Clinical trial NCT02044653: Study to Evaluate the Efficacy and Safety of GX-E2 in the Anemic Patients Diagnosed With Chronic Kidney Disease (CKD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Chronic Kidney Disease
Keywords: Phase 2
Lead sponsor: Genexine, Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-24
Enrollment: 257
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: average change of Hemoglobin level
timeFrame: 6 weeks (Part A) & 14 weeks (Part B)
Secondary outcomes:
measure: change of red blood cell indices
timeFrame: 6 weeks (Part A) & 14 weeks (Part B)
measure: change of reticulocyte indices
timeFrame: 6 weeks (Part A) & 14 weeks (Part B)
measure: incidence, degree, outcome of adverse event
timeFrame: 6 weeks (Part A) & 14 weeks (Part B)
measure: incidence, frequency, amount of blood transfusion
timeFrame: 6 weeks (Part A) & 14 weeks (Part B)
measure: immunogenicity: ratio of neutralizing antibody & binding antibody in subjects
timeFrame: 6 weeks (Part A) & 14 weeks (Part B)
Other outcomes:
Locations:
city: Bucheon
country: Korea, Republic of
facility: Bucheon St. Mary's Hospital
city: Gumi
country: Korea, Republic of
facility: Bundang Seoul National University College of Medicine
city: Incheon
country: Korea, Republic of
facility: The Catholic University of Korea Incheon St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam severance hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St.Mary's Hospital
Study officials:
affiliation: 222 Banpo-daero, Seocho-gu, Seoul, Korea
name: Chul-Woo Yang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 56 Dongsuro, Pupyung-Gu, Incheon, Korea
name: Seok Joon Shin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 82 Gumi-ro, 173 Beon-gil, Bundnag-gu, Seongnam-si, Gyeonggi-do, Korea
name: Ki Young Na, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 327 sosaro, onemi-Gu, bucheon, Korea
name: Ho cheol Song, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 211 Eonju-ro, Gangnam-gu, Seoul, Korea
name: Hyeong cheoon Park, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 123 Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, Korea
name: Young Sun Kang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 176 Gudeok-ro, Seo-gu, Busan, Korea
name: Eun Young Seong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 130 Dongdeok-ro, Jung-gu, Dae-gu, Korea
name: Yong-Lim Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 892 Dongnam-ro, Gangdong-gu, Seoul, Korea
name: Sangho Lee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 365 Pilmun-daero, Dong-gu, Gwangju Metropolitan City
name: Byung Chul Shin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 102 Heukseok-ro, Dongjak-gu, Seoul, Korea
name: Su-Hyun Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 93 Jungbu-daero, Paldal-gu, Suwon, Gyeonggi-do, Korea
name: Hyung Wook Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 20 Geonjiro Deokjin-gu, Jeonju-si, Jeollabuk-do, Korea
name: Won Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 4-12 Hwayang-dong, Gwangjin-gu, Seoul, Korea
name: Young-il Jo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 100 Ilsan-ro, Ilsan-donggu, Goyang-si, Gyeonggi-do, Korea
name: Sug Kyun Shin, MD
role: PRINCIPAL_INVESTIGATOR
References: