Comparison of the Clinical Performance of 3 THERANOVA 400 Dialyzer Prototypes With a High-Flux Dialyzer in Hemodialysis Mode

Study Overview
=================
Brief Summary
-----------------
The study investigates the performance of a new dialyzer (Theranova 400) containing a membrane with increased pore sizes. The performance will be determined by the removal of middle molecules (with different molecular size) from the blood compartment. Three different Theranova 400 prototypes (AA, BB and CC) operated in hemodialysis mode will be compared with a Cordiax FX-80 dialyzer, operated in hemodialysis mode. Safety events and albumin loss into the dialysate will be monitored

Official Title
-----------------
Comparison of the Clinical Performance of 3 THERANOVA 400 Dialyzer Prototypes With a High-Flux Dialyzer in Hemodialysis Mode - A Pilot Study

Conditions
-----------------
End Stage Renal Disease

Intervention / Treatment
-----------------
* Device: THERANOVA 400 dialyzer prototype AA
* Device: THERANOVA 400 dialyzer prototype BB
* Device: THERNOVA 400 dialyzer prototype CC
* Device: FX CorDiax 80 dialyzer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has end-stage renal disease Patient is 18 years of age or older Patient is male or female Patient, if female, is non-pregnant; and if capable of becoming pregnant, will be using a medically acceptable means of contraception during participation in the study (Note: Female capable of becoming pregnant [defined as a woman less than 55 years old who has not had partial or full hysterectomy or oophorectomy] must have a negative serum beta human chorionic gonadotropin [β-hCG] test within 2 weeks of first study treatment) Patient has been receiving HD or HDF therapy (HDF patients are allowed if their treatments during the study can be safely and effectively performed with HD) for ≥3 months prior to study enrollment and is expected to survive for at least 12 months after enrollment Patient has a stable functioning native fistula, Gore-Tex graft, or double-lumen central venous catheter capable of providing a blood flow rate of ≥280 mL/min (with an acceptable recirculation rate, such that solute removal is not likely to be affected) based on the judgment of the treating physician Patient is in clinically stable condition as judged by the treating physician and as demonstrated by stable medical history for 30 days prior to enrollment, physical examination, and laboratory testing Patient is willing to comply with the study requirements for therapy during the entire study treatment period Patient is capable of providing written informed consent to participate in the study Exclusion Criteria: Patient is undergoing single-needle dialysis Patient has an abnormal κ/λ ratio (less than 0.37, or greater than 3.1) Patient has a known active infection and is currently receiving antibiotic treatment Patient has known active cancer Patient has a known positive serology test for human immunodeficiency virus (HIV) or hepatitis B, C or E Patient has a known serious hemostasis disorder Patient has a known monoclonal gammopathy (eg, monoclonal gammopathy of uncertain significance, smouldering [asymptomatic] multiple myeloma, symptomatic multiple myeloma, nonsecretory multiple myeloma, plasmacytomas, or plasma cell leukemia) Patient has a known polyclonal gammopathy (eg, connective tissue disease, liver disease, chronic infection, lymphoproliferative disorder, or other hematologic condition) Patient has any other known comorbidity that could, in the opinion of the Investigator, potentially conflict with the study purpose or procedures (eg, severe hypoalbuminemia or anemia) Patient has a known significant psychiatric disorder or mental disability that could interfere with the patient's ability to provide informed consent and/or comply with protocol procedures Patient has a history of non-compliance with the dialysis prescription, as assessed by the Investigator Patient has participated in another interventional clinical study in the past 3 months, or is currently participating in another interventional clinical study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THERANOVA 400 dialyzer prototype AA<br>THERANOVA 400 dialyzer prototype AA in hemodialysis treatment | Device: THERANOVA 400 dialyzer prototype AA<br>* Hemodialysis<br>|
| Experimental: THERANOVA 400 dialyzer prototype BB<br>THERANOVA 400 dialyzer prototype BB in hemodialysis treatment | Device: THERANOVA 400 dialyzer prototype BB<br>* Hemodialysis<br>|
| Experimental: THERANOVA 400 dialyzer prototype CC<br>THERANOVA 400 dialyzer prototype CC in hemodialysis treatment | Device: THERNOVA 400 dialyzer prototype CC<br>* Hemodialysis<br>|
| Active Comparator: FX CorDiax 80 dialyzer<br>FX CorDiax 80 dialyzer in hemodialysis treatment | Device: FX CorDiax 80 dialyzer<br>* Hemodialysis<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall clearance of lambda immunoglobulin free light chains (molecular weight 45 kDa) | The primary efficacy endpoint is the overall clearance of lambda immunoglobulin free light chains during a mid-week hemodialysis session, assessed once with each experimental and active comparator product | One mid-week dialysis session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Instantanous clearance of a set of molecules with molecular sizes between 60 Da and 45 kDa | One secondary efficacy endpoint is the instantaneous clearance of a set of molecules with molecular sizes from 60 Da to 45 kDa at 30 min after start of a mid-week hemodialysis session, assessed once with each experimental and active comparator product | At 30 min from start of a mid-week dialysis session | 
| Instantanous clearance of a set of molecules with molecular sizes between 60 Da and 45 kDa | One secondary efficacy endpoint is the instantaneous clearance of a set of molecules with molecular sizes from 60 Da to 45 kDa at 120 min after start of a mid-week hemodialysis session, assessed once with each experimental and active comparator product | at 120 min from start of a mid-week dialysis session | 
| Overall clearance of a set of molecules with molecular sizes between 60 Da and 40 kDa | One secondary efficacy endpoint is the overall clearance of a set of molecules from 60 Da to 40 kDa during one mid-week hemodialysis session, assessed once with each experimental and active comparator product | One mid-week dialysis session | 
| Total mass removed of a set of molecules with molecular sizes between 60 Da and 45 kDa | One secondary efficacy endpoint is the total mass removed of a set of molecules from 60 Da to 45 kDa during one mid-week hemodialysis session, assessed once with each experimental and active comparator product | One mid-week dialysis session | 
| Removal rate of a set of molecules with molecular sizes between 60 Da and 45 kDa | One secondary efficacy endpoint is the removal rate of a set of molecules from 60 Da to 45 kDa during one mid-week hemodialysis session, assessed once with each experimental and active comparator product | One mid-week dialysis session | 
| Total mass removed of albumin | One secondary safety endpoint is the total removed mass of albumin during one mid-week hemodialysis session, assessed once with each experimental and active comparator product | One mid-week dialysis session | 
| Post- to pre-dialysis changes in a set of hematology parameters (blood cell counts, hematocrit and hemoglobin) | One secondary safety endpoint is the change in hematology parameters during one mid-week hemodialysis session, assessed once with each experimental and active comparator product | One mid-week dialysis session | 
| Types and frequency of adverse events and device deficiencies as a measure of safety and dialyzer tolerability | Any adverse events and device deficiencies will be recorded. | Continuously, from signature of informed consent form until 1 week after last hemodialysis session with an experimental or active comparator product, an expected average of 29 days |