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

Phase 3

Completed

• Conditions: Anemia
• Interventions: Drug: HX575 epoetin alfa Hexal AG; Drug: ERYPO®, Janssen-Cilag

• Registration Number: NCT00666835
• Lead Sponsor: Sandoz

Brief Summary

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

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.

Study Timeline

• Study Start: 2004-04
• Primary Completion: 2006-01
• Study Completion: 2006-01
• Study First Submitted: 2008-04-23
• Study First Submitted QC: 2008-04-24
• Study First Posted: 2008-04-25
• Results First Submitted: 2017-04-24
• Results First Submitted QC: 2017-04-24
• Results First Posted: 2017-08-02
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-29
• Last Update Posted: 2023-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 478

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HX575 epoetin alfa Hexal AG	HX575 epoetin alfa Hexal AG	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.
ERYPO®, Janssen-Cilag	ERYPO®, Janssen-Cilag	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.

Primary Outcome Measures

Name	Time	Method
To Compare the Efficacy of HX575 Hexal AG and ERYPO® Janssen-Cilag.	28 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Mean Absolute Change in Hemoglobin Level From the Screening/Baseline Period to the Evaluation Period - ITT Population	28 weeks	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 \[-0.5 g/dL; 0.5 g/dL\].

Trial Locations

Locations (27)

Allgemeines Krankenhaus der Barmherzigen Brüder Graz; 🇦🇹 Graz, Austria

Dialyseinstitut Graz GmbH; 🇦🇹 Graz, Austria

Universitätsklinik Innsbruck, Klinische Abteilung für Nephrologie; 🇦🇹 Innsbruck, Austria

Allgemeines Öffentliches Krankenhaus St. Pölten, I. Med. Abteilung; 🇦🇹 St. Poelten, Austria

Wilhelminenspital der Stadt Wien, Abt. für Nephrologie und Dialyse; 🇦🇹 Vienna, Austria

Krankenanstalt Rudolfstiftung der Stadt Wien, 3. Med. Abteilung; 🇦🇹 Vienna, Austria

Dialysepraxis Drs. Riedasch/Schreiber; 🇩🇪 Coesfeld, Germany

Krankenhaus der Elisabethinen; 🇦🇹 Graz, Austria

Allgemeines öffentliches Krankenhaus Wiener Neustadt , 2. Interne Abteilung; 🇦🇹 Vienna, Austria

KfH Kuratorium für Dialyse und Nierentransplantation e.V; 🇩🇪 Sulzbach-Rosenberg, Germany

Praxis Dres. Sohn und Schaumann; 🇩🇪 Hameln, Germany

Praxis Dres.Hartmann, Schiele; 🇩🇪 Saarbruecken, Germany

Dialysepraxis; 🇩🇪 Freiberg, Germany

KfH Kuratorium für Nierentranplantation und Dialyse e.V.; 🇩🇪 Lohr, Germany

Dialysepraxis Prof. Rob, Dr. Wilhelm u. Dr. Schümann; 🇩🇪 Luebeck, Germany

Gemeinschaftspraxis Dr.Steger, Dr.Böhmer, Dr.Kirpal; 🇩🇪 Nuremberg, Germany

Kfh Kuratorium für Dialyse & Nierentransplantation e.V., 2.Etage; 🇩🇪 Leipzig, Germany

Dialysepraxis Dr.med. H.-D. Hoffmann; 🇩🇪 Menden, Germany

Dialysepraxis Bad Münder; 🇩🇪 Bad Münder, Germany

Landeskrankenhaus Feldkirch; 🇦🇹 Feldkirch, Austria

KfH Kuratorium für Dialyse und Nierentransplantation e.V.; 🇩🇪 Plauen, Germany

KfH - Prof. Dr. med. Heide Sperschneider; 🇩🇪 Jena, Germany

Praxis Dr. Kienle; 🇩🇪 Homberg, Germany

Dialysepraxis Dr. med. Stefan Holzmann; 🇩🇪 Heinsberg, Germany

Dialysepraxis Dr. Möller, Dr. Knee; 🇩🇪 Essen, Germany

Dialysezentrum; 🇩🇪 Potsdam, Germany

Dialysepraxis Dr. med. Matthias Anders; 🇩🇪 Leipzig, Germany