A Phase 3 Study Comparing the Effects of Intravenous Epoetin Hospira and Epoetin Alfa (Amgen) in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment. AiME - Anemia Management With Epoetin

Condition(s) targeted: Chronic Kidney Disease; Chronic Renal Failure

Intervention: Epoetin Hospira (Biological); Epogen (Amgen) (Biological)

Phase: Phase 3

Status: Completed

Sponsored by: Hospira, Inc.

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Difference between treatments (Epoetin Hospira and Epogen [Amgen]) in mean weekly Hb level during the last 4 weeks of the double-blind Treatment Period (i.e., Week 21 to Week 24)

Difference between treatments (Epoetin Hospira and Epogen [Amgen]) in mean weekly dosage per kg body weight during the last 4 weeks of the double-blind Treatment Period (i.e., Week 21 to Week 24)

Secondary outcome:

Difference between treatments (Epoetin Hospira and Epogen [Amgen]) in mean weekly Hb level in 24 weeks of treatment

Difference between treatments (Epoetin Hospira and Epogen [Amgen]) in mean weekly dosage per kg body weight delivered in 24 weeks of treatment

The total dose delivered during the 24 weeks of treatment in the Treatment Period

The proportion of patients with a weekly mean Hb level within the target range (9-11 g/dL) at Week 12 and Week 24 of the Treatment Period

The proportion of patients requiring permanent dose changes during the Treatment Period

The proportion of patients requiring temporary dose changes during the Treatment Period

The proportion of patients with any transient change of Hb level >1 g/dL during the Treatment Period

The proportion of patients with any Hb measurement outside the target range during the Treatment Period

Incidence of patients receiving blood transfusions for each treatment group

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

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)

Caguas 00725, Puerto Rico

Tempe, Arizona 85284, United States

Alhambra, California 91801, United States

Azusa, California 91702, United States

Bakersfield, California 93309, United States

Fairfield, California 94533, United States

Glendale, California 91204, United States

Granada Hills, California 91344, United States

Lakewood, California 90712, United States

Long Beach, California 90813, United States

Los Angeles, California 90022, United States

Los Angeles, California 90057, United States

Modesto, California 95350, United States

National City, California 91950, United States

Northridge, California 91324, United States

Ontario, California 91762, United States

Porterville, California 93257, United States

San Leandro, California 94578, United States

Tarzana, California 91356, United States

Whittier, California 90603, United States

Whittier, California 90606, United States

Yuba City, California 95991, United States

Middlebury, Connecticut 06762, United States

Coral Springs, Florida 33071, United States

Lauderdale Lakes, Florida 33313, United States

Miami, Florida 33015, United States

Naples, Florida 34110, United States

North Miami Beach, Florida 33169, United States

Ocala, Florida 34471, United States

Orlando, Florida 32801-3621, United States

Dublin, Georgia 31021, United States

Meridian, Idaho 83642, United States

Evergreen Park, Illinois 60805, United States

Gurnee, Illinois 60031, United States

Louisville, Kentucky 40202, United States

Marrero, Louisiana 70072, United States

New Orleans, Louisiana 70115, United States

Shreveport, Louisiana 71101, United States

Detroit, Michigan 48236-2152, United States

Gulfport, Mississippi 39501, United States

St. Louis, Missouri 63110, United States

Las Vegas, Nevada 89106, United States

Eatontown, New Jersey 07724, United States

Brooklyn, New York 11212, United States

New York, New York 10016, United States

Ashville, North Carolina 28801, United States

Greenville, North Carolina 27834, United States

New Bern, North Carolina 28562, United States

Winston-Salem, North Carolina 27103, United States

Cincinnati, Ohio 45220, United States

Columbus, Ohio 43215, United States

Erie, Pennsylvania 16507, United States

Philadelphia, Pennsylvania 19118, United States

Anderson, South Carolina 29621, United States

Columbia, South Carolina 29203, United States

Orangeburg, South Carolina 29118, United States

Sumter, South Carolina 29150, United States

Arlington, Texas 76015, United States

Greenville, Texas 75402, United States

Houston, Texas 77004, United States

Houston, Texas 77054, United States

Houston, Texas 77099, United States

Lubbock, Texas 79430, United States

McAllen, Texas 78503, United States

San Antonio, Texas 78229, United States

Fairfax, Virginia 22030, United States

Hampton, Virginia 23666, United States

Norfolk, Virginia 23502, United States

Starting date: November 2011
Last updated: May 1, 2015