Theranova 400 Dialyzer In End Stage Renal Disease (ESRD) Patients

Study Overview
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Brief Summary
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The study evaluates the efficacy and safety of the Theranova 400 dialyzer compared with Elisio-17 H dialyzer in end stage renal disease patients receiving hemodialysis treatment. Efficacy will be determined by the removal of middle molecules (with different molecular size) from the blood compartment. Safety will be evaluated by maintaining pre-dialysis serum albumin levels and other safety events including laboratory tests and adverse events. Patients will undergo 3 dialysis sessions per week, for 24 weeks.

Official Title
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A Multi-Center, Prospective, Randomized, Controlled, Open-label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer In End Stage Renal Disease (ESRD) Patients

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Device: Theranova 400 dialyzer
* Device: Elisio-17H dialyzer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ESRD patients age 22 and older, or between ages 18 and 21 with a weight ≥ 40kg. Clinically stable as judged by the treating physician and as demonstrated by stable medical history for 30 days prior to enrollment, physical examination, and laboratory testing. Hemodialysis therapy with high-flux dialyzers for at least 3 months immediately prior to study enrollment and expected to survive for the next 12 months. Expected to maintain an acceptable urea clearance (Kt/V) with a dialyzer of an approximate surface area of 1.7 m2. Currently being dialyzed at an in-center setting, on a schedule of 3 times per week. Able to give informed consent after an explanation of the proposed study, and who are willing to comply with the study requirements for therapy during the entire study treatment period. Have a stable functioning vascular access (arteriovenous fistula, graft, or dual lumen tunneled catheter); stable access will be confirmed by observed Kt/V >= 1.2 for past 2 measurements, and/or achievement of within 15% the prescribed blood flow rate over 3 treatments prior to study entry. Exclusion Criteria: Are female and pregnant, lactating, or planning to become pregnant during the study period. Note: Female subjects of childbearing potential, defined as a woman <55 years old who has not had a partial or full hysterectomy or oophorectomy, must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test at screening. Subjects of childbearing potential must use a medically acceptable means of contraception during their participation in the study. Have chronic liver disease. Have a known paraprotein-associated disease. Have known bleeding disorders (e.g., gastrointestinal bleed, colonic polyps, small bowel angiodysplasia, and active peptic ulcers). Have had a major bleeding episode (i.e. soft tissue bleeding, blood in stool, prolonged nose bleeds, joint damage, retinal bleeding, extensive mucosal bleeding, exsanguination, cerebral hemorrhage) ≤ 12 weeks prior to randomization. Have had a blood (red blood cell) transfusion ≤ 12 weeks prior to randomization. Have had an acute infection ≤ 4 weeks prior to randomization. Have active cancer, except for basal cell or squamous cell skin cancer. Have a known serum κ/λ FLC ratio that is less than 0.37, or greater than 3.1.b Have a known monoclonal gammopathy (monoclonal gammopathy of uncertain significance, smoldering [asymptomatic] multiple myeloma, symptomatic multiple myeloma, plasmacytomas, or plasma cell leukemia). Have a known polyclonal gammopathy (connective tissue disease, liver disease, chronic infection, lymphoproliferative disorder, or other hematologic condition). Have a positive serology test for human immunodeficiency virus or hepatitis infection. Have a significant psychiatric disorder or mental disability. Are scheduled for planned interventions requiring hospitalization > 1 week. Are scheduled for living-donor transplantation within the study period + 3 months, plan to change to PD therapy within the next 9 months, plan to change to a home hemodialysis treatment, or plan to relocate to an area where no study center is located. Are currently participating in another interventional clinical study or has participated in another interventional clinical study in the past 3 months. Have a history of non-compliance with HD as assessed by an investigator. Have had a major cardiovascular or cerebrovascular event within 3 months of study entry. Have a history with consistent evidence of intradialytic hypotension. Have uncontrolled (systolic BP > 180 mmHg) hypertension. Have had adverse reactions to dialyzer materials.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Theranova 400<br>Three (3) dialysis sessions per week in an in-center setting over 24-week period. | Device: Theranova 400 dialyzer<br>* Patients should continue with their pre-study hemodialysis prescriptions (in terms of treatment time, blood flow rate and dialysate flow rate) and prescriptions should be kept stable throughout the study.<br>* Other names: medium cut-off dialysis membrane;|
| Active Comparator: Elisio-17H<br>Three (3) dialysis sessions per week in an in-center setting over 24-week period. | Device: Elisio-17H dialyzer<br>* Patients should continue with their pre-study hemodialysis prescriptions (in terms of treatment time, blood flow rate and dialysate flow rate) and prescriptions should be kept stable throughout the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction Ratio of Lambda Immunoglobulin FLC at Week 24 | FLC=free light chains | Week 24 | 
| Pre-dialysis Serum Level of Albumin at Week 24 |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction Ratio of Lambda Immunoglobulin FLC at Week 4 and Week 24 | FLC=free light chains | Week 4 and Week 24 | 
| Reduction Ratio of Complement Factor D | CFD=complement factor D | Week 4 and 24 | 
| Reduction Ratio of κ FLC | κ FLC = Kappa Free light chains | Week 4 and 24 | 
| Reduction Ratio of Interleukin 6 | IL-6=interleukin 6 | Week 4 and 24 | 
| Reduction Ratio of Tumor Necrosis Factor Alpha | TNFα=tumor necrosis factor alpha | Week 4 and 24 | 
| Reduction Ratio of β2-microglobulin | β2=beta 2 | Week 4 and 24 | 
| Change From Baseline in Pre-dialysis β2-microglobulin at Week 24 |  | Baseline, Week 24 | 
| Kt/Vurea | Kt/Vurea = Dimensionless number used to quantify hemodialysis and peritoneal dialysis adequacy. | Week 4, 8, 12, 16, 20, 24 | 
| Change From Baseline in Pre-dialysis Serum Albumin by Visit |  | Baseline, Week 4, 8, 12, 16, 20, 24 | 
| Change From Baseline in Pre-dialysis Factor VII by Visit |  | Baseline, Week 12, Week 24 | 
| Change From Baseline in Pre-dialysis Protein C by Visit |  | Baseline, Week 12, Week 24 | 
| Change From Baseline in Pre-dialysis Vitamin A by Visit |  | Baseline, Week 4, Week 24 | 
| nPNA (nPCR) | nPNA=normalized Protein equivalent of Nitrogen Appearance, and nPCR=normalized Protein Catabolic Rate. | Week 4, 8, 12, 16, 20, 24 | 
| Change From Baseline in Pre-dialysis Factor II by Visit | Factor II (Prothrombin) | Baseline, Week 12, Week 24 | 
| Change From Baseline in Sodium (mmol/L) at End of Study (up to Week 24) |  | Baseline and Week 24 | 
| Change From Baseline in Potassium (mmol/L) at End of Study (up to Week 24) |  | Baseline and Week 24 | 
| Change From Baseline in Calcium (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Phosphate (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Chloride (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Bicarbonate (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Glucose (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Prothrombin Time (Sec) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Prothrombin Intl. Normalized Ratio at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Activated Partial Thromboplastin Time (Sec) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Hematocrit (L/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Hemoglobin (g/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (pg) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration (g/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Erythrocyte Mean Corpuscular Volume (fL) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Platelets at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Erythrocytes at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Leukocytes at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Basophils (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Eosinophils (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Lymphocytes (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Monocytes (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Neutrophils (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Pre-Dialysis Blood Urea Nitrogen (mmol Urea/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Post-Dialysis Blood Urea Nitrogen (mmol Urea/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in BUN Reduction Ratio at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Creatinine (μmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Kt/Vurea by Visit |  | Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | 
| Change From Baseline in Vitamin A (μmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Cholesterol (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in HDL Cholesterol (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in LDL Cholesterol (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Triglycerides (mmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Alkaline Phosphatase (U/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Alanine Aminotransferase (U/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Aspartate Aminotransferase (U/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Direct Bilirubin (μmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Bilirubin (μmol/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Gamma Glutamyl Transferase (U/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Protein (g/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Globulin (g/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in High-sensitivity C-reactive Protein (mg/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Prothrombin Activity (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Albumin (g/dL) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Factor XIV Activity (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Tumor Necrosis Factor (pg/mL) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Factor VII Activity (%) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Lambda Light Chain, Free (mg/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Interleukin 6 (pg/mL) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Complement Factor D (mcg/mL) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Kappa Light Chain, Free (mg/L) at End of Study (up to Week 24) |  | Baseline, Week 24 | 
| Change From Baseline in Beta-2 Microglobulin (mg/L) at End of Study (up to Week 24) |  | Baseline, Week 24 |