A MULTI-CENTER, MULTI-NATIONAL, DOUBLE-BLIND, RANDOMIZED, ACTIVE-CONTROLLED, PARALLEL-GROUP CLINICAL STUDY TO ASSESS SAFETY AND EFFICACY OF PDA10 (EPOETIN-ALFA) COMPARED TO EPREX® IN PATIENTS WITH ANEMIA OF CHRONIC RENAL FAILURE
PG-EPO-Ph3 Trial
General Information
Non-clinical studies in cell line, mice mdoel as well as in beagle dopgs have demonstrated pharmacokinetics (PK) and pharmacodynamics (PD) equivalence between PDA10 and Eprex. A Phase I study (PG-EPO-Ph1) in healthy human subjects has also demosntrated similar safety, PK and PD profile;s between PDA10 and Eprex.
Study Information
Inclusion & Exclusion Criteria
1. Anemic patients with end stage renal failure (ESRD) on chronic hemodialysis
2. Patients must be at least 18 years old but less than 75 years old at Screening Visit
3. Patients on hemodialysis through a functioning native arterio-venous fistula
4. Patients must be at their dry body weight or within 5% of it during the baseline period (observation period)
5. Patients must be able to understand the information provided to them and to give written Informed Consent
6. Female patients of childbearing potential must have a negative serum pregnancy test at the Screening Visit and Baseline Visit. Females must be surgically sterile, postmenopausal for at least 1 year prior to Screening Visit or must be using an acceptable method of birth control ([oral, non-oral or implantable] hormone contraceptives, intrauterine contraceptive device or blockers and spermicides) effectively. Abstinence is not an acceptable method of contraception for the study.
7. Patients must have the following at Screening Visit or prior to randomization and have the baseline period (or observation period)
- Patients on erythropoietin treatment prior to Screening. Note: If patients who have been on Eprex® treatment before this study have hemoglobin level less than 10 g/dl during the baseline period (observation period), they must participate in the titration phase.
- Hemoglobin level with 10 - 12 g/dl and a stable IV dose of Eprex® without transfusion prior to randomization (A stable IV dose is defined as less than 25% change up or down in weekly dose and no change in frequency of injections for the baseline period [observation period])
- Patients on Eprex® treatment for at least 12 weeks; patients on stable and adequate hemodialysis at least 3 times a week and with a documented URR > 65% or delivered KT/V ≥ 1.2 in the past 6 months prior to randomization (If patients meet this criteria, they will be randomized without participating in the titration phase)
- Serum ferritin level at least 100 ng/ml and transferrin saturation (TSAT) at least 20% prior to randomization
Exclusion Criteria
1. Patients with a temporary or permanent catheters or synthetic grafts
2. Patients with uncontrolled hypertension, defined as a pre-dialysis systolic blood pressure (BP) > 170mmHg and/or diastolic BP of greater than 110 within 12 weeks prior to randomization
3. Patients with a current or recent history of thrombotic vascular events, (including but not limited to stroke, transient ischemic attack, myocardial infarction, cerebrovascular accident, coronary artery disease, and deep venous thrombosis) and decompensate congestive heart failure (New York Heart Association [NYHA] class IV) within the past 5 years
4. Surgery patients who for any reason cannot receive adequate antithrombotic prophylaxis or treatment
5. Patients with a current or recent known history of a severe hyperparathyroidism or (PTH > 800 pg/ml within 12 weeks prior to randomization)
6. Patients with hyperkalemia
7. Patients with epilepsy
8. Patients with malnutrition (serum albumin < 3.5g/dl)
9. Patients with an acute infection, viral infection or HIV infection
10. Patients with significant inflammation (CRP >10 mg/L within 12 weeks prior to randomization)
11. Patients with a history of gastrointestinal bleeding
12. Patients with any active, uncontrolled systemic or inflammatory disease that in the Investigator's opinion may be significant to exclude participation in the study
13. Patients of need for blood transfusions within 12 weeks prior to randomization
14. Patients with history of pure red cell aplasia (PRCA) or anti-erythropoietin antibodies
15. Patients with a history of malignancy of any organ system within the last 5 years prior to Screening
16. Patients with a current diagnosis of anemia due to folic acid and/or Vitamin B12 deficiencies, hemolysis, or gastrointestinal bleeding or a history of/or active blood or bleeding disorders
17. Patients who have received immunosuppressive treatment or use of other medication known to influence erythropoiesis 12 weeks prior to randomization
18. Patients with hypersensitivity to the active substance or to any of the excipients
19. Patients who have been treated with any other investigational drug within 4 weeks prior to Screening
20. Patients who currently are pregnant or lactating
21. Patients who are not cooperative or not able to follow the clinical study procedures
22. Patients who are judged to be ineligible to the clinical study at the Investigators discretion for other reasons such as alcohol and drug abuse
1. Anemic patients with end stage renal failure (ESRD) on chronic hemodialysis
2. Patients must be at least 18 years old but less than 75 years old at Screening Visit
3. Patients on hemodialysis through a functioning native arterio-venous fistula
4. Patients must be at their dry body weight or within 5% of it during the baseline period (observation period)
5. Patients must be able to understand the information provided to them and to give written Informed Consent
6. Female patients of childbearing potential must have a negative serum pregnancy test at the Screening Visit and Baseline Visit. Females must be surgically sterile, postmenopausal for at least 1 year prior to Screening Visit or must be using an acceptable method of birth control ([oral, non-oral or implantable] hormone contraceptives, intrauterine contraceptive device or blockers and spermicides) effectively. Abstinence is not an acceptable method of contraception for the study.
7. Patients must have the following at Screening Visit or prior to randomization and have the baseline period (or observation period)
- Patients on erythropoietin treatment prior to Screening. Note: If patients who have been on Eprex® treatment before this study have hemoglobin level less than 10 g/dl during the baseline period (observation period), they must participate in the titration phase.
- Hemoglobin level with 10 - 12 g/dl and a stable IV dose of Eprex® without transfusion prior to randomization (A stable IV dose is defined as less than 25% change up or down in weekly dose and no change in frequency of injections for the baseline period [observation period])
- Patients on Eprex® treatment for at least 12 weeks; patients on stable and adequate hemodialysis at least 3 times a week and with a documented URR > 65% or delivered KT/V ≥ 1.2 in the past 6 months prior to randomization (If patients meet this criteria, they will be randomized without participating in the titration phase)
- Serum ferritin level at least 100 ng/ml and transferrin saturation (TSAT) at least 20% prior to randomization
Exclusion Criteria
1. Patients with a temporary or permanent catheters or synthetic grafts
2. Patients with uncontrolled hypertension, defined as a pre-dialysis systolic blood pressure (BP) > 170mmHg and/or diastolic BP of greater than 110 within 12 weeks prior to randomization
3. Patients with a current or recent history of thrombotic vascular events, (including but not limited to stroke, transient ischemic attack, myocardial infarction, cerebrovascular accident, coronary artery disease, and deep venous thrombosis) and decompensate congestive heart failure (New York Heart Association [NYHA] class IV) within the past 5 years
4. Surgery patients who for any reason cannot receive adequate antithrombotic prophylaxis or treatment
5. Patients with a current or recent known history of a severe hyperparathyroidism or (PTH > 800 pg/ml within 12 weeks prior to randomization)
6. Patients with hyperkalemia
7. Patients with epilepsy
8. Patients with malnutrition (serum albumin < 3.5g/dl)
9. Patients with an acute infection, viral infection or HIV infection
10. Patients with significant inflammation (CRP >10 mg/L within 12 weeks prior to randomization)
11. Patients with a history of gastrointestinal bleeding
12. Patients with any active, uncontrolled systemic or inflammatory disease that in the Investigator's opinion may be significant to exclude participation in the study
13. Patients of need for blood transfusions within 12 weeks prior to randomization
14. Patients with history of pure red cell aplasia (PRCA) or anti-erythropoietin antibodies
15. Patients with a history of malignancy of any organ system within the last 5 years prior to Screening
16. Patients with a current diagnosis of anemia due to folic acid and/or Vitamin B12 deficiencies, hemolysis, or gastrointestinal bleeding or a history of/or active blood or bleeding disorders
17. Patients who have received immunosuppressive treatment or use of other medication known to influence erythropoiesis 12 weeks prior to randomization
18. Patients with hypersensitivity to the active substance or to any of the excipients
19. Patients who have been treated with any other investigational drug within 4 weeks prior to Screening
20. Patients who currently are pregnant or lactating
21. Patients who are not cooperative or not able to follow the clinical study procedures
22. Patients who are judged to be ineligible to the clinical study at the Investigators discretion for other reasons such as alcohol and drug abuse
Study Timeline