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.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Drug: HX575 epoetin alfa Hexal AG; Drug: ERYPO®, Janssen-Cilag

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 Type: Interventional
• Enrollment (Actual): 478
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria
    • Landeskrankenhaus Feldkirch
  • Graz, Austria
    • Allgemeines Krankenhaus der Barmherzigen Brüder Graz
  • Graz, Austria
    • Dialyseinstitut Graz GmbH
  • Graz, Austria
    • Krankenhaus der Elisabethinen
  • Innsbruck, Austria
    • Universitätsklinik Innsbruck, Klinische Abteilung für Nephrologie
  • St. Poelten, Austria
    • Allgemeines Öffentliches Krankenhaus St. Pölten, I. Med. Abteilung
  • Vienna, Austria
    • Allgemeines öffentliches Krankenhaus Wiener Neustadt , 2. Interne Abteilung
  • Vienna, Austria
    • Krankenanstalt Rudolfstiftung der Stadt Wien, 3. Med. Abteilung
  • Vienna, Austria
    • Wilhelminenspital der Stadt Wien, Abt. für Nephrologie und Dialyse
• Germany
  • Aschaffenburg, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Bad Münder, Germany
    • Dialysepraxis Bad Münder
  • Bad Nauheim, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Bamberg, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Bayreuth, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Bergisch Gladbach, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Berlin, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Bischofswerda, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V.
  • Bremerhaven, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V.
  • Coburg, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V.
  • Coesfeld, Germany
    • Dialysepraxis Drs. Riedasch/Schreiber
  • Deggendorf, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Donaueschingen, Germany
    • Dialysepraxis
  • Eberswalde, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Erkelenz, Germany
    • Dialysepraxis Dr. med. Stefan Holzmann
  • Essen, Germany
    • Dialysepraxis Dr. Möller, Dr. Knee
  • Freiberg, Germany
    • Dialysepraxis
  • Freiburg, Germany
    • Dialysezentrum
  • Fürstenzell, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Greifswald, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Guenzburg, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Gummersbach, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Hameln, Germany
    • Praxis Dres. Sohn und Schaumann
  • Hannover, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Haßfurt, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Heinsberg, Germany
    • Dialysepraxis Dr. med. Stefan Holzmann
  • Homberg, Germany
    • Praxis Dr. Kienle
  • Ingolstadt, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Jena, Germany
    • KfH - Prof. Dr. med. Heide Sperschneider
  • Kronach, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Leipzig, Germany
    • Dialysepraxis Dr. med. Matthias Anders
  • Leipzig, Germany
    • Kfh Kuratorium für Dialyse & Nierentransplantation e.V., 2.Etage
  • Lohr, Germany
    • KfH Kuratorium für Nierentranplantation und Dialyse e.V.
  • Luebeck, Germany
    • Dialysepraxis Prof. Rob, Dr. Wilhelm u. Dr. Schümann
  • Menden, Germany
    • Dialysepraxis Dr.med. H.-D. Hoffmann
  • Muenchen, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Neuried, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Noerdlingen, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Nuremberg, Germany
    • Gemeinschaftspraxis Dr.Steger, Dr.Böhmer, Dr.Kirpal
  • Oberschleißheim, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Plauen, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V.
  • Potsdam, Germany
    • Dialysezentrum
  • Saarbruecken, Germany
    • Praxis Dres.Hartmann, Schiele
  • Straubing, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V
  • Sulzbach-Rosenberg, Germany
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: HX575 epoetin alfa Hexal AG; HX575 Solution for i.v. injection Containing 1000, 2000 and 4000 IU of rh erythropoietin; Other Names: Binocrit, Abseamed
Active Comparator: 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.	Drug: ERYPO®, Janssen-Cilag; Solution for i.v. injection; Other Names: EPREX®; Solution for i.v. injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sandoz
• Collaborators: Hexal AG
• Investigators: Principal Investigator: Marianne Haag-Weber, Prof., Dialysezentrum Straubing, Germany

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2004
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: April 23, 2008
• First Submitted That Met QC Criteria: April 24, 2008
• First Posted (Estimated): April 25, 2008

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Treatment of anemia in hemodialysis patients
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: 2003-29-INJ-9

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED