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
Phase: NA
Conditions: End Stage Renal Disease
Sponsor: Vantive Health LLC



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Confidentiality Statement 
This protocol contains information that is proprietary to Baxter Healthcare Corporation (Baxter). This 
information is provided to you for the purpose of conducting a clinical study for Baxter. The 
Investigators may disclose the contents of this protocol to study personnel under their supervision and 
to Institutional Review Board(s) and Independent Ethics Committee(s), provided that such persons 
shall understand the confidentiality of this protocol and undertake to keep the protocol confidential. 
You may not disclose the contents of this protocol to any other parties (unless such disclosure is 
required by government regulations or laws, in which case, Baxter will be notified of the disclosure at 
least 5 business days prior to the disclosure) without prior written permission from Baxter. 
Any supplemental information (e.g., protocol amendment) that may be added to this document is also 
proprietary to Baxter and will be handled using the same disclosure procedure. 

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Table of Contents 
SYNOPSIS ..........................................................................................................................7 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..............................12 
1. INTRODUCTION........................................................................................................14 
1.1 Background and Rationale ...................................................................................14 
1.2 Benefits and Risks for the Study Population .......................................................15 
1.3 Study Sponsor ........................................................................................................16 
2. STUDY OBJECTIVES ................................................................................................16 
2.1 Primary Objective(s) .............................................................................................16 
2.2 Secondary Objective(s) ..........................................................................................17 
2.3 Exploratory Objectives ..........................................................................................17 
3. INVESTIGATIONAL PLAN .....................................................................................17 
3.1 Overall Study Design and Plan .............................................................................17 
3.2 Study Endpoints .....................................................................................................19 
3.2.1 Primary Endpoints .........................................................................................19 
3.2.2 Secondary Endpoints ......................................................................................19 
3.2.3 Exploratory Assessments ...............................................................................20 
3.3 Rationale for Study Design and Control Group .................................................20 
3.3.1 Other Considerations .....................................................................................21 
3.4 Study Duration and Dates .....................................................................................21 
3.5 Study Discontinuation Rules .................................................................................21 
3.5.1 Procedure for Resuming the Clinical Investigation after Temporary 
Suspension .......................................................................................................22 
4. STUDY POPULATION SELECTION ......................................................................22 
4.1 Study Population ....................................................................................................22 
4.2 Inclusion Criteria ...................................................................................................22 
4.3 Exclusion Criteria ..................................................................................................23 
4.4 Recruitment ............................................................................................................25 
4.5 Removal of Patients from Therapy, Assessment, or Study ................................25 
4.6 Missed Visits ...........................................................................................................26 
5. STUDY TREATMENT(S) ..........................................................................................26 
5.1 Description of Treatment(s) ..................................................................................26 
5.1.1 Study Device – Theranova 400 dialyzer ........................................................26 

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5.1.2 Study Device – Elisio-17H dialyzer ...............................................................26 
5.2 Treatments Administered .....................................................................................27 
5.3 Selection and Timing for Each Patient ................................................................27 
5.4 Method of Assigning Patients to Treatment Groups ..........................................27 
5.5 Blinding ...................................................................................................................28 
5.6 Concomitant Therapy............................................................................................28 
5.7 Prohibitions and Restrictions ...............................................................................28 
5.8 Treatment Compliance ..........................................................................................29 
5.9 Packaging and Labeling ........................................................................................29 
5.10 Storage and Accountability .................................................................................29 
6. STUDY PROCEDURES .............................................................................................30 
6.1 Informed Consent ..................................................................................................30 
6.2 Demographics and Baseline Characteristics .......................................................31 
6.3 Physical Examination ............................................................................................32 
6.4 Vital Signs ...............................................................................................................32 
6.5 Clinical Laboratory Tests .....................................................................................32 
6.5.1 Laboratory Parameters ..................................................................................32 
6.5.2 Sample Collection, Storage, and Shipping ...................................................34 
6.6 Patient Reported Outcomes ..................................................................................34 
6.7 Appropriateness of Measurements.......................................................................34 
7. DATA COLLECTION FOR SAFETY ASSESSMENTS AND REPORTING .....34 
7.1 Definition of Adverse Events and Product Complaints .....................................34 
7.2 Safety Reporting ....................................................................................................36 
7.2.1 Serious Adverse Events (SAEs) and Product Complaint (PC) 
Reporting .........................................................................................................39 
7.2.1.1 Anticipated Adverse Events Related to Theranova and 
Hemodialysis ............................................................................................39 
7.2.2 Product Complaints/Product Issues ..............................................................40 
7.3 Medical Monitor ....................................................................................................40 
7.4 Safety Reporting to Authorities and IRB ............................................................40 
8. STUDY ACTIVITIES .................................................................................................40 
8.1 Schedule of Evaluations and Procedures .............................................................40 
8.2 Training for Theranova 400 dialyzer ...................................................................40 
8.3 Training for Elisio-17H dialyzer ..........................................................................41 
8.4 Screening Period (Days –14 to -1) ........................................................................41 
8.4.1 Assessments and Procedures .........................................................................41 
8.5 Treatment Period (Day 1 to Day 168) ..................................................................42 
8.5.1 Visit Procedures ..............................................................................................42 
8.6 End of Study Visitor Early Termination Procedures .........................................42 

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9. DATA MANAGEMENT, QUALITY CONTROL AND QUALITY 
ASSURANCE ...............................................................................................................43 
9.1 Auditing ..................................................................................................................43 
10. PLANNED STATISTICAL METHODS .................................................................43 
10.1 General Considerations .......................................................................................43 
10.2 Determination of Sample Size .............................................................................44 
10.3 Analysis Populations ............................................................................................45 
10.4 Demographics and Baseline Characteristics .....................................................45 
10.5 Primary Endpoint(s) ............................................................................................46 
10.5.1 Primary Safety Endpoint(s) .........................................................................46 
10.5.2 Primary Efficacy Endpoint(s) ......................................................................47 
10.6 Secondary Endpoint(s) ........................................................................................47 
10.6.1 Secondary Safety Endpoint(s) .....................................................................47 
10.6.2 Secondary Efficacy Endpoint(s) ..................................................................49 
10.7 Exploratory Endpoints ........................................................................................49 
10.8 Interim Analysis ...................................................................................................50 
11. ADMINISTRATIVE CONSIDERATIONS ............................................................50 
11.1 Investigators and Study Administrative Structure ...........................................50 
11.2 Institutional Review Board Approval ................................................................51 
11.3 Food and Drug Administration ..........................................................................51 
11.4 Ethical Conduct of the Study ..............................................................................52 
11.5 Patient Information and Consent .......................................................................52 
11.6 Patient Confidentiality ........................................................................................52 
11.6.1 HIPAA Authorization Procedures ..............................................................53 
11.7 Study Monitoring .................................................................................................53 
11.8 Case Report Forms and Study Records .............................................................53 
11.9 Protocol Violations/Deviations ............................................................................54 
11.10 Access to Source Documentation ......................................................................54 
11.11 Data Generation and Analysis ..........................................................................54 
11.12 Retention of Data ...............................................................................................55 
11.13 Financial Disclosure ...........................................................................................55 
11.14 Publication and Disclosure Policy ....................................................................55 
12. REFERENCE LIST ...................................................................................................56 
 
List of In-Text Tables 
Table 1. List of Laboratory Tests ...................................................................................33 
Table 2. Adverse Event Term Definition .......................................................................34 

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Table 3. Definition of Terms ...........................................................................................36 
Table 4. Severity Assessments .........................................................................................38 
Table 5. Causality Assessment ........................................................................................38 
Table 6. Outcome Conclusion .........................................................................................39 
Table 7. Study Administrative Structure.......................................................................50 
 
List of In-Text Figures 
Figure 1. Trial Schematic ................................................................................................18 
 
List of Appendices 
Appendix 1 Schedule of Evaluations and Procedures ..................................................58 
Appendix 2 Schedule of Clinical Laboratory Evaluations ...........................................60 
Appendix 3 Formulas for Calculation of Endpoints .....................................................62 
Appendix 4 Sponsor Signatures ......................................................................................64 
Appendix 5 Investigator’s Signature ..............................................................................66 
 

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SYNOPSIS 
Sponsor: 
Baxter Healthcare Corporation 
One Baxter Parkway 
Deerfield, IL 60015 
Name of Finished Product: 
Theranova 400 Dialyzer  
Comparator Product:  
Elisio-17H Dialyzer 
Study Title: 
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  
Study Number: 
7905001 
Study Phase:  
Not Applicable 
Primary Objective(s):  
The primary efficacy objective of this study is to demonstrate that the Theranova 400 dialyzer has 
performance superiority to the Elisio-17H dialyzer in removing lambda immunoglobulin free light chains 
(λ FLCs). 
The primary safety objective of this study is to demonstrate that performance of the Theranova 400 dialyzer 
compared to the Elisio-17H dialyzer is non-inferior, in regards to maintaining pre-dialysis serum albumin. 
Secondary Objective(s): 
The secondary objectives of this study are to evaluate the performance of the Theranova 400 dialyzer 
compared to the Elisio-17H dialyzer in removing serum middle molecules, dialysis adequacy, levels of 
coagulation factors, and characterize monthly trends in pre-dialysis serum albumin levels. 
Study Design: 
This is a multi-center, prospective, randomized, controlled, open-label, parallel study to evaluate medically 
stable end stage renal disease (ESRD) patients receiving dialysis treatment with either the Theranova 400 
dialyzer or the Elisio-17H dialyzer for 3 sessions weekly, over 24 weeks. 
Study Population:  
The study population consists of subjects with ESRD who have been stable and receiving hemodialysis 
(HD) therapy at least 3 times a week for 3 months prior to enrollment. A sufficient number of patients will 
be enrolled in the study in order to randomize one hundred and sixty-six (166) patients in a 1:1 manner to 
either Theranova 400 dialyzer or the Elisio-17H dialyzer. The study will be conducted in up to thirty (30) 
study centers in the USA. 
Test Product and Mode of Administration:  
Theranova 400 dialyzer, a medium cut-off dialyzer. 
Duration of Treatment:  
Up to 24 weeks. 
Efficacy Assessments: 
The primary efficacy endpoint is the Reduction Ratio (RR) of λ FLC after 24 weeks of treatment. 
Secondary efficacy endpoints include: 
• 
Reduction ratio of λ FLC measured on the first day of treatment and after 4 weeks of treatment. 

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• 
Reduction ratio of complement factor D (CFD; MW = 27 kDa), κ FLC (MW = 23 kDa), 
interleukin 6 (IL-6; MW = 25 kDa), tumor necrosis factor alpha (TNFα; MW = 51 kDa), and β2-
microglobulin (MW = 11.6 kDa) measured after 4 weeks and after 24 weeks of treatment. 
• 
Change in pre-dialysis β2-microglobulin measured on the first day of treatment and after 24 weeks 
of treatment. 
• 
Kt/Vurea measured after every 4 weeks of treatment. 
Safety Assessments: 
The primary safety endpoint is the pre-dialysis serum level of albumin after 24 weeks of treatment. 
Secondary safety endpoints include: 
• 
Pre-dialysis serum albumin measured on the first day of treatment and after every 4 weeks of 
treatment. 
• 
Pre-dialysis Factor VII (MW = 50 kDa), Protein C (MW = 53-62 kDa) and Factor II (MW = 72 
kDa) measured on the first day of treatment, after 4 weeks and after 24 weeks of treatment. 
• 
Pre-dialysis Vitamin A measured on the first day of treatment, after 4 weeks and after 24 weeks of 
treatment. 
• 
nPNA(nPCR) [normalized Protein equivalent of Nitrogen Appearance (normalized Protein 
Catabolic Rate)] calculated after every 4 weeks of treatment. 
• 
Change from baseline to final measure in chemistry and hematology laboratory tests. 
• 
Monitoring of adverse events (AEs), serious adverse events (SAEs) and Product Complaints (PCs) 
for Baxter related devices. 
Statistical Methods:  
Determination of Sample Size: 
The sample size for this study is driven by the primary safety endpoint. The sample size calculation was 
performed using PASS procedure Non-inferiority Tests for the Difference Between Two Means. The power 
is based on a t-test with one-sided alpha level of 0.025 where the true difference in means is assumed to be 
zero (0) and the non-inferiority margin is 5%. 
Pre-dialysis serum albumin was not evaluated in the previous Theranova 400 dialyzer HD study, only the 
mass (G) of albumin in the dialysate was assessed. However, a study published in PLoS ONE did use a 
prototype of the Theranova dialyzer (MCO-CI) where in pre-dialysis albumin levels were collected after a 
month of therapy and, based on these data, a mean and standard deviation (SD) of 35.3 and 3.7 was 
observed. Comparable pre-dialysis albumin levels are expected with body study dialyzers and with sample 
size of 70 patients per group, a t-test with 0.025 one-sided significance level will have 80% power to 
demonstrate non-inferiority of the Theranova 400 dialyzer compared to the Elisio-17H dialyzer as assessed 
by pre-dialysis serum albumin with a non-inferiority margin of 5%. To allow for 15% of patients to drop 
out, a total of 166 patients will be randomized 1:1 to treatment with the Theranova 400 dialyzer or 
treatment with the Elisio-17H dialyzer (i.e. 83 patients per group). 
The 5% non-inferiority margin is based on results from 2 observational studies. These studies looked at the 
association between serum albumin levels and mortality in large US cohorts of HD and PD patients, 
respectively. In both, variations in serum albumin of +/- 1 g/L over 6 months (corresponds to +/- 0.1 g/dL) 
have been defined as “stable serum albumin levels”. A variation of +/- 1 g/dL is a range with a width of 2 
g/L, which is larger than 5% if applied to the reported mean baseline serum albumin levels. Therefore, a 
5% variation in serum albumin can be justified as having no clinical significance. 
 A previously conducted Theranova 400 dialyzer prototype HDF study was used to obtain λ FLC reduction 
ratio mean and standard deviation (SD) of 37.8 and 8.26. With a total sample size of 140 evaluable subjects 
as determined based on the primary safety endpoint (70 in the Theranova 400 dialyzer treatment group and 
70 in the Elisio-17H dialyzer treatment group), a difference of 4.56 in the λ FLC reduction ratio in favor of 
the Theranova 400 dialyzer can be detected with 90% power at a two-sided 0.05 significance level using a 
two-sided two-sample t-test assuming equal variances. Analysis Populations: 
The Per-protocol (PP) set will include all randomized patients who have received at least three months 

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treatment with a study dialyzer and do not have any major protocol violations that might impact the 
primary analysis. 
The intent-to-treat full analysis (FA) set will include all randomized. 
The primary analyses will be performed on the FA set and supported by an analysis using the PP set. All 
other analyses will be performed on the FA set unless otherwise noted. 
Primary Safety Endpoint: 
For the primary safety endpoint of pre-dialysis serum albumin after 24 weeks of treatment, let µT denote the 
Theranova dialyzer pre-dialysis serum albumin mean and let µR denote the Elisio-17H dialyzer pre-dialysis 
serum albumin mean. Then the null hypothesis to demonstrate non-inferiority using a 5% margin can be 
expressed as 
Ho: µT- µR ≤ -1.765. The alternative hypothesis is expressed as Ha µT- µR > -1.765. 
An ANCOVA model with fixed effects of treatment and site and the continuous fixed covariate of baseline 
pre-dialysis serum albumin will be used to generate a two-sided 95% confidence interval (CI) for the 
difference in treatment means (µT- µR). If the lower bound is > -1.765 then non-inferiority will be 
demonstrated.  
Primary Efficacy Endpoint: 
For the primary efficacy endpoint of RR of λ FLC after 24 weeks of treatment, let µT denote the Theranova 
dialyzer RR of λ FLC mean at 24 weeks and let µR denote the Elisio-17H dialyzer RR of λ FLC mean at 24 
weeks. 
The primary safety analysis will be conducted first. If the primary safety analysis demonstrates non-
inferiority, an ANCOVA model with fixed effects of treatment and site will be used to generate a two-sided 
95% CI for the difference in treatment means (µT- µR). If the lower bound is > 0 then superiority will be 
demonstrated.  The statistical testing of the primary efficacy endpoint of the reduction ratio (RR) of λ FLC 
after 24 weeks of treatment is contingent upon the outcome of the analysis of the primary safety endpoint 
and will only be conducted once non-inferiority could be established for the primary safety endpoint. This 
hierarchical testing approach guarantees that the overall type 1 error is controlled at a two-sided 0.05 
significance level. 
Secondary Safety Endpoint(s): 
Pre-dialysis serum albumin: 
A Mixed-effect Model Repeated Measurement (MMRM) model will be used to evaluate differences 
between treatment groups in the change from baseline in pre-dialysis serum albumin after each four weeks 
of treatment. The model will include the fixed effect of treatment, visit; the continuous, fixed covariate of 
baseline measurement; and the random effect of patient.  
Pre-dialysis serum albumin will be further categorized at baseline and final measurement into 4 categories: 
<3.5, ≥3.5-3.9, ≥4.0-4.4, ≥4.5. Shift tables will be generated to cross tabulate the number of patients within 
each category by treatment. 
Pre-dialysis Factor VII, Protein C, Vitamin A, and Factor II: 
An MMRM model will be used to evaluate the differences between treatment groups in the change from 
baseline in pre-dialysis Factor VII, Protein C, Vitamin A, and Factor II after 4 weeks and after 24 weeks of 
treatment. The model will include the fixed effect of treatment, visit the continuous, fixed covariate of 
baseline measurement; and the random effect of patient.  
nPNA (nPCR): 
An MMRM model will be used to evaluate differences between treatment groups in nPNA (nPCR) 
collected after each 4 weeks of treatment. The model will include the fixed effect of treatment, visit, and 
the random effect of patient.  
AEs, SAEs, and Product Complaints: 
The summary of AEs will include AEs that occur on the day of or after the first study treatment. Adverse 
events will be mapped to a Primary System Organ Class (SOC) and Preferred Term (PT) according to 
MedDRA and summarized descriptively by SOC, PT and treatment group. Treatment group comparability 
in the incidence rates of adverse events will be evaluated using Fisher’s exact test. 

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An overview (overall) summary table of all AEs will be generated that includes the total number of AEs, 
number and percentage of patient with at least one AE, number and percentage of patients with at least one 
SAE, number and percentage of patients with at least one severe AE, number and percentage of patients 
with at least one AE probably associated with study treatment, number and percentage of patients with an 
AE leading to study discontinuation and, number and percentage of patients with an AE leading to death. 
This summary table will be presented by treatment group and combining both groups (Total). 
Furthermore, separate AE summary tables will be provided by SOC and PT for SAEs and AEs leading to 
study withdrawal. Separate AE summary tables will be provided to show a breakdown of AEs by SOC, PT 
and 
a. 
Severity (mild, moderate or severe) 
b. Relationship to study treatment (probably related, possibly related, unable to determine, unlikely 
related or not related). 
Study dialyzer related product complaints will be summarized descriptively by study dialyzer. 
Chemistry and hematology: 
Mean differences between treatment groups in the change from baseline to final measure in chemistry and 
hematology laboratory tests will be analyzed using an ANCOVA with a fixed effect of treatment and a 
fixed continuous covariate of baseline laboratory value. 
Secondary Efficacy Endpoint: 
In order to account for multiplicity, secondary efficacy analyses will be held to a hierarchical assessment 
and performed in the order outlined below. If the first analysis results in a p-value <0.05, then formal 
testing will continue to the second analysis. If the second analysis also results in a p-value of <0.05, then 
formal testing will continue to the third analysis, and so on. This method of hierarchical assessment will 
continue until an analysis results in a p-value >0.05, i.e., is considered statistically insignificant. This 
hierarchical approach guarantees that the overall alpha will not exceed 0.05. 
1. MMRM of RR of λ FLC 
2. MMRM of RR of CFD 
3. MMRM of RR of κ FLC 
4. MMRM of RR of IL-6 
5. MMRM of RR of TNFα 
6. MMRM of RR of β2-microglobulin 
7. Change in pre-dialysis β2-microglobulin from baseline to 24 weeks 
8. MMRM of Kt/Vurea 
An MMRM model will be used to evaluate differences between treatment groups in the reduction ratios of 
λ FLC, CFD, κ FLC, IL-6, TNFα, and β2-microglobulin after 4 weeks and after 24 weeks of treatment. The 
model will include the fixed effect of treatment, visit, and the random effect of patient.  
An ANCOVA with a fixed effect of treatment and a fixed continuous effect of baseline pre-dialysis β2-
microglobulin will be used to evaluate differences between treatment groups for the change from baseline 
in pre-dialysis β2-microglobulin after 24 weeks of treatment. 
An MMRM model will be used to evaluate differences between treatment groups in Kt/Vurea collected after 
each 4 weeks of treatment. The model will include the fixed effect of treatment, visit, and the random effect 
of patient. 
Exploratory Endpoints: 
An MMRM model will be used to evaluate differences between treatment groups in the change from 

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baseline in pre-dialysis serum levels of High sensitivity C-reactive Protein (hs-CRP) after each 4 weeks of 
treatment. The model will include the fixed effect of treatment, visit, as well as the continuous, fixed 
covariate of baseline measurement and the random effect of patient. 
An MMRM model will be used to evaluate differences between treatment groups in the change from first 
day of treatment in KDQOL-36 and EQ-5D-5L after 12 weeks and after 24 weeks of treatment. The model 
will include the fixed effect of treatment, visit,  as well as the continuous, fixed covariate of screening 
measurement and the random effect of patient. 
Appropriate models will be used to evaluate differences between treatment groups in the utilization for 
medications (i.e., Erythropoiesis-stimulating agent (ESA), anti-hypertensives, iron). 
Interim Analysis: 
 An interim analysis will be conducted when 60% of enrollment is completed. The purpose of the interim 
analysis is a blinded sample size reassessment using the approach by Friede and Kieser for an absolute 
difference in means which is based on the observed one-sample standard deviation calculated from the 
pooled data across treatment groups. This blinded sample size reassessment will be carried out by an 
independent statistician (who otherwise is not involved in the study conduct) using the 8 week 
measurements of the pre-dialysis serum albumin levels after 100 total patients have been enrolled 
(assuming 15% drop out, this corresponds to 84 evaluable patients). In case the observed pooled standard 
deviation at 8 weeks is larger than the assumed standard deviation of 3.7, the method will require an 
increase in overall sample size in order to maintain an overall power of 80%. If the observed standard 
deviation is smaller than the assumed standard deviation of 3.7, the overall sample size will be kept at 166. 
Date of Original Approved Protocol: 2017 JUN 12 
Date of Amendment 1 of Protocol: 2017 JUL 25 
Date of Amendment 2 of Protocol: 2017 AUG 31 
Date of Amendment 3 of Protocol: 2017 OCT 11 
Date of Amendment 4 of Protocol: 2017 OCT 25 
Date of Most Recent Protocol Amendment: 2018 FEB 09 
Prepared in: Microsoft Word 2010 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase (SGPT) 
AST 
Aspartate Aminotransferase (SGOT) 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CFD 
Complement Factor D 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CO2 
Carbon Dioxide 
COV 
Coefficient of Variation 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
EQ-5D-5L 
EuroQol Five Dimensions Questionnaire 
ESA 
Erythropoiesis-Stimulating Agent 
ESRD 
End Stage Renal Disease 
FA 
Full Analysis 
FDA 
Food and Drug Administration 
FLC 
Free Light Chains 
GCP 
Good Clinical Practice 
HD 
Hemodialysis 
HDF 
Hemodiafiltration 
HIPAA 
Health Information Portability and Accountability Act 
hs-CRP 
High-sensitivity C-Reactive Protein 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
IDE 
Investigational Device Exemption 
IL-6 
Interleukin 6 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
KDQOL-36 
Kidney Disease Quality of Life Questionnaire 
Kt/Vurea 
Dimensionless number used to quantify hemodialysis and peritoneal dialysis adequacy 
MedDRA 
Medical Dictionary for Regulatory Activities 

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MMRM 
Mixed-effect Model Repeated Measurement 
MW 
Molecular Weight 
nPCR 
normalized Protein Catabolic Rate 
nPNA 
normalized Protein equivalent of Nitrogen Appearance 
PC 
Product Complaint 
PD 
Peritoneal Dialysis 
PI 
Principal Investigator 
PP 
Per-Protocol 
PRO 
Patient Reported Outcome 
PT 
Preferred Term 
PUR 
Polyurethane 
QB 
Blood Flow Rate 
QD 
Dialysate Flow Rate 
RCT 
Randomized Controlled Trial 
RR 
Reduction Ratio 
RRT 
Renal Replacement Therapy 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SGOT 
Serum Glutamic Oxaloacetic Transaminase (AST) 
SGPT 
Serum Glutamic Pyruvic Transaminase (ALT) 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TNFα 
Tumor Necrosis Factor Alpha 
USA 
United States of America 
β-hCG 
Beta Human Chorionic Gonadotropin 

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1. INTRODUCTION 
1.1 Background and Rationale 
The incidence and prevalence of chronic kidney disease are increasing worldwide, as is 
the number of patients progressing to end stage renal disease (ESRD). The number of 
patients with ESRD has been increasing by 5% to 8% per annum in higher-income 
countries, and by the same rate or more in lower-income countries.1-5 The incidence rate 
of treated ESRD in the United States of America (USA) was 370 per million 
population/year for 2014, and the prevalence of treated ESRD patients was 2076 per 
million population for 2014. In the USA alone, there was a 1.1% increase in new ESRD 
cases and 3.8% increase of patients treated for ESRD from 2013 to 2014.6 Understanding 
these trends is important in evaluating and predicting the global impact of ESRD on 
public health. 
Without renal replacement therapy (RRT), either in the form of maintenance dialysis or 
transplantation, ESRD is fatal. Given the limited supply of donor kidneys, dialysis 
remains the mainstay treatment for patients with ESRD. Although dialysis is more 
commonly used in ESRD patients requiring chronic RRT (> 30 days), it can also be used 
in clinical settings of acute kidney injury. Dialysis may be prescribed when less than 10% 
of kidney function remains available. Dialysis may be started even earlier in patients with 
serious complications, such as volume overload (usually secondary to acute heart failure), 
hyperkalemia, metabolic acidosis, or if renal failure cannot be controlled by medication. 
Patients undergoing hemodialysis (HD) therapy receive treatments intermittently for a 
specific number of hours per session and a specific number of sessions per week. All 
extracorporeal dialytic therapies require the removal of blood from the patient’s 
circulatory system and the circulation of this blood through a circuit. This circuit contains 
a semi-permeable membrane within a dialyzer device to remove nitrogenous end-
products of catabolism and begin the correction of the salt, water and acid-base 
derangements associated with renal failure. As dialysis treatment requires access to the 
blood circulation, a vascular access is required, which can be in the form of a fistula, 
graft or a HD catheter. 
The molecular weight (MW) range of uremic toxins, including β2-microglobulin, free 
light chains (FLCs), cytokines and other inflammatory mediators, is about 10 to 50 kDa. 
There is a growing body of evidence that large uremic solutes in the range of 20 to 50 
kDa play a significant role in clinical complications in dialysis patients.7-10 Recent 
reviews on uremic toxicity indicate that an abundance of middle molecules accumulate in 
serum leading to uremia; many uremic toxins are in a size above 15 kDa.11 Other 

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investigators have shown that some of those proteins, particularly isoforms containing 
post-translational modifications induced by the uremic environment, qualify as uremic 
toxins. Emerging evidence based on new methodology suggests that some of the 
morbidity associated with uremia is the result of the collective retention of many such 
modified proteins, suggesting a role for dialytic strategies aimed at their collective 
removal. 
While conventional high-flux membranes are designed to remove β2-microglobulin 
effectively, the removal of larger middle molecules is substantially less effective when 
such membranes are used in HD12 due to the rapid fall-off in diffusive clearance with 
increasing molecular size.13 Hemodiafiltration (HDF) is a therapy designed to increase 
convective solute removal when conventional high-flux membranes are used, with a 
special focus on middle molecule uremic solutes.14 Hemodiafiltration is increasingly 
practiced in Europe, and many other parts of the world outside USA, recently estimated 
to account for approximately 27% of hemodialysis treatments in Europe.15 Although an 
HDF system has been approved for use in USA (K112314, April 2012), its use in USA is 
negligible. 
Hemodiafiltration has shown to offer outcome benefits in large randomized controlled 
trials (RCTs). However, special equipment and large volumes of replacement fluid are 
needed to deliver HDF at a treatment dose for which outcome benefits have been 
demonstrated in RCTs. With the Theranova dialyzer, a middle molecule clearance 
equivalent to HDF therapy can be obtained without the need to use the more complex 
equipment and high volumes of replacement fluid. Replacement fluid is used in HDF 
therapy as it addresses middle sized uremic solutes, while sparing larger sized molecules 
such as albumin. 
1.2 Benefits and Risks for the Study Population 
The risks and benefits of hemodialysis are well characterized. The same risks and 
benefits will apply to patients undergoing dialysis with Theranova dialyzers. During 
dialysis, toxins and beneficial molecules can be removed. Theranova dialyzers can 
remove a larger size range of molecules, therefore patients may see greater removal of 
“middle molecules”, including coagulation factors. Studying these molecules in vivo is 
expected to complement previous in vitro investigations on single (simulated) treatment 
removal of coagulation factors by providing longer term data. 
Studies of therapies that remove middle molecules more effectively than HD with typical 
high permeability dialyzers do not suggest that there is an increased risk from removing 
solutes of this size, and indicate that there may be benefits to removal of the uremic 

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toxins. The recent progress in dialysis treatment may improve the removal of these toxins 
and though there is insufficient evidence on reducing mortality there may be benefits on 
patient outcomes.12 
Although the Theranova dialyzer is known to remove more albumin per treatment than 
high-flux dialyzers, the albumin sieving of the membrane is <1%, which is below what is 
given by Ward as definition of protein-leaking membranes (1-3%). The average clinical 
albumin loss of 3 g per 4 h hemodialysis session16 is also at the lower end of his 
definition (2-6 g/4 h). Increased patient mortality is correlated with low serum albumin 
levels, but not directly correlated with albumin loss per treatment. Human serum albumin 
homeostasis in general and in various disease states17, particularly in patients on dialysis, 
has been extensively reviewed. Although observational studies have shown a significant 
association between lower serum albumin level and greater risk of all-cause death, in HD 
patients as well as in peritoneal dialysis (PD) patients recent research has led to the 
conclusion that the association between serum albumin and outcome is principally 
mediated by inflammation and that, at least in renal failure patients, there is evidence that 
plasma concentration is determined primarily by the rate of liver albumin synthesis, and 
this synthesis is decreased in inflammatory states. Albumin is a negative acute phase 
reactant and uremic inflammation, which is common in dialysis patients, is a main 
determinant of a low serum albumin level through reduced synthesis of albumin.18,19 
Inflammation is in itself a significant and powerful risk factor for poor outcome in 
dialysis patients.20 
1.3 Study Sponsor 
Baxter Healthcare Corporation 
One Baxter Parkway 
Deerfield, IL 60015 USA 
2. STUDY OBJECTIVES 
2.1 Primary Objective(s) 
The primary efficacy objective of this study is to demonstrate that the Theranova 400 
dialyzer has performance superiority to the Elisio-17H dialyzer in removing lambda 
immunoglobulin free light chains (λ FLCs). 
The primary safety objective of this study is to demonstrate that performance of the 
Theranova 400 dialyzer compared to the Elisio-17H dialyzer is non-inferior, in regards to 
maintaining pre-dialysis serum albumin. 

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2.2 Secondary Objective(s) 
The secondary objectives of this study are to evaluate the performance of the Theranova 
400 dialyzer compared to the Elisio-17H dialyzer in removing serum middle molecules, 
dialysis adequacy, levels of coagulation factors, and characterize monthly trends in pre-
dialysis serum albumin levels. 
2.3 Exploratory Objectives 
The exploratory objectives for this study include: 
• Evaluation of patient reported quality-of-life assessments. 
• Evaluation of serum levels of the inflammatory marker high sensitivity C-
Reactive Protein. 
3. INVESTIGATIONAL PLAN 
3.1 Overall Study Design and Plan 
This is a multi-center, prospective, randomized, controlled, open-label, parallel study to 
evaluate medically stable ESRD patients receiving dialysis treatment with either the 
Theranova 400 dialyzer or the Elisio-17H dialyzer for 3 sessions weekly, over 24 weeks. 
A sufficient number of patients will be enrolled in the study in order to randomize 166 
patients in a 1:1 manner to either the Theranova 400 dialyzer or the Elisio-17H dialyzer. 
The study will be conducted in up to 30 study centers in the USA. 
The study will have an overall duration of approximately 27 weeks per patient. This 
period will consist of up to 2 weeks screening period, followed by a first treatment day 
visit and consequent3 dialysis sessions per week in an in-center setting over a 24 week 
period, at the end of the study there will be a visit occurring on the next HD session. The 
assessments performed, on a monthly basis, are shown in the Schedules of Evaluation in 
Appendix 1 and Appendix 2. Patients will initiate their HD treatment on their randomized 
study dialyzer, either Theranova 400 dialyzer or Elisio-17H dialyzer, at the midweek HD 
session (Wednesday or Thursday), and will then continue to have 3 dialysis sessions per 
week. During the treatment period, initial blood samples will be taken on the day of the 
first study dialyzer treatment and subsequent blood sampling samples will be taken after 
each 4 weeks of treatment, during the midweek HD session as illustrated in Appendix 1. 
A scheme for the study is shown in Figure 1 below. The overall duration of the complete 
study will be approximately 9 months to allow sufficient time for patient recruitment.

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3.2 Study Endpoints 
3.2.1 Primary Endpoints 
The primary efficacy endpoint is the Reduction Ratio (RR) of λ FLC after 24 weeks of 
treatment. 
The primary safety endpoint is the pre-dialysis serum level of albumin after 24 weeks of 
treatment. 
3.2.2 Secondary Endpoints 
Secondary efficacy endpoints include: 
• Reduction ratio of λ FLC measured on the first day of treatment and after 4 weeks 
of treatment. 
• Reduction ratio of complement factor D (CFD; MW = 27 kDa), κ FLC (MW = 23 
kDa), interleukin 6 (IL-6; MW = 25 kDa), tumor necrosis factor alpha (TNFα; 
MW = 51 kDa), and β2-microglobulin (MW = 11.6 kDa) measured after 4 weeks 
and after 24 weeks of treatment. 
• Change in pre-dialysis β2-microglobulin measured on the first day of treatment 
and after 24 weeks of treatment. 
• Kt/Vurea measured after every 4 weeks of treatment. 
Secondary safety endpoints include: 
• Pre-dialysis serum albumin measured on the first day of treatment and after every 
4 weeks of treatment. 
• Pre-dialysis Factor VII (MW = 50 kDa), Protein C (MW = 53-62 kDa) and Factor 
II (MW = 72 kDa) measured on the first day of treatment, after 4 weeks and after 
24 weeks of treatment. 
• Pre-dialysis Vitamin A measured on the first day of treatment, after 4 weeks and 
after 24 weeks of treatment. 
• nPNA (nPCR) calculated after every 4 weeks of treatment. 
• Change from baseline to final measure in chemistry and hematology laboratory 
tests (see Table 1). 
• Monitoring of adverse events (AEs), serious adverse events (SAEs) and product 
complaints (PCs) for Baxter related devices. 

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3.2.3 Exploratory Assessments 
Exploratory assessments include: 
• Inflammatory marker high-sensitivity C-Reactive protein (hs-CRP) measured pre-
dialysis on the first day of treatment and after every 4 weeks of treatment. 
• KDQOL-36 measured on the first day of treatment, after 12 weeks and after 24 
weeks of treatment. 
• EQ-5D-5L measured on the first day of treatment, after 12 weeks and after 24 
weeks of treatment. 
• Changes in utilization for medication (i.e., erythropoiesis-stimulating agent (ESA), 
anti-hypertensives, iron). 
3.3 Rationale for Study Design and Control Group 
This multi-center, prospective, randomized, controlled, open-label, parallel study is 
designed to demonstrate superiority of the Theranova 400 dialyzer compared to the 
Elisio-17H dialyzer in regards to removal of λ FLCs and safety of the Theranova 400 
dialyzer during extended use (study duration 24 weeks). The Elisio-17H dialyzer is a 
marketed, Food and Drug Administration (FDA) cleared hemodialyzer device with 
comparable design, membrane polymers and surface area, and performance specifications 
to the study device. The main difference between the Theranova 400 dialyzer and the 
Elisio-17H dialyzer is the larger pore size within the Theranova 400 dialyzer, which 
allows a wider range of molecules to diffuse across the device membrane without the 
need of convection. 
Both devices will be studied in medically stable patients who require chronic 
hemodialysis therapy due to end stage renal disease. The dialysis prescriptions for the 
Theranova 400 dialyzer follow the same method as for a conventional high-flux dialyzer; 
no device-specific modifications to the dialysis prescriptions are required. Use of the 
study devices during the study treatment period is consistent with conventional, current 
institutional practice.21 
Benefits of the Theranova dialyzer products are associated with the removal of serum 
middle molecules. The removal of serum middle molecules such as λ FLCs, may be 
associated with a reduction in both patient morbidity and mortality.22-25 Data from this 
clinical study will also be used to support the new device classification for Theranova 
dialyzer, as a new device modality that effectively reduces serum levels of middle 
molecules such as λ FLCs during individual HD treatments. 

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As part of this evaluation, Baxter has chosen to study representative beneficial molecules 
in addition to uremic toxins. Baxter has selected three beneficial molecules to study. The 
pre-dialysis serum levels of the following molecules will be measured on the first day of 
treatment, after 4 and after 24 weeks of treatment: 
1. Factor VII (Activates IX, X): 50,000 Da (bleeding diathesis) 
2. Protein C: 53,000-62,000 Da (deficiency causes hypercoagulable state) 
3. Factor II: 72,000 Da (deficiency causes bleeding disorder) 
In addition, Vitamin A levels will be measured on the first day of treatment, after 4 weeks 
and after 24 weeks of treatment. 
We have focused on coagulation factors because coagulation abnormalities such as 
hypercoagulability and thrombosis are common in patients with end stage renal disease 
on maintenance hemodialysis. The selected molecules have deficiencies that manifest 
phenotypically, are well described (Factor VII deficiency, Factor II deficiency, Protein C 
deficiency), and represent different parts of the coagulation cascade. They are too large to 
be effectively removed by high-flux hemodialysis only, but represent the higher end of 
the Theranova dialyzer removal range. Studying these molecules in vivo is also expected 
to complement previous in vitro investigations on single (simulated) treatment removal of 
coagulation factors by providing longer term data for potential changes in coagulation 
factors. Baxter believes that the comparison of the Theranova dialyzer cohort to the high-
flux dialysis control group will examine the significance of changes in serum levels. 
3.3.1 Other Considerations 
The participating healthcare professionals must be familiar with the use of both 
Theranova 400 dialyzer and Elisio-17H dialyzer. All participating healthcare 
professionals will be trained on both types of dialyzers before the first patient is treated. 
3.4 Study Duration and Dates 
Patients will undergo 3 dialysis sessions per week, for 24 weeks. The participating 
patients should continue with their pre-study HD prescriptions (in terms of treatment time, 
blood flow rate and dialysate flow rate) and prescriptions should be kept stable 
throughout the study. 
3.5 Study Discontinuation Rules 
The study should be suspended if suspicion of an unacceptable risk to the patients arises 
during the clinical investigation, or when instructed by the Institutional Review Board 

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(IRB) or regulatory authorities. Risks to patients could be indicated when any of the 
following events occur: 
• Device malfunction, considered by the investigators and/or Baxter Healthcare as 
possibly leading to a deficiency in the patient’s treatment 
• Repeated patient discomfort with the product 
• Unexpected/Unanticipated Serious Adverse Device Effect (SADE) 
The Sponsor shall review untoward events and assess risks during the conduct of the 
clinical investigation. Decision to restart the study will be made jointly by Baxter 
Healthcare and the coordinating investigator following evaluation of the problems 
encountered and implementation of mitigation steps. The Sponsor shall terminate the 
clinical investigation if an unacceptable risk is confirmed to be not mitigatable. 
3.5.1 Procedure for Resuming the Clinical Investigation after Temporary 
Suspension 
When the Sponsor concludes an analysis of the reasons(s) for the study suspension, 
implements the necessary corrective actions and decides to lift the temporary suspension, 
the Sponsor shall inform the principal investigators (PIs), the IRB, and where appropriate, 
the regulatory authority of the rationale and provide them with the relevant data 
supporting this decision. 
Concurrence shall be obtained from the IRB and, where appropriate, regulatory 
authorities before the clinical investigation resumes. 
If patients have been informed of the suspension, the PI or authorized designee shall 
inform them of the reasons for resumption. 
4. STUDY POPULATION SELECTION 
4.1 Study Population 
The study population consists of subjects with ESRD who have been stable and receiving 
HD therapy at least 3 times a week for 3 months prior to enrollment. A sufficient number 
of patients will be enrolled in the study in order to randomize 166 patients in a 1:1 
manner to either Theranova 400 dialyzer or the Elisio-17H dialyzer. The study will be 
conducted in up to 30 study centers in the USA. 
4.2 Inclusion Criteria 
All of the following criteria must be met for the patient to be enrolled in this study. 

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1. ESRD patients age 22 and older, or between ages 18 and 21 with a weight ≥ 40 kg. 
2. 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. 
3. 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. 
4. Expected to maintain an acceptable urea clearance (Kt/V) with a dialyzer of an 
approximate surface area of 1.7 m2. 
5. Currently being dialyzed at an in-center setting, on a schedule of 3 times per week. 
6. 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. 
7. 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. 
 
4.3 Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study. This 
study will exclude subjects who: 
1. Are female and pregnant, lactating, or planning to become pregnant during the 
study period. Note: Female subjects of childbearing potential, defined as women 
< 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. 
2. Have chronic liver disease. 
3. Have a known paraprotein-associated disease. 
4. Have known bleeding disorders (e.g., gastrointestinal bleed, colonic polyps, small 
bowel angiodysplasia, and active peptic ulcers). 

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5. 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. 
6. Have had a blood (red blood cell) transfusion ≤ 12 weeks prior to randomization. 
7. Have had an acute infection ≤ 4 weeks prior to randomization. 
8. Have active cancer, except for basal cell or squamous cell skin cancer. 
9. Have a known serum κ/λ FLC ratio that is less than 0.37, or greater than 3.1.b 
10. Have a known monoclonal gammopathy (monoclonal gammopathy of uncertain 
significance, smoldering [asymptomatic] multiple myeloma, symptomatic 
multiple myeloma, plasmacytomas, or plasma cell leukemia). 
11. Have a known polyclonal gammopathy (connective tissue disease, liver disease, 
chronic infection, lymphoproliferative disorder, or other hematologic conditions). 
12. Have a positive serology test for human immunodeficiency virus or hepatitis 
infection. 
13. Have a significant psychiatric disorder or mental disability. 
14. Are scheduled for planned interventions requiring hospitalization > 1 week. 
15. 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. 
16. Are currently participating in another interventional clinical study or has 
participated in another interventional clinical study in the past 3 months. 
17. Have a history of non-compliance with HD as assessed by an investigator. 
18. Have had a major cardiovascular or cerebrovascular event within 3 months of 
study entry. 
19. Have a history with consistent evidence of intradialytic hypotension. 
20. Have uncontrolled (systolic blood pressure (BP) > 180 mmHg) hypertension. 
21. Have had adverse reactions to dialyzer materials. 
                                                 
b In patients with renal impairment 0.37 to 3.1 is the normal range for serum κ/λ FLC ratio. 

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4.4 Recruitment 
Recruitment for the study will commence after review and approval from the IRB for 
each respective study center. After the patient has received the Informed Consent Form 
(ICF) and allowed time to consider their participation in the study, inclusion and 
exclusion criteria will be verified. Patients will be considered enrolled in the study once 
the ICF has been signed and inclusion/exclusion criteria have been confirmed. 
4.5 Removal of Patients from Therapy, Assessment, or Study 
Patients are considered withdrawn/prematurely discontinued from the study if their 
participation is discontinued before completion of the required evaluations as described 
in this protocol. Patients may be withdrawn/prematurely discontinued for any of the 
following reasons: 
1. AE 
2. Inadequate dialysis based on Investigator judgement 
3. Protocol violations (i.e. the patient fails to meet protocol entry criteria or does not 
adhere to protocol requirements) 
4. Pregnancy 
5. Lost to follow-up (i.e. patient fails to return for study visits) 
6. Voluntary withdrawal (i.e. patient’s request) 
7. Termination of study 
8. Investigator’s discretion 
9. Renal transplantation 
10. Switch to PD 
11. Death 
12. Change to another dialysis center, that is not a clinical study site 
13. Missing 3 consecutive study treatments 
14. Other reason (with reason noted on the electronic case report form [eCRF]) 
The Investigator may terminate a patient’s study participation at any time during the 
study if he/she judges it to be in the patient’s best interest. In addition, a patient may 
discontinue his or her participation any time during the study without having to justify 
his/her decision. If a patient’s participation is discontinued, the reason(s) must be 
recorded in the source documents and on the eCRF. If a patient discontinues for any 
reason, every effort should be made to perform all of the procedures that are scheduled 

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for the follow-up visit occurring at the pre-dialysis on the next treatment day. In addition, 
SAEs (related or not) and adverse device effects (ADEs), will be followed until 
resolution or stable, including following the patient after the end of the study if necessary. 
The Investigator or designee should inform their site monitor the moment any patient is 
withdrawn or discontinued from the study, regardless of the reason(s) for withdrawal or 
discontinuation. 
4.6 Missed Visits 
In general, missed dialysis session visits will not be replaced. If a patient misses a mid-
week dialysis session, where a study treatment visit was scheduled to occur, the missed 
study visit procedures will be performed during the next mid-week dialysis session and 
subsequent visits and follow-up visit will occur as planned. However, if the patient fails 
to return for that mid-week dialysis session and also misses the subsequent week (a third 
mid-week session), then the patient will be terminated from the study. Study termination 
also applies if the patient misses 3 consecutive study treatments (i.e. missing a full week 
of dialysis). Reasons for missed visits will be captured on the eCRF. 
5. STUDY TREATMENT(S) 
5.1 Description of Treatment(s) 
5.1.1 Study Device – Theranova 400 dialyzer 
Theranova dialyzers are indicated for treatment of chronic and acute renal failure by 
dialysis. This study is intended to support an indication for extended hemodialysis to 
remove middle molecular uremic toxins. 
The membrane used in Theranova 400 dialyzer is a blend of polyarylethersulfone and 
polyvinylpyrrolidone. Each hollow fiber has an inner diameter of approximately 180 µm 
and a wall thickness of approximately 35 µm, the effective membrane length is 236 mm, 
with an effective surface area of 1.7 m2. On each end of the device the hollow fibers are 
potted in polyurethane (PUR) to isolate the blood compartment from the filtrate dialysate 
compartment. The housing and the end caps of the dialyzer are made of polycarbonate. 
Dialysis fluid and blood connectors are designed according to ISO 8637. Theranova 400 
dialyzer is sterilized by steam, according to ISO 17665-1. 
5.1.2 Study Device – Elisio-17H dialyzer 
The membrane used in the Elisio-17H dialyzer (Polynephron™) is made of 
Polyethersulfone and Polyvinylpyrrolidone. The fiber walls are 40 µm thick, and have an 
internal diameter of about 200 µm. The effective length is 271 mm, with an effective 
surface area of 1.7 m2. On each end of the device the hollow fibers are potted in PUR to 

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isolate the blood compartment from the filtrate dialysate compartment. The housing and 
the end caps of the dialyzer are made of Polypropylene. The Elisio-17H dialyzer is 
sterilized by dry gamma irradiation. 
Hemodialysis with an Elisio-17H hemodialyzer is indicated for patients with acute or 
chronic renal failure when conservative therapy is judged to be inadequate. It may also be 
indicated in the treatment of patients intoxicated with poisons or drugs. It is FDA cleared 
under 510(k) K131935. 
5.2 Treatments Administered 
All randomized patients will receive dialysis treatments with either Theranova 400 
dialyzer or Elisio-17H dialyzer, 3 times weekly for a period of 24 weeks. Trained HD 
staff will administer all treatments. 
5.3 Selection and Timing for Each Patient 
Treatments will occur at sites that routinely implement high-flux dialysis. Dialysis 
prescription and management will be performed per institutional practice. All patients 
will receive in-center HD treatments, 3 times per week for a total of 24 weeks using the 
study device which he/she has been randomized to. Actual treatment duration of the 
individual dialysis session will vary based on clinical requirements determined by the 
treating physician. 
Hemodialysis treatment duration per session for each individual patient will vary based 
on clinical requirements determined by the Investigator, based on the patient’s need, 
residual renal function (via estimated Glomerular Filtrations Rate), access function, 
tolerance to HD and other relevant factors. The participating patients’ HD prescriptions 
should be kept stable throughout the study; any changes to the prescriptions must be 
recorded. 
5.4 Method of Assigning Patients to Treatment Groups 
All patients who sign the ICF will be assigned a unique patient identification number. 
Only patients confirmed to meet screening eligibility will be randomized and allowed to 
continue in the study. A sufficient number of patients will be enrolled in the study in 
order to randomize 166 patients across up to 30 study sites. 
The type of study dialyzer each patient will use during their treatment sessions will be 
determined according to a central randomization scheme provided by Baxter (via the 
Electronic Data Capture [EDC] system used for the study). Patients will be randomly 
assigned to receive one of the following two study dialyzers in a 1:1 ratio: 

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• Theranova 400 dialyzer 
• Elisio-17H dialyzer 
Randomization will be stratified by site and dynamic allocation will be used. 
5.5 Blinding 
This is an open-label study and will not have blinding of any investigational products. 
However, the Medical Monitor, Study Statistician, Data Management and the central 
laboratory will be blinded to treatment as a means to minimize potential bias. A non-
blinded statistician will be assigned to this study. 
5.6 Concomitant Therapy 
The PI should review any additions or changes in concomitant therapy. All medications 
should be recorded in the source documents or equivalent. Prior medications, defined as 
all medications at screening and any ESA taken in the last 30 days before the study 
begins (ICF), will be recorded on the eCRF. Concomitant medications, including dose, 
unit, frequency, route of administration, start and stop dates and indication for use, will 
be recorded on the eCRF throughout the study. Sites will not enter “other” or 
“prophylaxis” as indications. 
Erythropoiesis-stimulating agents are often used to stimulate red blood cell production in 
dialysis patients. During the course of this study, ESAs should be administered according 
to each clinic’s standard practices, either subcutaneously or intravenously. If 
administered intravenously, it should be done post-dialysis or in the venous part of the 
extracorporeal circuit (downstream of the dialyzer). 
A treatment medication will be anything given once the patient enters Visit 1. 
5.7 Prohibitions and Restrictions 
Sites must demonstrate they have monthly microbiological water/dialysate quality testing 
done according to current Centers for Medicare and Medicaid Services regulations for 
dialysis water (ANSI/AAMI RD62:2001) and conventional dialysate (ANSI/AAMI 
RD52). Sites will also adhere to all requirements stipulated by their respective IRB. 
There are no activity or diet restrictions specific to the study. Patients should discuss their 
daily diet and activities with their physician. Medical management of HD patients is per 
institutional practice. Dialysis prescription and management will be per institutional 
practice. 

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5.8 Treatment Compliance 
Each patient should receive 73 treatments during the 24 week study period. Treatment 
compliance will be assessed by counting the number of scheduled treatments delivered to 
each patient within the study period. A patient may be withdrawn from the study if more 
than 3 consecutive treatments with the randomized dialyzer/treatment mode are missed. 
5.9 Packaging and Labeling 
The investigational product, Theranova 400 dialyzer, will be provided by the sponsor in 
sterilized individual peel pouches. All other products used in the management and care of 
patients in the trial will be provided by the site. Each dialyzer will be labeled, at a 
contract research organization approved facility, with a unique number for product 
accountability. 
Each Theranova 400 dialyzer overpouch will be labeled per Title 21 of the Code of 
Federal Regulations (CFR) Part 812.5 and Part 801.1. 
All Theranova dialyzers in the USA will minimally include the investigational statement 
on the peel pouch: 
“Caution – Investigational Device. Limited by Federal (or United States) law to 
investigational use.” 
5.10 Storage and Accountability 
The Theranova 400 dialyzers will be imported from Germany to a clinical locker in the 
USA. The investigators at each site will then be supplied with the investigational product 
for this clinical study. Baxter will sponsor the cost associated with ordering the Elisio-
17H dialyzers; these dialyzers will be stored at a Clinical locker and/or at the study site. 
The person in charge of receiving the products at site must initiate the accountability 
documentation process. The recording method defined and approved during the “study 
initiation visit” shall apply and the required documents (“Good Clinical Practice [GCP] 
forms”) shall be filled out as needed, and when required. 
The Theranova 400 dialyzers must be stored below +30°C and the Elisio-17H dialyzers 
must be stored per label claims, in a safe space, with restricted access and only used to 
treat patients included in the study. 
The Investigator will ensure study devices are tracked by unique identifier and maintain 
adequate records of the disposition of the study devices. The following requirements 
must be noted: 

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1. The date of receipt at the study site 
2. Identification of each study device (unique identification assigned by clinical 
locker) 
3. The date of use 
4. Patient identification 
5. The date of return of unused, expired or malfunctioning study devices, if 
applicable. 
Prior to initiating treatment the study monitor must ensure that the investigator has 
sufficient number of products (or material) at his/her disposition, that products have been 
duly counted and that the products are being used correctly, according to their intended 
use as labeled. 
All investigational devices will be provided, reconciled and accounted for throughout the 
study. Periodically throughout the study, the site monitor will collect copies of 
accountability documentation. In addition at the conclusion of the study, copies of 
accountability records will be collected showing investigational product delivery, 
inventory, dispensation, return and disposition from the clinical locker, investigational 
site and study patients. 
All unused study devices at investigational sites will be returned to the Sponsor/designee. 
If needed, the Sponsor may authorize an alternative disposition of unused products. 
However, disposition can only occur after the Sponsor has been notified and given 
written authorization. The Sponsor will maintain a written record of any authorized 
disposition of the investigational products. 
All used disposable products at investigational sites must be disposed of per site standard 
operating procedures (SOPs). 
6. STUDY PROCEDURES 
6.1 Informed Consent 
Prior to collecting any study data, written patient informed consent must be obtained in 
accordance with 21 CFR Part 50. The Investigators must ensure that the patients have 
received all relevant information, orally and in writing, relating to the type, objective and 
possible risks and benefits of the study. Patients must also be informed that they are free 
to withdraw from the study at any time. The information will be given in reasonable time 
before study start. The informed consent statement will be reviewed, signed and dated by 
the patient and the person who administered the informed consent. A copy of the signed 

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ICF will be given to the patient and the original will be placed in the patient’s medical 
record. Confirmation of a patient’s informed consent must also be documented in the 
patient’s medical records prior to any data collection under this protocol. An IRB 
approved patient ICF will be provided to the Investigator. The ICF must not be altered 
without the prior agreement of the relevant IRB and Baxter. 
If modifications are needed according to local regulations, or if new information becomes 
available (e.g., from Baxter) that can significantly affect a patient’s future health and 
medical care, a new version of the patient information and informed consent form must 
be prepared in cooperation with the investigator(s) and approved by Baxter. Patients still 
participating in the study must provide written informed consent by signing the updated 
consent form and will receive a copy of the signed form and the patient information. A 
copy of the new version of the form and patient information shall be given to each 
previously enrolled patient for information. 
Upon signature of the ICF, the study patient will be screened to verify eligibility (see 
Inclusion and Exclusion Criteria in Sections 4.2 and 4.3, respectively). 
6.2 Demographics and Baseline Characteristics  
Demographics will include the date of birth, gender, and ethnicity. 
A complete medical history including a review of all major body systems and medical 
history, as applicable, will be performed. 
Information regarding the type and frequency of dialysis therapy received prior to 
enrollment in this study, and the type of access will be obtained. The information 
gathered will include mean duration of treatments, blood flow rate (QB), dialysate flow 
rate (QD) and the type and mean dosage of heparin, erythropoietin and intravenous iron 
administered.  
Relevant medical history for each patient will be obtained during Screening. Medication 
history, if applicable, will also be evaluated during the Screening period. Past and present 
conditions, as well as surgical procedures, will be recorded for the main body systems. 
Renal medical history, date and type of first chronic dialysis treatment, date of last 
transplant (if applicable), date of last transplant failure (HD resumed, if applicable), 
primary renal disease etiology will also be captured in the eCRF. In addition, all 
medications being taken at Screening and any ESA taken in the 30 days before Screening 
will be recorded. 

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6.3 Physical Examination 
Physical examinations will be performed during Screening and at the End of Study visit 
which will be conducted after the patient’s last study treatment. During the study, any 
new condition or worsening of a pre-existing condition from the time a patient signs the 
ICF will be noted and recorded on the AE eCRF page. Height will be measured at 
screening only. 
A complete physical exam will be performed; edema status, height (at Screening) and 
body weight will be recorded. Weight will be measured at Screening and at the end of 
study visit. 
A final physical examination will be performed on patients who complete Screening, 
enter the study, but discontinue from the study early. 
6.4 Vital Signs 
Vital signs will be assessed at screening, during treatment period visits and at the end of 
study visit. Vital signs will include measurements of sitting blood pressure, sitting 
respiratory rate, temperature and sitting pulse rate. Blood pressure will be measured with 
an appropriate cuff size after the patient has been sitting for 5 minutes. Any new 
condition or worsening of a pre-existing condition from signing of the ICF will be noted 
and recorded on the AE eCRF. 
6.5 Clinical Laboratory Tests 
6.5.1 Laboratory Parameters 
Laboratory tests will include tests for hematology and serum chemistry as listed in 
Table 1. These tests will be carried as per schedule in Appendix 2. 
The Investigator will receive the laboratory results directly from the central laboratory for 
review and signature. The Investigator will be notified of any laboratory value that is 
outside of the normal range, as defined by the laboratory. If a clinically significant 
change from Screening or the previous visit occurs for any laboratory value and results in 
medical intervention, as judged by the Investigator, the laboratory abnormality will be 
recorded as an AE on the eCRF. The Clinical Laboratory Evaluations eCRF page will 
capture and reconcile with the electronic laboratory data transfer, the sample date and 
time, test accession number, and if the test is an initial or re-test. 
Patients will be in a seated or supine position during blood collection. Clinical laboratory 
tests will include the following: 

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Table 1. List of Laboratory Tests 
Hematology: 
• Hematocrit 
• Hemoglobin 
• Mean corpuscular hemoglobin 
• Mean corpuscular hemoglobin 
concentration 
• Mean corpuscular volume 
• Platelet count 
• Red blood cell count 
• White blood cell count with differential 
Coagulation: 
• Prothrombin time 
• INR 
• Activated partial thromboplastin time 
 
• λ FLC 
• κ FLC 
• TNFα 
• IL-6 
• β2-microglobulin 
• CFD 
• Vitamin A 
• Factor VII 
• Protein C 
• Factor II 
• hs-CRP 
• Hepatitis A, B and C 
• Human Immunodeficiency Virus 
• β-hCG (if applicable) 
Serum Chemistry: 
• Albumin 
• Alkaline phosphatase 
• ALT; SGPT 
• AST; SGOT 
• BUN 
• Calcium 
• Bicarbonate 
• Chloride 
• Creatinine 
• Gamma-glutamyl transferase 
• Globulin 
• Glucose 
• Phosphorus 
• Potassium 
• Sodium 
• Total bilirubin 
• Direct bilirubin 
• Total protein 
• Total cholesterol 
• HDL cholesterol 
• LDL cholesterol 
• Triglycerides 
Note: λ FLC – Lambda Free light chains, κ FLC – Kappa Free light chains, TNFα – Tumor necrosis 
factor alpha, IL-6 – Interleukin 6, CFD – Complement factor D, hs-CRP – high-sensitivity C-reactive 
Protein, β-hCG – Beta human chorionic gonadotropin, ALT;SGPT – Alanine aminotransferase; Serum 
glutamic pyruvic transaminase, AST;SGOT – Aspartate aminotransferase; Serum glutamic oxaloacetic 
transaminase, BUN – Blood urea nitrogen, HDL – High-density lipoprotein, LDL – Low-density 
lipoprotein 
 

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6.5.2 Sample Collection, Storage, and Shipping 
All blood samples, as part of the collection of dialysis treatment data, will be collected by 
the sites and stored, shipped and processed according to the central laboratory 
requirements and procedures. Methods, units and ranges for those parameters shall be 
made available to the Sponsor before the start of the study. 
Patients will be in a seated or supine position during blood collection. No puncture of the 
patient is necessary, as the blood samples will be taken from the fistula needle or from 
the sampling port of the blood line. 
6.6 Patient Reported Outcomes 
Patients will be asked to complete 2 surveys as part of the exploratory assessments. These 
patient reported outcomes (PROs) surveys are KDQOL-36 and EQ-5D-5L. 
These questionnaires will be completed independently and this will be done on ePRO 
devices. Study sites will be instructed to ensure that the study subjects complete the 
questionnaires. 
6.7 Appropriateness of Measurements 
Measurements for the primary and secondary endpoints have been aligned with FDA for 
the purposes of a future pre-market submission. Hematology and other chemistry 
measurements used to evaluate safety are standard for the indication or patient population 
being studied. 
7. DATA COLLECTION FOR SAFETY ASSESSMENTS AND REPORTING 
7.1 Definition of Adverse Events and Product Complaints 
Table 2. Adverse Event Term Definition 
Term 
Definition 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or on toward 
clinical signs (including abnormal laboratory findings) in patients, users or 
other persons, whether or not related to the medical device. This includes 
events related to the investigational device or the comparator. This includes 
events related to the procedures involved. For users or other persons, this 
definition is restricted to events related to investigational medical devices. (ISO 
14155) 
Adverse Device Effect 
(ADE) 
Adverse event related to the use of an investigational medical device 
This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device. 
This definition includes any event resulting from use error or from intentional 

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Table 2. Adverse Event Term Definition 
Term 
Definition 
misuse of the investigational medical device. (ISO 14155) 
Serious Adverse Event 
(SAE) 
An adverse event that led to serious deterioration in the health of the patient, 
that either resulted in: 
• death 
• a life-threatening illness or injury 
• a permanent impairment of a body structure or a body function 
• in-patient or prolonged hospitalization 
• medical or surgical intervention to prevent life-threatening illness or 
injury 
• led to fetal distress, fetal death or a congenital abnormality or birth 
defect 
A planned hospitalization for pre-existing condition, or a procedure required by 
the Clinical Investigation Plan, without serious deterioration in health, is not 
considered a serious adverse event. (ISO 14155) 
Important medical events that may not result in death, be life threatening, or 
require hospitalization may be considered an SAE when, based upon 
appropriate medical judgment, they may jeopardize the patient and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in in-patient hospitalization, or the 
development of drug dependency or drug abuse. 
Product Complaint (PC) 
Any written, electronic, or oral communication that alleges deficiencies related 
to the identity, quality, durability, reliability, usability, safety, effectiveness, or 
performance of a product after it is released for distribution or related to a 
service that affects the performance of such product. A complaint may involve 
the possible failure of the product itself, its packaging, or its labeling (i.e., 
product label, package insert, or any instructions for use). The complaint need 
not be confirmed by the manufacturer to be considered a complaint. 
Serious Adverse Device 
Effect (SADE) 
A serious ADE is defined as an ADE that has resulted in any of the 
consequences characteristic of an SAE. (ISO 14155) 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
Any serious adverse device effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan or application (including a supplementary 
plan or application), or any other unanticipated serious problem associated with 
a device that relates to the rights, safety, or welfare of patients. (21 CFR 
812.3(s)) 

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Table 3. Definition of Terms 
Term 
Definition 
Investigational product 
For this protocol, the term “investigational product” is 
synonymous with Theranova 400 dialyzer. 
Comparator product 
For this protocol, the term “comparator product” is 
synonymous with Elisio-17H dialyzer. 
Date of Onset 
The date when the signs and symptoms of the AE begin. 
Signs & Symptoms vs Diagnosis 
If a definitive diagnosis has been medically established 
by the physician caring for the patient or by the 
Investigator, this diagnosis should then be recorded as the 
AE. If a definitive diagnosis has not been medically 
established, the signs and symptoms should then be 
recorded as the AEs. 
Diagnosis vs Complications 
A patient experiences not only a diagnosis, but also 
additionally a complication of the diagnosis (i.e., 
myocardial infarction with congestive heart failure); both 
the diagnosis and the medical complication should be 
collected and recorded as separate AEs. 
Awareness Date or Baxter Awareness Date 
The date on which any Baxter employee or their agent 
becomes aware of an AE. This date is considered Day 0 
on the regulatory reporting time clock. 
 
7.2 Safety Reporting 
All AEs and PCs observed by the study personnel or reported by the patient during the 
course of the study will be documented from the time of signing the ICF (i.e. enrollment) 
through the end of study visit. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s 
condition deteriorates at any time during the study, it will be recorded as an AE. 
An elective procedure/surgery that occurs during the course of a study, but is being 
performed for a documented pre-existing condition and was pre-planned prior to study 
entry will not qualify as an AE. If, however, the pre-existing condition unexpectedly 
deteriorates during the study requiring the procedure/surgery to be performed earlier than 
planned, the condition for which the procedure/surgery is being performed will qualify as 
an AE. 
Laboratory and vital sign abnormalities qualify as AEs if medical intervention is required 
to treat or address the abnormality, if the patient must be discontinued from the study due 

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to the abnormality, or if the value exceeds specific limits defined by the standard-of-care 
as qualifying it as an AE. 
If a patient experiences a diagnosis, but also additionally a complication of the diagnosis 
(i.e., myocardial infarction with congestive heart failure); both the diagnosis and the 
medical complication should be collected and recorded on eCRFs as separate AEs. 
Adverse events that change in severity will be documented as an additional AE to allow 
an assessment of the event at each level of severity. 
If an AE or PC occurs, a full description of the event should be recorded including the 
date and time of onset, as well as outcome, seriousness, severity, event description, 
actions taken, and causal relationship of the AE. Investigators should review and 
reference the severity (see Table 4) and causality definitions (see Table 5) when 
determining relationship of the AE or PC to the study product. The investigators may also 
discuss the event(s) with the Baxter Medical Monitor or designee. 
All AEs and PCs should be actively solicited and, no matter how common they are for a 
particular patient and regardless of the causality assigned by the Investigator. 
Additionally, any AE voluntarily reported by the patient should be recorded and verified 
by the Investigator or designee with the relevant source documents and eCRF pages. 
Supporting source documents should be de-identified. Each SAE will be documented on 
a separate SAE report form. 
The outcome/resolution of all AEs will be determined by the Investigator and 
documented on the AE eCRF report form. Investigators will be instructed to follow all 
AEs as follows: Unrelated AEs will be followed until resolution or until the end of the 
study whichever comes first. Adverse device effects (related AEs) and all SAEs (related 
or not) will be followed until resolution or they become stable, including following the 
patient after the end of study if necessary. 
An AE can result from the use of the investigational product in accordance with the 
protocol, as well as from an accidental or intentional misuse or malfunction of the 
investigational product or any other treatment error such as unintentional administration 
or use of another product during the course of the study. 
For the outcome categories that can be used on the eCRF by the Investigator please refer 
to Table 6. 

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Table 4. Severity Assessments 
Criterion 
Definition 
Mild 
Is a transient discomfort and does not interfere in a significant manner with the 
patient’s normal functioning level. The AE resolves spontaneously or may 
require minimal therapeutic intervention. 
Moderate 
Produces limited impairment of function and can require therapeutic 
intervention, but produces no sequelae. 
Severe 
Results in a marked impairment of function and can lead to temporary inability 
to resume usual life pattern. The AE produces sequelae requiring (prolonged) 
therapeutic intervention. 
 
Table 5. Causality Assessment 
Classification 
Causality Criteria 
Causal Association 
Probably Associated 
Event or laboratory test abnormality, with reasonable 
time relationship to medical device use 
Unlikely to be attributed to disease, procedure or other 
drugs/devices used 
Response to withdrawal clinically reasonable 
Re-challenge not required 
YES 
Possibly Associated 
Event or laboratory test abnormality, with reasonable 
time relationship to medical device use 
Could also be explained by disease, procedure or other 
drugs/devices used 
Information on device withdrawal may be lacking or 
unclear 
YES 
Unable to Determine 
Clinical event or laboratory test abnormality cannot be 
judged because information is insufficient or missing 
Data cannot be supplement or verified 
YES 
Unlikely Associated 
Event or laboratory test abnormality, with a time to 
device use that makes a relationship improbable (but 
not impossible) 
Disease, procedure or other drugs/devices used provide 
plausible explanations 
NO 
Not Associated 
Event or laboratory test abnormality, with a time to 
device use that makes a relationship impossible 
Disease, procedure or other drugs/devices used provide 
plausible explanations 
NO 
 

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Table 6. Outcome Conclusion 
Criteria 
Death 
Permanent Injury 
Disease Aggravation 
Resolved without Medical Intervention 
Resolved with Medical Intervention 
Ongoing 
Unknown 
 
7.2.1 Serious Adverse Events (SAEs) and Product Complaint (PC) Reporting 
The PI shall: 
• Record every AE and observed PC, together with an assessment, 
• Report to Baxter or designee, within 24 hours, all SAEs and PCs that could have 
led to a serious adverse device effect (SADE), 
• Report to the IRB SAEs and PCs that could have led to a SADE if required by the 
national regulations or by the IRB, 
• Supply Baxter or designee, upon Baxter’s or designee’s request, with any 
additional information related to the safety reporting of a particular event, 
• Report any SAE if becoming aware after study completion of an SAE or PCs that 
could have led to a SADE that occurred in a patient during their participation in 
the study, the SAE must be reported on the SAE Form within 24 hours after 
awareness. 
Baxter or designee shall report to regulatory authorities, SAEs and PCs that could have 
led to a SADE, as required by the national regulations. 
7.2.1.1 Anticipated Adverse Events Related to Theranova and Hemodialysis 
Anticipated Adverse Events related to the device or therapy can be found in the 
Investigator’s Brochure (IB), investigational plan or application (including a 
supplementary plan or application). 

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7.2.2 Product Complaints/Product Issues 
Any product complaints identified by the investigator or designee will be recorded in the 
PCs form and forwarded to Baxter within 5 days of becoming aware. 
7.3 Medical Monitor 
The medical monitor will regularly review data collected from eCRFs for potential safety 
concerns. A formal review plan of aggregate AEs/SAEs and PCs will be documented in a 
study Safety Management Plan. 
Periodic review of reported AEs will be completed by Baxter or designee. At the site 
level the Investigator must assess risk and clinical significance of events to each 
individual study patient, including removing the patient from the study if necessary. 
7.4 Safety Reporting to Authorities and IRB 
It is the responsibility of the Investigator to report any SAEs to IRB according to local 
regulatory requirements. 
Baxter or designee will assess each SAE reported by the Investigator to determine if the 
event qualifies as an Expedited Report according to local regulations. Expedited safety 
reports and associated Investigator letters will be submitted to the appropriate Authority 
and the Principal Investigator by Baxter or designee. The Investigator will file this 
Investigator letter and Expedited Safety Report in their study file. Additionally, a copy of 
the Safety Report and Investigator Letter will need to be submitted by the Investigator to 
their IRB, as appropriate per local regulations. 
8. STUDY ACTIVITIES 
8.1 Schedule of Evaluations and Procedures 
All clinical study evaluations will be performed according to Appendix 1 and the 
instructions listed below. If a patient discontinues from the study prematurely, every 
attempt will be made to perform all of the procedures and evaluations that are scheduled 
for the final visit (i.e. end of study visit). 
8.2 Training for Theranova 400 dialyzer 
Study personnel performing treatments with the Theranova 400 dialyzer for this clinical 
study will be comprised of physicians, HD nurses and other clinicians. Study staff will be 
trained on the use of the Theranova 400 dialyzer by the Sponsor’s representative prior to 
patient enrolment. Training dates and training material will be documented and filled in 
the Investigator Site File per GDP. 

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8.3 Training for Elisio-17H dialyzer 
Training will be provided on Elisio-17H dialyzers as applicable. 
8.4 Screening Period (Days –14 to -1) 
Prior to performing any study procedures, an IRB approved ICF must be signed and 
dated by each study patient and the person who administered the ICF. Prior to 
participation in the trial, the patient will receive a copy of the signed/dated ICF. The 
original signed/dated ICF must be retained at the site and confirmation of informed 
consent documented in the patient’s medical record. All IRB approved revisions to the 
ICFs must be signed/dated by all patients who are currently enrolled in the study. The 
patient will receive a copy of the signed/dated revised ICF. Patients will be instructed to 
sign, or initial the consent form using their legal names (not nicknames). 
Signing of the ICF and the initial Screening visit may occur on the same day, if necessary. 
8.4.1 Assessments and Procedures 
After providing written informed consent, patients will enter the Screening period. The 
aim of the Screening period is to assess the eligibility of patients for randomization and 
participation in the study. The maximum duration of the Screening period is 2 weeks. 
Screening period of 2 weeks was designed to provide adequate time to obtain screening 
lab results and complete all screening procedures. This period may not be used to repeat 
tests if initial tests result in study exclusion. 
A complete medical history will include a review for all major body systems and renal 
history (primary etiology of renal disease, and current HD prescription). Medical history 
will also include an assessment of all medications being taken at the time of Screening, 
and any ESA taken in the 30 days prior to Screening, with each medication having a 
corresponding indication recorded on the concomitant medication eCRF form. Treatment 
parameters as described in Section 8.5.1 will be collected during treatment visits. 
Further assessments include: 
• Demographics 
• Physical examination  
• Vital signs 
• Pregnancy test for women with child bearing potential 
• AEs/SAEs 

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• Clinical laboratory evaluation as outlined in Appendix 2 
• Randomization 
8.5 Treatment Period (Day 1 to Day 168) 
Study treatment period will consist of 3 weekly in-center treatments over a period of 24 
weeks, where patients will receive HD treatment with either the Theranova 400 dialyzer 
or Elisio-17H dialyzer. 
Please refer to Appendix 1 for details of the Treatment Period activities and samplings. 
8.5.1 Visit Procedures 
Clinical laboratory evaluations will be taken at the first study dialyzer treatment and after 
every 4 weeks of treatment (i.e., Day 1 [first day of treatment], Week 4, Week 8, Week 
12, Week 16, Week 20 and Week 24). 
On the day of the study visit, the following dialysis treatment data will be collected: 
• Treatment parameters: 
- 
Programmed QB, QD and ultrafiltration flow rate (QUF); (all in mL/min) 
- 
Actual Total Ultrafiltration volume at end of treatment (mL/Session) 
- 
QB will be documented at the start, every 30 minutes, and at the end of every 
study treatment 
- 
Total dialysis time 
• Duration of and reasons for any treatment interruptions 
• Concomitant medications 
• AEs/SAEs/ADEs/PCs 
• PRO measurements (KDQOL-36 and EQ-5D-5L) 
• Vital signs 
• Pre- and post-dialysis body weight 
• Clinical laboratory evaluation as outlined in Appendix 2 
 
8.6 End of Study Visitor Early Termination Procedures 
The following information will be collected and procedures or evaluations will be 
performed during the End of Study visit (first non-study treatment, Week 25) or Early 
Termination. 

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• Physical examination including weight 
• Vital signs 
• AEs/SAEs/ADEs/PCs  
• Concomitant medications 
• Clinical laboratory evaluation as outlined in Appendix 2 
If a patient discontinues from the study prematurely, every attempt should be made to 
perform all of the procedures and evaluations that are scheduled for the End of Study 
visit. 
9. DATA MANAGEMENT, QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor is responsible for implementing and maintaining quality assurance and 
quality control systems with written SOPs to ensure that studies are conducted and that 
the data are generated, documented and reported in compliance with the protocol and 
applicable regulatory requirements. Quality control will be applied to all stages of data 
handling to ensure reliability and correct processing. The Sponsor is responsible for 
securing agreement from all involved parties to ensure direct access to all study related 
centers, source documents and reports for the purpose of monitoring and auditing. 
Agreements made with the Investigator/institution will be in writing. 
9.1 Auditing 
The sponsor and/or sponsor’s representatives may conduct audits to evaluate study 
conduct and compliance with the protocol, standard operating procedures, other written 
instructions/agreements, International Conference on Harmonization (ICH) GCP, the IRB 
and applicable regulatory guidelines/requirements. The investigator will permit auditors 
to visit the study site, as described in the Clinical Study Agreement. Auditing processes 
specific to the study will be described in the auditing plan. 
10. PLANNED STATISTICAL METHODS 
10.1 General Considerations 
Further details of the planned statistical methods will be provided in the study statistical 
analysis plan (SAP). The purpose of the SAP is to further elaborate the statistical 
methods described in the protocol and describes analysis conventions to guide the 
statistical programming work. The SAP will be finalized at least two months prior to 
database lock. Any further clarification to the statistical methods described in the 
protocol will be documented in the SAP. 

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Unless otherwise noted, all analyses will be performed using SAS/GRAPH® 9.4 
software, SAS/STAT® 14.1 software and Base SAS® 9.4. Copyright© 2002-2012, SAS 
Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered 
trademarks or trademarks of SAS Institute Inc., Cary, NC, USA. All Rights Reserved. 
Differences between treatment groups will be evaluated at a two-sided significance level 
of 0.050 (when rounded to 3 decimal places) and p-values < 0.050 will be considered 
statistically significant, unless otherwise noted. 
Baseline measure for laboratory assessments is defined as the last non missing value 
obtained prior to dialysis on the day of the first study treatment. The final measure for 
laboratory assessments is defined as the last non missing value obtained after the day of 
the first study treatment. 
10.2 Determination of Sample Size 
The sample size for this study is driven by the primary safety endpoint. The sample size 
calculation was performed using PASS® 15.0.1 software, procedure Non-Inferiority 
Tests for the difference between Two Means. Copyright© 2017, NCSS, LLC. All Rights 
Reserved. The power is based on a t-test with a one-sided alpha level of 0.025 where the 
true difference in means is assumed to be zero (0) and the non-inferiority margin is 5%.  
Pre-dialysis serum albumin was not evaluated in the previous Theranova 400 dialyzer HD 
study, only the mass (G) of albumin in the dialysate was assessed. However, a study 
published in PLoS ONE26 did use a prototype of the Theranova dialyzer (MCO-CI) 
where in pre-dialysis albumin levels were collected after a month of therapy and, based 
on these data, a mean and standard deviation (SD) of 35.3 and 3.7 was observed. 
Comparable pre-dialysis albumin levels are expected with both study dialyzers and with a 
sample size of 70 patients per group, a t-test with a 0.025 one-sided significance level 
will have 80% power to demonstrate non-inferiority of the Theranova 400 dialyzer 
compared to the Elisio-17H dialyzer as assessed by pre-dialysis serum albumin with a 
non-inferiority margin of 5%. To allow for 15% of patients to drop out, a total of 166 
patients will be randomized 1:1 to treatment with the Theranova 400 dialyzer or 
treatment with the Elisio-17H dialyzer (i.e., 83 patients per group). 
The 5% non-inferiority margin is based on results from 2 observational studies.27,28 These 
studies looked at the association between serum albumin levels and mortality in large US 
cohorts of HD and PD patients, respectively. In both studies, variations in serum albumin 
of +/- 1 g/L over 6 months (corresponds to +/-0.1 g/dL) have been defined as “stable 
serum albumin levels”. A variation of +/- 1 g/L is a range with a width of 2 g/L, which is 

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larger than 5% if applied to the reported mean baseline serum albumin levels. Therefore, 
a 5% variation in serum albumin can be justified as having no clinical significance. 
A previously conducted Theranova 400 dialyzer prototype HDF study (Comparison of 
the Clinical Performance of Two Theranova 400 Dialyzer Prototypes in Hemodialysis 
Mode with the Performance of a High-Flux Dialyzer in Hemodialysis Mode and a High-
Flux Dialyzer in High-volume Hemodiafiltration Mode – A Pilot Study, registered at 
clinicaltrials.gov, NCT02377622) was used to obtain λ FLC reduction ratio mean and 
standard deviation (SD) of 37.8 and 8.26. With a total sample size of 140 evaluable 
subjects as determined based on the primary safety endpoint (70 in the Theranova 400 
dialyzer treatment group and 70 in the Elisio-17H dialyzer treatment group), a difference 
of 4.56 in the λ FLC reduction ratio in favor of the Theranova 400 dialyzer can be 
detected with 90% power at a two-sided 0.05 significance level using a two-sided two-
sample t-test assuming equal variances. The sample size calculation for the primary 
efficacy endpoint was performed using PASS® 15.0.1 software, procedure Two-Sample 
T-Test Assuming Equal Variance. 
10.3 Analysis Populations 
The Per-protocol (PP) set will include all randomized patients who have received at least 
three months treatment with a study dialyzer and do not have any major protocol 
violations that might impact the primary analyses. 
The intent-to-treat full analysis (FA) set will include all randomized patients.  
The primary analyses will be performed on the FA set and supported by an analysis using 
the PP set. All other analyses will be performed on the FA set unless otherwise noted. 
10.4 Demographics and Baseline Characteristics 
Continuous demographic and baseline characteristics including age, height, screening 
laboratory tests and screening vital signs will be summarized descriptively by treatment 
group and overall using sample size (N), mean, SD, minimum and maximum. A t-test 
will be used to evaluate mean differences between treatment groups or a non-parametric 
procedure, as appropriate. 
Categorical demographic and baseline characteristics including gender, race and medical 
history will be summarized descriptively by treatment group using frequencies and 
percentages. Treatment group comparability will be evaluated using Fisher’s exact test. 
Medical history; medical condition or surgery items collected on the eCRF will be coded 

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to the appropriate System Organ Class (SOC) and Preferred Term (PT) using the Medical 
Dictionary for Regulatory Activities (MedDRA), Version 18 or higher. 
10.5 Primary Endpoint(s) 
The primary endpoints will be analyzed in a hierarchical manner, starting with the 
primary safety endpoint. 
The primary analyses will be performed using a multiple imputation approach. Multiple 
imputations using SAS Proc MI will be used to impute missing data under the missing at 
random assumption and the data sets generated will be analyzed using SAS Proc 
MIANALYZE. It is expected that the missing values will be monotone (i.e., when a 
variable Yj is missing for an individual i, then subsequent variables Yk, k > j, are all 
missing for the individual i). Thus, the regression method for imputation will be used.  
Using the primary safety analysis as an example, if a subject is missing serum albumin 
values at weeks 20 and 24, a regression model is first fitted using the non-missing values 
prior to week 20 (baseline, weeks 4, 8, 12, and 16) in order to impute the missing value 
for week 20. This method is then repeated in order to impute the missing value for week 
24 using the non-missing values of the prior weeks plus the newly imputed value for 
week 20. 
Twenty complete data sets will be analyzed for the multiple imputation of the primary 
endpoint data. The impact of missing data on the primary safety and efficacy analyses will 
be further explored as sensitivity analyses using observed data as well as last observation 
carried forward. 
10.5.1 Primary Safety Endpoint(s) 
For the primary safety endpoint of pre-dialysis serum albumin after 24 weeks of 
treatment, let µT denote the Theranova dialyzer pre-dialysis serum albumin mean and let 
µR denote the Elisio-17H dialyzer pre-dialysis serum albumin mean. Then the null 
hypothesis to demonstrate non-inferiority using a 5% margin can be expressed as: 
Ho: µT- µR ≤ -1.765. The alternative hypothesis is expressed as Ha: µT- µR > -1.765. 
An ANCOVA model with fixed effects of treatment and site and the continuous fixed 
covariate of baseline pre-dialysis serum albumin will be used to generate a two-sided 
95% confidence interval (CI) for the difference in treatment means (µT- µR). If the lower 
bound is > -1.765 then non-inferiority will be demonstrated.  

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10.5.2 Primary Efficacy Endpoint(s) 
For the primary efficacy endpoint of RR of λ FLC after 24 weeks of treatment, let µT 
denote the Theranova dialyzer RR of λ FLC mean at 24 weeks and let µR denote the 
Elisio-17H dialyzer RR of λ FLC mean at 24 weeks. Then the null hypothesis to 
demonstrate superiority can be expressed as: 
Ho: µT- µR = 0. The alternative hypothesis is expressed as Ha: µT- µR ≠ 0. 
The primary safety analysis will be conducted first. If the primary safety analysis 
demonstrates non-inferiority, an ANCOVA model with fixed effects of treatment and site 
will be used to generate a two-sided 95% CI for the difference in treatment means (µT- 
µR). If the lower bound is > 0 then superiority will be demonstrated. The statistical testing 
of the primary efficacy endpoint of the reduction ratio (RR) of λ FLC after 24 weeks of 
treatment is contingent upon the outcome of the analysis of the primary safety endpoint 
and will only be conducted once non-inferiority could be established for the primary 
safety endpoint. This hierarchical testing approach guarantees that the overall type 1 error 
is controlled at a two-sided 0.05 significance level. 
10.6 Secondary Endpoint(s) 
10.6.1 Secondary Safety Endpoint(s) 
Pre-dialysis serum albumin: 
A Mixed-effect Model Repeated Measurement (MMRM) model will be used to evaluate 
differences between treatment groups in the change from baseline in pre-dialysis serum 
albumin after each four weeks of treatment. The model will include the fixed effect of 
treatment, visit; the continuous, fixed covariate of baseline measurement; and the random 
effect of patient.  
Pre-dialysis serum albumin will be further categorized at baseline and final measurement 
into 4 categories: <3.5, ≥3.5-3.9, ≥4.0-4.4, ≥4.5. Shift tables will be generated to cross 
tabulate the number of patients within each category by treatment. 
Pre-dialysis Factor VII, Protein C, Vitamin A, and Factor II: 
An MMRM model will be used to evaluate the differences between treatment groups in 
the change from baseline in pre-dialysis Factor VII, Protein C, Vitamin A, and Factor II 
after 4 weeks and after 24 weeks of treatment. The model will include the fixed effect of 
treatment, visit; the continuous, fixed covariate of baseline measurement; and the random 
effect of patient. 

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nPNA (nPCR): 
An MMRM model will be used to evaluate differences between treatment groups in 
nPNA(nPCR) collected after each 4 weeks of treatment. The model will include the fixed 
effect of treatment, visit, and the random effect of patient.  
AEs, SAEs, and Product Complaints: 
The summary of AEs will include AEs that occur on the day of or after the first study 
treatment. AEs will be mapped to a Primary SOC and PT according to MedDRA and 
summarized descriptively by SOC, PT and treatment group. Treatment group 
comparability in the incidence rates of adverse events will be evaluated using Fisher’s 
exact test. 
An overview (overall) summary table of all AEs will be generated that includes the total 
number of AEs, number and percentage of patients with at least one AE, number and 
percentage of patients with at least one SAE, number and percentage of patients with at 
least one severe AE, number and percentage of patients with at least one AE probably 
associated with study treatment, number and percentage of patients with an AE leading to 
study discontinuation and number and percentage of patients with an AE leading to death. 
This summary table will be presented by treatment group and combining both groups 
(Total). 
Furthermore, separate AE summary tables will be provided by SOC and PT for SAEs and 
AEs leading to study withdrawal. Separate AE summary tables will be provided to show 
a breakdown of AEs by SOC, PT and 
a. severity (mild, moderate or severe),  
b. relationship to study treatment (probably related, possibly related, unable to 
determine, unlikely related or not related). 
Study dialyzer related product complaints will be summarized descriptively by study 
dialyzer. 
Chemistry and hematology: 
Mean differences between treatment groups in the change from baseline to final measure 
in chemistry and hematology laboratory tests will be analyzed using an ANCOVA with a 
fixed effect of treatment and a fixed continuous covariate of baseline laboratory value. 

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10.6.2 Secondary Efficacy Endpoint(s) 
In order to account for multiplicity, secondary efficacy analyses will be held to a 
hierarchical assessment and performed in the order outlined below. If the first analysis 
results in a p-value <0.05, then formal testing will continue to the second analysis. If the 
second analysis also results in a p-value <0.05, then formal testing will continue to the 
third analysis, and so on. This method of hierarchical assessment will continue until an 
analysis results in a p-value > 0.05, i.e., is considered statistically insignificant. This 
hierarchical approach guarantees that the overall alpha will not exceed 0.05. 
1. MMRM of reduction ratio of λ FLC  
2. MMRM of reduction ratio of CFD 
3. MMRM of reduction ratio of κ FLC  
4. MMRM of reduction ratio of IL-6  
5. MMRM of reduction ratio of TNFα  
6. MMRM of reduction ratio of β2-microglobulin 
7. Change in pre-dialysis β2-microglobulin from baseline to 24 weeks 
8. MMRM of Kt/Vurea 
An MMRM model will be used to evaluate differences between treatment groups in the 
reduction ratios of λ FLC, CFD, κ FLC, IL-6, TNFα, β2-microglobulin after 4 weeks and 
after 24 weeks of treatment. The model will include the fixed effect of treatment, visit, 
and the random effect of patient.  
An ANCOVA with a fixed effect of treatment and a fixed continuous effect of baseline 
pre-dialysis β2-microglobulin will be used to evaluate differences between treatment 
groups for the change from baseline in pre-dialysis β2-microglobulin after 24 weeks of 
treatment. 
An MMRM model will be used to evaluate differences between treatment groups in 
Kt/Vurea collected after each 4 weeks of treatment. The model will include the fixed effect 
of treatment, visit, and the random effect of patient. 
10.7 Exploratory Endpoints 
An MMRM model will be used to evaluate differences between treatment groups in the 
change from baseline in pre-dialysis serum levels of hs-CRP after each 4 weeks of 
treatment. The model will include the fixed effect of treatment, visit, as well as the 
continuous, fixed covariate of baseline measurement and the random effect of patient. 

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An MMRM model will be used to evaluate differences between treatment groups in the 
change from first day of treatment in KDQOL-36 and EQ-5D-5L after 12 weeks and after 
24 weeks of treatment. The model will include the fixed effect of treatment, visit, as well 
as the continuous, fixed covariate of screening measurement and the random effect of 
patient. 
Appropriate models will be used to evaluate differences between treatment groups in the 
utilization for medications (i.e., ESA, anti-hypertensives, iron). 
10.8 Interim Analysis 
An interim analysis will be conducted when 60% of enrollment is completed. The 
purpose of the interim analysis is a blinded sample size reassessment using the approach 
by Friede and Kieser29 for an absolute difference in means which is based on the 
observed one-sample standard deviation calculated from the pooled data across treatment 
groups. This blinded sample size reassessment will be carried out by an independent 
statistician (who otherwise is not involved in the study conduct) using the 8 week 
measurements of the pre-dialysis serum albumin levels after 100 total patients have been 
enrolled (assuming 15% drop out, this corresponds to 84 evaluable patients). In case the 
observed pooled standard deviation at 8 weeks is larger than the assumed standard 
deviation of 3.7, the method will require an increase in overall sample size in order to 
maintain an overall power of 80%. If the observed standard deviation is smaller than the 
assumed standard deviation of 3.7, the overall sample size will be kept at 166. 
11. ADMINISTRATIVE CONSIDERATIONS 
11.1 Investigators and Study Administrative Structure 
The study administrative structure of the study is described in Table 7. Ultimately it is the 
investigator who is responsible for the conduct of all aspects of the study at the study 
center. 
Table 7. Study Administrative Structure 
Role 
Person Responsible 
Sponsor: 
Baxter Healthcare Corporation 
Medical Monitor: 
 
Project Manager: 
 
Therapeutic Area Expert: 
 
 
Statistician: 
 

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Table 7. Study Administrative Structure 
Role 
Person Responsible 
Medical Writera 
 
a Considered an author of this protocol. 
 
11.2 Institutional Review Board Approval 
The responsible IRB must be constituted according to the applicable local and national 
requirements of each participating location. The Sponsor or its designee will require 
documentation noting all names and titles of members who compose the respective IRB. 
If any member of the IRB has direct participation in this trial, written notification 
regarding his or her abstinence from voting must also be obtained. 
The Sponsor or its designee will supply relevant documents for PIs to submit to their 
respective IRB for review and approval of the protocol. The Investigator will not enroll 
patients into the study until the Investigator has received written approval for, or written 
favorable opinion on, the protocol, the informed consent document(s), and any patient-
facing materials from their IRB. The IRB approval must refer to the study by exact 
protocol title, number, and version date; identify version of other documents (e.g., patient 
or care partner ICFs) reviewed; and state the approval date. The Investigator will make 
all required progress reports to their IRB in writing in a timely manner and will obtain all 
required approvals in writing (at least annually in all cases) to continue to participate in 
the study. 
The Investigator will promptly report to their IRB any unanticipated problems associated 
with the study devices involving risks to patients or others, whether encountered at their 
site or provided as a safety report by Baxter. 
The Investigator will promptly notify their IRB of any protocol amendment and will not 
implement any protocol amendment until the IRB has provided written approval of, or 
written favorable opinion on, the amendment. 
11.3 Food and Drug Administration 
The sponsor is in charge of submissions to FDA. 
The Baxter Project Manager must receive a copy of the Investigational Device 
Exemption (IDE) approval document supplied by the FDA, prior to the inclusion of 
patients in the study and before sending investigational products to study sites. 

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11.4 Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki, the ethical and quality standards of good clinical 
practice (ICH E6) and all applicable regulatory requirements and laws. 
The PI will provide all necessary information on the protocol and the study device to all 
physicians, nurses, and other personnel who participate in this study under the PI’s 
supervision and will discuss this material with them as needed, to ensure that they are 
fully informed regarding the conduct of the study and the potential effects of the study 
device. 
11.5 Patient Information and Consent 
Preparation of the ICF is the responsibility of the PI and must include all elements 
required by GCP and applicable regulatory requirements and must adhere to GCPs and to 
ethical principles that have their origin in the Declaration of Helsinki. All ICFs will be 
reviewed by the Sponsor prior to IRB approval. 
In all respects, the consent form must comply with Title 21, Part 50 of the CFR and ICH 
GCP 4.8, which both pertain to informed consent. 
11.6 Patient Confidentiality 
The Investigator must ensure that the patient’s confidentiality is maintained. Patient 
medical information obtained for the purposes of this study is confidential and disclosure 
to third parties, other than Health Authority representatives, Baxter representatives, or the 
site’s IRB, is prohibited. Patients should not be identified by name or medical record 
number on any documents or materials (samples, slides) sent to Baxter or its 
representatives or during verbal communications. Patients should be identified only by 
the study-assigned unique patient identification number. 
To help maintain patient confidentiality, each patient will be assigned a unique patient 
identification number. Furthermore, only the site Investigator and designated site staff 
will have access to patient identifying information. All data will be compiled to construct 
a dataset comprising unique patient identification numbers in lieu of specific patient 
identifying data; study datasets shared outside of Baxter will be password-protected. 
While there is always a risk of loss of privacy when participating in a research program, 
reasonable efforts will be made to ensure the confidentiality of patient data. Under no 
circumstances shall any patient identifying information be shared with or disclosed to a 
third party for promotional uses. As stated above, the patient must be informed that his/ 

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her personal study-related data will be used by Baxter and its representatives in 
accordance with country law or local IRB data protection directives. 
11.6.1 HIPAA Authorization Procedures 
Preparation of the Health Insurance Portability and Accountability Act (HIPAA) 
authorization form is the responsibility of the PI and must include all elements required 
by the Department of Health and Human Service’s Privacy Rule. Prior to the beginning 
of the study, the PI must have the IRB or the appropriate institution privacy board’s 
written approval/favorable opinion of the HIPAA authorization form. The PI must 
provide the patient or legally-authorized representative with a copy of the HIPAA 
authorization form in the language in which the patient is most proficient. The language 
must be nontechnical and easily understood. The PI should allow the time necessary for 
the patient or the patient’s legally-authorized representative to inquire about the details of 
the authorization. The HIPAA authorization must be signed and personally dated by the 
patient or by the patient’s legally-authorized representative and by the person who 
obtained the authorization. The patient or legally-authorized representative should receive 
a copy of the HIPAA authorization form prior to the patient’s participation in the trial. 
11.7 Study Monitoring 
The sponsor team or designee will monitor the study data on site and remotely as part of 
safety management and clinical monitoring. Monitoring will occur at regularly scheduled 
intervals at the study site to allow for verification by sampling of source documents and 
comparing these with information recorded on the eCRFs. In addition, eCRFs will also be 
monitored remotely during the course of study participation. Full details on eCRF 
monitoring will be specified in the Clinical Operations Plan.  
The PI or a designated member of the PI’s staff must be available during monitoring 
visits to review data and resolve any queries and to allow direct access to the patient’s 
records (e.g. medical records, office charts, hospital charts and study-related charts) for 
source data verification. The eCRFs should be completed prior to each visit and be made 
available to the monitor so that their accuracy and completeness may be checked. 
More detailed information about Study Monitoring can be obtained from the Clinical 
Operation Plan. 
11.8 Case Report Forms and Study Records 
All clinical data associated with this study will be collected and reported electronically 
via a web address and secure password. The database will be housed on a physically and 
logically secure computer server maintained in accordance with written security policies. 

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The EDC system meets approved established standards for the security of health 
information and is validated per 21 CFR Part 11. The system also meets the ICH 
guideline E6R1 regarding electronic study data handling and is available for audit upon 
request. Patient confidentiality will be strictly maintained. Patient identifying information 
will not be included in the database, but must be maintained in a secure fashion at the 
Investigator site. 
11.9 Protocol Violations/Deviations 
The Investigator will not deviate from this protocol except in cases of medical emergency. 
The Investigator may deviate from the protocol without prior approval only when the 
change is necessary to eliminate an apparent immediate hazard to the patient. In that 
event, the Investigator will notify the Sponsor immediately by phone, notify the IRB and 
confirm notification to the Sponsor in writing as soon as possible, but within 5 working 
days after the change is implemented. 
Protocol violations/deviations will be documented in source documentation, the 
Investigator’s research study files, as applicable, and also recorded in the EDC. Baxter 
will be responsible for the Protocol Deviations master list. The clinical team will review 
deviations at a study level on a regular basis. 
11.10 Access to Source Documentation 
Representatives of the sponsor, or its designee, must be allowed to visit the study site 
regularly to assess the data quality and the integrity of the study. These representatives 
will review study records on site and directly compare these with the source documents, 
discuss the conduct of the study with the PI and verify that the facilities remain 
acceptable. In addition, the study may be evaluated by the sponsor’s internal auditors or a 
designee and/or by government inspectors, who must be allowed access to eCRFs, source 
documents and other study files. 
11.11 Data Generation and Analysis 
Web-based electronic data entry must be completed for all patients enrolled in the study. 
The electronic data entry will be the responsibility of the Investigator. The database will 
be maintained by Baxter.  
Electronic Investigator signatures will be used to attest to the accuracy of data entered 
into the EDC system. The Study Monitor, in collaboration with the Investigators, must 
ensure that data entered into the EDC system are correct. Computerized data checks will 
be used to supplement manual review to check for data omissions, inconsistencies and 

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out of range values. An electronic audit trail system will be used to track all changes in 
the database.  
Data management will be carried out by Baxter Global Science and Technology, Biometrics 
department or assigned designee. 
Baxter or their assigned designee is responsible for the creation of the study eCRF and 
the associated electronic study database. 
11.12 Retention of Data 
The PI will retain study records and data in paper or electronic form in compliance with 
applicable regulatory requirements and for at least 15 years after the completion of the 
clinical trial. The PI must contact the Sponsor before destroying any records associated 
with the study. The Sponsor or its designee will notify the PI when the trial records are no 
longer needed. If the PI withdraws from the study (e.g., relocation, retirement), the 
records shall be transferred to a mutually agreed upon designee (e.g. another PI, IRB). 
Baxter will be notified in writing of any such transfer. 
11.13 Financial Disclosure 
The financial aspects of the study will be documented in an agreement between the 
Sponsor and the Investigator. 
11.14 Publication and Disclosure Policy 
Any information shared by the sponsor regarding this study, including this protocol, is 
considered proprietary information and should be kept confidential. 
The data generated by this clinical study are the property of the sponsor. This data may 
be used by the sponsor, now and in the future, for presentation or publication at the 
sponsor’s discretion or for submission to regulatory agencies. In addition, the sponsor 
reserves the right of prior review and approval of data from this study relative to the 
potential release of proprietary information to any publication or for any presentation. 

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12. REFERENCE LIST 
1. 
Grassmann A, Gioberge S, Moeller S, Brown G. ESRD patients in 2004: global 
overview of patient numbers, treatment modalities and associated trends. Nephrol Dial 
Transplant. 2005;20(12):2587-2593. 
2. 
Kramer A, Stel VS, Abad Diez JM, et al. Renal replacement therapy in Europe-a 
summary of the 2010 ERA-EDTA Registry Annual Report. Clin Kidney J. 
2013;6(1):105-115. 
3. 
Wetmore JB, Collins AJ. Global challenges posed by the growth of end-stage 
renal disease. Renal Replacement Therapy. 2016;2(1):15. 
4. 
Zuo L, Wang M, Chinese Association of Blood Purification Management of 
Chinese Hospital A. Current burden and probable increasing incidence of ESRD in China. 
Clin Nephrol. 2010;74 Suppl 1:S20-22. 
5. 
Sun L, Zou LX, Han YC, et al. Forecast of the incidence, prevalence and burden 
of end-stage renal disease in Nanjing, China to the Year 2025. BMC Nephrol. 
2016;17(1):60. 
6. 
Saran R, Robinson B, Abbott KC, et al. US Renal Data System 2016 Annual Data 
Report: Epidemiology of Kidney Disease in the United States. American Journal of 
Kidney Diseases. 2017;69(3):A7-A8. 
7. 
Vanholder R, De Smet R, Glorieux G, et al. Review on uremic toxins: 
classification, concentration, and interindividual variability. Kidney Int. 2003;63(5):1934-
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8. 
Vanholder R, Schepers E, Meert N, Lameire N. What is uremia? Retention versus 
oxidation. Blood Purif. 2006;24(1):33-38. 
9. 
Duranton F, Cohen G, De Smet R, et al. Normal and pathologic concentrations of 
uremic toxins. J Am Soc Nephrol. 2012;23(7):1258-1270. 
10. 
Meert N, Schepers E, De Smet R, et al. Inconsistency of reported uremic toxin 
concentrations. Artif Organs. 2007;31(8):600-611. 
11. 
Neirynck N, Vanholder R, Schepers E, Eloot S, Pletinck A, Glorieux G. An 
update on uremic toxins. Int Urol Nephrol. 2013;45(1):139-150. 
12. 
Chmielewski M, Cohen G, Wiecek A, Carrero JJ. The peptidic middle molecules: 
is molecular weight doing the trick? Seminars in nephrology: Elsevier; 2014:118-134. 
13. 
Ouseph R, Hutchison CA, Ward RA. Differences in solute removal by two high-
flux membranes of nominally similar synthetic polymers. Nephrol Dial Transplant. 
2008;23(5):1704-1712. 
14. 
Tattersall JE, Ward RA, group E. Online haemodiafiltration: definition, dose 
quantification and safety revisited. Nephrol Dial Transplant. 2013;28(3):542-550. 
15. 
Karaboyas A, Port FK, Robinson BM, et al. International trends in 
hemodiafiltration (HDF) use in the dialysis outcomes and practice patterns study 
(DOPPS). 52nd Congress of the European Renal Association-European Dialysis and 
Transplant Assocation (ERA-EDTA); 2015. 
16. 
Maduell F, Arias-Guillen M, Fontseré N, et al. Elimination of large uremic toxins 
by a dialyzer specifically designed for high-volume convective therapies. Blood Purif. 
2014;37(2):125-130. 

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17. 
Levitt DG, Levitt MD. Human serum albumin homeostasis: a new look at the 
roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value 
of serum albumin measurements. Int J Gen Med. 2016;9:229-255. 
18. 
de Mutsert R, Grootendorst DC, Indemans F, et al. Association between serum 
albumin and mortality in dialysis patients is partly explained by inflammation, and not by 
malnutrition. J Ren Nutr. 2009;19(2):127-135. 
19. 
Kaysen GA, Dubin JA, Müller HG, et al. Inflammation and reduced albumin 
synthesis associated with stable decline in serum albumin in hemodialysis patients. 
Kidney Int. 2004;65(4):1408-1415. 
20. 
Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation 
enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 
1999;55(2):648-658. 
21. 
Foundation NK. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 
2015 update. Am J Kidney Dis. 2015;66(5):884-930. 
22. 
Maduell F, Moreso F, Pons M, et al. High-efficiency postdilution online 
hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol. 
2013;24(3):487-497. 
23. 
Hutchison CA, Burmeister A, Harding SJ, et al. Serum polyclonal 
immunoglobulin free light chain levels predict mortality in people with chronic kidney 
disease. Mayo Clin Proc. 2014;89(5):615-622. 
24. 
Thomas G, Jaber BL. Innovation in the Treatment of Uremia: Proceedings from 
the Cleveland Clinic Workshop: Convective Therapies for Removal of Middle Molecular 
Weight Uremic Toxins in End‐Stage Renal Disease: A Review of the Evidence. 
Seminars in Dialysis: Wiley Online Library; 2009:610-614. 
25. 
Nagai K, Tsuchida K, Ishihara N, et al. Implications of Albumin Leakage for 
Survival in Maintenance Hemodialysis Patients: A 7‐year Observational Study. 
Therapeutic Apheresis and Dialysis. 2017. 
26. 
Zickler D, Schindler R, Willy K, et al. Medium Cut-Off (MCO) Membranes 
Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical 
Trial. PLoS One. 2017;12(1):e0169024. 
27. 
Kalantar-Zadeh K. Recent advances in understanding the malnutrition-
inflammation-cachexia syndrome in chronic kidney disease patients: What is next? Semin 
Dial. 2005;18(5):365-369. 
28. 
Mehrotra R, Duong U, Jiwakanon S, et al. Serum albumin as a predictor of 
mortality in peritoneal dialysis: comparisons with hemodialysis. Am J Kidney Dis. 
2011;58(3):418-428. 
29. 
Friede T, Kieser M. Blinded sample size reassessment in non-inferiority and 
equivalence trials. Stat Med. 2003;22(6):995-1007. 

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Appendix 1 Schedule of Evaluations and Procedures 
Evaluation 
Screen
ing 
Visit 
Days -
14 to -
1 
Treatment Period 
End of 
Study 
Visit 
Visit 1 
1st Treatment Day 
Visit 2 
Week 4 
Visit 3 
Week 8 
Visit 4 
Week 12 
Visit 5 
Week 16 
Visit 6 
Week 20 
Visit 7 
Week 24 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical histories (past 
and present) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
including weighta 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomizationb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE/SAE/ADE/PCc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medicationsd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HD prescription and 
Ultrafiltratione 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Body weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Evaluationsf 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient Reported 
outcomesg 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Note: All sampling visits will be performed during the mid-week treatment  
a Weight will be measured at screening and end of study, height will be measured only at screening  
b Eligible patients will be randomized at the end of the Screening Period  
c AEs, SAEs and PCs will be collected after the informed consent is signed and throughout the study, until the end of study visit  ADEs will be collected throughout the treatment period  
d Medications will be collected throughout the study  

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e Ultrafiltration (UF) will be obtained at the end of treatment of each 4 week treatment period  
f Collection of laboratory samples is presented in the Schedule of Clinical Laboratory Evaluations below  
g Patient reported outcomes (PROs) will include KDQOL-36 and EQ-5D-5L  All PROs will initially be assessed during the first treatment day, after 12 weeks of treatment and at the end of the study, following 24 weeks of 
treatment  

Theranova 400 Dialyzer 
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Clinical Trial Protocol: 7905001, Amendment 5 
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Appendix 2 Schedule of Clinical Laboratory Evaluations 
Evaluation 
Screening Visit 
Days -14 to -1 
Treatment Period 
End of Study 
Visit 
Visit 1 
1st Treatment Day 
Visit 2 
Week 4 
Visit 3 
Week 8 
Visit 4 
Week 12 
Visit 5 
Week 16 
Visit 6 
Week 20 
Visit 7 
Week 24 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysis 
Post-
dialysis 
Pre-
dialysi
s 
Post-
dialysis 
β-hCGa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
λ FLCb 
X 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
β2 
Microglobulin 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
Serum 
Albumin 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Liver functionc 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
CFDd 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
IL-6 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
TNFα 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
κ FLCb 
X 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
Vitamin A 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
BUN 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Factor VII 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
Protein C 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
Factor II 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
hs-C-Reactive 
Protein 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
Hematologye 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
HAVf, HBVg, 
HCVh, HIVi 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Trial Protocol: 7905001, Amendment 5 
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Coagulationj 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Serum 
phosphorus 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Comprehensive 
metabolic 
panelk 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Lipidsl 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Notes: All sampling visits will be performed during the mid-week treatment  
A serum beta human chorionic gonadotrophin (β-hCG) will be performed within 3 weeks prior to the 1st treatment in the study for women of childbearing potential  
a 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 β-hCG pregnancy test at Screening  Subjects of 
childbearing potential must use a medically acceptable means of contraception during their participation in the study  
b Lambda free light chains and Kappa free light chains 
c Include: Alkaline phosphatase (ALK-P), Alanine aminotransferase (ALT; SGPT), Aspartate aminotransferase (AST; SGOT), and Gamma-glutamyl-transferase (GGT), total bilirubin, direct bilirubin, globulin, total protein  
d Complement Factor D 
e Includes: Hemotocrit, Hemoglobin, Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), Mean corpuscular volume (MCV), Platelet count, Red blood cell (RBC) Count, White 
blood cell (WBC) Count with Differential 
f Hepatitis A Virus 
g Hepatitis B Virus 
h Hepatitis C Virus 
i Human Immunodeficiency Virus 
j Includes: PT (INR), PT (Sec), aPTT 
k Includes: Sodium, Potassium, Chloride, Calcium, Bicarbonate, Glucose, Creatinine 
l Includes: Total cholesterol, HDL cholesterol, LDL cholesterol, Triglycerides 
 

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Clinical Trial Protocol: 7905001, Amendment 5 
2018 FEB 09 
 
 
 
 
 
 
 
Appendix 3 Formulas for Calculation of Endpoints 
Reduction Ratios (RR) 
The RR for each solute, based on the change in the arterial plasma concentration over the 
dialysis session, will be calculated as: 
 
where CPre and CPost are measured arterial plasma concentration of the solute before and 
after dialysis, respectively.c 
However, for the middle molecules (λ FLC and β2-microglobulin) CPost will be first 
corrected (CPost-corr) for the decrease in total extracellular volume due to fluid removal, as 
follows: 
 
where CPost is the measured plasma concentration of the solute after dialysis; and BWPre 
and BWPost are the patient’s body weight before and after dialysis, respectively.d 
Kt/Vurea (quantification of hemodialysis treatment adequacy) 
The linear equation used to calculate Kt/Vurea when applied to HD administered 3 times a 
week is as follows: 
 
where R is the ratio of post-dialysis to pre-dialysis BUN; V is the body water volume and 
Weightloss is expressed in the same units; and T is treatment time in hours.ef 
                                                 
c Krieter DH, Lemke HD, Wanner C. A new synthetic dialyzer with advanced permselectivity for enhances 
low-molecular weight protein removal. Artif Organs. 2008;32(7):547-554. 
d Bergström J, Wehle B. No change in corrected β2-microglobulin concentration after cuprophane 
haemodialysis. Lancet. 1987;1:628-629. 

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Clinical Trial Protocol: 7905001, Amendment 5 
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nPNA (nPCR) 
The below equations are used to calculate the midweek PNA (PCR) when applied to HD 
patients is as follows: 
 
where C0 is the pre-dialysis BUN. 
SpKt/V is calculated as per below equation: 
 
where R is the post-dialysis/pre-dialysis BUN, t is the dialysis session in hours, UF is the 
ultrafiltration volume in liters, and W is the post-dialysis weight in kilograms.g 
V is calculated as per Watson formulas below: 
 
 
where V is the total body water.h 
PNA should be normalized to adjust to a specific body size. This will be done using the 
formula below: 
 
                                                                                                                                                 
e National Kidney Foundation. KDOQI Clinical Practice Guideline for Hemodialysis Adequancy: 2015 
Update. Am J Kidney Dis. 2015;66(5):884-930. 
f Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis 
of error. J Am Soc Nephrol. 1993;4(5):1205-1213. 
g Depner TA, Daugirdas T. Equations for Normalized Protein Catabolic Rate Based on two-Point Modeling 
of Hemodialysis Urea Kinetics. J Am Soc Nephrol. 1996;7:780-785. 
h National Kidney Foundation. NKF_DOQI Clinical Practice Guidelines: Measurement of dialysis 
adequacy. Am J Kidney Dis. 1997;30(2):S22-S31. 

Theranova 400 Dialyzer 
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Clinical Trial Protocol: 7905001, Amendment 5 
2018 FEB 09 
 
 
 
 
 
 
 
Appendix 5 Investigator’s Signature 
Study Title: 
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 
Study Number: 
7905001 
Final Date: 
2017 JUN 12 
Amendment 1: 
2017 JUL 25 
Amendment 2: 
2017 AUG 31 
Amendment 3: 
2017 OCT 11 
Amendment 4: 
2017 OCT 25 
Amendment 5: 
2018 FEB 09 
I have read the protocol described above. I agree to comply with all applicable 
regulations and to conduct the study as described in the protocol.  
 
 
Signed: 
 
 
Date: