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

Genexine

Status and phase: Completed; Phase 2

Conditions: Chronic Kidney Disease; Anemia

Treatments: Drug: NESP; Drug: MIRCERA; Drug: GX-E2

Study type: Interventional

Funder types: Industry

Identifiers

NCT02044653

GX-E2_P2

Details and patient eligibility

About

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

Full description

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

Enrollment: 257 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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257 participants in 13 patient groups

Group A (Part A)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 3ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group B (Part A)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 5ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group C (Part A)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 8ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group D (Part A)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 3ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group E (Part A)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 5ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group F (Part A)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 8ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group G (Part B)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 5ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group H (Part B)

Experimental group

Description:

GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 8ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group I (Part B)

Active Comparator group

Description:

MIRCERA : Subcutaneously injection every 2 weeks (Q2W) at dose 0.6ug/kg

Treatment:

Drug: MIRCERA

Group J (Part B)

Experimental group

Description:

GX-E2 : Intravenously injection every week (Q1W) at dose 5ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group K (Part B)

Experimental group

Description:

GX-E2 : Intravenously injection every week (Q1W) at dose 8ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group L (Part B)

Experimental group

Description:

GX-E2 : Intravenously injection every 2 weeks (Q2W) at dose 8ug/kg

Treatment:

Drug: GX-E2

Drug: GX-E2

Drug: GX-E2

Group M (Part B)

Active Comparator group

Description:

NESP : Intravenously injection every week (Q1W) at dose 30ug

Treatment:

Drug: NESP