Clinical Trials List
Protocol NumberGX-E4-CKD-002
2023-12-28 - 2027-02-28
Phase III
Recruiting5
ICD-10D63.1
Anemia in chronic kidney disease
ICD-9285.21
Anemia in end-stage renal disease
A Phase III, Randomized, Investigator-Blinded, Active-Controlled Study of Efficacy and Safety of Efepoetin Alfa for Treatment of Anemia in Patients with Chronic Kidney Disease on Dialysis
-
Sponsor
無
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/10/31
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林冠宏 Division of Nephrology
- 高芷華 Division of Nephrology
- Mei-Yi Wu Division of Nephrology
- 洪冠予 Division of Nephrology
- Chia-Te Liao Division of Nephrology
- Mai-Szu Wu Division of Nephrology
- Li-Yee Hong Division of Nephrology
- Cai-Mei Zheng Division of Nephrology
- I-jen Chiu Division of Nephrology
- YUNG-HO HSU Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Yuh-Mou Sue
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Chronic Kidney Disease on Dialysis
Objectives
To evaluate the efficacy of efepoetin alfa compared to darbepoetin alfa in terms of hemoglobin
(Hb) level control (non-inferiority) in hemodialysis patients with anemia due to chronic kidney
disease (CKD).
Test Drug
Efepoetin alfa (GX-E4)
Active Ingredient
Efepoetin alfa
Efepoetin alfa
Efepoetin alfa
Efepoetin alfa
Efepoetin alfa
Dosage Form
084
Dosage
0.3 mg/0.3 mL
0.6 mg/ 0.6 mL
1 mg/ 1 mL
0.6 mg/ 0.6 mL
1 mg/ 1 mL
Endpoints
Mean change from Baseline in Hb averaged over Week 20 to Week 28 without the use of
rescue therapy (defined in Section 7.9.1) within 6 weeks prior to and during the 8-week
evaluation period. Baseline value is defined as the mean of the last screening value and Day1
(Visit 2) value.
rescue therapy (defined in Section 7.9.1) within 6 weeks prior to and during the 8-week
evaluation period. Baseline value is defined as the mean of the last screening value and Day1
(Visit 2) value.
Inclution Criteria
1) Adult males and females aged 18 years or older.
2) After a detailed explanation of the nature of the trial and patient questioning, the patient (or their legal representative) voluntarily signed and dated a participant consent form approved by the Ethics Committee (EC) or Institutional Review Board (IRB).
3) The patient is classified as having stage 5 chronic kidney disease as defined by estimated glomerular filtration rate (GFR) (eGFR, ≤15 mL/min/1.73 m²) and has undergone at least 12 weeks of adequate hemodialysis prior to Day 1 of the trial.
[Note] Estimated glomerular filtration rate is calculated using the CKD-EPI Creatinine Equation.
4) Hemodialysis patients with a single-pool urea clearance index (SQL/V) ≥ 1.2 or a urea reduction rate ≥ 65% within the four weeks prior to screening or during the screening period.
*Single-pool urea clearance index (SQL/V) or urea reduction rate will be based on results measured within the four weeks prior to screening or during the screening period.
5) Prior to Day 1 of the trial, patients must receive a stable dose of an intravenous erythropoiesis stimulating agent (ESA) (including biosimilars) for at least 6 weeks.
*A stable dose is defined as maintaining Hb between 9.0 g/dL and 12.0 g/dL.
The following are the minimum recommended doses for erythropoiesis-stimulating agents:
✓ Epoetin alfa, epoetin beta, and epoetin kappa: ≥1,500 U/week
✓ Darbepoetin alfa: ≥20 μg/week
✓ MirceraR: ≥30 μg/2 weeks
6) The average of two most recent local laboratory heme (Hb) screening values obtained at least 6 days apart must be between 9.0 g/dL and 12.0 g/dL (inclusive), with the difference between the highest and lowest values ≤1.5 g/dL.
7) Patients with serum ferritin ≥100 ng/mL at screening.
8) Patients with transferrin saturation (TSAT) ≥20% at screening.
9) At screening, serum folate concentration ≥ lower limit of normal (LLN).
10) At screening, serum total vitamin B12 concentration ≥ lower limit of normal.
1) In addition to glomerulonephritis, acute or chronic infections that may affect erythropoiesis or C-reactive protein levels > 40 mg/L (high-sensitivity C-reactive protein levels > 10 mg/L), or poorly controlled or symptomatic inflammatory diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) may also be considered.
2) Based on medical history or current clinical data, patients with active acute hepatitis B virus (HBV) or hepatitis C virus (HCV) infection should be excluded. This program does not require regular screening for HBV, HCV, and human immunodeficiency virus (HIV) infection. Chronic HBV/HCV infection with liver function tests (LFT) >3 times the normal value will be excluded. Known HIV-positive patients will be excluded.
3) The participating physician will determine whether participation will be affected by the patient's cardiovascular, blood, liver, or other physical history and clinical data.
4) Any of the following laboratory abnormalities observed during the screening visit:
• Alanine transaminase (ALT) >3 x Upper Limit of Normal (ULN)
• Aspartate aminotransferase (AST) >3 x ULN
• Total bilirubin >1.5 x ULN
5) Chronic congestive heart failure (New York Heart Association Class 3 or 4).
6) High-risk individuals who prematurely withdraw from or interrupt the study within 12 weeks prior to screening or during screening (due to myocardial infarction, severe or unstable coronary artery disease, stroke, or severe liver disease).
7) Poorly controlled hypertension defined as sitting systolic blood pressure ≥170 mmHg and/or diastolic blood pressure ≥100 mmHg.
8) History of active malignancy, excluding: cancer with confirmed cure or remission for ≥5 years, radically resected basal cell or squamous cell skin cancer, or carcinoma in situ at any site.
9) Patients with a history of significant gastrointestinal bleeding or any other bleeding event associated with a decrease in hemoglobin ≥1 g/dL within the past 8 weeks prior to screening.
10) History of known myelodysplastic syndrome, multiple myeloma, hereditary blood disorders (such as thalassemia, sickle cell anemia, pure red cell aplasia) or other known causes of anemia besides chronic kidney disease, hemosiderinosis, hemochromatosis, known coagulation disorders, or hypercoagulable states.
11) Any previous functional organ transplant or planned organ transplant, or renal absence (one or both kidneys). 12) Planned elective surgery during the study period that may result in significant bleeding.
13) Hypoalbuminemia (serum albumin <2.5 g/dL) at the screening visit.
14) Treatment with androgens, deferoxamine, deferiprone, or deferasirox within 12 weeks prior to Day 1.
15) Life expectancy <12 months.
16) Cognitive or psychiatric illness that prevents the patient from cooperating with and completing study requirements.
17) Hypersensitivity to any investigational drug or its excipients.
18) Received a blood transfusion (including red blood cell transfusion) within 12 weeks prior to screening, or is expected to receive a blood transfusion during the study period (excluding temporary transfusions due to accidental or surgical blood loss). 19) Received immunosuppressive therapy (tacrolimus/cyclosporine, and corticosteroids not used for chronic disease treatment) within 12 weeks prior to Day 1 of the trial.
20) Have a history of alcohol or drug abuse within the past 2 years and cannot avoid consuming more than 3 alcoholic beverages per day.
21) Use of investigational drugs/treatments, participation in interventional studies/treatments, and residual effects.
22) Women of childbearing potential or men who are unable/unwilling to use adequate contraception as specified in the protocol during the trial, or at least 4 months after the end of the trial for male patients, or at least 7 months after the end of the trial for female patients. Women who have a positive pregnancy test within 24 hours prior to entering the study, know they are pregnant, plan to become pregnant within the next 12 months, or are currently breastfeeding. The Clinical Trial Facilitation Group recommends the following highly effective methods of contraception:
• Combined hormonal contraceptives (containing estrogen and progesterone) associated with ovulation suppression:
o Oral
o Intravaginal
o Dermal absorption
• Hormonal contraceptives containing only progesterone associated with ovulation suppression:
o Oral
o Injectable
o Implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal obstruction
• Partner vasectomy
• Abstinence
23) Patients must be staff members performing this trial and their family members, or trial personnel supervised by the trial physician, or employees of the trial commissioning organization or the entrusted research institution. 24) For patients with very limited functional capacity, a target Hb level of 12 g/dL may have a lower benefit/risk ratio.
25) Any medical condition (patients weighing over 150 kg) that, as assessed by the trial physician, poses a safety risk to patients in this trial, may confound assessments of efficacy or safety, or may interfere with the study.
2) After a detailed explanation of the nature of the trial and patient questioning, the patient (or their legal representative) voluntarily signed and dated a participant consent form approved by the Ethics Committee (EC) or Institutional Review Board (IRB).
3) The patient is classified as having stage 5 chronic kidney disease as defined by estimated glomerular filtration rate (GFR) (eGFR, ≤15 mL/min/1.73 m²) and has undergone at least 12 weeks of adequate hemodialysis prior to Day 1 of the trial.
[Note] Estimated glomerular filtration rate is calculated using the CKD-EPI Creatinine Equation.
4) Hemodialysis patients with a single-pool urea clearance index (SQL/V) ≥ 1.2 or a urea reduction rate ≥ 65% within the four weeks prior to screening or during the screening period.
*Single-pool urea clearance index (SQL/V) or urea reduction rate will be based on results measured within the four weeks prior to screening or during the screening period.
5) Prior to Day 1 of the trial, patients must receive a stable dose of an intravenous erythropoiesis stimulating agent (ESA) (including biosimilars) for at least 6 weeks.
*A stable dose is defined as maintaining Hb between 9.0 g/dL and 12.0 g/dL.
The following are the minimum recommended doses for erythropoiesis-stimulating agents:
✓ Epoetin alfa, epoetin beta, and epoetin kappa: ≥1,500 U/week
✓ Darbepoetin alfa: ≥20 μg/week
✓ MirceraR: ≥30 μg/2 weeks
6) The average of two most recent local laboratory heme (Hb) screening values obtained at least 6 days apart must be between 9.0 g/dL and 12.0 g/dL (inclusive), with the difference between the highest and lowest values ≤1.5 g/dL.
7) Patients with serum ferritin ≥100 ng/mL at screening.
8) Patients with transferrin saturation (TSAT) ≥20% at screening.
9) At screening, serum folate concentration ≥ lower limit of normal (LLN).
10) At screening, serum total vitamin B12 concentration ≥ lower limit of normal.
1) In addition to glomerulonephritis, acute or chronic infections that may affect erythropoiesis or C-reactive protein levels > 40 mg/L (high-sensitivity C-reactive protein levels > 10 mg/L), or poorly controlled or symptomatic inflammatory diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) may also be considered.
2) Based on medical history or current clinical data, patients with active acute hepatitis B virus (HBV) or hepatitis C virus (HCV) infection should be excluded. This program does not require regular screening for HBV, HCV, and human immunodeficiency virus (HIV) infection. Chronic HBV/HCV infection with liver function tests (LFT) >3 times the normal value will be excluded. Known HIV-positive patients will be excluded.
3) The participating physician will determine whether participation will be affected by the patient's cardiovascular, blood, liver, or other physical history and clinical data.
4) Any of the following laboratory abnormalities observed during the screening visit:
• Alanine transaminase (ALT) >3 x Upper Limit of Normal (ULN)
• Aspartate aminotransferase (AST) >3 x ULN
• Total bilirubin >1.5 x ULN
5) Chronic congestive heart failure (New York Heart Association Class 3 or 4).
6) High-risk individuals who prematurely withdraw from or interrupt the study within 12 weeks prior to screening or during screening (due to myocardial infarction, severe or unstable coronary artery disease, stroke, or severe liver disease).
7) Poorly controlled hypertension defined as sitting systolic blood pressure ≥170 mmHg and/or diastolic blood pressure ≥100 mmHg.
8) History of active malignancy, excluding: cancer with confirmed cure or remission for ≥5 years, radically resected basal cell or squamous cell skin cancer, or carcinoma in situ at any site.
9) Patients with a history of significant gastrointestinal bleeding or any other bleeding event associated with a decrease in hemoglobin ≥1 g/dL within the past 8 weeks prior to screening.
10) History of known myelodysplastic syndrome, multiple myeloma, hereditary blood disorders (such as thalassemia, sickle cell anemia, pure red cell aplasia) or other known causes of anemia besides chronic kidney disease, hemosiderinosis, hemochromatosis, known coagulation disorders, or hypercoagulable states.
11) Any previous functional organ transplant or planned organ transplant, or renal absence (one or both kidneys). 12) Planned elective surgery during the study period that may result in significant bleeding.
13) Hypoalbuminemia (serum albumin <2.5 g/dL) at the screening visit.
14) Treatment with androgens, deferoxamine, deferiprone, or deferasirox within 12 weeks prior to Day 1.
15) Life expectancy <12 months.
16) Cognitive or psychiatric illness that prevents the patient from cooperating with and completing study requirements.
17) Hypersensitivity to any investigational drug or its excipients.
18) Received a blood transfusion (including red blood cell transfusion) within 12 weeks prior to screening, or is expected to receive a blood transfusion during the study period (excluding temporary transfusions due to accidental or surgical blood loss). 19) Received immunosuppressive therapy (tacrolimus/cyclosporine, and corticosteroids not used for chronic disease treatment) within 12 weeks prior to Day 1 of the trial.
20) Have a history of alcohol or drug abuse within the past 2 years and cannot avoid consuming more than 3 alcoholic beverages per day.
21) Use of investigational drugs/treatments, participation in interventional studies/treatments, and residual effects.
22) Women of childbearing potential or men who are unable/unwilling to use adequate contraception as specified in the protocol during the trial, or at least 4 months after the end of the trial for male patients, or at least 7 months after the end of the trial for female patients. Women who have a positive pregnancy test within 24 hours prior to entering the study, know they are pregnant, plan to become pregnant within the next 12 months, or are currently breastfeeding. The Clinical Trial Facilitation Group recommends the following highly effective methods of contraception:
• Combined hormonal contraceptives (containing estrogen and progesterone) associated with ovulation suppression:
o Oral
o Intravaginal
o Dermal absorption
• Hormonal contraceptives containing only progesterone associated with ovulation suppression:
o Oral
o Injectable
o Implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal obstruction
• Partner vasectomy
• Abstinence
23) Patients must be staff members performing this trial and their family members, or trial personnel supervised by the trial physician, or employees of the trial commissioning organization or the entrusted research institution. 24) For patients with very limited functional capacity, a target Hb level of 12 g/dL may have a lower benefit/risk ratio.
25) Any medical condition (patients weighing over 150 kg) that, as assessed by the trial physician, poses a safety risk to patients in this trial, may confound assessments of efficacy or safety, or may interfere with the study.
Exclusion Criteria
Patients meeting any of the following exclusion criteria will not be eligible to participate in this study:
1) Active acute or chronic infections, other than glomerulonephritis, that may affect erythropoiesis or C-reactive protein levels >40 mg/L (high-sensitivity C-reactive protein levels >10 mg/L), or poorly controlled or symptomatic inflammatory diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease).
2) Patients with active acute hepatitis B virus (HBV) or hepatitis C virus (HCV) infection should be excluded based on their medical history or current clinical data. Regular screening for HBV, HCV, and human immunodeficiency virus (HIV) infection is not required in this study. Chronic HBV/HCV infection will be excluded if liver function tests (LFT) are 3 times the normal value. Known HIV-positive patients will be excluded.
3) The investigating physician may determine whether participation in the trial is affected by the patient's cardiovascular, blood, liver, or other physical history and clinical data.
4) Any of the following laboratory abnormalities present at the screening visit:
• Alanine transaminase (ALT) >3 x Upper Limit of Normal (ULN)
• Aspartate aminotransferase (AST) >3 x ULN
• Total bilirubin >1.5 x ULN
5) Chronic congestive heart failure (New York Heart Association Class 3 or 4). 6) High-risk individuals who withdraw from or interrupt the study within 12 weeks prior to screening or during screening (due to myocardial infarction, severe or unstable coronary artery disease, stroke, or severe liver disease).
7) Poorly controlled hypertension is defined as a sitting systolic blood pressure ≥170 mmHg and/or a diastolic blood pressure ≥100 mmHg.
8) History of active malignancy, except for: cancer that has been definitively cured or slowed for ≥5 years, radically resected basal cell or squamous cell skin cancer, or carcinoma in situ at any location.
9) Patients with a significant history of gastrointestinal bleeding or any other bleeding event associated with a decrease in hemoglobin ≥1 g/dL within the past 8 weeks prior to screening.
10) History of known myelodysplastic syndrome, multiple myeloma, hereditary blood disorders (such as thalassemia, sickle cell anemia, pure red cell aplasia) or other known causes of anemia besides chronic kidney disease, hemosiderinosis, hemochromatosis, known coagulation disorders, or hypercoagulable states.
11) Any previous functional organ transplant or planned organ transplant, or renal agenesis (one or both kidneys).
12) Planned elective surgery during the study period that may result in significant bleeding.
13) Hypoalbuminemia (serum albumin <2.5 g/dL) at the screening visit. 14) Received androgen, deferoxamine, deferiprone, or deferasirox treatment within 12 weeks prior to Day 1.
15) Life expectancy <12 months.
16) Cognitive or mental illness preventing the patient from cooperating with and completing the study requirements.
17) Hypersensitivity to any of the investigational drugs or their excipients.
18) Received a blood transfusion within 12 weeks prior to screening.
1) Active acute or chronic infections, other than glomerulonephritis, that may affect erythropoiesis or C-reactive protein levels >40 mg/L (high-sensitivity C-reactive protein levels >10 mg/L), or poorly controlled or symptomatic inflammatory diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease).
2) Patients with active acute hepatitis B virus (HBV) or hepatitis C virus (HCV) infection should be excluded based on their medical history or current clinical data. Regular screening for HBV, HCV, and human immunodeficiency virus (HIV) infection is not required in this study. Chronic HBV/HCV infection will be excluded if liver function tests (LFT) are 3 times the normal value. Known HIV-positive patients will be excluded.
3) The investigating physician may determine whether participation in the trial is affected by the patient's cardiovascular, blood, liver, or other physical history and clinical data.
4) Any of the following laboratory abnormalities present at the screening visit:
• Alanine transaminase (ALT) >3 x Upper Limit of Normal (ULN)
• Aspartate aminotransferase (AST) >3 x ULN
• Total bilirubin >1.5 x ULN
5) Chronic congestive heart failure (New York Heart Association Class 3 or 4). 6) High-risk individuals who withdraw from or interrupt the study within 12 weeks prior to screening or during screening (due to myocardial infarction, severe or unstable coronary artery disease, stroke, or severe liver disease).
7) Poorly controlled hypertension is defined as a sitting systolic blood pressure ≥170 mmHg and/or a diastolic blood pressure ≥100 mmHg.
8) History of active malignancy, except for: cancer that has been definitively cured or slowed for ≥5 years, radically resected basal cell or squamous cell skin cancer, or carcinoma in situ at any location.
9) Patients with a significant history of gastrointestinal bleeding or any other bleeding event associated with a decrease in hemoglobin ≥1 g/dL within the past 8 weeks prior to screening.
10) History of known myelodysplastic syndrome, multiple myeloma, hereditary blood disorders (such as thalassemia, sickle cell anemia, pure red cell aplasia) or other known causes of anemia besides chronic kidney disease, hemosiderinosis, hemochromatosis, known coagulation disorders, or hypercoagulable states.
11) Any previous functional organ transplant or planned organ transplant, or renal agenesis (one or both kidneys).
12) Planned elective surgery during the study period that may result in significant bleeding.
13) Hypoalbuminemia (serum albumin <2.5 g/dL) at the screening visit. 14) Received androgen, deferoxamine, deferiprone, or deferasirox treatment within 12 weeks prior to Day 1.
15) Life expectancy <12 months.
16) Cognitive or mental illness preventing the patient from cooperating with and completing the study requirements.
17) Hypersensitivity to any of the investigational drugs or their excipients.
18) Received a blood transfusion within 12 weeks prior to screening.
The Estimated Number of Participants
-
Taiwan
32 participants
-
Global
429 participants
