To Evaluate the Efficacy, Safety, and Immunogenicity of Subcutaneous Eporon Versus Epoetin Alfa (Eprex)

Study Overview
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Brief Summary
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This study is to evaluate 24-week efficacy and 52 week immunogenicity of subcutaneous Eporon versus Epoetin Alfa (Eprex) in the treatment of anemia associated with chronic renal failure in pre-dialysis patients. A total of 214 patients will be enrolled in Turkey.

Official Title
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A Randomized, Active Comparator-Controlled, Parallel-Group, Single-Blind, Multicenter, Phase III Study to Evaluate the Efficacy, Safety and Immunogenicity of Subcutaneous Eporon Versus Epoetin Alfa (Eprex) in the Treatment of Anemia Associated With Chronic Renal Failure in Pre-dialysis Patients

Conditions
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Anemia of Chronic Kidney Disease

Intervention / Treatment
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* Drug: EPORON
* Drug: EPREX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Glomerular Filtration Rate <60 mL/min/1.73m2 (estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation) Hemoglobin (Hb) level in the range of ≥7 g/dL and <10 g/dL at screening Erythropoiesis Stimulating Agent (ESA) naïve subjects or previously treated subjects with ESA-free period of >3 months (in case of pre-treatment with long-acting ESA such as pegylated epoetin, the long-acting ESA-free period of >6 months) Exclusion Criteria: Subjects who have received steady dialysis or subjects who are currently on dialysis Subjects who have rapid progression of chronic renal failure (as per investigators' discretion; e.g., a GFR decrease of >20% within 12 weeks prior to screening) Subjects who have already undergone renal transplantation or who are scheduled for renal transplantation

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 74 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPORON<br><Part 1 Treatment Period> Week 1 to Week 24 Initial Phase (Week 1 to Week 4) : 50 IU/kg of Erythropoietin Alpha, three times a week (3 x 50 IU/kg/week) No dose adjustments will be permitted during the first 4 weeks of the study. Maintenance Phase (Week 5 to Week 24) The dose will be adjusted to maintain Hb levels between 10 and 12 g/dL. <Part 2 Treatment Period> : Week 25 to Week 52 The dose of Erythropoietin Alpha will be adjusted to maintain hemoglobin levels between 10 and 12 g/dL as subcutaneous administration in accordance with the given dosing algorithm. The further details are the same as those for maintenance phase of Part 1 Treatment Period. | Drug: EPORON<br>* Strength : 3000 IU/0.3 mL, 5000 IU/0.5 mL, 6000IU/0.6 mL Formulation : Solution in PFS<br>* Other names: Erythropoietin Alpha;|
| Active Comparator: EPREX<br><Part 1 Treatment Period> Week 1 to Week 24 Initial Phase (Week 1 to Week 4) : 50 IU/kg of Erythropoietin Alpha, three times a week (3 x 50 IU/kg/week) No dose adjustments will be permitted during the first 4 weeks of the study. Maintenance Phase (Week 5 to Week 24) The dose will be adjusted to maintain Hb levels between 10 and 12 g/dL. <Part 2 Treatment Period> : Week 25 to Week 52 The dose of Erythropoietin Alpha will be adjusted to maintain hemoglobin levels between 10 and 12 g/dL as subcutaneous administration in accordance with the given dosing algorithm. The further details are the same as those for maintenance phase of Part 1 Treatment Period. | Drug: EPREX<br>* Strength : 2000 IU/0.3 mL, 3000 IU/0.5 mL, 4000IU/0.6 mL Formulation : Solution in PFS<br>* Other names: Erythropoietin Alpha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Absolute Change in Hb levels | The primary endpoint is the mean absolute change in Hb levels between the screening/baseline period (Week -2 to Day 1 of Week 1) and the evaluation period (Week 21 to Week 24). Hb level at screening/baseline period is defined as the mean of the Hb measurements at screening and on Day 1 of Week 1 (prior to dosing). Hb level at evaluation period is defined as the mean of the Hb measurements at Week 21, 22, 23, and 24 (in detail, Day 1 of Week 21, Day 1 of Week 22, Day 1 of Week 23, and Day 1 of Week 24). | Week -2 Week 1 (Prior to Dose), Week 1, Week 21, Week 22, Week 23, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin Responder Rate |  | Week -2 Week 1 (Prior to Dose), Week 1, Week 21, Week 22, Week 23, Week 24 | 
| Mean EPO dosage (Week 1 to Week 24) |  | Week 1   Week 24 | 
| Mean EPO dosage (Week 21 to Week 24) |  | Week 21   Week 24 |