CKD-11101 Phase 3 SC Study

Study Overview
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Brief Summary
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The aim of this study was to compare and evaluate efficacy and safety of subcutaneous CKD-11101 versus Darbepoetin alfa in patients who have renal anemia not on dialysis.

Detailed Description
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This was designed as randomized, double-blind, multi-center, Phase 3 clinical study to evaluate the efficacy and safety of subcutaneous CKD-11101 versus Darbepoetin Alfa in patients who had stage 3, stage 4, and stage 5 chronic renal failure not on hemodialysis or peritoneal dialysis. The selection criteria will be evaluated in patients who are receiving anemia correction among patients with 19 years of age or older and who had anemia in chronic renal failure of stage 3 or above. Subjects who are identified to meet all inclusion criteria will be randomized to test group and control group at 1:1 ratio and go through 24-week correction period and efficacy evaluation period. During correction period and efficacy evaluation period, subjects will visit the clinical study center every 2 weeks to receive processes designated for each visit and be administered investigational product from the investigator in charge of drug administration. In the safety evaluation period, all subjects will be administered test drug for 28weeks.

Official Title
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A Randomized, Double-blind, Multi-center, Phase 3 Trial to Evaluate the Efficacy and Safety of Subcutaneous CKD-11101 Versus Darbepoetin Alfa in Patients Who Had Renal Anemia Not on Dialysis

Conditions
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Anemia of Chronic Kidney Disease

Intervention / Treatment
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* Biological: CKD-11101(Darbepoetin alfa)
* Biological: NESP(Darbepoetin alfa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients with 19 years of age or older Patients with chronic renal failure of stage 3 or above who are not on dialysis Patients with the Hb levels of 8 to 10g/dl measured at screening Patients with enough body iron stores who meet the following item: -Serum ferritin ≥ 100ng/ml or Transferrin saturation ≥ 20% Patients who have provided written consent to participate in the clinical trial voluntarily Exclusion Criteria Patients who are expected to need dialysis within a year or patients with rapidly progressive chronic renal failure Patients who have received drug treatment such as erythropoiesis stimulating agent for the purpose of correcting anemia within 12 weeks prior to screening Patients who have received red blood cell transfusion within 12 weeks prior to screening Patients with uncontrolled hypertension Patients who had hypersensitivity to erythropoietin agents Patients who had known hypersensitivity to mammalian cell-derived products or additives Patients with history of severe cardiovascular diseases Patients whose anemia is not caused by chronic renal failure or may affect anemia correction including the following conditions: Patients whose AST/ALT test results performed at screening exceeds twice of normal upper limit Patients who have experience of positive result in anti-erythropoietin antibody in previous treatment with erythropoiesis stimulating agent

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: Randomized, double-blind, multi-center, phase 3 clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CKD-11101(Darbepoetin alfa)<br>The dose of investigational product (Darbepoetin alfa) is adjusted according to the principles reflecting the MFDS (Ministry of Food and Drug Safety) approval for NESP, but is determined by the investigator's judgment considering various factors of the subjects that may affect the treatment of anemia. | Biological: CKD-11101(Darbepoetin alfa)<br> <br> |
| Active Comparator: NESP(Darbepoetin alfa)<br>The dose of investigational product (Darbepoetin alfa) is adjusted according to the principles reflecting the MFDS (Ministry of Food and Drug Safety) approval for NESP, but is determined by the investigator's judgment considering various factors of the subjects that may affect the treatment of anemia. | Biological: NESP(Darbepoetin alfa)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changed amount of mean hemoglobin level in evaluation period compared to the baseline | The equivalence test on mean hemoglobin level of test drug and reference drug administration groups in evaluation period (Weeks 20 - 24) compared to the baseline (Week 0) will be conducted. | ([Mean of hemoglobin measured in Weeks 20 - 24] - [Hemoglobin measured at Week 0]) | 
| Mean administration dose in evaluation period: Mean dose administered in Weeks 20 - 24 | The equivalence test on mean administration dose of test drug and reference drug administration groups in evaluation period (Weeks 20 - 24) will be conducted. | Weeks 20 - 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of subjects who achieve target level of hemoglobin | Ratio of subjects who achieve target level of hemoglobin: Compare the number of subjects who achieve target level of hemoglobin during the evaluation period between groups | Weeks 20 - 24 | 
| Days taken to reach target level of hemoglobin | Days taken to achieve target level of hemoglobin: Compare days taken to achieve target level of hemoglobin between groups | Days taken to reach up to 24 weeks | 
| Mean hemoglobin level for each week | Mean hemoglobin level for each week: Compare Weeks 4, 8, 12, 16, 20, 24, and 52 between groups | Weeks 4, 8, 12, 16, 20, 24, and 52 | 
| Changed amount of mean hemoglobin level at Weeks 20, 24, and 52 compared to the baseline | Compare the mean change of hemoglobin level at Weeks 20, 24, and 52 compared to the baseline | Weeks 20, 24, and 52 | 
| Ratio of subjects who receive transfusion | Ratio of subjects who receive red blood cell transfusion: Compare ratio of subjects who receive red blood cell transfusion during treatment period and evaluation period between groups | Weeks 0 - 24 |