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

Phase 2
Completed
Conditions
Anemia
Chronic Kidney Disease
Interventions
Registration Number
NCT02044653
Lead Sponsor
Genexine, Inc.
Brief Summary

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

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
257
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group E (Part A)GX-E2GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 5ug/kg
Group B (Part A)GX-E2GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 5ug/kg
Group F (Part A)GX-E2GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 8ug/kg
Group J (Part B)GX-E2GX-E2 : Intravenously injection every week (Q1W) at dose 5ug/kg
Group A (Part A)GX-E2GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 3ug/kg
Group D (Part A)GX-E2GX-E2 : Subcutaneously injection every 4 weeks (Q4W) at dose 3ug/kg
Group L (Part B)GX-E2GX-E2 : Intravenously injection every 2 weeks (Q2W) at dose 8ug/kg
Group C (Part A)GX-E2GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 8ug/kg
Group H (Part B)GX-E2GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 8ug/kg
Group I (Part B)MIRCERAMIRCERA : Subcutaneously injection every 2 weeks (Q2W) at dose 0.6ug/kg
Group K (Part B)GX-E2GX-E2 : Intravenously injection every week (Q1W) at dose 8ug/kg
Group G (Part B)GX-E2GX-E2 : Subcutaneously injection every 2 weeks (Q2W) at dose 5ug/kg
Group M (Part B)NESPNESP : Intravenously injection every week (Q1W) at dose 30ug
Primary Outcome Measures
NameTimeMethod
average change of Hemoglobin level6 weeks (Part A) & 14 weeks (Part B)

change from baseline in Hemoglobin level

Secondary Outcome Measures
NameTimeMethod
change of reticulocyte indices6 weeks (Part A) & 14 weeks (Part B)

change from baseline in reticulocyte indices

incidence, degree, outcome of adverse event6 weeks (Part A) & 14 weeks (Part B)

Incidence of adverse events

change of red blood cell indices6 weeks (Part A) & 14 weeks (Part B)

change from baseline in red blood cell indices

immunogenicity: ratio of neutralizing antibody & binding antibody in subjects6 weeks (Part A) & 14 weeks (Part B)

comparison from pre-treatment to post-treatment

incidence, frequency, amount of blood transfusion6 weeks (Part A) & 14 weeks (Part B)

Incidence of adverse events

Trial Locations

Locations (5)

Bundang Seoul National University College of Medicine

🇰🇷

Gumi, Korea, Republic of

Gangnam severance hospital

🇰🇷

Seoul, Korea, Republic of

Bucheon St. Mary's Hospital

🇰🇷

Bucheon, Korea, Republic of

The Catholic University of Korea Incheon St.Mary's Hospital

🇰🇷

Incheon, Korea, Republic of

Seoul St.Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

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