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CompletedNCT04036253Updated Mar 20, 2025Results posted

Study of HEMAX PFS Versus EPREX/ ERYPO® in Predialysis Chronic Kidney Disease

A Phase 3 interventional study of Erythropoietin alfa in Anemia of Chronic Kidney Disease, sponsored by Bio Sidus SA. Completed at 11 sites in 2 countries. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2025-03-20.

Sponsored by Bio Sidus SA · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
43
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

Study summary

Phase III, multicenter, randomized, open, controlled clinical trial. A study designed as phase III, in 120 patients with chronic renal failure in the pre-dialysis stage, evaluate efficacy and safety of Hemax PFS® (PFS: prefilled syringes) vs the innovator erythropoietin alfa product (Eprex®).

Read the detailed description

This was a Phase IIIB, multicenter, randomized, open-label study to compare two products with epoetin alfa (HEMAX® PFS versus EPREX/ERYPO®).

This trial was open-label for both the patient and the investigator, but blinded in the performance of laboratory analyses.

The overall objective of the study was to evaluate the efficacy and the safety of HEMAX® PFS compared to EPREX/ERYPO®, following a dose-titration and maintenance scheme similar to the one used in the regular clinical practice.

All patients received HEMAX® PFS or EPREX/ERYPO® twice a week subcutaneously during 12 weeks of titration, switching then to an equivalent weekly dose during 12 additional maintenance weeks. During the dosing scheme switch from twice a week to once weekly, each patient continued receiving the treatment assigned at randomization.

The study conclude with n=43 patients.

02

Conditions studied

  • Anemia of Chronic Kidney Disease

Keywords

  • epoetin
  • erythropoietin
  • Eprex
  • Hemax
  • Anemia
  • Chronic Kidney Disease
  • pre-dialysis
03

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients older than 18 years
  • Patients with pre-dialysis chronic renal failure (CRF) defined by a glomerular filtration rate (calculated with the Modification of Diet in Renal Disease Study formula) ≥15 ml/ min and \<60 ml/ min, by 1.73 m2
  • Anemic patients that should be treated and levels of hemoglobin \<10.5 g/dl and ≥ 7.5 g/dl.
  • Patients that have the will and capacity to sign a written inform consent.
  • Post-menopause women for at least 2 years, or sterile by surgery for at least 6 months. Women of childbearing age must have a negative pregnancy test at baseline and be willing to get an adequate method of contraception.

Exclusion criteria

Exclusion Criteria:

  • Patients that are planned to be on dialysis or have a renal transplant in the following 6 months.
  • Transferrin iron Saturation \< 20%.
  • Etiology of renal failure (as secondary to autoimmune diseases) that, to the judge to the physician, can affect the normal development of the protocol.
  • Active bleeding or history of hemorrhage that have led to a significative decrease of hematocrit in the last 30 days.
  • Non-controlled hypertension (≥160 mm Hg of systolic pressure and/or ≥100 mm Hg of diastolic pressure with anti-hypertensive treatment).
  • Anemia caused by any other cause than renal disease.
  • Having a transfusion in the last 3 months before basal visit or during screening.
  • Treatment with an erythropoiesis stimulant in the last 3 months before basal visit or screening.
  • Increase risk of thromboembolic disease: history of arterial thromboembolia (stroke, transient ischemic attack, Acute coronary syndrome, etc.) in the last 6 months or venous in the last 12 months before screening; surgery in the last month before screening; prolong immobilization or orthopedic surgery programmed in the following 6 months or any other condition that to the judge of the investigator can increase the risk of thromboembolism.
  • Hematological disease or myelodysplastic syndrome or history of hematological neoplasm or solid tumor in the last 5 years.
  • History of congestive heart failure
  • Pregnancy or breast feeding
  • Refuse to participate in the protocol or any medical condition, that in the investigator opinion, is significant to prevent the participant from being included in the trial.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
43 participants (actual)

Study arms

  • Active comparator
    Eprex/Erypo

    Receive EPREX/ ERYPO® subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks.

    Biological: Erythropoietin alfa

  • Experimental
    Hemax PFS

    receive HEMAX® PFS subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks.

    Biological: Erythropoietin alfa

Interventions

  • BiologicalErythropoietin alfa

    Prefilled syringes of erythropoietin

05

What researchers measure

Primary outcomes

  1. Efficacy Evaluation Through Change in Hemoglobin Levels

    Evaluate the efficacy of treatment with erythropoietin alfa through the measured changes in levels of hemoglobin from baseline value to the mean value of the 8 to 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus EPREX/ ERYPO®.

    Time frame: 12 weeks of treatment

  2. Adverse Events and Adverse Reactions (Safety and Tolerability) at Weeks 12 and 24.

    Evaluate the safety through the incidence of adverse events and adverse reactions asessed after 12 and 24 weeks of treatment (week 24 reported which includes those evaluated at week 12), comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®.

    Time frame: 24 weeks of treatment

Secondary outcomes

  1. Percentage of Responder Patients

    Evaluate the efficacy of treatment with erythropoietin alfa through the percentage of responder patients (increase of Hb ≥ 1g/ dl) after 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®.

    Time frame: 12 weeks of treatment

  2. Percentage of Patients That Required Any Transfusion

    Evaluate the percentage of transfusional requirements after 12 weeks of treatment, comparing patients treated with HEMAX PFS versus those treated with EPREX/ ERYPO®.

    Time frame: 12 weeks of treatment

  3. Change of Hemoglobin Level at Week 12 of Treatment

    Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of treatment with erythropoietin alfa through the change in the level of hemoglobin from baseline in every visit until the week 12 visit.

    Time frame: Intragroup efficacy until week 12

  4. Evaluate the Efficacy Between Arms 24 Weeks: Week Doses in the Titration

    Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of the change from the twice - a - week doses in the titration phase to a weekly dose in the maintenance phase through the changes in the hemoglobin levels from week 12 to weeks 16, 20 and 24 of treatment

    Time frame: Intragroup efficacy until week 24

  5. Incidence of Anti-drug Antibodies (Immunogenicity)

    An anti-erythropoietin alfa antibody determination will be performed to evaluate treatment immunogenicity at week 12 and 24 visit

    Time frame: 12 and 24 weeks of treatment

  6. Concentration of Hepcidin

    Hepcidin will be analyzed by ELISA at baseline, week 12 and 24 in order to evaluate the treatment response.

    Time frame: 24 weeks of treatment

06

Results

Posted Mar 20, 2025

Participant flow

Participant flow — Overall Study
MilestoneEprex/ErypoHemax PFS
Started2023
Completed1620
Not completed43

Outcome measures

PrimaryEfficacy Evaluation Through Change in Hemoglobin Levels

Evaluate the efficacy of treatment with erythropoietin alfa through the measured changes in levels of hemoglobin from baseline value to the mean value of the 8 to 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus EPREX/ ERYPO®.

Time frame:
12 weeks of treatment
Reported as:
Mean · Hemoglobin levels (g/dL)
Efficacy Evaluation Through Change in Hemoglobin Levels
Hemoglobin levels (g/dL)Eprex/ErypoHemax PFS
Baseline hemoglobin levels9.56 ± 0.609.44 ± 0.81
Average hemoglobin levels between visits 8 and 1211.05 ± 0.7411.11 ± 1.11
Hemoglobin levels change between both times1.49 ± 0.991.66 ± 1.05
PrimaryAdverse Events and Adverse Reactions (Safety and Tolerability) at Weeks 12 and 24.

Evaluate the safety through the incidence of adverse events and adverse reactions asessed after 12 and 24 weeks of treatment (week 24 reported which includes those evaluated at week 12), comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®.

Time frame:
24 weeks of treatment
Reported as:
Number · Adverse Events
Adverse Events and Adverse Reactions (Safety and Tolerability) at Weeks 12 and 24.
Adverse EventsEprex/ErypoHemax PFS
Overall Adverse Events2330
Serious Events44
SecondaryPercentage of Responder Patients

Evaluate the efficacy of treatment with erythropoietin alfa through the percentage of responder patients (increase of Hb ≥ 1g/ dl) after 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®.

Time frame:
12 weeks of treatment
Reported as:
Number · percentage of participants
Percentage of Responder Patients
percentage of participantsEprex/ErypoHemax PFS
Non-Responders5.564.55
Responders94.4495.45
SecondaryPercentage of Patients That Required Any Transfusion

Evaluate the percentage of transfusional requirements after 12 weeks of treatment, comparing patients treated with HEMAX PFS versus those treated with EPREX/ ERYPO®.

Time frame:
12 weeks of treatment
Reported as:
Number · Percentage of patients
Percentage of Patients That Required Any Transfusion
Percentage of patientsEprex/ErypoHemax PFS
Percentage of Patients That Required Any Transfusion50
SecondaryChange of Hemoglobin Level at Week 12 of Treatment

Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of treatment with erythropoietin alfa through the change in the level of hemoglobin from baseline in every visit until the week 12 visit.

Time frame:
Intragroup efficacy until week 12
Reported as:
Mean · Hemoglobin levels (g/dL)
Change of Hemoglobin Level at Week 12 of Treatment
Hemoglobin levels (g/dL)Eprex/ErypoHemax PFS
Baseline9.56 ± 0.609.44 ± 0.81
Week 8 to 1211.05 ± 0.7411.11 ± 1.11
Change1.49 ± 0.991.66 ± 1.05
SecondaryEvaluate the Efficacy Between Arms 24 Weeks: Week Doses in the Titration

Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of the change from the twice - a - week doses in the titration phase to a weekly dose in the maintenance phase through the changes in the hemoglobin levels from week 12 to weeks 16, 20 and 24 of treatment

Time frame:
Intragroup efficacy until week 24
Reported as:
Mean · Hemoglobin levels (g/dL)
Evaluate the Efficacy Between Arms 24 Weeks: Week Doses in the Titration
Hemoglobin levels (g/dL)Eprex/ErypoHemax PFS
Week 1211.08 ± 0.911.16 ± 0.8
Week 1610.9 ± 0.9710.82 ± 1.12
Week 2010.51 ± 0.9010.71 ± 1.09
Week 2410.97 ± 0.9610.85 ± 1.44
SecondaryIncidence of Anti-drug Antibodies (Immunogenicity)

An anti-erythropoietin alfa antibody determination will be performed to evaluate treatment immunogenicity at week 12 and 24 visit

Time frame:
12 and 24 weeks of treatment
Reported as:
Number · Participants with positive result
Incidence of Anti-drug Antibodies (Immunogenicity)
Participants with positive resultEprex/ErypoHemax PFS
Week 1200
Week 2401
SecondaryConcentration of Hepcidin

Hepcidin will be analyzed by ELISA at baseline, week 12 and 24 in order to evaluate the treatment response.

Time frame:
24 weeks of treatment
Reported as:
Mean · ng hepcidin/ml
Concentration of Hepcidin
ng hepcidin/mlEprex/ErypoHemax PFS
Baseline84.80 ± 67.6774.21 ± 64.26
Week 12107.80 ± 96.3156.07 ± 55.62
Week 2483.60 ± 58.2960.93 ± 44.16

Adverse events

Collected over After 12 and 24 weeks of treatment. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Eprex/Erypo1/20 (5%)4/20 (20%)8/20 (40%)
Hemax PFS0/23 (0%)3/23 (13%)5/23 (21.7%)
Most frequent serious events
Most frequent serious events
EventEprex/ErypoHemax PFS
Urinary tract infectionRenal and urinary disorders0/202/23
SepsisInfections and infestations1/200/23
Gastrointestinal angiodysplasiaGastrointestinal disorders1/200/23
Worsening of renal functionRenal and urinary disorders1/200/23
Worsened conditionGeneral disorders1/200/23
Foot ulcerVascular disorders0/201/23
Most frequent other events
Showing 10 of 32
Most frequent other events
EventEprex/ErypoHemax PFS
Increased blood pressureCardiac disorders3/203/23
Lower limb edemaCardiac disorders0/202/23
Increased lipidsMetabolism and nutrition disorders0/202/23
Acute bronchitisInfections and infestations0/202/23
HypervolemiaCardiac disorders1/200/23
HypotensionCardiac disorders1/200/23
Acute diarrheaGastrointestinal disorders1/200/23
DyspepsiaGastrointestinal disorders1/200/23
SplenomegalyBlood and lymphatic system disorders1/200/23
Increased creatinine levelsMetabolism and nutrition disorders1/200/23

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Eprex/ErypoHemax PFSTotal
<=18 years000
Between 18 and 65 years202343
>=65 years000
Age, Continuous
Age, Continuous(years)Eprex/ErypoHemax PFSTotal
Median60.5 (20 to 80)64 (18 to 83)61 (18 to 83)
Sex: Female, Male
Sex: Female, Male(Participants)Eprex/ErypoHemax PFSTotal
Female151732
Male5611
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Eprex/ErypoHemax PFSTotal
Hispanic or Latino202343
Not Hispanic or Latino000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Eprex/ErypoHemax PFSTotal
Argentina172239
Paraguay314
Hemoglobin blood level
Hemoglobin blood level(g/dL)Eprex/ErypoHemax PFSTotal
Mean9.56 ± 0.609.44 ± 0.819.50 ± 0.72
07

Study locations

11 sites
  • CEMEDIC
    Buenos Aires, Argentina
  • CEREHA
    Buenos Aires, Argentina
  • CIMEL
    Buenos Aires, Argentina
  • CIPREC (Centro de Investigación y Prevención Cardiovascular)
    Caba, Argentina
  • GEMA Consultorio
    Caba, Argentina
  • Hospital Argerich
    Caba, Argentina
  • Hospital Británico de Buenos Aires
    Caba, Argentina
  • Hospital Durand
    Caba, Argentina
  • Hospital Fernandez
    Caba, Argentina
  • Hospital Ramos Mejía
    Caba, Argentina
  • IPHIC
    Asunción, Paraguay
08

References and documents

Study documents

  • Study protocol · Jun 26, 2018
  • Statistical analysis plan · Mar 31, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT04036253
Lead sponsor
Bio Sidus SA
Responsible party
Sponsor
First posted
Jul 29, 2019
Start date
Feb 28, 2018
Primary completion
Jun 15, 2021
Completion
Aug 31, 2021
Results posted
Mar 20, 2025
Last update
Mar 20, 2025

Study contacts

Diego Ambrogetti, MD
principal investigator · Instituto de Investigaciones médicas Alfredo Lanari

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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