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
Condition: Anemia; Chronic Renal Insufficiency
MeSH terms: Renal Insufficiency; Renal Insufficiency, Chronic; Anemia
Intervention: HX575 recombinant human erythropoietin alfa; ERYPO
Intervention description: Solution for injection (s.c.); Solution for injection (s.c.)
Intervention MeSH terms: Epoetin Alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 337.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Treatment; associated; with CRI

Summary:

      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.
    

Eligibility criteria:

        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.