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)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Chronic Renal Failure; Chronic Kidney Disease	Biological: Epoetin Hospira; Biological: Epogen Amgen	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	320 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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
Actual Study Start Date :	January 17, 2012
Actual Primary Completion Date :	February 28, 2014
Actual Study Completion Date :	February 28, 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Epoetin Hospira; Epoetin Hospira	Biological: Epoetin Hospira; Variable dose
Active Comparator: Epogen (Amgen); Epogen (Amgen)	Biological: Epogen Amgen; Variable dose; Other Name: Epoetin Alfa

Outcome Measures

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Primary Outcome Measures :

1. Mean Weekly Hemoglobin Level From Week 30 to Week 34: Maintenance Period [ Time Frame: Week 30 up to Week 34 ]
2. Mean Weekly Dosage of Study Medication From Week 30 to Week 34: Maintenance Period [ Time Frame: Week 30 up to Week 34 ]

Secondary Outcome Measures :

1. Mean Weekly Hemoglobin Level From Week 19 to Week 34: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
2. Mean Weekly Dosage of Study Medication From Week 19 to Week 34: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
3. Total Dose of Study Medication Administered: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
   In this outcome measure mean of total dose of study medication administered in maintenance period was reported.
4. Percentage of Participants With Mean Weekly Hemoglobin Level Within the Target Range: Maintenance Period [ Time Frame: Week 26, 34 ]
   Percentage of participants who had hemoglobin level within the target range of 9 to 11 g/dL for the specified weeks were reported.
5. Percentage of Participants Who Required Permanent Dose Changes: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
6. Percentage of Participants Who Required Temporary Dose Changes: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
7. Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 1.0 Gram Per Deciliter (g/dL): Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
8. Percentage of Participants With Mean Weekly Hemoglobin Level Outside the Target Range: Maintenance Period [ Time Frame: Week 26, 34 ]
   Percentage of participants who had hemoglobin level outside the target range of 9 to 11 g/dL for the specified weeks were reported.
9. Percentage of Participants Who Qualified as Optimally Titrated and Stable: Titration Period [ Time Frame: Week 1 up to Week 18 ]
10. Percentage of Participants Who Received Blood Transfusions: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
11. Number of Participants With Change in Mean Dose of Study Medication Based on Hemoglobin Level: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
    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
12. Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 2.0 Gram Per Deciliter (g/dL) in Hemoglobin Level: Maintenance Period [ Time Frame: Week 19 up to Week 34 ]

Other Outcome Measures:

1. Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL): Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
2. Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL): Maintenance Period [ Time Frame: Week 19 up to Week 34 ]
3. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38 ]
   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.
4. Number of Participants With Treatment-Emergent Adverse Events by Severity [ Time Frame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38 ]
   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).
5. Number of Participants With Treatment Related Adverse Events (AEs) [ Time Frame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38 ]
   An AE was any untoward medical occurrence in a participant who received study drug.
6. Number of Participants With Outcome of Treatment-Emergent Adverse Events (AEs) [ Time Frame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38 ]
   Outcome of AEs in participants who had at least 1 AE was defined as participants' discontinuation from study drug (Epoetin Hospira, Epogen) due to any AE.
7. Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters [ Time Frame: 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 ]
   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.
8. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: 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 ]
   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.
9. Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) [ Time Frame: 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 ]
   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.
10. Number of Participants With Clinically Significant Change From Baseline in Physical Examination [ Time Frame: 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 ]
    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.
11. Percentage of Participants With Anti-Recombinant Human Erythropoietin (Anti-rhEPO) Antibodies [ Time Frame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38 ]
    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.
12. Percentage of Participants With General Tolerability [ Time Frame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38 ]
    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.
13. Percentage of Participants With Local Tolerability [ Time Frame: Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38 ]
    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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

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  Show 73 Study Locations

Sponsors and Collaborators

Pfizer

Hospira, now a wholly owned subsidiary of Pfizer

Investigators

Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

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Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01473420 History of Changes
Other Study ID Numbers:	EPOE-10-13; C3461003 ( Other Identifier: Alias Study Number )
First Posted:	November 17, 2011
Results First Posted:	June 20, 2018
Last Update Posted:	June 20, 2018
Last Verified:	May 2018

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic	Urologic Diseases; Epoetin Alfa; Hematinics