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

Chronic Kidney Disease Clinical Trial

— AiME - 13  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01473420
• Other study ID #: EPOE-10-13
• Secondary ID: C3461003
• Status: Completed
• Phase: Phase 3
• Start date: January 17, 2012
• Est. completion date: February 28, 2014

Study information

• Verified date: July 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: February 28, 2014
• Est. primary completion date: February 28, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Chronic Renal Failure
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Biological:
• Epoetin Hospira
Variable dose
• Epogen Amgen
Variable dose

Locations

Country	Name	City	State
United States	CSRA Renal Services, LLC	Aiken	South Carolina
United States	Dialysis Clinic, Inc. - Albany	Albany	Georgia
United States	Renal Care Partners of Pentagon City	Arlington	Virginia
United States	Western Nephrology and Metabolic Bone Disease, PC	Arvada	Colorado
United States	Newtown Dialysis Center	Astoria	New York
United States	Kidney Care Associates	Augusta	Georgia
United States	Fresenius Medical Care - Austin North Dialysis	Austin	Texas
United States	Research Management, Inc	Austin	Texas
United States	Research Management, Inc.	Austin	Texas
United States	North America Research Institute	Azusa	California
United States	National Institute of Clinical Research	Bakersfield	California
United States	Neomedica Marquette Park	Chicago	Illinois
United States	University of Cincinnati College of Medicine	Cincinnati	Ohio
United States	Columbia Nephrology Associates, PA	Columbia	South Carolina
United States	Fresenius Medical Care Midtown JV	Columbia	South Carolina
United States	Dallas Veterans Affairs Medical Center	Dallas	Texas
United States	Renal Physicians of Georgia, PC	Dublin	Georgia
United States	Research by Design, LLC	Evergreen Park	Illinois
United States	Clinical Research and Consulting Center, LLC	Fairfax	Virginia
United States	Renal Care Partners of Fairfax	Fairfax	Virginia
United States	New York Hospital Medical Center Queens Institutional Review Board	Flushing	New York
United States	Grand Prairie Dialysis Center	Grand Prairie	Texas
United States	Mission Bend Dialysis	Houston	Texas
United States	Research Across America	Houston	Texas
United States	Southwest Houston Research, Ltd.	Houston	Texas
United States	Westminster Dialysis	Houston	Texas
United States	Fresenius Medical Care Irmo JV	Irmo	South Carolina
United States	Fresenius Medical Care-Gull Road	Kalamazoo	Michigan
United States	Fresenius Medical Care-Kalamazoo	Kalamazoo	Michigan
United States	Fresenius Medical Care-Kalamazoo East	Kalamazoo	Michigan
United States	Fresenius Medical Care-Oshtemo	Kalamazoo	Michigan
United States	Nephrology Center DBA Paragon Health PC	Kalamazoo	Michigan
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	Kansas City Renal Center	Kansas City	Missouri
United States	Renal Advantage, Inc.	Kansas City	Missouri
United States	Knoxville Kidney Center, PLLC	Knoxville	Tennessee
United States	New York Harbor Health Care System	Lafayette	Louisiana
United States	Research Nurse Specialists, LLC	Lafayette	Louisiana
United States	Long Beach Dialysis Center	Long Beach	California
United States	Academic Medical Research Institute	Los Angeles	California
United States	East Texas Nephrology Associates	Lufkin	Texas
United States	Westbank Nephrology Associates	Marrero	Louisiana
United States	Northwest Physicians Associates, PC	Meadville	Pennsylvania
United States	Nephrology Specialists, PC	Mechanicsville	Virginia
United States	Long Beach Dialysis Center	Modesto	California
United States	Parker Jewish Institute for Health Care and Rehabilitation	New Hyde Park	New York
United States	New York Harbor Health Care System	New York	New York
United States	University of Cincinnati College of Medicine.	North Brunswick	New Jersey
United States	Innovative Dialysis Center of Northridge, LLC	Northridge	California
United States	Valley Renal Medical Group	Northridge	California
United States	Western Institutional Review Board	Olympia	Washington
United States	FMC Opelousas	Opelousas	Louisiana
United States	South Carolina Nephrology and Hypertension Center, Inc.	Orangeburg	South Carolina
United States	Research Management Inc.	Paramount	California
United States	Pines Clinical Research Inc.	Pembroke Pines	Florida
United States	Pleasanton Dialysis Center	Pleasanton	California
United States	Wake Nephrology Associates, PA	Raleigh	North Carolina
United States	Sunset Dialysis Center	Rancho Cordova	California
United States	Capital Nephrology Medical Group	Sacramento	California
United States	Metro Hypertension and Kidney Center	Saint Louis	Missouri
United States	San Antonio Kidney Disease Center	San Antonio	Texas
United States	Chabot Nephrology Medical Group	San Leandro	California
United States	San Leandro Dialysis	San Leandro	California
United States	Renal Consultants Medical Group	Santa Clarita	California
United States	Northwest Louisiana Nephrology	Shreveport	Louisiana
United States	Private Practice of Kenneth Lempert	Toledo	Ohio
United States	Nephrology & Hypertension Associates of NJ	Voorhees	New Jersey
United States	Kidney Center of Westminster, LLC	Westminster	Colorado
United States	Western Nephrology and Metabolic Bone Disease, PC	Westminster	Colorado
United States	American Institute of Research	Whittier	California
United States	Intercommunity Dialysis Center	Whittier	California
United States	Whittier Kidney Dialysis Center	Whittier	California
United States	Kansas Nephrology Physicians, PA	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Hospira, now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL): Maintenance Period		Week 19 up to Week 34
Other	Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL): Maintenance Period		Week 19 up to Week 34
Other	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. 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.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Other	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. 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).	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Other	Number of Participants With Treatment Related Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Other	Number of Participants That Discontinued Treatment Due to a Treatment Emergent Adverse Event	In this outcome measure number of participants discontinued from study drug (Epoetin Hospira, Epogen) due to any AE were reported.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Other	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.	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
Other	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.	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
Other	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.	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
Other	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.	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
Other	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.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Other	Percentage of Participants With General Tolerability	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.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Other	Percentage of Participants With Local Tolerability	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.	Titration Period: Week 1 up to Week 18 and Maintenance Period: Week 19 up to Week 38
Primary	Mean Weekly Hemoglobin Level From Week 30 to Week 34: Maintenance Period		Week 30 up to Week 34
Primary	Mean Weekly Dosage of Study Medication From Week 30 to Week 34: Maintenance Period		Week 30 up to Week 34
Secondary	Mean Weekly Hemoglobin Level From Week 19 to Week 34: Maintenance Period		Week 19 up to Week 34
Secondary	Mean Weekly Dosage of Study Medication From Week 19 to Week 34: Maintenance Period		Week 19 up to Week 34
Secondary	Total Dose of Study Medication Administered: Maintenance Period	In this outcome measure mean of total dose of study medication administered in maintenance period was reported.	Week 19 up to Week 34
Secondary	Percentage of Participants With Mean Weekly Hemoglobin Level Within the Target Range: Maintenance Period	Percentage of participants who had hemoglobin level within the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 26, 34
Secondary	Percentage of Participants Who Required Permanent Dose Changes: Maintenance Period		Week 19 up to Week 34
Secondary	Percentage of Participants Who Required Temporary Dose Changes: Maintenance Period		Week 19 up to Week 34
Secondary	Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 1.0 Gram Per Deciliter (g/dL): Maintenance Period		Week 19 up to Week 34
Secondary	Percentage of Participants With Mean Weekly Hemoglobin Level Outside the Target Range: Maintenance Period	Percentage of participants who had hemoglobin level outside the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 26, 34
Secondary	Percentage of Participants Who Qualified as Optimally Titrated and Stable: Titration Period		Week 1 up to Week 18
Secondary	Percentage of Participants Who Received Blood Transfusions: Maintenance Period		Week 19 up to Week 34
Secondary	Number of Participants With Change in Mean Dose of Study Medication Based on Hemoglobin Level: Maintenance Period	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 19 up to Week 34
Secondary	Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 2.0 Gram Per Deciliter (g/dL) in Hemoglobin Level: Maintenance Period		Week 19 up to Week 34