Clinical trial NCT01473420: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Renal Failure
Chronic Kidney Disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2011-11-17
Enrollment: 320
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 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.


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) 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)

Primary outcomes:
measure: Mean Weekly Hemoglobin Level From Week 30 to Week 34: Maintenance Period
timeFrame: Week 30 up to Week 34
measure: Mean Weekly Dosage of Study Medication From Week 30 to Week 34: Maintenance Period
timeFrame: Week 30 up to Week 34
Secondary outcomes:
measure: Mean Weekly Hemoglobin Level From Week 19 to Week 34: Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Mean Weekly Dosage of Study Medication From Week 19 to Week 34: Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Total Dose of Study Medication Administered: Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Percentage of Participants With Mean Weekly Hemoglobin Level Within the Target Range: Maintenance Period
timeFrame: Week 26, 34
measure: Percentage of Participants Who Required Permanent Dose Changes: Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Percentage of Participants Who Required Temporary Dose Changes: Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 1.0 Gram Per Deciliter (g/dL): Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Percentage of Participants With Mean Weekly Hemoglobin Level Outside the Target Range: Maintenance Period
timeFrame: Week 26, 34
measure: Percentage of Participants Who Qualified as Optimally Titrated and Stable: Titration Period
timeFrame: Week 1 up to Week 18
measure: Percentage of Participants Who Received Blood Transfusions: Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Number of Participants With Change in Mean Dose of Study Medication Based on Hemoglobin Level: Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 2.0 Gram Per Deciliter (g/dL) in Hemoglobin Level: Maintenance Period
timeFrame: Week 19 up to Week 34
Other outcomes:
measure: Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL): Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL): Maintenance Period
timeFrame: Week 19 up to Week 34
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
measure: Number of Participants With Treatment-Emergent Adverse Events by Severity
timeFrame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
measure: Number of Participants With Treatment Related Adverse Events (AEs)
timeFrame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
measure: Number of Participants That Discontinued Treatment Due to a Treatment Emergent Adverse Event
timeFrame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
timeFrame: 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
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: 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
measure: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
timeFrame: 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
measure: Number of Participants With Clinically Significant Change From Baseline in Physical Examination
timeFrame: 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
measure: Percentage of Participants With Anti-Recombinant Human Erythropoietin (Anti-rhEPO) Antibodies
timeFrame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
measure: Percentage of Participants With General Tolerability
timeFrame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
measure: Percentage of Participants With Local Tolerability
timeFrame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Locations:
city: Azusa
country: United States
facility: North America Research Institute
state: California
city: Bakersfield
country: United States
facility: National Institute of Clinical Research
state: California
city: Long Beach
country: United States
facility: Long Beach Dialysis Center
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Modesto
country: United States
facility: Long Beach Dialysis Center
state: California
city: Northridge
country: United States
facility: Innovative Dialysis Center of Northridge, LLC
state: California
city: Northridge
country: United States
facility: Valley Renal Medical Group
state: California
city: Paramount
country: United States
facility: Research Management Inc.
state: California
city: Pleasanton
country: United States
facility: Pleasanton Dialysis Center
state: California
city: Rancho Cordova
country: United States
facility: Sunset Dialysis Center
state: California
city: Sacramento
country: United States
facility: Capital Nephrology Medical Group
state: California
city: San Leandro
country: United States
facility: Chabot Nephrology Medical Group
state: California
city: San Leandro
country: United States
facility: San Leandro Dialysis
state: California
city: Santa Clarita
country: United States
facility: Renal Consultants Medical Group
state: California
city: Whittier
country: United States
facility: Intercommunity Dialysis Center
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Whittier
country: United States
facility: Whittier Kidney Dialysis Center
state: California
city: Arvada
country: United States
facility: Western Nephrology and Metabolic Bone Disease, PC
state: Colorado
city: Westminster
country: United States
facility: Kidney Center of Westminster, LLC
state: Colorado
city: Westminster
country: United States
facility: Western Nephrology and Metabolic Bone Disease, PC
state: Colorado
city: Pembroke Pines
country: United States
facility: Pines Clinical Research Inc.
state: Florida
city: Albany
country: United States
facility: Dialysis Clinic, Inc. - Albany
state: Georgia
city: Augusta
country: United States
facility: Kidney Care Associates
state: Georgia
city: Dublin
country: United States
facility: Renal Physicians of Georgia, PC
state: Georgia
city: Chicago
country: United States
facility: Neomedica Marquette Park
state: Illinois
city: Evergreen Park
country: United States
facility: Research by Design, LLC
state: Illinois
city: Wichita
country: United States
facility: Kansas Nephrology Physicians, PA
state: Kansas
city: Lafayette
country: United States
facility: Research Nurse Specialists, LLC
state: Louisiana
city: Lafayette
country: United States
facility: New York Harbor Health Care System
state: Louisiana
city: Marrero
country: United States
facility: Westbank Nephrology Associates
state: Louisiana
city: Opelousas
country: United States
facility: FMC Opelousas
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Kalamazoo
country: United States
facility: Fresenius Medical Care-Kalamazoo East
state: Michigan
city: Kalamazoo
country: United States
facility: Fresenius Medical Care-Kalamazoo
state: Michigan
city: Kalamazoo
country: United States
facility: Nephrology Center DBA Paragon Health PC
state: Michigan
city: Kalamazoo
country: United States
facility: Fresenius Medical Care-Oshtemo
state: Michigan
city: Kalamazoo
country: United States
facility: Fresenius Medical Care-Gull Road
state: Michigan
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Renal Center
state: Missouri
city: Kansas City
country: United States
facility: Renal Advantage, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Metro Hypertension and Kidney Center
state: Missouri
city: North Brunswick
country: United States
facility: University of Cincinnati College of Medicine.
state: New Jersey
city: Voorhees
country: United States
facility: Nephrology & Hypertension Associates of NJ
state: New Jersey
city: Astoria
country: United States
facility: Newtown Dialysis Center
state: New York
city: Flushing
country: United States
facility: New York Hospital Medical Center Queens Institutional Review Board
state: New York
city: New Hyde Park
country: United States
facility: Parker Jewish Institute for Health Care and Rehabilitation
state: New York
city: New York
country: United States
facility: New York Harbor Health Care System
state: New York
city: Raleigh
country: United States
facility: Wake Nephrology Associates, PA
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Toledo
country: United States
facility: Private Practice of Kenneth Lempert
state: Ohio
city: Meadville
country: United States
facility: Northwest Physicians Associates, PC
state: Pennsylvania
city: Aiken
country: United States
facility: CSRA Renal Services, LLC
state: South Carolina
city: Columbia
country: United States
facility: Fresenius Medical Care Midtown JV
state: South Carolina
city: Columbia
country: United States
facility: Columbia Nephrology Associates, PA
state: South Carolina
city: Irmo
country: United States
facility: Fresenius Medical Care Irmo JV
state: South Carolina
city: Orangeburg
country: United States
facility: South Carolina Nephrology and Hypertension Center, Inc.
state: South Carolina
city: Knoxville
country: United States
facility: Knoxville Kidney Center, PLLC
state: Tennessee
city: Austin
country: United States
facility: Fresenius Medical Care - Austin North Dialysis
state: Texas
city: Austin
country: United States
facility: Research Management, Inc.
state: Texas
city: Austin
country: United States
facility: Research Management, Inc
state: Texas
city: Dallas
country: United States
facility: Dallas Veterans Affairs Medical Center
state: Texas
city: Grand Prairie
country: United States
facility: Grand Prairie Dialysis Center
state: Texas
city: Houston
country: United States
facility: Research Across America
state: Texas
city: Houston
country: United States
facility: Westminster Dialysis
state: Texas
city: Houston
country: United States
facility: Mission Bend Dialysis
state: Texas
city: Houston
country: United States
facility: Southwest Houston Research, Ltd.
state: Texas
city: Lufkin
country: United States
facility: East Texas Nephrology Associates
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center
state: Texas
city: Arlington
country: United States
facility: Renal Care Partners of Pentagon City
state: Virginia
city: Fairfax
country: United States
facility: Clinical Research and Consulting Center, LLC
state: Virginia
city: Fairfax
country: United States
facility: Renal Care Partners of Fairfax
state: Virginia
city: Mechanicsville
country: United States
facility: Nephrology Specialists, PC
state: Virginia
city: Olympia
country: United States
facility: Western Institutional Review Board
state: Washington
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.