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

Chronic Kidney Disease Clinical Trial

— AiME - 01  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01473407
• Other study ID #: EPOE-10-01
• Secondary ID: C3461001
• Status: Completed
• Phase: Phase 3
• Start date: January 31, 2012
• Est. completion date: February 11, 2014

Study information

• Verified date: August 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 612
• Est. completion date: February 11, 2014
• Est. primary completion date: February 11, 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) 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)

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
Puerto Rico	Consolidated Medical Plaza	Caguas
United States	Lakhi M. Sakhrani, MD A Medical Coporation	Alhambra	California
United States	Nephrology and Internal Medicine of Anderson	Anderson	South Carolina
United States	South Arlington Dialysis Center	Arlington	Texas
United States	Mountain Kidney and Hypertension Associates, PA	Asheville	North Carolina
United States	North America Research Institute	Azusa	California
United States	DaVita Dialysis Center-Bakersfield Dialysis Center	Bakersfield	California
United States	Brookdale Physician Dialysis Associates	Brooklyn	New York
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	Cincinnati VA Medical Center	Cincinnati	Ohio
United States	DaVita Dialysis Centers	Clinton Township	Michigan
United States	Columbia Nephrology Associates, P.A.	Columbia	South Carolina
United States	Columbia Nephrology Associates, PA	Columbia	South Carolina
United States	HNC Dialysis Ltd.	Columbus	Ohio
United States	South Florida Nephrology, Inc.	Coral Springs	Florida
United States	St. Clair Specialty Physicians, P.C.	Detroit	Michigan
United States	Renal Physicians of Georgia, PC	Dublin	Georgia
United States	Hypertension & Nephrology Associates	Eatontown	New Jersey
United States	Bayview Nephrology, Inc	Erie	Pennsylvania
United States	DaVita-Erie Dialysis Center	Erie	Pennsylvania
United States	UPMC Hamot Clinical Trials Department	Erie	Pennsylvania
United States	Research by Design, LLC	Evergreen Park	Illinois
United States	Clinical Research and Consulting Center, LLC	Fairfax	Virginia
United States	Ong, Rubin, Shahmir A Medical Corp DBA: Solano Kidney Care	Fairfield	California
United States	A Medical Corporation	Glendale	California
United States	Renal Consultants Medical Group	Granada Hills	California
United States	East Carolina University, ECU School of Medicine, Department of Internal Medicine	Greenville	North Carolina
United States	Texas Renal Care	Greenville	Texas
United States	South Mississippi Medical Research, PLLC	Gulfport	Mississippi
United States	North Suburban Nephrology, LLC	Gurnee	Illinois
United States	Peninsula Kidney Associates	Hampton	Virginia
United States	Med Center Dialysis	Houston	Texas
United States	Meyerland Dialysis	Houston	Texas
United States	Millenium Clinical Research, Inc.	Houston	Texas
United States	Millennium Clinical Research, Inc.	Houston	Texas
United States	Research Across America	Houston	Texas
United States	Southwest Houston Dialysis	Houston	Texas
United States	Southwest Houston Research, Ltd.	Houston	Texas
United States	La Puente Dialysis Center	La Puente	California
United States	Advanced Medical Research, LLC	Lakewood	California
United States	Kidney Specialists of Southern Nevada	Las Vegas	Nevada
United States	South Florida Research Institute	Lauderdale Lakes	Florida
United States	Bayview Nephrology, Inc	Long Beach	California
United States	DaVita Bixby Knolls Dialysis	Long Beach	California
United States	Academic Medical Research Institute	Los Angeles	California
United States	Texas Tech University Health Sciences Center	Lubbock	Texas
United States	Westbank Nephrology Associates	Marrero	Louisiana
United States	Private practice of Roberto Mangoo-Karim MD	McAllen	Texas
United States	Boise Kidney & Hypertension Institute, PLLC	Meridian	Idaho
United States	Nephrology Specialists, PC	Merrillville	Indiana
United States	Nephrology Associates of South Miami	Miami	Florida
United States	San Marcus Research Clinic, Inc	Miami	Florida
United States	Nephrology and Hypertension Associates	Middlebury	Connecticut
United States	Missouri City Dialysis	Missouri City	Texas
United States	Desert Nephrology Medical Group	Modesto	California
United States	Montgomery Kidney Specialists	Montgomery	Alabama
United States	ARA Naples South Dialysis Center	Naples	Florida
United States	ARA- Naples Dialysis Center, LLC	Naples	Florida
United States	La Jolla Clinical Research, Inc.	National City	California
United States	Eastern Nephrology Associates, PLLC	New Bern	North Carolina
United States	Internal Medicine Specialists	New Orleans	Louisiana
United States	Lower Manhattan Dialysis Center	New York	New York
United States	Internal Medicine Kidney and Hypertension Center	Norfolk	Virginia
United States	Innovative Medical Research of South Florida, Inc.	North Miami Beah	Florida
United States	Valley Renal Medical Group	Northridge	California
United States	Discovery Medical Research Group, Inc.	Ocala	Florida
United States	Ontario Dialysis Inc	Ontario	California
United States	Palmetto Nephrology, PA	Orangeburg	South Carolina
United States	South Carolina Nephrology and Hypertension Center, Inc.	Orangeburg	South Carolina
United States	Central Florida Kidney Centers	Orlando	Florida
United States	Delaware Valley Nephrology and Hypertension Associates, PC	Philadelphia	Pennsylvania
United States	Franklin Dialysis Center	Philadelphia	Pennsylvania
United States	Discovery medical Research Group, Inc.	Porterville	California
United States	Chromalloy American Kidney Center	Saint Louis	Missouri
United States	DaVita Dialysis Center-Floyd Curl Dialysis	San Antonio	Texas
United States	San Antonio Kidney Disease Center Physicians Group, P.L.L.C.	San Antonio	Texas
United States	Northwest Louisiana Nephrology	Shreveport	Louisiana
United States	Desert Nephrology Medical Group	Sumter	South Carolina
United States	Nephrology Educational Services and Research, Inc	Tarzana	California
United States	Southwest Clinical Research Institute, LLC	Tempe	Arizona
United States	Queen Dialysis Center	West Covina	California
United States	American Institute of Research	Whittier	California
United States	Mark C. Lee, Inc. Santa Fe Springs Dialysis	Whittier	California
United States	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina
United States	North Valley Nephrology	Yuba City	California

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL)		Week 1 up to Week 24
Other	Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL)		Week 1 up to Week 24
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. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events from first dose of study drug to the end of study (up to Week 28) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.	Week 1 up to Week 28
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. Treatment-emergent were events between first dose of study drug to the end of study (up to Week 28) that were absent before treatment or that worsened relative to pre-treatment 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).	Week 1 up to Week 28
Other	Number of Participants With Treatment Related Adverse Events (AEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.	Week 1 up to Week 28
Other	Number of Participants That Discontinued Treatment Due to a Treatment Emergent Adverse Event	In this outcome measure number of participants who discontinued from study drug (Epoetin Hospira, Epogen) due to any AE were reported.	Week 1 up to Week 28
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.	Baseline up to Week 28
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.	Baseline up to Week 28
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.	Baseline up to Week 28
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.	Baseline up to Week 28
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.	Week 1 up to Week 28
Primary	Mean Weekly Hemoglobin Level From Week 21 to Week 24		Week 21 up to Week 24
Primary	Mean Weekly Dosage of Study Medication From Week 21 to Week 24		Week 21 up to Week 24
Secondary	Mean Weekly Hemoglobin Level Through 24 Weeks		Week 1 up to Week 24
Secondary	Mean Weekly Dosage of Study Medication Through 24 Weeks		Week 1 up to Week 24
Secondary	Total Dose of Study Medication Administered		Week 1 up to Week 24
Secondary	Percentage of Participants With Mean Weekly Hemoglobin Level Within the Target Range	Percentage of participants who had hemoglobin level within the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 12, 24
Secondary	Percentage of Participants Who Required Permanent Dose Changes of Study Medication		Week 1 up to Week 24
Secondary	Percentage of Participants Who Required Temporary Dose Changes of Study Medication		Week 1 up to Week 24
Secondary	Percentage of Participants With Any Transient Change of Hemoglobin Level Greater Than (>) 1 Gram Per Deciliter (g/dL)		Week 1 up to Week 24
Secondary	Percentage of Participants With Mean Weekly Hemoglobin Level Outside the Target Range	Percentage of participants who had hemoglobin level outside the target range of 9 to 11 g/dL for the specified weeks were reported.	Week 12, 24
Secondary	Percentage of Participants Who Received Blood Transfusions		Week 1 up to Week 24
Secondary	Number of Participants With Change in Mean Dose of Study Medication Based on Hemoglobin Level	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 1 up to Week 24
Secondary	Percentage of Participants With Any Transient Change of Hemoglobin Greater Than (>) 2.0 Gram Per Deciliter (g/dL) in Hemoglobin Level		Week 1 up to Week 24