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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Anemia, Chronic Renal Insufficiency

Intervention / Treatment
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* Drug: HX575 recombinant human erythropoietin alfa
* Drug: ERYPO


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>HX575, EPO HEXAL | Drug: HX575 recombinant human erythropoietin alfa<br>* Solution for injection (s.c.)<br>|
| Active Comparator: 2<br>ERYPO | Drug: ERYPO<br>* Solution for injection (s.c.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin Level | Mean absolute change in hemoglobin (baseline to end of study week 13) | 13 weeks | 
| Weekly Epoetin Dose | Mean weekly epoetin dose [IU/kg] in study weeks 11-13 | weeks 11-13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Number of participants with antibody formation against Epoetin during treatment period (safety set) | 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, associated, with CRI