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

Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00666835
• Other study ID #: 2003-29-INJ-9
• Status: Completed
• Phase: Phase 3
• Start date: April 2004
• Est. completion date: January 2006

Study information

• Verified date: June 2023
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 478
• Est. completion date: January 2006
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia

Intervention

Drug:
• HX575 epoetin alfa Hexal AG
HX575 Solution for i.v. injection Containing 1000, 2000 and 4000 IU of rh erythropoietin
• ERYPO®, Janssen-Cilag
Solution for i.v. injection

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Feldkirch	Feldkirch
Austria	Allgemeines Krankenhaus der Barmherzigen Brüder Graz	Graz
Austria	Dialyseinstitut Graz GmbH	Graz
Austria	Krankenhaus der Elisabethinen	Graz
Austria	Universitätsklinik Innsbruck, Klinische Abteilung für Nephrologie	Innsbruck
Austria	Allgemeines Öffentliches Krankenhaus St. Pölten, I. Med. Abteilung	St. Poelten
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	Vienna
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Aschaffenburg
Germany	Dialysepraxis Bad Münder	Bad Münder
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	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	Dialysepraxis Drs. Riedasch/Schreiber	Coesfeld
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Deggendorf
Germany	Dialysepraxis	Donaueschingen
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Eberswalde
Germany	Dialysepraxis Dr. med. Stefan Holzmann	Erkelenz
Germany	Dialysepraxis Dr. Möller, Dr. Knee	Essen
Germany	Dialysepraxis	Freiberg
Germany	Dialysezentrum	Freiburg
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	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	Praxis Dres. Sohn und Schaumann	Hameln
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Hannover
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Haßfurt
Germany	Dialysepraxis Dr. med. Stefan Holzmann	Heinsberg
Germany	Praxis Dr. Kienle	Homberg
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Ingolstadt
Germany	KfH - Prof. Dr. med. Heide Sperschneider	Jena
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Kronach
Germany	Dialysepraxis Dr. med. Matthias Anders	Leipzig
Germany	Kfh Kuratorium für Dialyse & Nierentransplantation e.V., 2.Etage	Leipzig
Germany	KfH Kuratorium für Nierentranplantation und Dialyse e.V.	Lohr
Germany	Dialysepraxis Prof. Rob, Dr. Wilhelm u. Dr. Schümann	Luebeck
Germany	Dialysepraxis Dr.med. H.-D. Hoffmann	Menden
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Muenchen
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Neuried
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Noerdlingen
Germany	Gemeinschaftspraxis Dr.Steger, Dr.Böhmer, Dr.Kirpal	Nuremberg
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Oberschleißheim
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Plauen
Germany	Dialysezentrum	Potsdam
Germany	Praxis Dres.Hartmann, Schiele	Saarbruecken
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Straubing
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V	Sulzbach-Rosenberg

Sponsors (2)

Lead Sponsor	Collaborator
Sandoz	Hexal AG

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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