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

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

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.

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)