Study to Evaluate the Efficacy and Safety of GX-E2 in the Anemic Patients Diagnosed With Chronic Kidney Disease (CKD)

Study Overview
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Brief Summary
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The primary objective of study is Part A : To explore the optimal fixed starting dose and dosing interval of GX-E2 Part B : To evaluate the proof of concept (POC) of GX-E2

Detailed Description
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The secondary objective of study is to evaluate: change of red blood cell indices in anemic patients with chronic kidney disease receiving hemodialysis/peritoneal dialysis when administering GX-E2 intravenously/subcutaneously change of reticulocyte indices in anemic patients with chronic kidney disease receiving hemodialysis/peritoneal dialysis when administering GX-E2 intravenously/subcutaneously safety of GX-E2 when administering intravenously/subcutaneously incidence of blood transfusion in anemic patients with chronic kidney disease receiving hemodialysis/peritoneal dialysis when administering GX-E2 intravenously/subcutaneously Immunogenicity in anemic patients with chronic kidney disease receiving hemodialysis/peritoneal dialysis when administering GX-E2 intravenously/subcutaneously

Official Title
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Phase II Clinical Trial to Explore the Optimal Fixed Starting Dose & Dosing Interval and to Evaluate the Safety of GX-E2 in the Anemic Patients Diagnosed With Chronic Kidney Disease and Receiving Hemodialysis (HD) / Peritoneal Dialysis (PD)

Conditions
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Anemia, Chronic Kidney Disease

Intervention / Treatment
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* Drug: GX-E2
* Drug: GX-E2
* Drug: GX-E2
* Drug: NESP
* Drug: MIRCERA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent ≥18 yr of age Chronic Kidney diseases with hemodialysis, peritoneal dialysis with Kt/V ≥ 1.2 (hemodialysis) or Kt/V ≥ 1.7 (peritoneal dialysis) within a year Adequate transferrin saturation (≥20%), serum ferritin (≥100ug/L) Should have received Vitamine B12 ≥ 3 months before the first dose of study agent Should have received Folate ≥3 months before the first dose of study agent No erythropoietin (EPO) therapy within 2 months before the planned first dose of GX-E2 and Hb<10g/dL or No EPO therapy within a month (peritoneal dialysis) or 2 weeks (hemodialysis) before the planned first dose of GX-E2 and Hb<10g/dL. Exclusion Criteria: Refractory to erythropoiesis stimulating agent (ESA) treatment History of blood transfusion within 3 months Donation or loss of blood for more than 400 milliliters (mL) within 8 weeks History of a known or suspected hypersensitivity, shock, or past history to the investigational drug or to similar ESA drugs Acute or chronic organ seizure disorder (including asthma and chronic obstructive pulmonary disease) which may be clinically deteriorated by the drug administration Active infection or history of infection that required intravenous injection of antibiotics in the last two months Grand Mal epilepsy Major surgery within 3 months other than access surgery Malignant tumor within 5 years other than successfully treated skin cancer that is not melanoma Ischemic stroke within 3 years Chest x-ray findings determined that they cannot participate in the study for clinically abnormal findings by the baseline chest x-ray findings or previously taken chest x-ray findings Uncontrolled hypertension Congestive heart failure more severe than NYHA functional class III; unstable Coronary artery disease (CAD); myocardial infraction within 3 months Uncontrolled arrhythmia High risk of thrombosis and embolism Systemic blood diseases (e.g. Pure red cell anemia, sickle cell anemia, myelodysplastic syndromes, hematologic malignancy, myeloma, hemolytic anemia) Absolute neutrophil count below 1,500 per microliter (uL) within screening periods Platelet count less than 5e10 per liter (L) within screening periods Hyperparathyrodism / hypothyrodism Splenomegaly caused by anemia or severe splenomegaly (>20cm) Blood aspartate aminotransferase/alanine aminotransferase (ALT/AST) concentration exceeds three times Upper Normal Limit of Normal (UNL) Blood total bilirubin concentration exceeds 1.5 times Upper Normal Limit of Normal (UNL) Blood albumin concentration below 3g per deciliter (dl) History of drug or alcohol abuse in the 6 months prior to the screening History of psychotropic or narcotic analgesic drugs dependence within 6 months prior to the screening Mental disorder or other central nervous system disorder determined that the study evaluation cannot be conducted Lack of understanding of the study and cooperation (one with no intention to give efforts to perform each evaluation visit and extend previously planned elective surgery) Female subjects with childbearing potential who are pregnant, breastfeeding or intends to become pregnant Participation in any drug study within 30 days prior to dosing Any other ineligible condition at the direction of the investigator that would be ineligible to participate the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Group A (Part A)<br>GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 3ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=10) will be administered GX-E2 3ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group B (Part A)<br>GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 5ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=10) will be administered GX-E2 3ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group C (Part A)<br>GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 8ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=10) will be administered GX-E2 3ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group D (Part A)<br>GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 3ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=10) will be administered GX-E2 3ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group E (Part A)<br>GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 5ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=10) will be administered GX-E2 3ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group F (Part A)<br>GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 8ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=10) will be administered GX-E2 3ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group G (Part B)<br>GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 5ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=24) will be administered GX-E2 5ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group H (Part B)<br>GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 8ug/kg | Drug: GX-E2<br>* Each Group of Peritoneal dialysis patients (n=24) will be administered GX-E2 5ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Active Comparator: Group I (Part B)<br>MIRCERA : Subcutaneously injection every 2 weeks (Q2W) at dose 0.6ug/kg | Drug: MIRCERA<br>* Each Group of Peritoneal dialysis (n=24) will be administered MIRCERA 0.6ug/kg<br>* Other names: Methoxy Polyethylene glycol-epoetin beta;|
| Experimental: Group J (Part B)<br>GX-E2 : Intravenously injection every week (Q1W) at dose 5ug/kg | Drug: GX-E2<br>* Each Group of Hemodialysis patients (n=30) will be administered GX-E2 5ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group K (Part B)<br>GX-E2 : Intravenously injection every week (Q1W) at dose 8ug/kg | Drug: GX-E2<br>* Each Group of Hemodialysis patients (n=30) will be administered GX-E2 5ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Experimental: Group L (Part B)<br>GX-E2 : Intravenously injection every 2 weeks (Q2W) at dose 8ug/kg | Drug: GX-E2<br>* Each Group of Hemodialysis patients (n=30) will be administered GX-E2 5ug/kg to 8ug/kg<br>* Other names: GC1113;|
| Active Comparator: Group M (Part B)<br>NESP : Intravenously injection every week (Q1W) at dose 30ug | Drug: NESP<br>* Each Group of Hemodialysis (n=30) will be administered NESP 30ug<br>* Other names: Darbepoetin alfa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| average change of Hemoglobin level | change from baseline in Hemoglobin level | 6 weeks (Part A) & 14 weeks (Part B) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of red blood cell indices | change from baseline in red blood cell indices | 6 weeks (Part A) & 14 weeks (Part B) | 
| change of reticulocyte indices | change from baseline in reticulocyte indices | 6 weeks (Part A) & 14 weeks (Part B) | 
| incidence, degree, outcome of adverse event | Incidence of adverse events | 6 weeks (Part A) & 14 weeks (Part B) | 
| incidence, frequency, amount of blood transfusion | Incidence of adverse events | 6 weeks (Part A) & 14 weeks (Part B) | 
| immunogenicity: ratio of neutralizing antibody & binding antibody in subjects | comparison from pre-treatment to post-treatment | 6 weeks (Part A) & 14 weeks (Part B) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 2