Status Approved
First Submitted Date
2021/03/19
Registered Date
2021/03/25
Last Updated Date
2021/03/19
CRIS Required
WHO ICTRP (International Clinical Trial Registry Platform) Required
1. Background
CRIS Registration Number |
KCT0006024 |
---|---|
Unique Protocol ID | 20130425/16-2013-64/051 |
Public/Brief Title | 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 |
Scientific Title | 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 |
Acronym | |
MFDS Regulated Study | Yes |
IND/IDE Protocol | Yes |
Registered at Other Registry | No |
Healthcare Benefit Approval Status | Not applicable |
2. Institutional Review Board / Ethics Committee
Board Approval Status | Submitted approval |
---|---|
Board Approval Number | 20130425/16-2013-64/051 |
Approval Date | 2013-06-19 |
Institutional Review Board Name | SMG-SNU Boramae Medical Center Institutional Review Board |
Institutional Review Board Address | 20, Boramae-ro 5-gil, Dongjak-gu, Seoul |
Institutional Review Board Telephone | 02-870-1852 |
Data Monitoring Committee | No |
3. Contact Details
Contact Person for Principal Investigator / Scientific Queries | |
---|---|
Name | Chun Soo Lim |
Title | MD, PhD |
Telephone | +82-2-870-2215 |
Affiliation | Seoul Metropolitan Government Seoul National University Boramae Medical Center |
Address | 20 Boramae-ro 5-gil, Dongjak-gu, Seoul |
Contact Person for Public Queries | |
Name | Hyunju Song |
Title | General Manager |
Telephone | +82-70-7542-8776 |
Affiliation | PanGen Biotech |
Address | Woncheon-dong, 4F Innoplex 2-dong 306, Sinwon-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, Republic of Korea |
Contact Person for Updating Information | |
Name | Hyunju Song |
Title | G |
Telephone | +82-70-7542-8776 |
Affiliation | PanGen Biotech |
Address | Woncheon-dong, 4F Innoplex 2-dong 306, Sinwon-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, Republic of Korea |
4. Status
Study Site | Multi-center Number of center : 2 - Multi-national} | |
---|---|---|
Overall Recruitment Status | Completed | |
Date of First Enrollment | 2013-10-23 Actual | |
Target Number of Participant | 316 | |
Primary Completion Date | 2017-04-04 , Actual | |
Study Completion Date | 2017-12-20 , Actual | |
Recruitment Status by Participating Study Site 1 | ||
Name of Study | Seoul Metropolitan Government Seoul National University Boramae Medical Center | |
Recruitment Status | Completed | |
Date of First Enrollment | 2013-10-23 , | |
Recruitment Status by Participating Study Site 2 | ||
Name of Study | Chung-Ang Univerisity Hospital | |
Recruitment Status | Completed | |
Date of First Enrollment | 2013-10-28 , |
5. Source of Monetary / Material Support
1. Source of Monetary/Material Support | |
---|---|
Organization Name | PanGen Biotech |
Organization Type | Pharmaceutical Company |
Project ID |
6. Sponsor Organization
1. Sponsor Organization | |
---|---|
Organization Name | PanGen Biotech |
Organization Type | Pharmaceutical Company |
7. Study Summary
Lay Summary | This clinical study will be a multi-center, multi-national, randomized, double-blind, active-controlled and parallel group clinical trial. This study will consist of a 12-week of titration phase designed to assess the stability of patients’ disease and to establish each patient’s baseline characteristics. In substantiated cases, a prolongation of the titration phase will be allowed up to 20 weeks. The titration phase will be followed by a 28-week double-blind treatment phase (maintenance phase) including the evaluation period (the last 4 weeks of the maintenance phase). Eligible patients will be randomized to receive one of the two study treatment regimen (PDA10 or Eprex®) in a 1:1 ratio according to the randomization scheme. All subjects are to continue their treatment PDA10 or Eprex®, and to receive study medication 1-3 times weekly intravenously (IV). Prior to performing any procedures or evaluation, written informed consent will be obtained. Prospective patients will be screened to confirm their eligibility for the study entry prior to randomization. During the 12-week of the titration phase, all subjects will receive Eprex®, then those with hemoglobin within the target range of 10.0 to 12.0 g/dl and a stable IV dose (a dosage titrated and individualized) of Eprex® during baseline period will be randomly assigned to one of two study drugs, either to the test product, PDA10, or to the reference product, Eprex®. However, patients on Eprex® treatment for at least 12 weeks and with hemoglobin within the target range of 10.0 to 12.0 g/dl and a stable IV dose of Eprex® will participate in the process of confirming the entry criteria for this study, and have a four-week of the baseline period (or observation period) without the titration phase. During the maintenance phase, the efficacy and safety will be evaluated every 2 or 4 weeks. Subjects who complete the study at Week 28 will be offered continuation of PDA10 treatment by entering a 24-week of open-label extension phase, and the long-term safety and tolerability will be evaluated. Subjects must complete the Week 28 (Visit 11) assessments before entering the open-label extension phase. Visit 11 at Week 28 of the study will serve as the entry visit for the open label extension phase. |
---|
8. Study Design
Study Type | Interventional Study |
---|---|
Study Purpose | Treatment |
Phase | Phase3 |
Intervention Model | Parallel |
Blinding/Masking | Double |
Blinded Subject | Subject, Investigator |
Allocation | RCT |
Intervention Type | /Biological/Vaccine, /Non-Stem Cell |
Intervention Description | Test product and its dosage and mode of administration: - Test product and its dosage: PDA10 Pre-filled syringe injection 2000 IU - Mode of administration: by intravenous (IV), 1~3 times/week Reference product and its dosage and mode of administration: - Reference product and its dosage: Eprex® (2000 IU/0.5 mL) Eligible patients are randomized to receive one of the two study treatment regimen (PDA10 or Eprex®) in a 1:1 ratio according to the randomization scheme. All subjects are to continue their treatment of PDA10 or Eprex®, and to receive study medication 1-3 times weekly intravenously (IV). - Mode of administration: by intravenous (IV), 1~3 times/week |
Number of Arms | 2 |
Arm 1 |
Arm Label Test (PDA10) |
Target Number of Participant 126 |
|
Arm Type Experimental |
|
Arm Description The IV dose has to be adjusted individually to maintain hemoglobin between 10 - 12 g/dl. The hemoglobin, hematocrit, and dose will be monitored every two weeks during the maintenance phase. Investigators will decide to change or maintain the dosage of Eprex® or PDA10 every four weeks based on Hb level. The dosage will be determined according to the dose adjustment scheme below, and if hemoglobin level is not increased by more than 1 g/dl in any 2-week period or is not approaching 12 g/dl or below 10 g/dl, the dose will be maintained. The maintenance dose should be individualized, and the recommended total weekly dose should not exceed 300 IU/kg. If the hemoglobin increases by more than 1 g/dl in any 2-week period or the hemoglobin is approaching 12 g/d1, the dose should be reduced by approximately 25%. If the hemoglobin continues to increase or exceed 12 g/dl, the dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose. If dose reduction is needed, either the amount given per dose or the number of weekly injections will be reduced, or both will be reduced. If the hemoglobin is below 10 g/dl, the dose may be increased by approximately 25% of the previous dose. When a change in Eprex® or PDA10 dose is indicated, a one-step change (25% of current dosage). |
|
Arm 2 |
Arm Label Reference (Eprex) |
Target Number of Participant 126 |
|
Arm Type Active comparator |
|
Arm Description The IV dose has to be adjusted individually to maintain hemoglobin between 10 - 12 g/dl. The hemoglobin, hematocrit, and dose will be monitored every two weeks during the maintenance phase. Investigators will decide to change or maintain the dosage of Eprex® or PDA10 every four weeks based on Hb level. The dosage will be determined according to the dose adjustment scheme below, and if hemoglobin level is not increased by more than 1 g/dl in any 2-week period or is not approaching 12 g/dl or below 10 g/dl, the dose will be maintained. The maintenance dose should be individualized, and the recommended total weekly dose should not exceed 300 IU/kg. If the hemoglobin increases by more than 1 g/dl in any 2-week period or the hemoglobin is approaching 12 g/d1, the dose should be reduced by approximately 25%. If the hemoglobin continues to increase or exceed 12 g/dl, the dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose. If dose reduction is needed, either the amount given per dose or the number of weekly injections will be reduced, or both will be reduced. If the hemoglobin is below 10 g/dl, the dose may be increased by approximately 25% of the previous dose. When a change in Eprex® or PDA10 dose is indicated, a one-step change (25% of current dosage). |
9. Subject Eligibility
Condition(s)/Problem(s) |
* (N00-N99)Diseases of the genitourinary system (N18.5)Chronic kidney disease, stage 5 End stage renal failure (ESRD) |
---|---|
Rare Disease | No |
Inclusion Criteria |
Gender Both |
Age 18Year~75Year |
|
Description To be eligible to participate in the study, patients must meet the following 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 as well as at 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 not more than 25% change up or down in weekly dose and no clinically relevant change of regimen in frequency of haemodialysis 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/or transferrin saturation (TSAT) at least 20% prior to randomization |
|
Exclusion Criteria |
Patients who meet any of the following criteria will not be eligible to participate in the study: 1. Patients with a temporary or permanent catheters or synthetic grafts 2. Patients with uncontrolled hypertension, defined as a pre-dialysis diastolic BP of greater than 110 within 12 weeks prior to randomization 3. Patients with severe diseases within the last 6 months prior to randomization (e.g. stroke, transient ischemic attack, myocardial infarction, cerebrovascular accident, coronary artery bypass graft, deep venous thrombosis, unstable angina, decompensate congestive heart failure (New York Heart Association [NYHA] class III~IV), or other thromboembolic events) 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 > 1500 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 prior to randomization) 9. Patients with an acute infection, acute hepatitis (including A, B, C type) or chronic hepatitis B or C requiring treatment , or HIV infection 10. Patients with significant inflammation (CRP >30 mg/L within 12 weeks prior to randomization) 11. Patients with a history of gastrointestinal bleeding within the last 6 months before Screening 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 active blood or bleeding disorders within the last 6 months before Screening 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 Investigator’s discretion for other reasons such as alcohol and drug abuse |
Healthy Volunteers | No |
10. Outcome Measure(s)
Type of Primary Outcome | Bio-Equivalence | |
---|---|---|
Primary Outcome(s) 1 | ||
Outcome | Mean change in hemoglobin level between the baseline period and the evaluation period |
|
Timepoint | The baseline period is the last four weeks of titration phase or the observation period and the evaluation period is the last four weeks of maintenance phase. |
|
Primary Outcome(s) 2 | ||
Outcome | Mean change in weekly dosage per kg body weight between the baseline period and the evaluation period |
|
Timepoint | The baseline period is the last four weeks of titration phase or the observation period and the evaluation period is the last four weeks of maintenance phase. |
|
Secondary Outcome(s) 1 | ||
Outcome | Mean change in hematocrit levels between the baseline period and the evaluation period |
|
Timepoint | The baseline period is the last four weeks of titration phase or the observation period and the evaluation period is the last four weeks of maintenance phase. |
|
Secondary Outcome(s) 2 | ||
Outcome | Proportion of patients with hemoglobin level out of the target range during the maintenance phase |
|
Timepoint | Maintenance phase period |
|
Secondary Outcome(s) 3 | ||
Outcome | Proportion of patients with hemoglobin level within the target range during the evaluation period |
|
Timepoint | Evaluation period |
|
Secondary Outcome(s) 4 | ||
Outcome | Frequency of patients with changes in the dosage per kg body weight |
|
Timepoint | Maintenance phase period |
|
Secondary Outcome(s) 5 | ||
Outcome | Incidence of blood transfusions |
|
Timepoint | Maintenance phase period |
11. Study Results and Publication
Result Registered | No |
---|
12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)
Sharing Statement | No |
---|
TOP
BOTTOM
화면 최하단으로 이동