Clinical trial NCT01473407: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Chronic Renal Failure
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2011-11-17
Enrollment: 612
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Mean Weekly Hemoglobin Level From Week 21 to Week 24
timeFrame: Week 21 up to Week 24
measure: Mean Weekly Dosage of Study Medication From Week 21 to Week 24
timeFrame: Week 21 up to Week 24
Secondary outcomes:
measure: Mean Weekly Hemoglobin Level Through 24 Weeks
timeFrame: Week 1 up to Week 24
measure: Mean Weekly Dosage of Study Medication Through 24 Weeks
timeFrame: Week 1 up to Week 24
measure: Total Dose of Study Medication Administered
timeFrame: Week 1 up to Week 24
measure: Percentage of Participants With Mean Weekly Hemoglobin Level Within the Target Range
timeFrame: Week 12, 24
measure: Percentage of Participants Who Required Permanent Dose Changes of Study Medication
timeFrame: Week 1 up to Week 24
measure: Percentage of Participants Who Required Temporary Dose Changes of Study Medication
timeFrame: Week 1 up to Week 24
measure: Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 1 Gram Per Deciliter (g/dL)
timeFrame: Week 1 up to Week 24
measure: Percentage of Participants With Mean Weekly Hemoglobin Level Outside the Target Range
timeFrame: Week 12, 24
measure: Percentage of Participants Who Received Blood Transfusions
timeFrame: Week 1 up to Week 24
measure: Number of Participants With Change in Mean Dose of Study Medication Based on Hemoglobin Level
timeFrame: Week 1 up to Week 24
measure: Percentage of Participants With Any Transient Change of Hemoglobin Greater Than (>) 2.0 Gram Per Deciliter (g/dL) in Hemoglobin Level
timeFrame: Week 1 up to Week 24
Other outcomes:
measure: Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL)
timeFrame: Week 1 up to Week 24
measure: Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL)
timeFrame: Week 1 up to Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Week 1 up to Week 28
measure: Number of Participants With Treatment-Emergent Adverse Events by Severity
timeFrame: Week 1 up to Week 28
measure: Number of Participants With Treatment Related Adverse Events (AEs)
timeFrame: Week 1 up to Week 28
measure: Number of Participants That Discontinued Treatment Due to a Treatment Emergent Adverse Event
timeFrame: Week 1 up to Week 28
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
timeFrame: Baseline up to Week 28
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to Week 28
measure: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
timeFrame: Baseline up to Week 28
measure: Number of Participants With Clinically Significant Change From Baseline in Physical Examination
timeFrame: Baseline up to Week 28
measure: Percentage of Participants With Anti-Recombinant Human Erythropoietin (Anti-rhEPO) Antibodies
timeFrame: Week 1 up to Week 28
Locations:
city: Montgomery
country: United States
facility: Montgomery Kidney Specialists
state: Alabama
city: Tempe
country: United States
facility: Southwest Clinical Research Institute, LLC
state: Arizona
city: Alhambra
country: United States
facility: Lakhi M. Sakhrani, MD A Medical Coporation
state: California
city: Azusa
country: United States
facility: North America Research Institute
state: California
city: Bakersfield
country: United States
facility: DaVita Dialysis Center-Bakersfield Dialysis Center
state: California
city: Fairfield
country: United States
facility: Ong, Rubin, Shahmir A Medical Corp DBA: Solano Kidney Care
state: California
city: Glendale
country: United States
facility: A Medical Corporation
state: California
city: Granada Hills
country: United States
facility: Renal Consultants Medical Group
state: California
city: La Puente
country: United States
facility: La Puente Dialysis Center
state: California
city: Lakewood
country: United States
facility: Advanced Medical Research, LLC
state: California
city: Long Beach
country: United States
facility: DaVita Bixby Knolls Dialysis
state: California
city: Long Beach
country: United States
facility: Bayview Nephrology, Inc
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Modesto
country: United States
facility: Desert Nephrology Medical Group
state: California
city: National City
country: United States
facility: La Jolla Clinical Research, Inc.
state: California
city: Northridge
country: United States
facility: Valley Renal Medical Group
state: California
city: Ontario
country: United States
facility: Ontario Dialysis Inc
state: California
city: Porterville
country: United States
facility: Discovery medical Research Group, Inc.
state: California
city: Tarzana
country: United States
facility: Nephrology Educational Services and Research, Inc
state: California
city: West Covina
country: United States
facility: Queen Dialysis Center
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Whittier
country: United States
facility: Mark C. Lee, Inc. Santa Fe Springs Dialysis
state: California
city: Yuba City
country: United States
facility: North Valley Nephrology
state: California
city: Middlebury
country: United States
facility: Nephrology and Hypertension Associates
state: Connecticut
city: Coral Springs
country: United States
facility: South Florida Nephrology, Inc.
state: Florida
city: Lauderdale Lakes
country: United States
facility: South Florida Research Institute
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic, Inc
state: Florida
city: Miami
country: United States
facility: Nephrology Associates of South Miami
state: Florida
city: Naples
country: United States
facility: ARA Naples South Dialysis Center
state: Florida
city: Naples
country: United States
facility: ARA- Naples Dialysis Center, LLC
state: Florida
city: North Miami Beah
country: United States
facility: Innovative Medical Research of South Florida, Inc.
state: Florida
city: Ocala
country: United States
facility: Discovery Medical Research Group, Inc.
state: Florida
city: Orlando
country: United States
facility: Central Florida Kidney Centers
state: Florida
city: Dublin
country: United States
facility: Renal Physicians of Georgia, PC
state: Georgia
city: Meridian
country: United States
facility: Boise Kidney & Hypertension Institute, PLLC
state: Idaho
city: Evergreen Park
country: United States
facility: Research by Design, LLC
state: Illinois
city: Gurnee
country: United States
facility: North Suburban Nephrology, LLC
state: Illinois
city: Merrillville
country: United States
facility: Nephrology Specialists, PC
state: Indiana
city: Marrero
country: United States
facility: Westbank Nephrology Associates
state: Louisiana
city: New Orleans
country: United States
facility: Internal Medicine Specialists
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Clinton Township
country: United States
facility: DaVita Dialysis Centers
state: Michigan
city: Detroit
country: United States
facility: St. Clair Specialty Physicians, P.C.
state: Michigan
city: Gulfport
country: United States
facility: South Mississippi Medical Research, PLLC
state: Mississippi
city: Saint Louis
country: United States
facility: Chromalloy American Kidney Center
state: Missouri
city: Las Vegas
country: United States
facility: Kidney Specialists of Southern Nevada
state: Nevada
city: Eatontown
country: United States
facility: Hypertension & Nephrology Associates
state: New Jersey
city: Brooklyn
country: United States
facility: Brookdale Physician Dialysis Associates
state: New York
city: New York
country: United States
facility: Lower Manhattan Dialysis Center
state: New York
city: Asheville
country: United States
facility: Mountain Kidney and Hypertension Associates, PA
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University, ECU School of Medicine, Department of Internal Medicine
state: North Carolina
city: New Bern
country: United States
facility: Eastern Nephrology Associates, PLLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center
state: Ohio
city: Columbus
country: United States
facility: HNC Dialysis Ltd.
state: Ohio
city: Erie
country: United States
facility: Bayview Nephrology, Inc
state: Pennsylvania
city: Erie
country: United States
facility: DaVita-Erie Dialysis Center
state: Pennsylvania
city: Erie
country: United States
facility: UPMC Hamot Clinical Trials Department
state: Pennsylvania
city: Philadelphia
country: United States
facility: Franklin Dialysis Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Delaware Valley Nephrology and Hypertension Associates, PC
state: Pennsylvania
city: Anderson
country: United States
facility: Nephrology and Internal Medicine of Anderson
state: South Carolina
city: Columbia
country: United States
facility: Columbia Nephrology Associates, P.A.
state: South Carolina
city: Columbia
country: United States
facility: Columbia Nephrology Associates, PA
state: South Carolina
city: Orangeburg
country: United States
facility: Palmetto Nephrology, PA
state: South Carolina
city: Orangeburg
country: United States
facility: South Carolina Nephrology and Hypertension Center, Inc.
state: South Carolina
city: Sumter
country: United States
facility: Desert Nephrology Medical Group
state: South Carolina
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Arlington
country: United States
facility: South Arlington Dialysis Center
state: Texas
city: Greenville
country: United States
facility: Texas Renal Care
state: Texas
city: Houston
country: United States
facility: Med Center Dialysis
state: Texas
city: Houston
country: United States
facility: Meyerland Dialysis
state: Texas
city: Houston
country: United States
facility: Millenium Clinical Research, Inc.
state: Texas
city: Houston
country: United States
facility: Millennium Clinical Research, Inc.
state: Texas
city: Houston
country: United States
facility: Research Across America
state: Texas
city: Houston
country: United States
facility: Southwest Houston Dialysis
state: Texas
city: Houston
country: United States
facility: Southwest Houston Research, Ltd.
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: McAllen
country: United States
facility: Private practice of Roberto Mangoo-Karim MD
state: Texas
city: Missouri City
country: United States
facility: Missouri City Dialysis
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
state: Texas
city: San Antonio
country: United States
facility: DaVita Dialysis Center-Floyd Curl Dialysis
state: Texas
city: Fairfax
country: United States
facility: Clinical Research and Consulting Center, LLC
state: Virginia
city: Hampton
country: United States
facility: Peninsula Kidney Associates
state: Virginia
city: Norfolk
country: United States
facility: Internal Medicine Kidney and Hypertension Center
state: Virginia
city: Caguas
country: Puerto Rico
facility: Consolidated Medical Plaza
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.