine of Anderson
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, PA
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, P.A.
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology and Hypertension Center, Inc.
    • Orangeburg, South Carolina, United States, 29118
      • Palmetto Nephrology, PA
    • Sumter, South Carolina, United States, 29150
      • Desert Nephrology Medical Group
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Southeast Renal Research Institute
  • Texas
    • Arlington, Texas, United States, 76015
      • South Arlington Dialysis Center
    • Greenville, Texas, United States, 75402
      • Texas Renal Care
    • Houston, Texas, United States, 77054
      • Research Across America
    • Houston, Texas, United States, 77099
      • Southwest Houston Research, Ltd.
    • Houston, Texas, United States, 77004
      • Med Center Dialysis
    • Houston, Texas, United States, 77035
      • Meyerland Dialysis
    • Houston, Texas, United States, 77054-11801
      • Millenium Clinical Research, Inc.
    • Houston, Texas, United States, 77054-11801
      • Millennium Clinical Research, Inc.
    • Houston, Texas, United States, 77071
      • Southwest Houston Dialysis
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
    • McAllen, Texas, United States, 78503
      • Private practice of Roberto Mangoo-Karim MD
    • Missouri City, Texas, United States, 77489
      • Missouri City Dialysis
    • San Antonio, Texas, United States, 78229
      • San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
    • San Antonio, Texas, United States, 78240
      • DaVita Dialysis Center-Floyd Curl Dialysis
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Clinical Research and Consulting Center, LLC
    • Hampton, Virginia, United States, 23666
      • Peninsula Kidney Associates
    • Norfolk, Virginia, United States, 23502
      • Internal Medicine Kidney and Hypertension Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 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) treatment for at least 4 weeks prior to randomization, for whom the following apply (during this period):

   • Epogen (Amgen) dose has been administered intravenously 1 to 3 times per week with no more than a 10% dose change from the mean for at least 4 weeks prior to randomization

   • Stable hemoglobin, defined as meeting all of the following:

     • Mean hemoglobin during the 4 weeks prior to randomization between 9.0 and 11.0 g/dL
     • No more than one hemoglobin outside of range from 9.0-11.0 g/dL during the 4 weeks prior to randomization
     • No hemoglobin result more than ±1 g/dL from the mean hemoglobin level during the 4 week period prior to randomization
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 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 either postmenopausal for at least 1 year prior to randomization, surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or practicing at least 1 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 3 months 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 (including demyelinating diseases such as multiple sclerosis) that in the Investigator's opinion may be significant to exclude participation in the study, including but not limited to 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
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 21 to Week 24	Week 21 up to Week 24
Mean Weekly Dosage of Study Medication From Week 21 to Week 24	Week 21 up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Weekly Hemoglobin Level Through 24 Weeks		Week 1 up to Week 24
Mean Weekly Dosage of Study Medication Through 24 Weeks		Week 1 up to Week 24
Total Dose of Study Medication Administered		Week 1 up to Week 24
Percentage of Participants With Mean Weekly Hemoglobin Level Within the Target Range	Percentage of participants who had hemoglobin level within the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 12, 24
Percentage of Participants Who Required Permanent Dose Changes of Study Medication		Week 1 up to Week 24
Percentage of Participants Who Required Temporary Dose Changes of Study Medication		Week 1 up to Week 24
Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 1 Gram Per Deciliter (g/dL)		Week 1 up to Week 24
Percentage of Participants With Mean Weekly Hemoglobin Level Outside the Target Range	Percentage of participants who had hemoglobin level outside the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 12, 24
Percentage of Participants Who Received Blood Transfusions		Week 1 up to Week 24
Number of Participants With Change in Mean Dose of Study Medication Based on Hemoglobin Level	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 1 up to Week 24
Percentage of Participants With Any Transient Change of Hemoglobin Greater Than (>) 2.0 Gram Per Deciliter (g/dL) in Hemoglobin Level		Week 1 up to Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL)		Week 1 up to Week 24
Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL)		Week 1 up to Week 24
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. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events from first dose of study drug to the end of study (up to Week 28) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.	Week 1 up to Week 28
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. Treatment-emergent were events between first dose of study drug to the end of study (up to Week 28) that were absent before treatment or that worsened relative to pre-treatment 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).	Week 1 up to Week 28
Number of Participants With Treatment Related Adverse Events (AEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.	Week 1 up to Week 28
Number of Participants That Discontinued Treatment Due to a Treatment Emergent Adverse Event	In this outcome measure number of participants who discontinued from study drug (Epoetin Hospira, Epogen) due to any AE were reported.	Week 1 up to Week 28
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.	Baseline up to Week 28
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.	Baseline up to Week 28
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.	Baseline up to Week 28
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.	Baseline up to Week 28
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.	Week 1 up to Week 28

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 31, 2012
• Primary Completion (Actual): February 11, 2014
• Study Completion (Actual): February 11, 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): September 10, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 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-10-01; C3461001 (Other Identifier: Alias Study Number)