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

A Randomized, Comparative Study of HEMAX PFS® Versus EPREX/ ERYPO® in the Treatment of Anemia With Epoetin Alfa in Patients With Predialysis Chronic Kidney Disease

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®).

Study Overview

• Status: Unknown
• Conditions: Anemia of Chronic Kidney Disease
• Intervention / Treatment: Biological: Erythropoietin alfa

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Prefilled syringes of erythropoietin
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; Prefilled syringes of erythropoietin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Evaluation through the increase of Hemoglobin levels	Evaluate the efficacy of treatment with erythropoietin alfa through increased 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®.	12 weeks of treatment
Adverse Events and Adverse Reactions (safety and tolerability) at week 12	Evaluate the safety through the incidence of adverse events and adverse reactions after 12 and 24 weeks of treatment, comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®.	12 weeks of treatment
Adverse Events and Adverse Reactions (safety and tolerability) at week 24	Evaluate the safety through the incidence of adverse events and adverse reactions after 12 and 24 weeks of treatment, comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®.	24 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of responders 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®.	12 weeks of treatment
Percentage of patients that required any Transfusion	Evaluate the percentage of transfusional requirement after 12 weeks of treatment, comparing patients treated with HEMAX PFS versus those treated with EPREX/ ERYPO®.	12 weeks of treatment
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.	Intragroup efficacy until week 12
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	Intragroup efficacy until week 24
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	12 and 24 weeks of treatment
Concentration of Hepcidin	Hepcidin will be analyzed by ELISA at baseline, week 12 and 24 in order to evaluate the treatment response.	24 weeks of treatment

Collaborators and Investigators

• Sponsor: Bio Sidus SA

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 28, 2018
• Primary Completion (ANTICIPATED): July 30, 2021
• Study Completion (ANTICIPATED): January 30, 2022

Study Registration Dates

• First Submitted: July 12, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (ACTUAL): July 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Anemia; Chronic Kidney Disease; erythropoietin; Eprex; epoetin; pre-dialysis; Hemax
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: BIOS-HPFS-0115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No