A Phase 3, Long-Term Safety Study of Intravenous Epoetin Hospira in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment. AiME - Anemia Management With Epoetin (AiME - 03)

A Phase III, Open-label, Multicenter, Long-term Safety Study Of Intravenous Epoetin Hospira In Patients With Chronic Renal Failure Requiring Hemodialysis And Receiving Epoetin Maintenance Treatment

The purpose of the study is to determine the long-term safety in treatment-emergent adverse events (TEAEs) of intravenous (IV) administration of Epoetin Hospira for maintenance of target hemoglobin (Hgb) levels in patients treated for anemia associated with chronic renal failure and on hemodialysis.

Study Overview

• Status: Completed
• Conditions: Chronic Renal Failure Requiring Hemodialysis
• Intervention / Treatment: Biological: Epoetin Hospira

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Consolidated Medical Plaza
  • Humacao, Puerto Rico, 00791
    • Fresenius Medical Care·Humacao
• United States
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute
    • Bellflower, California, United States, 90706
      • Bellflower Dialysis Center
    • Commerce, California, United States, 90040
      • National Institute of Clinical Research
    • Cudahy, California, United States, 90201
      • DaVita Premier Dialysis Center
    • Encino, California, United States, 91316
      • Davita - South Valley Dialysis
    • Fairfield, California, United States, 94533
      • Ong, Rubin, Shahmir A Medical Corp DBA: Solano Kidney Care
    • Fairfield, California, United States, 94534
      • Fairfield Dialysis Center
    • Granada Hills, California, United States, 91344
      • Renal Consultants Medical Group
    • Lakewood, California, United States, 90712
      • Advanced Medical Research (Administrative)
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials
    • Long Beach, California, United States, 90806
      • Westcoast Dialysis
    • Long Beach, California, United States, 90813
      • Long Beach Dialysis
    • Long Beach, California, United States, 90807
      • DaVita Bixby Knolls Dialysis
    • Long Beach, California, United States, 90807
      • United Dialysis Center
    • Lynwood, California, United States, 90262
      • Kidney Research Center
    • Lynwood, California, United States, 90262
      • Imperial care Dialysis Center
    • Modesto, California, United States, 95350
      • Modesto Kidney Center
    • Modesto, California, United States, 95350
      • Novo Research d/b/a Foundation Research
    • Modesto, California, United States, 95350
      • Parkway Kindey Center
    • Oakdale, California, United States, 95361
      • Oakdale Kidney Center
    • Ontario, California, United States, 91762
      • Ontario Dialysis Center
    • Ontario, California, United States, 91762
      • National Institute of Clinical Research
    • Paramount, California, United States, 90723
      • Paramount Dialysis Center
    • Porterville, California, United States, 93257
      • Sierra View District Hospital
    • Porterville, California, United States, 93257
      • Sierra View Dialysis Center
    • Porterville, California, United States, 93257
      • Sierra View District Hospital Dialysis Center
    • Porterville, California, United States, CA
      • Sierra View Nephrology, Inc.
    • Tarzana, California, United States, 91356
      • Nephrology Educational Services and Research, Inc
    • Valencia, California, United States, 91355
      • Santa Clarita Kidney Center
    • Whittier, California, United States, 90603
      • American Institute of Research
    • Whittier, California, United States, 90606
      • Santa Fe Springs Dialysis
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Nephrology and Hypertension Associates,PC
    • Waterbury, Connecticut, United States, 06705
      • Waterbury Dialysis Center
    • Waterbury, Connecticut, United States, 06708
      • Greater Waterbury Dialysis
  • Florida
    • Aventura, Florida, United States, 33180
      • Innovative Medical Research of South Florida, Inc,
    • Boca Raton, Florida, United States, 33434
      • West Boca Dialysis Center
    • Lauderhill, Florida, United States, 33319
      • Florida Kidney Center
    • Laureda Lake, Florida, United States, 33313
      • South Florida Research Institute
    • Margate, Florida, United States, 33063
      • Coconut Creek Dialysis JV
    • Naples, Florida, United States, 34119
      • American Renal Associates Naples Dialysis Center
    • North Miami Beach, Florida, United States, 33169
      • Innovative Medical Research of South Florida, Inc.
    • North Miami Beach, Florida, United States, 33169
      • Physicians Dialysis of North Beach
    • Ocala, Florida, United States, 34471
      • Discovery Medical Research Group, Inc.
    • Ocala, Florida, United States, 34471
      • Discovery Medical Research Group, Inc.,
    • Ocala, Florida, United States, 34471
      • Ocala Regional Kidney Center, East
    • Ocala, Florida, United States, 34472
      • Silver Springs Shores Dialysis Center
    • Plantation, Florida, United States, 33312
      • Ft. Lauderdale Kidney Center
    • Plantation, Florida, United States, 33324
      • Plantation Kidney Center
    • Tamarac, Florida, United States, 33321
      • Tamarac Kidney Center
  • Georgia
    • Dublin, Georgia, United States, 31021
      • Renal Physicians of Georgia, PC
    • Dublin, Georgia, United States, 31021
      • Dialysis of Dublin
  • Idaho
    • Caldwell, Idaho, United States, 83605
      • Liberty Dialysis/Boise Kidney & Hypertension Institute
    • Meridian, Idaho, United States, 83642
      • Liberty Dialysis/Boise Kidney & Hypertension Institute
    • Meridian, Idaho, United States, 83642
      • Pacific Renal Research Institute/Boise Kidney & Hypertension Institute
    • Nampa, Idaho, United States, 83686
      • Liberty Dialysis/Boise Kidney & Hypertension Institute
  • Illinois
    • Chicago, Illinois, United States, 60617
      • Neomedica South
    • Chicago, Illinois, United States, 60621
      • FMC Ross Englewood Dialysis
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design, LLC
    • Evergreen Park, Illinois, United States, 60805
      • Neomedica Evergreen Park
    • Gurnee, Illinois, United States, 60031
      • North Suburban Nephrology, LLC
    • Round Lake, Illinois, United States, 60073
      • Neomedica Round Lake
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Clinton Township Dialysis
    • Detroit, Michigan, United States, 48236
      • Renaissance Renal Research Institute, LLC
    • Detroit, Michigan, United States, 48224
      • Grosse Pointe Dialysis
  • Mississippi
    • Biloxi, Mississippi, United States, 39530
      • Biloxi Dialysis
    • Gulfport, Mississippi, United States, 39501
      • South Mississippi Medical Research, PLLC
    • Gulfport, Mississippi, United States, 39501
      • FMC/South Mississippi Kidney Center of Gulfport
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Barnes-Jewish Dialysis Center
    • Saint Louis, Missouri, United States, 63110
      • Chromalloy American Kidney Center Washington University School of Medicine
  • New York
    • New York, New York, United States, 10003
      • Lower Manhattan Dialysis Center II
  • North Carolina
    • Asheville, North Carolina, United States, 28805
      • Asheville Kidney Center
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates, P A
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Greenville, North Carolina, United States, 27834-2847
      • ECU Nephrology and Hypertension
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Cincinnati VA Medical Center
    • Columbus, Ohio, United States, 43215
      • HNC Dialysis, Ltd.
    • Columbus, Ohio, United States, 43215
      • Fresenius Greater Columbus Regional Dialysis Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19118
      • Delaware Valley Nephrology and Hypertension Associates, PC
    • Philadelphia, Pennsylvania, United States, 19118
      • Fresenius Medical Care- Mt. Airy Kidney Center
    • Philadelphia, Pennsylvania, United States, 19138
      • Fresenius Medical Care - Olney Dialysis Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
    • Anderson, South Carolina, United States, 29621
      • Nephrology and Internal Medicine of Anderson
    • Anderson, South Carolina, United States, 29621
      • Anderson Dialysis Clinic
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, PA
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, P. A.
    • Columbia, South Carolina, United States, 29203
      • Fresenius Medical Care Columbia JV
    • Columbia, South Carolina, United States, 29203
      • Fresenius Medical Care Meadowlake JV
    • Columbia, South Carolina, United States, 29203
      • Fresenius Medical Care South Columbia JV
    • Columbia, South Carolina, United States, 29209
      • Fresenius Medical Care SE Columbia JV
    • Sumter, South Carolina, United States, 29150
      • Sumter Dialysis Clinic
  • Texas
    • Edinburg, Texas, United States, 78539
      • Gamma Medical Research Inc.
    • 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, 77071
      • Southwest Houston Dialysis
    • Houston, Texas, United States, 77030
      • Fresenius Medical Care Kidney Center
    • Houston, Texas, United States, 77054
      • Millennium Clinical Research, Inc.
    • Houston, Texas, United States, 77073
      • DaVita North Park
    • Houston, Texas, United States, 77091
      • North Shepherd Dialysis Center
    • Lubbock, Texas, United States, 79430
      • Dialysis Center of Lubbock
    • McAllen, Texas, United States, 78503
      • Fresenius Medical Care McAllen
    • Mission, Texas, United States, 78572
      • Fresenius Medial Care Mission
    • 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, 78229
      • NW Medical Center DaVita Dialysis
    • San Antonio, Texas, United States, 78240
      • Floyd Curl DaVita Dialysis Center
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Peninsula Kidney Associates
    • Hampton, Virginia, United States, 23666
      • Butler Farm Dialysis

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 the risks and benefits of the study have been explained prior to any study-related activities.
2. Patient previously completed the core study Treatment Period up to and including Week 24 study assessments per protocol and is willing to continue open-label Epoetin Hospira for up to 48 weeks.

3. If female, patient must be postmenopausal for at least 1 year prior to enrollment, 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 enrollment
   • Intrauterine device
   • 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 enrollment. 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 open-label dose.

4. Adequate methods of contraception to prevent pregnancy are to be maintained throughout the course of the study in both male and female study subjects.

Exclusion Criteria:

1. Patient had a serious or severe adverse event in the core study that, in the opinion of the Investigator, was probably or definitely related to epoetin use and precluded safe use of epoetin.

2. Any of the following that developed during the core study and prior to enrollment:

   • 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)
3. A patient with any active, uncontrolled systemic, inflammatory, or malignant disease that developed during the core study and 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.
4. Any newly developed 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 study participation.
5. A female patient who is pregnant, lactating, or planning a pregnancy during the study.
6. History of drug abuse or alcohol abuse during the core study prior to enrollment as determined by the Investigator.
7. Current participation or participation in a drug or other investigational research study within 30 days prior to enrollment (except the core study or any observational studies with prior written approval from Hospira).
8. 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.
9. Evidence of human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg).
10. A patient who, in the Investigator's opinion, has any clinically significant abnormal laboratory results that may impact patient safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epoetin Hospira; Epoetin Hospira will be administered by IV bolus injection 1 to 3 times per week per each patient's dosing schedule. Other ESAs (except for long-acting) may be used as rescue therapy.	Biological: Epoetin Hospira; Intravenous (IV) injection; Other Names: ESA; Erythropoetin Stimulating Agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Week 1	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.	Up through 7 days after first dose of study drug (Week 1)
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 1 to 12	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.	Week 1 up to Week 12
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 13 to 24	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.	Week 13 up to Week 24
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 25 to 36	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.	Week 25 up to Week 36
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 37 to 48	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.	Week 37 up to Week 48
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 1 to 48	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.	Week 1 up to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Weekly Dosage of Epoetin Hospira for Interval of 12 Weeks		Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48
Mean Hemoglobin Levels: Over Week 1 to 48		Week 1 up to Week 48
Mean Hemoglobin Levels for Interval of 12 Weeks		Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48
Mean Hematocrit Levels: Over Week 1 to 48	Hematocrit is defined as the percentage of red blood cells in the blood.	Week 1 up to Week 48
Mean Hematocrit Levels for Interval of 12 Weeks	Hematocrit is defined as the percentage of red blood cells in the blood.	Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48
Percentage of Participants Who Received Blood Transfusions		Week 1 up to Week 48
Mean Weekly Dosage of Epoetin Hospira : Over Week 1 to 48		Week 1 up to Week 48
Percentage of Participants With Hemoglobin Level Outside the Target Range	Percentage of participants with hemoglobin level outside the target range of 9.0 to 11.0 g/dL were reported.	Week 1 up to Week 48

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 48
Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL)		Week 1 up to Week 48
Number of Participants Who Received Concomitant Medication		Week 1 up to Week 48
Number of Participants With Clinically Significant Change From Baseline in Laboratory Tests	Laboratory tests included: Hematology (hematocrit, hemoglobin, red blood cells count, reticulocytes, white blood cells count, neutrophils, bands, lymphocytes, monocytes, basophils, eosinophils, platelets, mean corpuscular volume); Coagulation panel (prothrombin time, international normalized ratio, activated partial thromboplastin time); Chemistry (blood urine nitrogen, creatinine, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, calcium, gamma-glutyl transpeptidase, phosphorus, uric acid, total protein, glucose, albumin, C-reactive protein); iron status (plasma ferritin, transferrin saturation). Participants with clinically significant change from baseline in laboratory tests were based on investigator's discretion.	Baseline up to Week 48
Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiogram (ECG)	ECG parameters included: PR interval, QRS complex, QT interval and QTC interval. Participants with clinically significant change from baseline in 12-lead ECGs were based on investigator's discretion.	Baseline up to Week 48
Number of Participants With Clinically Significant Change From Baseline in Hemoglobin Levels	Participants with clinically significant change from baseline in hemoglobin levels were upon investigator's discretion.	Baseline up to Week 48
Number of Participants With Clinically Significant Change From Baseline in Physical Examinations	Physical examination included examination of the skin, eyes, ears, nose, throat, head, neck, thyroid, lungs, chest, abdomen, extremities, lymphatic, cardiovascular, musculoskeletal and neurological systems. Participants for any clinically significant changes in physical examination were based on the investigator's discretion.	Baseline up to Week 48
Percentage of Participants With Anti-Recombinant Human Erythropoietin (Anti-rhEPO) Antibodies	Percentage of participants with at least 1 positive anti-rhEPO antibody were reported. Radioimmunoprecipitation assay was used to determine the presence of anti-rhEPO antibodies.	Baseline, Week 48

Collaborators and Investigators

• Sponsor: 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): July 16, 2012
• Primary Completion (Actual): January 2, 2015
• Study Completion (Actual): January 2, 2015

Study Registration Dates

• First Submitted: June 22, 2012
• First Submitted That Met QC Criteria: June 22, 2012
• First Posted (Estimate): June 26, 2012

Study Record Updates

• Last Update Posted (Actual): July 19, 2018
• Last Update Submitted That Met QC Criteria: June 22, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Chronic renal failure; hemodialysis
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Hematinics; Epoetin Alfa
• Other Study ID Numbers: EPOE-11-03; C3461004 (Other Identifier: Alias Study Number)