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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Anemia

Intervention / Treatment
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* Drug: HX575 epoetin alfa Hexal AG
* Drug: ERYPO®, Janssen-Cilag


Participation Criteria
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Eligibility Criteria
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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

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: HX575 epoetin alfa Hexal AG<br>Eligible patients were switched from the comparator ERYPO®, to epoetin alfa HX575 Hexal AG in ratio 2:1 to be intravenously treated with HX575 in pre-filled syringes for 24 weeks (solution for injection i.v.). The maximum weekly dose was 300 UI/kg body weight (given 1 to 3 times) to maintain hemoglobin levels between 10-13 g/dL. | Drug: HX575 epoetin alfa Hexal AG<br>* HX575 Solution for i.v. injection Containing 1000, 2000 and 4000 IU of rh erythropoietin<br>* Other names: Binocrit, Abseamed;|
| Active Comparator: ERYPO®, Janssen-Cilag<br>Eligible patients were randomized and continued to be treated with ERYPO® Janssen-Cilag in pre-filled syringes intravenously (solution for injection i.v.) for 24 weeks. The maximum weekly dose was 300 UI/kg body weight (given 1 to 3 times) to maintain hemoglobin levels between 10-13 g/dL. | Drug: ERYPO®, Janssen-Cilag<br>* Solution for i.v. injection<br>* Other names: Solution for i.v. injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Compare the Efficacy of HX575 Hexal AG and ERYPO® Janssen-Cilag. | Primary endpoint was the mean absolute change in Hb level between the screening/baseline and the evaluation period. A two-sided 95 % confidence interval for the difference in mean change (mean of evaluation period - mean of screening/baseline period) in Hb between epoetin alfa HX575 Hexal AG and ERYPO® Janssen-Cilag was computed. The difference was estimated from an analysis of a co-variance model including factors treatment, center, mean baseline Hb (<11.5 and ≥11.5 g/dL) as factors and change of the mean weekly dose from screening/baseline to the evaluation period (of HX575 epoetin alfa Hexal AG or ERYPO® Janssen-Cilag) as a covariate. HX575 Hexal AG was considered at least as good as ERYPO® Janssen-Cilag if the 95 % confidence interval of the difference in mean changes in Hb levels between HX575 Hexal AG and ERYPO® Janssen-Cilag lied entirely within the interval [-0.5 g/dL; 0.5 g/dL]. Primary Endpoint was analyzed based on intent-to-treat (ITT) population. | 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Absolute Change in Hemoglobin Level From the Screening/Baseline Period to the Evaluation Period - ITT Population | The mean absolute change in Hb levels between the screening/baseline period and the evaluation period was analyzed for the intent-to-treat (ITT) population in the same way as the primary efficacy endpoint. A two-sided 95 % confidence interval for the difference in mean change (mean of evaluation period - mean of screening/baseline period) in Hb between HX575 epoetin alfa Hexal AG and ERYPO® Janssen-Cilag was computed. The difference was estimated from an analysis of a co-variance model including factors treatment, center, mean baseline Hb (<11.5 and ≥11.5 g/dL) as factors and change of the mean weekly dose from screening/baseline to the evaluation period (of HX575 epoetin alfa Hexal AG or ERYPO® Janssen-Cilag) as a covariate. HX575 Hexal AG was considered at least as good as ERYPO® Janssen-Cilag if the 95 % confidence interval of the difference in mean changes in Hb levels between HX575 Hexal AG and ERYPO® Janssen-Cilag lied entirely within the interval [-0.5 g/dL; 0.5 g/dL]. | 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment of anemia in hemodialysis patients