CClinicalTrials.gg
Sign In
CompletedNCT00666835Updated Jul 3, 2023Results posted

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

A Phase 3 interventional study of HX575 epoetin alfa Hexal AG and ERYPO®, Janssen-Cilag in Anemia, sponsored by Sandoz. Completed at 54 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-03.

Sponsored by Sandoz · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Registered 4 years after the study started (first participant enrolled Apr 2004, registered Apr 2008).
Phase
Phase 3
Study type
Interventional
Enrollment
478
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Anemia

Browse trials for

Keywords

  • Treatment of anemia in hemodialysis patients
03

In context

Anemia

1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.

This study's enrollment of 478 is above the median of 94 across 1,291 interventional studies indexed under Anemia.

Browse Anemia studies →

Lead sponsor

Sandoz is the lead sponsor of 136 studies on the registry; none are open to participants now.

Of its 10 completed or terminated interventional studies of FDA-regulated products, 5 (50%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
478 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugHX575 epoetin alfa Hexal AG

    HX575 Solution for i.v. injection Containing 1000, 2000 and 4000 IU of rh erythropoietin

    Also known as: Binocrit, Abseamed

  • DrugERYPO®, Janssen-Cilag

    Solution for i.v. injection

    Also known as: EPREX®, Solution for i.v. injection

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 28 weeks

Secondary outcomes

  1. 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 \[-0.5 g/dL; 0.5 g/dL\].

    Time frame: 28 weeks

07

Results

Posted Aug 2, 2017

Participant flow

A total of 568 patients were screened. 479 were eligible for inclusion and were randomized. 478 patients were started on treatment with either epoetin alfa HX575 Hexal AG or ERYPO®, Janssen-Cilag. As the randomization followed a 2:1 scheme, 314 patients received HX575 Hexal AG and 164 patients received ERYPO®.

Participant flow — Overall Study
MilestoneHX575 Epoetin Alfa Hexal AGERYPO®, Janssen-Cilag
Started314164
Completed261142
Not completed5322
Withdrew: Withdrawal by subject52
Withdrew: Lack of efficacy01
Withdrew: Incl./excl. not fulfilled72
Withdrew: Adverse event76
Withdrew: Protocol violation20
Withdrew: Death154
Withdrew: Kidney transplantation (ntx)102
Withdrew: Hemoglobulin concentration43
Withdrew: Planned operation20
Withdrew: Physician decision12

Outcome measures

PrimaryTo 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.

Time frame:
28 weeks
Reported as:
Least squares mean · g/dL
To Compare the Efficacy of HX575 Hexal AG and ERYPO® Janssen-Cilag.
g/dLHX575 Epoetin Alfa Hexal AGERYPO®, Janssen-Cilag
To Compare the Efficacy of HX575 Hexal AG and ERYPO® Janssen-Cilag.0.147 ± 0.0920.063 ± 0.117
Statistical analysis
  • HX575 Epoetin Alfa Hexal AG · Point estimate of difference (ancova): 0.084 · 95% CI -0.170 to 0.338
SecondaryMean 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 \[-0.5 g/dL; 0.5 g/dL\].

Time frame:
28 weeks
Reported as:
Least squares mean · g/dL
Mean Absolute Change in Hemoglobin Level From the Screening/Baseline Period to the Evaluation Period - ITT Population
g/dLHX575 Epoetin Alfa Hexal AGERYPO®, Janssen-Cilag
Mean Absolute Change in Hemoglobin Level From the Screening/Baseline Period to the Evaluation Period - ITT Population0.003 ± 0.079-0.187 ± 0.105
Statistical analysis
  • HX575 Epoetin Alfa Hexal AG vs ERYPO®, Janssen-Cilag · Difference lsm of epo hexal & erypo: 0.189 · 95% CI -0.039 to 0.418

Adverse events

Collected over Recording of AEs included periods before first application and until the end of application of study medication. Occurrence of AEs was recorded from time when patient had given his/her informed consent until the final visit of the main study period (visit 28). By definition, AEs starting in the period after first application until the end of the main period were considered to be 'treatment-emergent' AEs. Analysis based on safety population: patients received at least 1 dose of treatment.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
HX575 Epoetin Alfa Hexal AG19/314 (6.1%)112/314 (35.7%)283/314 (90.1%)
ERYPO®, Janssen-Cilag5/164 (3%)57/164 (34.8%)154/164 (93.9%)
Most frequent serious events
Showing 10 of 128
Most frequent serious events
EventHX575 Epoetin Alfa Hexal AGERYPO®, Janssen-Cilag
Cardiac and vascular procedural complicationsInjury, poisoning and procedural complications24/31414/164
Ischaemic coronary artery disordersCardiac disorders17/3147/164
Lower respiratory tract and lung infectionsInfections and infestations14/3145/164
Bacterial infections NECInfections and infestations8/3141/164
Peripheral vasoconstriction, necrosis and vascular insufficiencyVascular disorders8/3142/164
Sepsis, bacteraemia and viraemiaInfections and infestations7/3141/164
Rate and rhythm disorders NECCardiac disorders6/3143/164
Cholecystitis and cholelithiasisHepatobiliary disorders3/3143/164
Supraventricular arrhythmiasCardiac disorders5/3140/164
Accelerated and malignant hypertensionVascular disorders5/3141/164
Most frequent other events
Showing 10 of 17
Most frequent other events
EventHX575 Epoetin Alfa Hexal AGERYPO®, Janssen-Cilag
Muscle spasmsMusculoskeletal and connective tissue disorders77/31438/164
NasopharyngitisInfections and infestations55/31435/164
DiarrhoeaGastrointestinal disorders63/31422/164
Haemodialysis-induced symptomInjury, poisoning and procedural complications49/31423/164
HypotensionVascular disorders48/31420/164
Procedural hypotensionInjury, poisoning and procedural complications44/31423/164
BronchitisInfections and infestations28/31419/164
VomitingGastrointestinal disorders27/31418/164
NauseaGastrointestinal disorders30/31414/164
HypertensionVascular disorders29/3149/164

Baseline characteristics

All randomized patients who received at least 1 dose of the study medication and for whom at least 1 post-baseline value of the primary endpoint Hb was available. A prerequisite for patients to be included in the Intention To Treat (ITT) population is that they were treated for four weeks with Hb values available during this period.

Age, Categorical
Age, Categorical(Participants)HX575 Epoetin Alfa Hexal AGERYPO®, Janssen-CilagTotal
<=18 years000
Between 18 and 65 years14584229
>=65 years16980249
Age, Continuous
Age, Continuous(years)HX575 Epoetin Alfa Hexal AGERYPO®, Janssen-CilagTotal
Mean62.3 ± 14.462.6 ± 13.862.4 ± 14.2
Sex: Female, Male
Sex: Female, Male(Participants)HX575 Epoetin Alfa Hexal AGERYPO®, Janssen-CilagTotal
Female13898236
Male17666242
Region of Enrollment
Region of Enrollment(participants)HX575 Epoetin Alfa Hexal AGERYPO®, Janssen-CilagTotal
Austria7037107
Germany244127371
Body weight
Body weight(kg)HX575 Epoetin Alfa Hexal AGERYPO®, Janssen-CilagTotal
Mean76.3 ± 15.576.0 ± 17.776.2 ± 16.2
08

Study locations

54 sites
  • 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, Austria
  • 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, Germany
09

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 3, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00666835
Lead sponsor
Sandoz
Collaborators
Hexal AG
Responsible party
Sponsor
First posted
Apr 25, 2008
Start date
Apr 2004
Primary completion
Jan 2006
Completion
Jan 2006
Results posted
Aug 2, 2017
Last update
Jul 3, 2023

Study contacts

Marianne Haag-Weber, Prof.
principal investigator · Dialysezentrum Straubing, Germany

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Anemia→

Other studies from this sponsor

Sandoz

Start the discussion