An Open-Label Clinical Study to Assess the Performance of the Dialyzer With Endexo™ in End-Stage Renal Disease Subjects
Phase: NA
Conditions: Kidney Failure, Chronic
Sponsor: Fresenius Medical Care North America

 
 
 
 
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FRESENIUS MEDICAL CARE  
RENAL THERAPIES GROUP (RTG), LLC 
 
 
TITLE: 
 
 
 
An Open-Label Clinical Study to Assess the 
Performance of the Dialyzer with EndexoTM in 
End-Stage Renal Disease Subjects 
 
PROTOCOL NUMBER: 
 
 
Endexo-001 
 
INVESTIGATIONAL PRODUCTS: 
Dialyzer with EndexoTM, Fresenius Medical 
Care North America; 
 
Optiflux® dialyzer, Fresenius Medical Care 
North America (cleared under 510(k) number 
K152367)  
 
SPONSOR:  
 
 
 
Fresenius Medical Care RTG, LLC  
 
 
 
Medical Department, Clinical Research 
 
 
 
920 Winter Street 
 
 
 
Waltham, MA 02451–1457 
 
 
Amended:                                                Version 3.0 [dated 26/OCTOBER/2018] 
 
NCT03536663 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL NUMBER: Endexo-001                                                                        Version Number: 3 
                                                                                                                           Date: 26 October /2018       
 
 
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1.0 PROTOCOL SYNOPSIS 
Title 
An Open-Label Clinical Study to Assess the Performance of the 
Dialyzer with EndexoTM in End-Stage Renal Disease Subjects 
Protocol 
Number 
Endexo-001 
Study Type 
Open-label single-arm clinical trial 
Investigational 
Products 
• Dialyzer with EndexoTM (“F5”), Fresenius Medical Care North 
America 
• 
Optiflux® dialyzer (F160NR), Fresenius Medical Care North 
America (cleared under 510(k) number K152367) 
Proposed 
Indication 
The dialyzers with Endexo are a series of single-use, high-flux 
dialyzers intended for treatment of patients with acute or chronic 
renal failure when conservative therapy is judged to be inadequate. 
The dialyzers with Endexo must be used in conjunction with 
dialysis machines equipped with ultrafiltration control and are to be 
used only as directed by a physician. 
Study 
Objectives 
The primary objective of the study is to collect data on the 
performance of the dialyzer with Endexo when used to perform 
hemodialysis (HD) in End-Stage Renal Disease (ESRD) subjects.   
 
The secondary objective is to collect and summarize adverse 
events with the dialyzer with Endexo when used to perform HD in 
ESRD subjects. 
Study Design 
This is a prospective, sequential, multi-center, open-label study 
with subjects on thrice-weekly (in-center) HD. After a Screening 
Period, there will be 12 HD treatments on the Optiflux dialyzer 
(Optiflux Period), followed by 38 HD treatments on the dialyzer with 
Endexo (Endexo Period), and then a Follow-up Visit.  

PROTOCOL NUMBER: Endexo-001                                                                        Version Number: 3 
                                                                                                                           Date: 26 October /2018       
 
 
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Study 
Population 
The study population will consist of ESRD subjects who are a 
minimum of 22 years of age, have been prescribed in-center thrice 
weekly HD continuously for at least 180 days prior to the date of 
signed informed consent, and have been prescribed the Optiflux 
F160NR dialyzer continuously for at least 30 days prior to the date 
of signed informed consent. 
Total Number of 
Subjects 
15-24 enrolled subjects, to achieve at least 12 subjects with a 
minimum of 36 HD treatments per subject on the dialyzer with 
Endexo  
Total Number of 
Sites 
3-4 (United States) 
Estimated 
Duration of 
Study 
Each subject will participate in the study for a maximum of 22 
weeks. 
 
The Screening Period is up to 4 weeks. 
 
The Optiflux Period is 12 HD treatments on the Optiflux dialyzer (4 
weeks in duration). The Endexo Period is 38 HD treatments on the 
dialyzer with Endexo (approximately 13 weeks in duration).  
 
There will be an in-center Follow-up Visit within 1 week of the 
subject’s last HD treatment in the study. 
 
After the subject’s last HD treatment in the study, the subject will 
resume HD with his/her physician-prescribed dialyzer. 
 
Inclusion 
Criteria 
 
A subject who signed the ICF must meet all the following inclusion 
criteria in order to be eligible for enrollment in the study: 
 
1. Must be an adult, defined as having had a 22nd birthday on or 
before the date of signed informed consent 
 
2. Has been prescribed in-center thrice-weekly HD continuously 
for at least 180 days prior to the date of signed informed 
consent 
 
3. Has 
been 
prescribed 
the 
Optiflux 
F160NR 
dialyzer 
continuously for at least 30 days prior to the date of signed 
informed consent 
 
4. Has a prescribed HD treatment time ≥180 minutes (3 hours) 

PROTOCOL NUMBER: Endexo-001                                                                        Version Number: 3 
                                                                                                                           Date: 26 October /2018       
 
 
Page 4 of 8                                     CONFIDENTIAL 
and ≤270 minutes (4.5 hours) at the time of signed informed 
consent 
 
5. Has been on heparin anticoagulation for dialysis and has had 
no change in heparin prescription within 14 days prior to the 
date of signed informed consent 
 
6. Has a most recent single pool Kt/V (spKt/V) ≥1.2 within 45 
days prior to the date of a signed informed consent 
 
7. Has a most recent hemoglobin ≥9 g/dL within 45 days prior to 
the date of a signed informed consent 
 
8. Has a most recent platelet count ≥100,000/mm3 within 45 
days prior to the date of a signed informed consent 
 
9. A female of childbearing potential must have a negative 
serum pregnancy test at the time of screening and agree to 
use an acceptable method of contraception during the study 
 
Exclusion 
Criteria 
A subject who signed the ICF is excluded from the study if any of 
the following criteria are met: 
 
1. Use of citric acid concentrate (such as Citrasate®) at the time 
of signed informed consent 
 
2. Known allergic reactions to Endexo 
 
3. Hospitalization within 30 days prior to the date of signed 
informed consent  
 
4. Presence of active malignancy, congestive heart failure New 
York Heart Association (NYHA) Class III or IV, or liver 
cirrhosis 
 
5. Are receiving or have received chemotherapy / radiation 
therapy / plasmapheresis therapy within 90 days prior to the 
date of signed informed consent 
 
6. Are receiving antibiotics or have used antibiotics within 14 
days prior to the date of signed informed consent 
 
7. Are currently enrolled in or have completed any other 
investigational product study within 30 days prior to the date 
of signed informed consent 
 

PROTOCOL NUMBER: Endexo-001                                                                        Version Number: 3 
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8. Has a life expectancy of less than 1 year 
 
Study 
Endpoints 
 
 
The primary endpoint is to collect data on the in vivo ultrafiltration 
coefficient (Kuf) of the dialyzer with Endexo during the first study 
use at 15 minutes (±5 minutes) after the recorded start of HD.   
 
The secondary endpoints include collecting the following data on 
the dialyzer with Endexo and the Optiflux dialyzer: 
• The number of any adverse events and device-related 
adverse events 
• Urea Reduction Ratio (URR) and spKt/V (calculated from 
pre- and post-HD BUN) for the first study use of the 
dialyzers 
• Pre- and post-HD albumin and beta-2-microglobulin for the 
first study use of the dialyzers 
 
Additional 
Assessments 
 
The following data will be collected on the dialyzer with Endexo 
and the Optiflux dialyzer: 
• Complement activation (C3a, C5a, SC5b-9) during the first 
study use of the dialyzer, collected pre-HD and at 30 
minutes (±10 minutes) after the recorded start of HD  
• Thrombus scoring, performed at the end of dialyzer use for 
every dialyzer used in the study. 
The graded scoring method has been adopted from: 
Dorsch et al. A multi-center, prospective, open-label, 
8-week study of certoparin for anticoagulation during 
maintenance hemodialysis--the membrane study 
BMC 
Nephrology 
2012 
Jun 
28;13:50. 
doi: 
10.1186/1471-2369-13-50. 
Laville et al. Results of the HepZero study comparing 
heparin-grafted membrane and standard care show 
that heparin-grafted dialyzer is safe and easy to use 
for heparin-free dialysis. Kidney Int. 2014 Dec 
;86(6):1260-7. doi: 10.1038/ki.2014.225. Epub 2014 
Jul 9. 
 
• URR and spKt/V (calculated from pre- and post-HD BUN), 
every 3-4 weeks  
• Saline flushes and saline infusions during Optiflux and 
Endexo Periods  
o Total volume (mL) per treatment, time of 

PROTOCOL NUMBER: Endexo-001                                                                        Version Number: 3 
                                                                                                                           Date: 26 October /2018       
 
 
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administration and the reason  
The following data will be collected on the dialyzer with Endexo 
only: 
• Collect data on TMP and UFR for calculating the in vivo 
ultrafiltration coefficient (Kuf) of the dialyzer with Endexo at 
15 minutes (±5 minutes) after the recorded start of HD 
during Visits 24, 27 and 30  
 
 
Data Collection 
The data listed below will be collected in the study.  
 
• Demographics 
• Medical History (and Historical Laboratory Values) 
• Concomitant Medications  
• Physical Exam, Vital Signs, Body Measurements (height, 
weight) 
• Adverse Events and Serious Adverse Events 
• Device Deficiencies 
• Laboratory Assessments  
• HD Prescription, HD Treatment Data, and HD Treatment-
related Medications 
• Machine 
Readings 
of 
Ultrafiltration 
Rate 
and 
Transmembrane Pressure for Kuf estimation 
• Thrombus Scoring 
• Collection of time of administration and volume (mL) per 
saline flush and saline infusion during each study visit under 
Optiflux and Endexo periods 
Sample Size 
Determination 
The sample size of 15-24 subjects is based on FDA’s Guidance for 
Industry and CDRH Reviewers: Guidance for the Content of 
Premarket Notifications for Conventional and High Permeability 
Hemodialyzers (August 7, 1998), which recommends that data be 
collected for a minimum of 12 subjects receiving 36 treatments 
each. 
 

PROTOCOL NUMBER: Endexo-001                                                                        Version Number: 3 
                                                                                                                           Date: 26 October /2018       
 
 
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Statistical 
Methods 
Descriptive statistics (n, mean, standard deviation, median, 
minimum and maximum) will be presented for continuous 
endpoints. Frequency and percent will be presented for categorical 
endpoints. Any missing values of an endpoint will be treated as 
completely missing at random and will not be imputed. 
 
Study analysis populations: 
• Safety population (spop): Subjects who sign the ICF, are 
eligible, are enrolled in the study, and have at least one HD 
treatment with the dialyzer with Endexo. 
• Analysis population (apop): Subjects who are in the spop,  
and have a minimum of 36 HD treatments with the dialyzer 
with Endexo.  
 
Analysis for primary endpoint: 
- For the Kuf for the dialyzer with Endexo, descriptive statistics will 
be presented. A 95% confidence interval will be calculated if 
appropriate.  
 
Analysis for secondary endpoints: 
- For URR and spKt/V for the first study use of both dialyzers, 
descriptive statistics will be presented, and a 95% confidence 
interval will be calculated if appropriate.  
 
- For albumin and beta-2-microglobulin, the relative percent change 
{((pre-HD – post-HD)/pre-HD) x 100} will be calculated. Descriptive 
statistics will be presented for the pre-HD and post-HD laboratory 
values and the relative percent change. The 95% confidence 
intervals will be calculated if appropriate. 
- Adverse events and device-related events per treatment will be 
calculated.  The 95% confidence intervals will be derived if 
appropriate. 
 
Analysis for additional assessments: 
- For the measurements of complement activation, the relative 
percent change {((30 minutes after the recorded start of HD – pre-
HD)/pre-HD) x 100} will be calculated. Descriptive statistics will be 
presented for the “pre-HD” and “30 minutes after the recorded start 
of HD” laboratory values and the relative percent change. The 95% 
confidence intervals will be calculated if appropriate.  
 
- For thrombus formation: 
• the number of subjects and percentages, and the number of 
HD treatments in each period for each grade category will 
be presented, and,  

PROTOCOL NUMBER: Endexo-001                                                                        Version Number: 3 
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• the proportion of treatments with full dialyzer clotting will be 
calculated for each subject in each period. Descriptive 
statistics of the proportions will be presented. A 95% 
confidence interval of the proportions will be calculated if 
appropriate. 
 
- As done for the analysis of the secondary endpoints, descriptive 
statistics will be presented for URR and spKt/V, and a 95% 
confidence interval will be calculated if appropriate.  
Safety 
Monitoring 
All adverse events and serious adverse events will be captured 
from the time the subject signs the ICF until the subject completes 
or withdraws from the study.  
 
The site investigator must inform the Sponsor of every SAE, within 
24 hours of becoming aware of the occurrence. 
 
The study medical monitor will evaluate and monitor safety of the 
subjects during the course of the study. 
 
If the Sponsor determines that an unanticipated adverse event or 
serious adverse event presents an unreasonable risk to the 
subjects, the Sponsor will terminate the study as soon as possible.