Study to Evaluate the Efficacy and Safety of HX575 Hexal AG vs ERYPO® for the Treatment of Anemia in Hemodialysis Patients

Randomized, Double-blind, Multicenter, Parallel-group, Equivalence Study to Evaluate the Efficacy and Safety of HX575 Hexal AG vs ERYPO® for the Treatment of Anemia in Hemodialysis Patients

This is a double-blind, randomized, multicenter, parallel-group, equivalence study involving about 462 clinically stable hemodialysis patients aged 18 years or above suffering from anemia and treated previously with a stable dose of ERYPO® intravenously.

The primary objective of this Phase III study is the evaluation of therapeutic equivalence of HX575 Hexal AG and a comparator of epoetin alfa, ERYPO® in the maintenance intravenous treatment of renal anemia. Efficacy, dosage and safety of HX575 Hexal AG in the long-term treatment were assessed.

Inclusion Criteria:

• Receiving dialysis for at least 6 months (3 times weekly) before screening
• Age: >=18
• Clinically stable, i.e. hemoglobin within the established range (10.0 to 13.0 g/dl) for at least 12 weeks before screening
• Stable intravenous dosage of ERYPO® three times weekly for at least 8 weeks before screening and during screening with a maximal weekly dosage of 300 IU/kg body weight (stable is defined as <25% change (up or down) in weekly dose and no change in frequency over 8 weeks prior screening and 10 weeks prior randomisation)
• Baseline hemoglobin concentration of 10.0 to 13.0 g/dl (mean of two pre-randomization pre-dialysis samples of Hb at visit -2 and visit 1)
• Serum ferritin >=100 µg/l and/or saturated transferrin levels >=20%
• C-reactive protein <15 mg/l (< 5 mg/l: normal; >= 5 mg/l < 10 mg/l: +; >=10mg/l < 100 mg/l: ++; >=100 mg/l: +++)
• Ability to follow study instructions and likely to complete all required visits
• Written informed consent of the patient

Exclusion Criteria:

• Anemia of non-renal causes
• Primary hematologic disorder (e.g. myelodysplastic syndrome, sickle cell anemia, hematological malignancy, hemolytic anemia)
• Evidence of severe hepatic dysfunction (ALT and/or AST above 2 x upper limit of normal range; or gamma-GT above 3 x upper limit of normal range)
• Clinical evidence of current uncontrolled hyperparathyroidism (serum parathyroid hormone >1500 pg/mL).
• Known history of bone marrow disease
• Any red blood cell transfusion(s) during the last 12 weeks before screening or during the screening/baseline period
• Insufficient concomitant iron treatment during the last 2 months before Visit -2
• Uncontrolled hypertension, defined as a predialysis diastolic blood pressure measurement >=110 mmHg during the screening period
• Congestive heart failure [New York Heart Association (NYHA) class III and IV]
• Unstable angina pectoris, active cardiac disease, cardiac infarction during the last six months before screening
• History of blood coagulation disease
• Thrombocytopenia (platelet count <100.000/µl)
• Leukopenia (white blood cell count < 2.000/µl)
• Overt bleeding (acute or chronic bleeding within 2 months of inclusion) or hemolysis
• Evidence of acute infectious disease or serious active inflammatory states within one months before screening (Visit -2) or during the screening/baseline period
• Suspicion or known PRCA (pure red cell aplasia)
• Previously diagnosed HIV or acute hepatitis infection
• Treatment for epilepsy within the past 6 months
• Planned surgery during the next 7 months (except vascular access surgery)
• Any androgen therapy within 2 months before visit -2 and during the study
• Therapy with immunosuppressants or any drug known to affect the hematocrit within 1 month before Visit -2 and during the study
• Clinical evidence of malignant diseases
• Pregnancy, breastfeeding women or women not using adequate birth control measures
• Known history of severe drug related allergies
• Known allergy to one of the ingredients of the test or reference products or hypersensitivity to mammalian-derived products
• Simultaneous participation in another clinical study or participation in a study in the month preceding the start of this study or previously randomized in this study
• Participation in an erythropoietin study in the 3 months preceding screening (visit -2)
• Any other condition which at the investigator´s discretion may put the patient at risk or which may confound the study results