Randomized, Controlled, Double-blind Multicenter Safety Study to Evaluate the Safety and Immunogenicity of Subcutaneous EPO HEXAL vs. ERYPO® in the Treatment of Anemia Associated With Chronic Renal Insufficiency in Predialysis Patients

Randomized, Controlled, Double-blind Multicenter Safety Study to Evaluate the Safety and Immunogenicity of Subcutaneous EPO HEXAL vs. ERYPO® in the Treatment of Anemia Associated With Chronic Renal Insufficiency in Predialysis Patients

This is a randomized, controlled, double-blind, multicenter multinational safety study involving about 300 predialysis patients aged 18 years or above suffering from anemia.

Symptomatic anemia will be corrected by s.c. application of EPO HEXAL or ERYPO® in order to achieve a hemoglobin target range of 10.0 -12.0 g/dL.

Inclusion Criteria:

• Known chronic renal insufficiency of at least 4 weeks duration; CKD stage at least 3 or higher
• Male and female patients, age: >=18
• Patients who are naïve to ESA treatment or previously ESA treated after 3 months of ESA-free period (i.v. or s.c.)
• Patients with symptomatic anemia, defined as Hb level below 11.0 g/dL and not lower than or equal to 7.5 g/dL on at least 2 visits during the screening period
• Adequate iron status, serum ferritin >= 100 µg/L or transferrin saturation >= 20%
• Ability to follow study instructions and likely to complete all required visits and compliant with subcutaneous administration
• Written informed consent of the patient.

Exclusion Criteria:

• Anemia of non-renal causes
• Therapy with immunosuppressants (other than corticosteroids for chronic treatment) within 3 months before screening and during the study for patients with renal allograft in place or other chronic conditions (e.g. lupus erythematosus, rheumatic arthritis)
• Patients previously treated with chronic dialysis within the last 6 months (exception: one session of acute dialysis)
• Patients with acute deterioration of renal function during the screening phase according to the investigator's judgment
• Patients receiving any RBC/whole blood transfusion during the screening period
• Primary hematological disorder (e.g. myeloma, myelodysplastic syndrome, sickle cell anemia, hematological malignancy, hemolytic anemia)
• Evidence of uncontrolled diabetes mellitus (HbA1c > 10 % at visit -2)
• Evidence of severe hepatic dysfunction (e.g. ALT and/or AST above 2x upper limit of normal range; or gamma-GT above 3x upper limit of normal range)
• Clinical evidence of current uncontrolled or symptomatic hyperparathyroidism, defined as parathyroid hormone > 500 ng/L at visit -2.
• Uncontrolled hypertension, defined as a systolic blood pressure of >= 160 mmHg and a diastolic blood pressure measurement >= 100 mmHg (average of two values with at least one day between measurements)
• Congestive heart failure and/or angina pectoris [New York Heart Association (NYHA) class III and IV]
• History of stroke or myocardial infarction during the last 6 months prior to visit -2
• Ongoing treatment with phenprocoumon or other cumarin derivates
• Thrombocytopenia (platelet count <100.000/µL) or leucopenia (white blood cell count < 2.000/µL)
• Gastrointestinal bleeding within the last 6 months prior to visit -2 or hemolysis
• Evidence of acute or chronic infection by a C-reactive protein value of > 30 mg/L
• Suspicion or known PRCA (pure red cell aplasia)
• Previously diagnosed HIV or acute hepatitis infection
• History of epilepsy or epileptic seizures or treatment for epilepsy within the past 6 months prior to screening
• Planned major surgery (with expected high blood loss) during the next 3 months or major surgery within the previous 3 months (except laser photocoagulation, access surgery)
• Clinical evidence of active malignant diseases within the last 5 years (except non-melanoma skin cancer)
• Pregnancy, breastfeeding women or women not using a highly effective birth control method (e.g. implants, injectables, combined oral contraceptives, IUD, sexual abstinence, vasectomised partner)
• Known history of severe drug related allergies (e.g. anaphylactic shock)
• Known allergy to one of the ingredients of the test product or hypersensitivity to mammalian-derived products
• Known or suspicion of any non-compliance with respect to subcutaneous treatment
• Simultaneous participation in another clinical study or participation in a study in the month preceding visit-2 or previously randomized in this study
• Participation in another ESA study in the 3 months preceding visit -2
• Any other condition which at the investigator's discretion may put the patient at risk or which may confound the study results.