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

Study Overview
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Brief Summary
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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®).

Official Title
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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

Conditions
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Anemia of Chronic Kidney Disease

Intervention / Treatment
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* Biological: Erythropoietin alfa


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Eprex/Erypo<br>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<br>* Prefilled syringes of erythropoietin<br>|
| Experimental: Hemax PFS<br>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<br>* Prefilled syringes of erythropoietin<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epoetin, erythropoietin, Eprex, Hemax, Anemia, Chronic Kidney Disease, pre-dialysis