Prospective Multi-Center Study for Clinical Validation of the Molecular-Based GenePOC CDiff System for the Detection of Toxin B Gene From Toxigenic Clostridium Difficile Strains in Unformed (Soft or Liquid) Human Stool Specimens
Phase: NA
Conditions: Clostridium Difficile Infection
Sponsor: Meridian Bioscience, Inc.

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Protocol No.: 
 
GenePOC CDiff_clinical-01 
 
 
Prospective Multi-Center Study for Clinical Validation of the 
Molecular-Based GenePOC CDiff system for the Detection of Toxin 
B gene from Toxigenic Clostridium difficile (C. difficile) Strains in 
unformed (soft or liquid) Human Stool Specimens. 
 
 
Protocol version 
Version date 
V1 
2016-Mar-01 
V2 
2016-May-16 
V3 
2016-Nov-18 
V4 
2017-May-12 
 
 
 
FOR INVESTIGATIONAL USE ONLY 
The performance characteristics of the GenePOC™ CDiff test have not been established.  
To be used by qualified investigators only.  
The GenePOC CDiff test must not be used as a diagnostic procedure without confirmation of the 
diagnosis by another medically established diagnostic product or procedure. 
 
CONFIDENTIAL AND PROPRIETARY 
The information contained herein is the property of GenePOC™ and is provided to you as an 
investigator or potential investigator for review by you, your staff, and the applicable independent 
ethics committee (IEC): Institutional Review Board (IRB) for the US or Research Ethics Board (REB) 
in Canada. By accepting this document, you agree to not disclose the information in part or in whole 
to a third party without written authorization from GenePOC Inc. per the separate Confidential 
Disclosure Agreement (CDA). Data obtained from this clinical investigation may be submitted to 
regulatory agencies. Terms regarding trial confidentiality, data ownership and publication can be 
found in the separate Clinical Trial Agreement (CTA). 
 
 

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REVISION SUMMARY 
 
 
This revision summary is intended as an aid in understanding the changes being implemented. 
Review of the summary alone does not ensure complete understanding. The actual text must be 
reviewed to ensure full understanding of the change(s).  
 
Versi
on 
Date 
Section 
Change(s) description 
Reason for change 
(s) 
V1 
2016-Mar-
01 
NA 
Original 
NA 
V2 
2016-May-
16 
Whole 
document 
Official Nomenclature of Device updated 
To ensure 
uniformity in all 
GenePOC 
documents 
Changes made in Section 1, 4.1, 4.4, 4.5, 5, 6.1, 6.6.1, 6.6.2, 
7.3, 7.5.1.1, 7.5.1.3, 7.5.2 and 13.2 
Complete list of changes is available upon request. 
Enhancement of 
clarity 
1 
Changed in planned study period: study start 
date June to July 
New information 
3.1 and 7.4 
Within CCFA-HB: Cycloserine Cefoxitin and 
Fructose Agar plate with Horse Blood, HB and 
Horse-Blood removed 
New information 
Added: BAP, GLC, MSI, QC and SOP 
acronyms 
Changed: CMG: Cooked Meat Glucose Broth 
changed for Chopped Meat carbohydrate broth 
6.2.2 and 
6.2.4 
Changed: No negative sample will be used for 
proficiency training. Instead 150 µL of SBT will 
be used as Negative Control. 
New information 
6.2.2, 
6.2.4, 6.6.2 
and 7.5.1.1 
Removed: (e.g. American Type Culture 
Collection, ATCC 43255) 
Positive external 
control strain not 
yet determined, will 
be added to Study 
Site Manual 
6.3 
6.3.1, added: “Unformed” stool  
6.3.1, Deleted: Not currently under treatment for 
CDI; 
6.3.2, Deleted: Patient under antibiotics 
treatment for CDI; 
Information not 
available on 
leftover specimens 
6.3.1, Added: “At least 1.25ml of” unformed 
stool specimen (defined as specimen assuming 
the shape of its container); 
To enhance clarity 
7.3.2 and 
7.5.2 
Completely changed 
To match Selected 
Reference Method 
site 
7.5.1.3 and 
10.2 
Added: generic clinical trial email address 
New information 

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V3
2016-Nov-
18 
Whole 
document 
Cdiff changed for CDiff
Changed: Stability of SBT and clinical 
specimens changed from 4 days to 7 days if 
kept at 2-8°C. 
Changed: freezing temperature from -70°C to 
-25°C or colder 
To match with 
official name of 
the Assay and PI 
Changed in Clinical Study Manager:
Catherine Lippe is replacing Rachelle Nadeau 
as Study Manager 
New information
Changed: Sample for specimen when 
applicable as described in section 3.2 
To match with 
official 
nomenclature 
Changed: Sample Transfer Device (STD) for 
Disposable transfer tool (DTT) 
To match with 
official 
nomenclature 
Minor changes made in other section for enhancement of clarity
Complete list of changes is available upon request. 
1.0
Changed in Clinical Trial Main Eligibility 
Criteria:  fresh specimens must be tested […] 
within 168 hours (7 days) […].  
New information
3.1
Added: NEC (Negative External Control) and 
PEC (positive external Control) 
Added: PrC, (new abbreviation for Process 
Control)
To enhance 
clarity 
3.2
Changed: Definition of sample changed and 
definition of specimen added. 
To match with 
official 
nomenclature 
Protocol 
synopsis 
and 4.2 
Changed: “test” for “assay” and “preparation” 
for “processing” 
To match with 
Package insert 
version 4 
4.3
Changed: image of inoculating loop (2)
To match with 
official name of 
the Assay and PI 
4.4
Added:[…] dipped into the homogenized 
stool specimen […]. 
To enhance 
clarity 
Protocol 
synopsis 
and 6.1 
Changed: up to seven (7) changed for up to 
(8) 
New information 
6.2.1 and 
6.2.2 
Changed: Negative control will consist of 150 
µL of SBT changed for BRU broth;  
New information
6.2.2
Added: data will be gathered (if available)
To enhance 
clarity 
6.2.4
Changed: SBT changed for NEC
New information
6.5.1
Changed: Specimen unique number changed 
from CXnnnnA to CXnnnA 
Error in previous 
version 
6.5.2
Changed: The operator will save the 
instrument data on a properly labeled USB 
keys on each testing day. Data saved on the 
USB key will be uploaded to the eClinical 
database.  The USB key must be maintained 
as a backup at the Clinical Center.
Paragraph re-
written due to 
new information 

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6.6.1
Deleted: “and shipping to GenePOC once or 
twice per week”; 
To match with 
new instructions 
in section 6.5.2 
Deleted: “Plastic bags to hold/store and ship 
PIE” 
New information, 
PIE will not be 
kept 
7.3
Changed: 1ml of stool specimen changed for 
500 µL of stool specimen 
Paragraphs 
rearranged 
to 
reflect 
the 
recommended workflow 
New information
7.3.1.1.1
Added :A picture should be taken of the PIE 
and sent to the Study Manager (please refer 
to Study Site Manual section 9 for 
instructions). . 
New information
7.3.2.1
Deleted: “to 54” in: “The plate will be 
incubated at 35-37°C in anaerobic conditions 
for 48 to 54 hours” 
New information
7.3.2.2
Deleted: .36 to. in: The tube will be incubated 
at 35-37°C in anaerobic conditions for 36 to 
48h.” 
Deleted: to 54 in: “The CCFA plate will be 
incubated anaerobically at 35-37°C for 48 to 
54h.” 
New information
7.3.2.4
Changed: (incubated 48 -72h […]) changed 
for (incubated up to 48 h […]) 
Added: An isolate cultured on BAP will be 
preserved in broth with 10-20% glycerol. 
Preserved isolates will be stored at-70°C or 
colder for possible future use. 
Deleted: “An aliquot of the CMC broth will be 
frozen with 10-20 glycerol at”. 
New information
7.4
Changed 2nd bullet: All Frozen stool 
specimen and CCMB-TAL Broth must be 
stored at -25°C or colder, and culture isolates 
at -70°C or colder and only specimens 
requested by the Study Manager will be 
shipped on dry ice to GenePOC; 
Deleted: stored between 2°C to 8°C in a 
plastic bag and shipped on icepacks to 
GenePOC as directed by Study Manager. 
Added: discarded in appropriate biological 
waste receptacle in accordance with country, 
federal, provincial, state and local regulations. 
New information
7.5.1.1
Changed: SBT for BRU Broth
New information
9.1.1
Deleted: sent to GenePOC at least once per 
week. The Clinical Center must keep one of 
the instrument back-up media  
Added: kept on site. 
Added: Data obtained from GenePOC 
instrument will be forwarded to GenePOC 
through the EDC system. 
New information
10.1
Deleted: (UNR or other) 
Error in previous 
version 

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13.1
Paragraph re-written: Make1 copy daily of 
runs from the GenePOC instrument. Keep the 
copy at site for all Instrument backups. 
Transfer instrument data to sponsor through 
EDC database 
New information
V4
11-May-
2017 
Whole 
Document 
Minor reformatting of the text to increase readability
Protocol 
Acceptabilit
y 
Removed:
Rachelle Nadeau 
Dany Leblanc 
Added: 
Catherine Lippe 
Keith Chiasson 
New information
Sponsor 
Contacts 
Catherine Lippé’s cell phone number was 
modified to +1 418 925-8597 
New information
6.2
Original Text:
consist of four (4) distinct segments: 
Proficiency testing, Clinical Accuracy testing, 
Discrepant testing (when required), and 
Reproducibility 
Replaced by: 
consist of five (5) distinct segments: 
Proficiency testing, Clinical Accuracy testing, 
Discrepant testing (when required), Frozen 
Specimen Testing and Reproducibility 
New information
6.2.5
Added:
6.2.5 Frozen Specimen testing 
In the event that additional results are 
needed, the frozen aliquots will be retested 
with the GenePOC CDiff assay on selected 
sites. The sites will be provided with a list of 
randomly selected specimens to thaw, and 
test again following the procedure in Section 
7.3.1. The frozen aliquots will not be tested by 
the Reference Method. 
New Section
10.1
Catherine Lippé’s cell phone number was 
modified to +1 418 925-8597 
New information
 
 

 
 
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PROTOCOL ACCEPTABILITY 
 
Protocol Proposed by: 
 
 
__________________________________  
 
_____________________ 
Catherine Lippe, MSc 
 
 
 
 
Date (yyyy-mmm-dd) 
Clinical Study Manager 
GenePOC Inc. 
 
Sponsor 
 
 
_________________________________  
 
_____________________ 
Keith Chiasson, PhD  
 
 
 
 
Date (yyyy-mmm-dd) 
Director, Clinical Operations 
GenePOC Inc  
 
Clinical Center: 
 
Address:   
________________________________ 
 
 
________________________________ 
 
 
________________________________ 
 
 
________________________________ 
 
__________________________________ 
Principal Investigator Name 
 
 
__________________________________  
 
_____________________ 
Principal Investigator Signature 
 
 
 
Date (yyyy-mmm-dd)
Acceptability 
I have reviewed and understood this protocol and agree to its provisions. Any modifications 
must be made by written mutual agreement. 

 
 
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TABLE OF CONTENTS 
1 
PROTOCOL SYNOPSIS ........................................................................................................... 10 
2 
SPONSOR CONTACTS ............................................................................................................ 14 
2.1 
Sponsor ......................................................................................................................... 14 
2.2 
Clinical Study Manager .................................................................................................. 14 
3 
TERMINOLOGY ........................................................................................................................ 15 
3.1 
Definitions...................................................................................................................... 16 
4 
INTRODUCTION ....................................................................................................................... 17 
4.1 
Protocol Scope .............................................................................................................. 17 
4.2 
lntended Use ................................................................................................................. 17 
4.3 
Device Description ......................................................................................................... 17 
4.4 
Test Principle ................................................................................................................. 18 
4.5 
Clinical Benefits and Justification for the Use of a New Technology ................................ 18 
5 
TRIAL OBJECTIVES ................................................................................................................. 20 
6 
STUDY DESIGN ....................................................................................................................... 21 
6.1 
Clinical Centers Requirements ....................................................................................... 21 
6.2 
Overview of the Evaluation ............................................................................................ 21 
6.2.1 
Proficiency Testing ..................................................................................................... 21 
6.2.2 
Clinical Accuracy Testing............................................................................................ 21 
6.2.3 
Discrepant Testing (when required)............................................................................ 22 
6.2.4 
Reproducibility Testing (for selected sites) ................................................................. 22 
6.2.5 
Frozen Specimen testing ............................................................................................ 23 
6.3 
Study Criteria ................................................................................................................. 23 
6.3.1 
Inclusion criteria .......................................................................................................... 23 
6.3.2 
Exclusion Criteria (left over)........................................................................................ 23 
6.4 
Specimen Size Justification ........................................................................................... 23 
6.5 
Data Collection .............................................................................................................. 24 
6.5.1 
Case Report Forms .................................................................................................... 24 
6.5.2 
GenePOC Data........................................................................................................... 25 
6.6 
Study Materials .............................................................................................................. 25 
6.6.1 
Provided by GenePOC ............................................................................................... 25 
6.6.2 
Provided by Investigator ............................................................................................. 25 
7 
LABORATORY TESTING PROCEDURES ................................................................................ 27 
7.1 
Specimen Collection ...................................................................................................... 27 
7.2 
Specimen Storage and Handling .................................................................................... 27 
7.3 
Testing Algorithm ........................................................................................................... 27 
7.3.1 
GenePOC CDiff test ................................................................................................... 27 

 
 
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7.3.2 
Reference Method ...................................................................................................... 28 
7.3.3 
Discrepant Testing ...................................................................................................... 30 
7.4 
Storage & Shipping ........................................................................................................ 30 
7.5 
Quality Control (QC) Testing .......................................................................................... 30 
7.5.1 
GenePOC CDiff test ................................................................................................... 30 
7.5.2 
Reference Method ...................................................................................................... 32 
8 
Clinical Trial Quality Assurance ................................................................................................. 33 
8.1 
Accountability of Investigational Materials ...................................................................... 33 
8.2 
Process for Protocol Changes and Deviations ................................................................ 33 
8.2.1 
Protocol Amendment .................................................................................................. 33 
8.2.2 
Protocol Deviations ..................................................................................................... 33 
8.3 
Trial Consistency and Integrity: Monitoring and Auditing ................................................. 34 
9 
DATA COLLECTION, MANAGEMENT AND REPORTING ........................................................ 35 
9.1 
Clinical Center Responsibility ......................................................................................... 35 
9.1.1 
General Instructions on Recording and Sending Data to GenePOC .......................... 35 
9.1.2 
Final Report ................................................................................................................ 35 
9.2 
GenePOC Responsibility ............................................................................................... 35 
9.3 
Data Confidentiality ........................................................................................................ 36 
9.4 
Data Verification and Validation Rules ........................................................................... 36 
10 CLINICAL TRIAL INCIDENTS, RISK MANAGEMENT AND ADVERSE EVENTS....................... 37 
10.1 
Clinical Trial Incidents .................................................................................................... 37 
10.2 
Reporting of Incidents .................................................................................................... 37 
10.3 
Risk Management .......................................................................................................... 38 
10.3.1 Potential Risks to the Subject ..................................................................................... 38 
10.3.2 Potential Risks to the Personnel operating the Product ............................................. 38 
10.4 
Adverse Events ............................................................................................................. 38 
11 REGULATORY AND ADMINISTRATIVE INFORMATION .......................................................... 39 
11.1 
Institutional Requirements .............................................................................................. 39 
11.2 
Ethical Conduct and Good Clinical Practice.................................................................... 39 
11.3 
Investigator Responsibilities ........................................................................................... 39 
11.4 
Subject Information Confidentiality ................................................................................. 39 
11.5 
Data Maintenance and Disclosure .................................................................................. 39 
11.6 
Clinical Center Compliance ............................................................................................ 40 
11.6.1 Investigator Responsibility .......................................................................................... 40 
11.6.2 Accountability of Materials .......................................................................................... 40 
11.6.3 Retention of Records .................................................................................................. 40 
11.7 
Trial management .......................................................................................................... 40 

 
 
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11.7.1 Study Initiation ............................................................................................................ 40 
11.7.2 Study Extension .......................................................................................................... 40 
11.7.3 Rules for Discontinuation ............................................................................................ 41 
12 REFERENCES ......................................................................................................................... 42 
13 APPENDIX ................................................................................................................................ 43 
13.1 
APPENDIX A: Regulatory Documents Requirements ..................................................... 43 
13.2 
APPENDIX B: Testing Algorithm .................................................................................... 44 
13.3 
APPENDIX C: Discrepant Testing Algorithm .................................................................. 45 
 
 
 

 
 
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1 
PROTOCOL SYNOPSIS 
Clinical Trial 
Protocol Number GenePOC-CDiff_clinical-01 
Protocol Title 
Prospective Multi-Center Study for Clinical Validation of the Molecular-Based 
GenePOC CDiff system for the Detection of Toxin B gene from Toxigenic 
Clostridium difficile (C. difficile) Strains in unformed (soft or liquid) Human Stool 
Specimens. 
Sponsor 
GenePOC Inc. 
System Summary 
The primary purpose of this clinical investigation is to verify the performance of 
the GenePOC CDiff test on the GenePOCTM instrument. This will be achieved 
by comparing the GenePOC CDiff test to the Toxigenic Culture (TC) and cell 
cytotoxicity neutralisation assay (CCNA), a conventional method considered 
as gold standard for detection of toxigenic Clostridium difficile in stool samples.
Study Locations 
Up to eight (8) geographically distributed Canadian and United States Clinical 
Centers are targeted, with each site testing high volumes of specimens for 
toxigenic C. difficile combined with high prevalence rates. GenePOC CDiff test
will be performed at each of the selected clinical centers. The reference 
method, the Toxigenic Culture (TC), is plan to be performed at a single 
reference laboratory. 
Intended Use 
The GenePOC CDiff assay performed on the GenePOC instrument is a 
qualitative in vitro diagnostic test that utilizes automated sample processing
and real-time polymerase chain reaction (rtPCR) to detect the toxin B (tcdB) 
gene of toxigenic Clostridium difficile (C. difficile) in unformed (liquid or soft) 
stool specimens obtained from patients suspected of having C. difficile
infection (CDI). The GenePOC CDiff assay is intended for use as an aid in the 
diagnosis of CDI in humans in conjunction with clinical and epidemiological risk 
factors. 
Investigational 
Product 
(IUO) 
The GenePOC CDiff test will be performed according to the Study Protocol 
using the GenePOC instrument. The GenePOC system, composed of 
GenePOC CDiff test and GenePOC instrument, used in conjunction with 
appropriate reagents, is capable of automated cell lysis, dilution of nucleic 
acids from multiple sample types as well as automated amplification and 
detection of target nucleic acid sequences. 

 
 
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Reference Method
Toxigenic Culture (TC) is defined as anaerobic culture to isolate a C. difficile
strain, then, if present, followed by confirmation of toxigenicity of the isolate by 
a cell cytotoxicity neutralisation assay (CCNA) 
More specifically, the C. difficile bacteria, when present, will be isolated from 
unformed (soft or liquid) stool specimens using a direct and an enriched culture 
method. Toxigenicity of the isolated C. difficile will be determined using a tissue 
culture cytotoxicity assay. 
For this clinical trial, the Reference Method will be performed, by one selected 
site only, on stool specimens coming from all Clinical Center. 
Phase 
Development Phase - Qualification of investigational device (IUO). 
Planned Study 
Period 
Clinical investigation to begin in July 2016 at the earliest and to be completed 
within approximately three (3) months. 
Planned Specimen 
Size 
The purpose of the clinical investigation is to enroll sufficient specimens to 
obtain a total of 150 positive specimens for C. difficile based on the Reference 
Method final result. With an estimated prevalence of approximately 10-20%, 
up to 1500 specimens will be tested across all Clinical Centers. The 
performance obtained and the confidence interval will be monitored during the 
study in order to stop the enrollment when appropriate. A minimum of 20 
positive results per site is expected but sites with a higher prevalence of C. 
difficile could contribute with more positive results to reach the required 
number. 
Objectives 
The primary objectives of this multi-site prospective investigational trial are: 
 
To establish the performance characteristics of the GenePOC CDiff test 
for its use to detect Toxin B gene from toxigenic Clostridium difficile strains. 
Sensitivity and specificity will be established in comparison to the 
Reference Method. 
 
To estimate the Positive and Negative Predictive Values (PPV and NPV) 
of the GenePOC CDiff test. 
 
To estimate the rate of unresolved results for the GenePOC CDiff test due 
to Sample Processing Control failure (Unresolved sample results). 
 
To determine the reproducibility of the GenePOC CDiff test between sites.

 
 
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Study Design 
Clinical Centers will be selected based on a number of criteria, such as 
investigator and site personnel availability, number of specimens of interest 
tested for Toxin B gene from Toxigenic Clostridium difficile isolates and CDI 
prevalence. 
 
The Site that will be selected to perform the Reference Method will have 
laboratory facilities where Toxigenic C. difficile isolates characterization 
methods are performed for routine, investigation or research purposes.  
This clinical investigation will be composed of the following segments: 
Proficiency testing, Clinical Accuracy, Discrepant testing (when required) 
Frozen Specimen Testing (at selected sites) and Reproducibility (at selected 
sites). 
 
There are no risks to the subject inherent to the execution of this investigation 
since it will:  
1. Be performed on excess de-identified specimens only; and 
2. Include parallel clinical routine testing by an approved and established 
method for reporting subject results. 
Study will be initiated from subjects suspected of having C. difficile infection 
(CDI) for whom diagnostic procedures are indicated and ordered. Unformed 
stool specimen will be tested as per clinical center standard test.  
Left over of this sampling will be collected by research personnel for the 
purpose of this clinical trial and tested on GenePOC CDiff system and sent to 
the selected Clinical Center for Reference method testing.  
Results obtained from testing using the GenePOC CDiff test will be compared 
to those obtained by the Reference Method. Investigators will ensure that, for 
a given specimen, the individuals performing the GenePOC CDiff test are 
masked from the result of the Reference Method and vice-versa. 
Electronic and/or paper Case Report Form(s) will be used to record pertinent 
specimen and laboratory information. No personal subject information will be 
collected by GenePOC. 
 
In cases of discrepant results between the Reference Method and the 
GenePOC CDiff test, GenePOC personnel will perform further 
characterization testing to elucidate the discrepancies. 
Clinical Trial Main 
Eligibility Criteria 
 
Specimens from subjects suspected of having CDI for whom diagnostic 
procedures are indicated and ordered. 
 
Only one (1) unformed stool specimen per subject will be included in the 
study. 
 
Fresh specimens must be tested with the GenePOC CDiff test within 48 
hours of collection if kept at 2-25oC or within 168 hours (7 days) of 
collection if kept at 2-8oC. Specimen kept in Anaerobe Transport Medium 
must be tested within 4 days of collection for Reference Method testing. 

 
 
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Clinical Study 
Statistical Methods
Results obtained with the GenePOC CDiff test will be compared to those 
obtained with the Reference Method. The statistical analyses will include all 
compliant specimens and will determine at least the following: 
 
The sensitivity and specificity, PPV and NPV as well as exact 95% 
confidence interval. 
 
The unresolved and indeterminate rates along with 95% exact confidence 
interval. 
 
Poolability of the data. 
 
Reproducibility percent agreements for qualitative and quantitative data. 
 
 
 
 
 
 
 
 
 

 
 
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2 
SPONSOR CONTACTS 
2.1 
Sponsor 
GenePOC Inc. 
360 rue Franquet, suite 100.  
Porte 3, Parc Technologique 
Québec, Qc 
Canada, G1P 4N3 
www.genepoc-diagnostic.com 
 
2.2 
Clinical Study Manager 
Catherine Lippe, M.Sc. 
Study Manager 
GenePOC Inc. 
360 rue Franquet, suite 100.  
Porte 3, Parc Technologique 
Québec, Qc 
Canada, G1P 4N3 
e-mail: catherine.lippe@genepoc.ca 
Phone: +1 418 650-3535 #269 
Cell: +1 418-925-8597 
 
 
 
 

 
 
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3 
TERMINOLOGY 
ADE
Adverse Device Effect 
AE
Adverse Event 
ATCC
American Type Culture Collection 
BAP
Blood Agar Plate 
bp
Base pairs 
CCFA
Cycloserine Cefoxitin and Fructose Agar plate  
CCMB-TAL
Cycloserine Cefoxitin Mannitol Broth with Taurocholate and Lysozyme 
CCNA
Cell Cytotoxicity Neutralisation Assay 
CDA
Confidentiality Disclosure Agreement 
CDC
Centers for Disease Control and Prevention 
CDI
Clostridium difficile Infection 
C. difficile 
Clostridium difficile 
CLIA
Clinical Laboratory Improvement Amendments 
CMC
Chopped Meat carbohydrate broth 
CRA
Clinical Research Associate 
CTA
Clinical Trial Agreement 
CTI
Clinical Trial Incident 
DNA
Deoxyribonucleic Acid 
EC
External control 
eCRF
Electronic Case Report Form 
EDC
Electronic Data Capture 
GLC
Gas Liquid Chromatography 
IEC
Independent Ethics Committee 
INC
Inconclusive 
IND
Indeterminate 
IRB
Investigational Review Board 
IUO
Investigational Use Only 
LOD
Limit of Detection 
MDR
Medical Device Reporting 
MSI
Microbiology Specialist Inc. 
NEC
Negative External Control 
NPV
Negative Predicative Value 
PC or PrC
Process Control 
PCR
Polymerase Chain Reaction 
PI
Principal investigator 
PEC
Positive External Control 
POC
Point of Care 
PPV
Positive Predictive Value 
QC
Quality Control 
REB
Research Ethic Board 
rtPCR
Real time Polymerase Chain Reaction 
SADE
Serious Adverse Device Effect 
SAE
Serious Adverse Event 
SBT
Sample Buffer Tube 
SOP
Standard Operating Procedures 
STD
Sample Transfer Device (also called Disposable transfer tool (DTT)) 
TAT
Turn-Around Time 
TC
Toxigenic Culture 
tcdB 
Toxin B gene 
UNR
Unresolved 
US
United States of America

 
 
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3.1 
Definitions 
Clinical Center(s) 
Site(s) that will perform the GenePOC CDiff test and/or the Reference 
Method for the clinical study. 
GenePOC 
CDiff 
system 
The system is composed of the GenePOC CDiff test which is used in 
conjunction with the GenePOC instrument. 
PCR Operator 
Participating laboratory technician who has successfully completed the 
proficiency testing  
(CDiff) PIE 
C. difficile disposable microfluidic cartridges (describe in this document as 
PIE because of the shape of the cartridge). 
Principal Investigator 
(PI) 
A person who actually conducts the clinical investigation, under whose 
immediate direction the test article (device) is used involving a sample 
derived from a human subject; or, in the event of an investigation conducted 
by a team of individuals, is the responsible leader of that team. 
Reference Method 
The Reference Method for this study will be Toxigenic Culture then, if C. 
difficile strain is present, it will be followed by confirmation of toxigenicity of 
the isolate by a cell cytotoxicity neutralisation assay (CCNA) 
Sample 
SBT inoculated with left over of unformed stool (soft or liquid) specimen 
Specimen 
Left over of unformed stool (soft or liquid) specimen intended for regular C. 
difficile diagnostic testing. 
 
 
 

 
 
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4 
INTRODUCTION 
4.1 
Protocol Scope 
The purpose of this clinical investigation is to establish the performance characteristics of the 
GenePOC CDiff test for its use in determining the presence of toxigenic C. difficile in human 
unformed stool specimens. Sensitivity and Specificity will be established in comparison to the 
Reference Method. For this trial the Reference Method will be Toxigenic Culture (TC) then, if C. 
difficile is present, it will be followed by confirmation of toxigenicity of the isolate by a Cell 
Cytotoxicity Neutralisation Assay (CCNA), gold standard method for CDI diagnosis. 
 
4.2 
lntended Use 
The GenePOC CDiff assay performed on the GenePOC™ instrument is a qualitative in vitro 
diagnostic test that utilizes automated sample processing and real-time polymerase chain 
reaction (rtPCR) to detect the toxin B (tcdB) gene of toxigenic Clostridium difficile (C. difficile) in 
unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile 
infection (CDI). The GenePOC CDiff assay is intended for use as an aid in the diagnosis of CDI 
in humans in conjunction with clinical and epidemiological risk factors. 
 
4.3 
Device Description 
The GenePOC CDiff test will be performed using the GenePOC instrument ((1) below). The 
GenePOC instrument, used in conjunction with appropriate reagents, is capable of automated 
lysis cells, dilution of nucleic acids from multiple sample types as well as automated amplification 
and detection of target nucleic acid sequences. 
 
(1)  
(2)  
(3)  
(4)  
(5) 
 
The GenePOC CDiff test kits consist of: 
Components 
Packaging 
(2) 
Transfer Loop 
Disposable 5µL inoculating loop to dip into the 
unformed stool specimen and transfer into the SBT 
(3) 
Sample Buffer Tube (SBT) 
A 4.5mL tube containing 1mL of sample buffer 
(4) 
Disposable transfer tool (DTT) 
Plastic disposable transfer pipette for transferring 
inoculated sample buffer into the PIE. 
(5) 
CDiff disposable microfluidic 
cartridges (PIE) 
Fully integrated disposable microfluidic cartridge for 
detection of C. difficile. 
 

 
 
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4.4 
Test Principle 
An unformed (soft or liquid) stool specimen is collected using standard stool collection device. 
Using a disposable 5µL inoculating loop (transfer loop) dipped into the homogenized stool 
specimen, stool material is transferred into SBT and vortexed. 
The sample processing (addition to buffer, mixing) is simple, but not automated. The GenePOC 
instrument automates and integrates nucleic acid purification and amplification, and detection 
of the target sequence in complex samples using real-time Polymerase Chain Reaction (rtPCR). 
The system consists of an instrument with embedded software for running tests and displaying 
the results. The system requires the use of single-use disposable cartridges (PIE) that contain 
the Polymerase Chain Reaction (PCR) reagents and host the amplification and detection 
process. Because the cartridges are self-contained, cross-contamination concerns are 
minimized. 
The GenePOC CDiff test includes reagents for the simultaneous detection of the target C. 
difficile DNA and a process control (PC) to monitor processing, amplification, and the absence 
of reaction inhibitors. The C. difficile primers and probe detect a target region of 263 base pairs 
(bp) of the toxin B gene (tcdB) of Clostridium difficile. The results are interpreted by the system 
from measured fluorescent signals and embedded calculation algorithms. Results may be 
viewed, be printed transferred and/or store by the user. 
 
4.5 
Clinical Benefits and Justification for the Use of a New Technology 
C. difficile is a naturally occurring bacteria in the gut of a small percentage of the population, 
prevalence of approximately 1-3% in healthy adults (Goudarzi, et al., 2014). In most cases, it 
does not cause any health problem because it lives in balance with the microorganisms which 
normally colonize the intestine of human beings.  
C. difficile is the leading cause of infectious diarrhea in hospitalized patients (Ghantoji, et al., 
2010) (Barbut, et al., 2014). According to the Center for Disease Control and Prevention (CDC), 
the annual incidence of C. difficile Infection (CDI) in the United States (US) is approaching 
500,000 cases with a mortality rate of between 1 and 2,5%, which would have resulted in around 
29,000 deaths in 2011 (Lessa, et al., 2015). 15-25% of nosocomial CDI would be consecutive 
to an antibiotic treatment (Shroeder, et al., 2014). 
In addition to the associated morbidity and mortality, CDI significantly increase health care costs 
due to the increased length of stay and readmissions frequency. In the US, the economic burden 
of CDI is estimated between 750 million and 3.2 billion (Ghantoji, et al., 2010). In Europe, the 
economic burden is estimated at 3 billion Euros (€) (Bouza, 2012). In fact, a meta-analysis of 
costs associated with CDI revealed that the care and treatment of a primary case of CDI costs 
is 2,871 to 4,846 US$2008 while for a recurring infection, costs increase at 13,655 to 18,067 
US$2008 per case (Ghantoji, et al., 2010). 
A recent econometric study, (Shroeder, et al., 2014) demonstrated that rapid diagnosis of CDI 
is more effective and less costly than traditional methods recommended by guidelines. In most 
environments, molecular diagnosis on request would be favorable economically in view of 
limiting false negatives diagnosis. 
Moreover, a recent feasibility and acceptability study of rapid C. difficile diagnostic at Point of 
Care (POC) revealed that in addition to allowing the decrease of the median waiting time results 
from 18 to just under 2 hours, the GeneXpert of Cepheid technology was well accepted by 
nurses and technical staff of two London hospitals (Goldenberg, et al., 2014). 
Early detection of CDI would directly and indirectly decrease the morbidity and mortality rate of 
this infection, directly by more effective management of patients and indirectly by a reduction in 

 
 
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nosocomial transmission attributable to the presence of an infected patient (not diagnosed) on 
the wards (Surawicz, et al., 2013). 
However, it is imperative that screening is performed only in infection symptomatic patients 
having produced ≥ 3 unformed (liquid or soft) stools in 24 hours (Bagdasarian, et al., 2015). The 
definitive diagnosis of CDI must be accompanied by a positive result for toxigenic C. difficile or 
one of its toxins or pseudomembranous colitis evidences. 
In an impact assessment carried out in the UK, study comparing the test Xpert C. difficile 
cytotoxin in the neutralization assay of C. difficile., it has been shown that the fastest PCR 
diagnosis (average TAT 1.5 hours vs. 22.5 to 46.5 hours for the positive/negative) reduces the 
length of stay for patients and generate savings of around £ 2,300 (~ 4500 CAD) per patient 
suspected to have a CDI (Sewell, et al., 2014). Rapid diagnosis would also allow better control 
of the empirical antibiotic therapy (Barbut, et al., 2014). 
Several molecular diagnostic tests are commercially available for the early detection of C. 
difficile (Le Guern, et autres, 2013). However, the GenePOC CDiff system is developed to 
enable the decentralized diagnosis of CDI, ideally at point of care (POC). 

 
 
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5 
TRIAL OBJECTIVES 
The objectives of this multi-center prospective clinical study are: 
 
To establish the performance characteristics of the GenePOC CDiff test for its use to detect 
Toxin B gene from toxigenic C. difficile in unformed (liquid or soft) stool specimens obtained 
from patients suspected of having C. difficile infection. Sensitivity and specificity will be 
established in comparison to the Reference Method. 
 
To estimate the Positive and Negative Predictive Values (PPV and NPV) of the GenePOC 
CDiff test. 
 
To estimate the rate of unresolved results for the GenePOC CDiff test due to Sample 
Processing Control failure (Unresolved sample results). 
 
To determine the reproducibility of the GenePOC CDiff test between sites. 

 
 
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6 
STUDY DESIGN 
6.1 
Clinical Centers Requirements 
Up to eight (8) Clinical Centers (with a minimum of 3 sites (1 Canada and 2 US) will participate 
in this clinical study. Clinical centers will be selected for this study based on a number of criteria, 
such as investigator and site personnel availability, number of specimens of interest tested for 
C. difficile, CDI prevalence, familiarity with the study Reference Method (for the selected site 
only), and experience with clinical investigations. 
For this clinical trial, the Reference Method will be performed by one selected site only, on 
unformed (liquid or soft) stool specimens coming from all Clinical Centers.  
Site(s) will have a laboratory where C. difficile characterization methods are performed for 
routine and/or research purposes. Results from clinical centers routine method will be collected. 
The Clinical Centers regulatory documents requirements are detailed in Appendix A. 
 
6.2 
Overview of the Evaluation 
The Clinical investigation will consist of five (5) distinct segments: Proficiency testing, Clinical 
Accuracy testing, Discrepant testing (when required), Frozen Specimen Testing (on selected 
sites) and Reproducibility (selected sites). 
 
6.2.1 
Proficiency Testing 
Each PCR operator who will participate in the GenePOC CDiff clinical trial will be trained by a 
GenePOC Study Manager (or CRA) on handling and performing the GenePOC CDiff test 
according to the Investigational Use Only (IUO) Package insert, the Study Site Manual and the 
GenePOC system User's Manual. 
A test panel containing negative samples and C. difficile positive samples will be used to assess 
each new participating technician proficiency with the protocol test methods. This panel will be 
provided in a sufficient number. Negative control will consist of 150 µL of BRU broth. A 
participating technician failing to achieve the qualification criteria on initial testing of the 
GenePOC CDiff test must repeat the training panel, and will be qualified if he/she meets the 
acceptance criteria for the repeated run. If the participating technician fails to meet the retest 
criteria, he/she cannot be qualified for participation in the GenePOC CDiff clinical study as a 
PCR operator for the GenePOC CDiff system unless re-training occurs and the participating 
technician is able to pass the proficiency test. 
To be qualified for participation in the GenePOC CDiff clinical trial as a PCR operator, each 
participating technician must achieve a correct answer for all positive samples and true negative 
(no target) samples in the molecular method using the provided proficiency panel. 
If a new participating technician is included in the study after the initial training and proficiency 
testing occurs, the training of this person can be performed by a GenePOC representative or by 
an authorized proficient PCR operator on-site. The new participating technician must also pass 
the proficiency test to participate in the study. 
 
6.2.2 
Clinical Accuracy Testing 
This clinical trial is designed in such a way that only one site may perform the Reference Method, 
which requires that the selected Clinical Center (for reference method) has laboratory facilities 

 
 
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where C. difficile characterization methods are performed for routine, investigation or research 
purposes.  
Specimens will be a leftover of unformed stool. Specimen testing will be performed according to 
Section 7 of this Protocol. Results obtained from testing of specimens using the GenePOC CDiff 
test will be compared to those obtained by the Reference Method. These results will serve to 
verify the GenePOC CDiff test performance. 
Investigators will ensure that, for a given specimen, the individuals performing the GenePOC 
CDiff test are masked from the results of the Reference Method and vice-versa. 
The purpose of the clinical investigation is to enroll sufficient specimens to obtain approximately 
150 positive specimens for C. difficile based on the Reference Method final result. With an 
estimated prevalence of approximately 10-20%, it is projected that up to 1500 specimens will be 
needed across all participating Clinical Centers. 
The Study Manager and/or CRA will monitor specimen enrollment and prevalence of C. difficile 
across all participating Clinical Centers. It may be necessary to increase the enrollment rate or 
to prematurely stop enrollment at one or more participating centers, depending upon the total 
number of specimens and the positive specimens obtained across all Clinical Centers. 
At least three (3) lots of the GenePOC CDiff test kits will be used for this Clinical trial. Each 
Clinical Center with test a minimum of two (2) lots. 
Electronic Case Report Form (eCRF) will be used to record all pertinent information. No personal 
subject information will be collected but the following general demographic data will be gathered 
(if available):  
 
Age category and  
 
Specimen origin (i.e. ln-patient for intensive and non-intensive care units, as well as long 
term care facility, out-patient, emergency). 
Once per day, a reference toxigenic C. difficile strain bearing the tcdB gene will be used as a 
positive external control (PEC) while 150µL of BRU broth will be used as a negative external 
control (NEC). If either or both of the ECs fail to give the expected result, all samples tested in 
that run will be repeated from the remaining SBT stored at 2-8°C containing the specimen along 
with new NEC and PEC. 
 
6.2.3 
Discrepant Testing (when required) 
In cases of discrepant results between the Reference Method and the GenePOC CDiff test, 
further characterization testing may be requested by GenePOC to be performed by the Clinical 
Center and possibly at GenePOC to attempt to resolve the discrepancy. See Appendix C for 
description of the minimal discrepant testing. An electronic or paper Discrepant Results Form 
will be used for recording discrepant testing information. 
 
6.2.4 
Reproducibility Testing (for selected sites) 
Reproducibility study will be performed with a panel of samples spiked at 3 different 
concentrations of C. difficile: Negative, Low positive (1-2x LOD) and Moderate positive (2-3x 
LOD). Each panel will consist of 3 samples with 3 replicates of each concentration. 
The site-to-site reproducibility will test the same reproducibility panel at three (3) designated 
sites (2 external sites and GenePOC laboratories) for the within-run (3 replicates), between-run 
(2 runs per day from two different operators) and between-day (5 days, consecutive or not) 
variance with multiple operators and instruments. A single lot of the GenePOC CDiff test will be 

 
 
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tested by all sites according to the training manual instructions and the IUO CDiff test Package 
Insert. 
The reproducibility panel will contain randomized moderate positive, low positive and true 
negative. 
Once per day, a reference toxigenic C. difficile strain bearing the tcdB gene will be used as a 
positive external control (EC) while 150µL of NEC will be used as a negative EC. If either or 
both of the ECs fail to give the expected result, all samples tested in that run will be repeated 
from the remaining SBT containing the sample stored at 2-8°C along with new positive and 
negative ECs. 
 
6.2.5 
Frozen Specimen testing 
In the event that additional results are needed, the frozen aliquots will be retested with the 
GenePOC CDiff assay on selected sites. The sites will be provided with a list of randomly 
selected specimens to thaw, and test again following the procedure in Section 7.3.1. The frozen 
aliquots will not be retested with the Reference Method. 
 
6.3 
Study Criteria 
Note: For this trial, specimens will not be collected for the express purposes of this evaluation. 
Excess de-identified specimens will be used. 
 
6.3.1 
Inclusion criteria 
 
Unformed Stool specimens from patients suspected of having CDI for whom diagnostic 
tests are indicated and ordered; 
 
At least 1.25mL of unformed stool specimen (defined as specimen assuming the shape of 
its container); 
 
Only one (1) specimen per patient will be included in the study; 
 
Materials use within their expiration date; 
 
Transport, storage times, and conditions (e.g. room temperature and/or refrigerated) 
within requested indications. 
 
6.3.2 
Exclusion Criteria (left over) 
 
Specimens from patients for whom CDI diagnostic tests have not been ordered; 
 
Transport and storage times and conditions that exceed these Study Protocol requirements; 
 
Formed or hard stool specimens or rectal swabs. 
 
6.4 
Specimen Size Justification 
The purpose of the clinical investigation is to enroll sufficient specimens to obtain a total of 150 
positive specimens for C. difficile based on the Reference Method final result. With an estimated 
prevalence of approximately 10-20%, up to 1500 specimens will be tested across all Clinical 
Centers. The performance obtained and the confidence interval will be monitored during the 
study in order to stop the enrollment when appropriate.  
A minimum of 20 positive results per site is expected but sites with a higher prevalence of C. 
difficile could contribute with more positive results to reach the required number. A potential 

 
 
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minimum of 150 specimens and a potential maximum of 300 total specimens will be obtained at 
each clinical center. 
The performance obtained and the statistical confidence intervals will be monitored during the 
study in order to stop the enrollment when deemed appropriate. 
 
6.5 
Data Collection 
The principal investigator (PI) will ensure that each designee and the scope of the designee's 
delegated authority are recorded on the Site Signature and Delegation of Authority Log. The 
designee's signature, initials, start and end dates and list of study related tasks, must be 
recorded on the form. 
 
6.5.1 
Case Report Forms 
All Clinical Centers will use electronic data capture (EDC) through an electronic Case Report 
Forms (eCRF). In case the eCRF would not be available for any given reason, a paper case 
report form will be available and sent electronically to Study Manager, eCRF will have to be 
completed once available again. 
An eCRF will be completed for each specimen enrolled in the study in order to record relevant 
demographic, clinical and laboratory information. These forms must be completed as described 
in the Study Site Manual.  
Subjects whose specimen will be included in the study will not be identified by name or by 
hospital medical record number on the eCRF. A field is available for a study-specific subject 
identifier code which will uniquely identify each subject. This code will be assigned by a 
designated individual at the Clinical Center, who is not directly involved in any other aspects of 
the study. This code will be a series of: 
 
5 digit XX-YYY (X being the site number and Y the specimens number attributed 
sequentially 
 
And three letters FML: (“F” being the first letter of the First Name; “M” being the first letter 
of the Middle Name or a dash (-) if the person does not have a middle name; “L” being the 
first letter of Last name). As per local regulations, initials can also be a series of three 
letters determined by clinical center. 
This code will have no relation with protected health information, and will be used only to track 
subject enrollment. A Study Subject Log associating each subject with its subject identifier code 
will be maintained in a secure on-site location by the designated individual assigning the codes 
to the subjects.  
Each enrolled specimen will be assigned a unique Study Number, which will be identified by bar 
code labels to be provided by GenePOC. Study Numbers will conform to seven (7) characters 
in a "CXnnnA" format: where "C" is a letter identifying the test (CDiff), "X" is a number identifying 
the site, "nnn" is an incrementing number identifying each specimen within a study segment and 
"A" is a letter denoting the study segment, ("A" for Accuracy or "D" for Discrepant testing). For 
panel members provided by GenePOC for testing, the same study number pattern will be used 
and the study segment will be identified as follows:  "P" for Proficiency, “R” for Reproducibility 
and "W" for Workflow Practice. 

 
 
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6.5.2 
GenePOC Data 
The operator will save the instrument data on a properly labeled USB keys on each testing day. 
Data saved on the USB key will be uploaded to the eClinical database.  The USB key must be 
maintained as a backup at the Clinical Center. 
 
6.6 
Study Materials 
6.6.1 
Provided by GenePOC 
 
GenePOC instrument 
 
GenePOC sample Racks; 
 
GenePOC system User's Manual; 
 
Tube Vortexer;  
 
Instructions and Training Materials for the Study (Study Site Manual); 
 
GenePOC CDiff test IUO kits (including PIE, SBT, transfer loop and disposable transfer 
tool); 
 
CRFs and other required electronic and printed forms; 
 
Barcode labels with study numbers for all specimens; 
 
Masked and randomized proficiency and reproducibility (if applicable) panel of 
characterized samples; 
 
Anaerobic Transport Medium (Anaerobe Systems); 
 
Shipping materials: shipping boxes, dangerous good shipping labels, GenePOC pre-
addressed FedEx waybills, shipping forms and other material and/or equipment needed 
for shipping; 
 
Freezer boxes, plastic microtubes and screw-caps; 
 
USB keys for instrument data daily backup; 
 
Swabs for environmental testing (as described in section 7.5.1.3); 
 
Listing for Study binder(s) indicating essential information for archiving purposes at the 
closing of the study; 
 
Technical and engineering support as needed; 
 
Miscellaneous supplies as agreed upon. 
 
6.6.2 
Provided by Investigator 
 
Specimens meeting the eligibility criteria outlined in Section 6.3 above; 
 
Copies of the laboratory’s procedures for the C. difficile collection, routine diagnostic 
method and quality control; 
 
Material for routine testing of C. difficile: 
 
Facilities, time and personnel necessary to perform the evaluation according to this Study 
Protocol, and manage the study records according to the Study Site Manual, the 
GenePOC instructions and Regulatory Requirements; 
 
Import permit provided by the CDC (into US only) for pathogens including at least 
Clostridium species. 
 
Trained personnel in the preparation and shipment of biological substances per CDC 
(USA sites only), Transportation of Dangerous Goods Regulations 14 (TDGR) (Canadian 
sites only), and IATA guidelines (all sites); 
 
Anaerobic workstation at 35-37°C (For Reference Method site only); 
 
Secure room temperature storage space for the GenePOC CDiff test kits (as required by 
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 
Adequate refrigerator (between 2oC and 8oC) for the storage and fresh specimens; 
 
Adequate storage space in a -25oC freezer or colder to hold frozen stool specimen, SBT, 
broths and panels; 
 
Control organisms for Reference Method,  
 
Dry ice to send frozen stool specimen and/or SBT; 
 
Site policies or procedures to prevent the release of personal information about subjects to 
the investigator; 
 
Miscellaneous supplies as agreed upon. 

 
 
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7 
LABORATORY TESTING PROCEDURES 
7.1 
Specimen Collection 
 
Collect unformed stool specimen in a clean, dry container or bedpan not contaminated 
with urine, residual soap, toilet paper, water, or disinfectants. 
 
Transfer appropriate volume of deidentified stool specimen to: 
o An aliquot for specimen freezing for further testing (if needed); 
o An Anaerobe Systems anaerobic transporter; 
o To sample buffer tube (SBT) 
 
7.2 
Specimen Storage and Handling 
Specimens should be transported to the laboratory according to the hospital's policies.  
 
Specimens that meet the study criteria should be labelled with a barcode study number 
provided by GenePOC; 
 
All relevant information regarding the specimen will be recorded on the appropriate 
Specimen Handling worksheet and data thereafter transferred to eCRF; 
 
Fresh specimens stored at 2-25°C can be tested with the GenePOC CDiff system within 
48 hours or within 7 days of collection if kept at 2-8oC. Specimen kept at room 
temperature in Anaerobe Transport Medium must be tested within 4 days of collection for 
Reference Method testing. 
 
Frozen specimens will be provided by GenePOC, and the detailed testing procedure will 
be provided as an addendum to the Study Site Manual. 
 
7.3 
Testing Algorithm 
Results obtained with the GenePOC CDiff test will be compared to those obtained with the 
Reference Method. All Clinical Centers will be shipping the stool specimen for Reference 
Method testing. The Reference Method is described in detail in Section 7.3.2 of this protocol. 
The unformed stool specimen will follow the normal hospital path up to the Hospital routine test, 
of which deidentified specimen left over will be divided in three parts. At least 1,25 mL will be 
needed for protocol requested analysis.  
First, approximatively 500 µL of stool specimen will be transferred into an Anaerobe Transport 
Medium kept at room temperature for shipment to the Selected site for Reference Method 
testing. The Reference method is toxigenic culture (TC) that is defined as anaerobic culture to 
isolate C. difficile, followed by evaluation of toxigenicity of the isolates through Cell Cytotoxicity 
Neutralisation Assay (CCNA). 
Second, a minimum of 250-500 µL of the homogenized stool specimen will be transferred in a 
collection tube to be frozen at -25°C (or colder) for further testing (if needed). 
Third, using a transfer loop, 5 µL of the homogenized stool specimen will be transferred to an 
appropriately labelled Sample Buffer Tube (SBT). The SBT will be closed and vortexed as 
described in the GenePOC CDiff test Package insert and/or Study Site Manual. The SBTs will 
be placed at 2-8°C in the event repeat testing is required. If the sample does not require repeat 
testing, the SBT will be frozen at -25°C or colder. 
 
7.3.1 
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The GenePOC CDiff test will be performed according to the test Package insert and Study Site 
Manual. 
 
 
Non-Reportable Results 
Samples that initially produce a non-reportable result (Unresolved, Indeterminate or External 
Control failure) will be repeated as described below. Samples that have a reportable (Positive, 
Negative) result upon repeat testing will be included in the data analyses. Repeated samples 
that do not give a reportable result will not be included in data analyses. They will be reported 
separately as non-reportable samples. 
7.3.1.1.1 Unresolved Samples (UNR) 
An Unresolved Sample is when the process control fails (no detection) and the target reaction 
(tcdB) also shows no detection. A picture should be taken of the PIE and sent to the Study 
Manager (please refer to Study Site Manual section 9 for instructions).  
An Unresolved sample will be repeated from the refrigerated SBT. These samples may be 
repeated alone, with other samples to be repeated, or included in a new run with fresh 
specimens. In cases where the sample is Unresolved again, no additional repeat testing will be 
performed. Please refer to section 7.3.3 for action to be taken with remaining SBT. 
7.3.1.1.2 Indeterminate Result (IND) 
For an Indeterminate (IND) result due to an instrument failure, testing of the sample(s) will be 
repeated from the refrigerated SBT and may be tested with other samples that require repeat 
testing, or included in a new run with fresh samples. For any IND result, the Study Manager 
should be contacted and the incident must be documented on the eCRF. In cases where the 
sample is Indeterminate again, no additional repeat testing will be performed. Please refer to 
section 7.3.3 for action to be taken with remaining SBT. 
7.3.1.1.3 External control failure 
ln case of a failure of either or both external control, the testing of all clinical samples and any 
repeated samples included in the run will be repeated from the refrigerated SBTs along with 
new external control (see Section 7.5 for details). In cases where external control fails again, 
the Study Manager should be contacted. 
 
7.3.2 
Reference Method 
The C. difficile bacteria, when present, will be isolated from soft or liquid stool specimens using 
direct and enriched culture method.  
Microbiology Specialists Incorporated (MSI) is the selected center for Reference Method. Their 
Standard Operating Procedures (SOP) will be utilized as summarized below. 
The specimens will be inoculated onto a standard cycloserine cefoxitin and fructose agar plate 
(CCFA) (direct culture, Section 7.3.2.1) and cycloserine cefoxitin mannitol broth with 
taurocholate and lysozyme (CCMB-TAL) (enriched culture, Section 7.3.2.2). After incubation, 
the broth will be sub-cultured to another CCFA plate. Colonies morphologically resembling C. 
difficile will be identified as described in Section 7.3.2.3. The isolate will be growing in chopped 
meat carbohydrate broth (CMC) for identification confirmation by gas liquid chromatography 
(GLC). If the isolated strain is identified as C. difficile, the same CMC will be used for toxigenicity 
assessment. The toxigenicity of the isolates using a tissue culture cytotoxicity assay will be 
determined as described in Section 7.3.2.4. The detailed methods are described in the 
Reference Method Laboratory's SOP. 

 
 
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Direct Culture (As per MSI SOP No. ST041 dated 2006/Jul/17) 
 
 
A commercially available standard CCFA plate will be inoculated using a swab of the stool 
specimen from the Anaerobic Transport Medium and streaked for isolation. 
 
The plate will be incubated at 35-37°C in anaerobic conditions for 48 hours. 
 
The plate will be examined for colonies characteristic of C. difficile. 
Note: Due to the very high sensitivity of C. difficile to oxygen, the plate should be put in aerobic 
conditions only when necessary and for a short period of time. 
 
 
Enriched Culture (As per MSI SOP No. ST041 dated 2006/Jul/17) 
 
The same swab that is utilized to inoculate the CCFA plate will be used to inoculate a 
CCMB-TAL broth tube. 
 
The tube will be incubated at 35-37°C in anaerobic conditions for 48h. 
 
The broth is then sub-cultured to another CCFA plate. The CCFA plate will be incubated 
anaerobically at 35-37°C for 48h. 
 
The plate will be examined for colonies characteristic of C. difficile. 
 
The enriched culture can be stopped as soon as a toxigenic C. difficile is confirmed in the 
direct culture for a given specimen 
Note: Due to the very high sensitivity of C. difficile to oxygen, the plate and broth should be put 
in aerobic conditions only when necessary and for a short period of time. 
 
 
C. difficile Identification (As per MSI SOP No. ST041 dated 2006/Jul/17) 
Colonies morphologically resembling C. difficile from the Direct or Enriched plates will be 
confirmed as follows: 
 
Gram stain, 
 
Characteristic barnyard-like odor, 
 
Aero intolerance on chocolate agar plates, in CO2 and a blood agar plate (BAP) under 
anaerobic conditions. The BAP plate contains a vancomycin (5 mcg) disc.   
 
Gas liquid chromatography (GLC) 
All tests above are required to confirm that the isolated strain is C. difficile. 
 
 
Toxigenicity Assessment (As per SOP No. ST040 dated 2012/Feb/24) 
Toxigenicity Assessment will be proceeding once C. difficile identification is confirmed by the 
presence of iso acids by GLC. The same CMC broth (incubated up to 48h at 35-37oC in 
anaerobic atmosphere) used for iso acids identification is used to perform the toxin assay.  
The procedures will follow the SOP noted above. 
An isolate cultured on BAP will be preserved in broth with 10-20% glycerol. Preserved isolates 
will be stored at-70°C or colder for possible future use. The remaining of the CMC broth will be 
kept at room temperature to inoculate a new CMC broth in case a repeat of the test is required. 
 

 
 
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)
 
lnconclusive Result 
For an Inconclusive (INC) result in the Reference Method due to a non-interpretable cytotoxicity 
test result (partial rounding of the cells, stretching instead of rounding), specimen(s) will be 
retested from a newly inoculated and incubated CMC broth. The CMC broth kept at room 
temperature should be used to inoculate a new CMC broth (using a dilution factor of around 
1/10) that should be processed as directed in Section 7.3.2.4, Toxigenicity Assessment. 
Specimens that have a reportable (Positive, Negative) result after the initial or repeated testing 
will be included in the data analyses. Repeated specimens that do not give a reportable result 
will not be included in data analyses. They will be reported separately as non-reportable 
specimens. 
 
7.3.3 
Discrepant Testing 
In cases of discrepant results between the Reference Method and the GenePOC CDiff test, 
further characterization testing may be requested by GenePOC to be performed by the Clinical 
Center.  
If results from Reference Method and GenePOC CDiff test remains discrepant after retesting, 
frozen stool specimen, CCMB-TAL Broth and/or frozen SBT coming from discrepant result 
specimen may be sent to GenePOC for further testing. 
During the course of the trial, the GenePOC Study Manager will inform the sites which 
specimens require to be shipped to GenePOC.  
 
7.4 
Storage & Shipping 
 
SBT samples must be kept at 2-8oC after testing for a maximum of seven (7) days. When it 
is confirmed that no repeat is necessary, they will be frozen at -25oC or colder for possible 
future discrepant testing; 
 
All Frozen stool specimen and CCMB-TAL Broth must be stored at -25oC or colder, and 
culture isolates at -70oC or colder and only specimens requested by the Study Manager will 
be shipped on dry ice to GenePOC; 
 
All PIEs (containing amplified product) must be discarded in appropriate biological waste 
receptacle in accordance with country, federal, provincial, state and local regulations. 
 
Detailed shipping instructions will be provided in the Study Site Manual. 
 
At the end of the trial, clinical center will be instructed by Study Manager to destroy, as per 
their institution policy, specimens that did not require shipment to GenePOC. 
 
7.5 
Quality Control (QC) Testing 
In addition to the quality assurance and quality control programs of each laboratory under their 
respective certification (e.g. CLIA, ISO 15189), the minimum quality control described below 
must be performed during the course of this study. 
 
7.5.1 
GenePOC CDiff test 
 
External Controls 
For each day in which samples are processed, appropriate positive and negative external control 
(ECs) will be tested. These external controls results will need to be kept in the Site File and 
forwarded to GenePOC. 

 
 
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External control materials are provided by GenePOC. A reference toxigenic C. difficile strain 
bearing the tcdB gene will be used as a positive external control (EC) while 150 µL of BRU broth 
will be used as a negative EC. If either or both of the ECs fail to give the expected result, all 
samples tested in that run will be repeated from the remaining SBT containing the specimen 
stored at 2-8°C along with new positive and negative ECs. 
Preparation of these controls will be detailed in the Package lnsert and in the Study Site Manual. 
 
 
Sample Process Control 
The Process Control (PC) is incorporated into GenePOC CDiff PIE and is intended to monitor 
for the effectiveness of liquid displacement, sample treatment (Lysis) and heating during the 
sample processing steps. The PC also monitors the integrity of the PCR reagents, the thermal 
cycling, and for the presence of inhibitory substances during the amplification and detection 
steps. A failed PC renders the sample Unresolved in absence of tcdB DNA target. 
 
 
Monitoring for the Presence of DNA Contamination 
At the request of the GenePOC Study Manager, the work area and equipment will be monitored 
for the presence of toxigenic C. difficile bearing the tcdB gene contamination using the 
GenePOC CDiff test. Should contamination arise, the Study Manager will instruct the site on the 
measures to be taken prior to testing additional specimens. 
 
 

 
 
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7.5.2 
Reference Method 
 
Media QC 
All media verified for physical appearance and sterility for each lot shipment and/or at the time 
of use. ln addition, culture media and vancomycin disk performance as assessed at a minimum 
for each lot shipment and periodically as described in the package inserts and clinical laboratory 
standard using the recommended and/or required strains. 
 
Media Performance Quality Control details 
Media or Reagent
Strains Tested for
Performance 
QC frequency
CCMB-TAL
C. difficile
Each lot or shipment
CCFA 
C. difficile 
C. perfringens
Each lot 
Vancomycin disk (5mcg) C. perfringens 
B. fragilis
Each lot and weekly 
CMC
P. anaerobius
Each lot and weekly
Chocolate Agar 
H. influenzae 
N. aonorrhoeae
Each lot or shipment 
Brucella Agar 
C. difficile 
B. fragilis
Each lot or shipment 
Blood Agar plate 
S. pyogenes 
S. pneumoniae 
E. faecalis 
Each lot or shipment 
 
 
GLC QC 
For GLC testing, quality control is performed each day of testing. A commercially available 
volatile acid standard mix is injected into the column. All volatile acids must be present in order 
to pass QC. 
 
 
Tissue Culture Cytotoxicity Assay QC 
Tissue Culture Cytotoxicity Assay QC will be performed as described in MSI SOP ST041 each 
testing day. 
 
 

 
 
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8 
Clinical Trial Quality Assurance 
The following measures will be taken to assure the quality of the trial conduct and data. 
 
8.1 
Accountability of Investigational Materials 
The Clinical Center will account for all GenePOC CDiff system investigational materials received 
from GenePOC. GenePOC clinical trial team will monitor site records for investigational 
materials accountability. All materials will be handled and disposed of according to Package 
Insert instructions, Study Site Manual or as directed by the GenePOC Study Manager. Upon 
completion of the study, all remaining supplies provided by GenePOC will be returned to 
GenePOC unless otherwise directed by the GenePOC Study Manager in writing. 
 
8.2 
Process for Protocol Changes and Deviations 
8.2.1 
Protocol Amendment 
A Protocol Amendment is a change to, or clarification of, the Study Protocol which may impact 
the conduct and potential benefit of the study, or participant safety. For each protocol 
amendment, changes must be reviewed, approved and signed by the GenePOC Study 
Manager, a representative of GenePOC and the Principal Investigator. All changes to the 
Protocol must be submitted to the Clinical Center IEC for examination and approval (if required). 
The Principal Investigator will ensure that protocol changes are implemented after written 
approval by all parties (including the IEC if needed), that all personnel using the protocol at the 
Clinical Center receive training for the change, and that the new protocol is maintained in the 
study records at the Clinical Center. Examples of such changes include, but are not limited to: 
the study objectives, study design, specimen sizes, study procedures, or administrative aspects. 
 
8.2.2 
Protocol Deviations 
Each protocol deviation reported to the GenePOC Study Manager by the Clinical Center, 
observed by the GenePOC Study Manager or CRA during monitoring contacts or visits, or 
observed through review of eCRFs will be documented by the GenePOC Study Manager, CRA 
or Clinical Center personnel on a Protocol Deviation Form. The Protocol Deviation Form will 
contain the description of the deviation, the impact on the trial or subject enrollment, the impact 
to the affected data and any corrective action taken to conform to the protocol. All Protocol 
Deviation Forms will be reviewed and signed by the GenePOC Study Manager or CRA and the 
Principal Investigator (if the Clinical Center was involved or concerned). A copy of each Protocol 
Deviation Form will be kept at the Clinical Center and the original at GenePOC. 
Examples of such deviations include, but are not limited to: 
 
not completing the testing required by the protocol; 
 
enrolling inappropriate specimens; 
 
failure to follow Package lnsert instructions for use and storage of the investigational device; 
 
failure to follow the Reference Method (e.g. use of expired materials); 
 
failure to perform EC as directed; 
 
not respecting the time to perform testing or retesting. 
Protocol deviations might render a data not eligible to be included in the final data analysis. 

 
 
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8.3 
Trial Consistency and Integrity: Monitoring and Auditing 
Monitoring will be accomplished either by on-site visit or through remote monitoring as detailed 
in the Clinical Monitoring Plan and recorded on Monitoring Visit Report.  
Periodic checks may be made with the Principal Investigator and/or his/her staff. It will include 
(but not limited to) availability of materials, subject and specimen enrollment, product 
accountability, and clarification of any questions. These checks may be accomplished via 
telephone conversations and/or written communication (emails or letters/memos) and 
documented on a Site Contact Report. 
Telephone conversations will be documented by the GenePOC Study Manager and/or CRA 
(recorded on the Site Contact Report). Critical study communications imparted by telephone to 
Clinical Center personnel (including but not limited to new instructions or training, identification 
of protocol deviations, corrective actions, or incidents) will be followed up with a written 
communication to the Clinical Center. Copies of relevant written communication (including e-
mails) will be kept by the GenePOC Study Manager and the Clinical Center. 
Monitoring may include review of IEC review status, laboratory accreditation, subject enrollment 
status, regulatory requirements, study compliance, eCRF and source data, adverse event and 
incident reporting, and study materials storage and disposition. Protocol Deviation 
documentation should be reviewed as well as eCRFs and applicable source data. Follow-up 
actions will be documented in writing to the Clinical Center. 
The GenePOC CRA or Study Manager will arrange for correction of discrepancies, missing data, 
or omissions on eCRFs by the Principal investigator or designee as appropriate.  
The GenePOC Study Manager will maintain close liaison to clarify any problems that may arise, 
and to ensure that the study is being carried out according to this protocol and the applicable 
regulatory requirements. The Clinical Center shall permit the GenePOC CRA, and other 
GenePOC personnel as indicated, to visit the Clinical Center and audit or inspect the study 
records and materials, to determine Principal Investigator’s compliance with the protocol, 
relevant guidelines and regulations for clinical trials. 

 
 
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9 
DATA COLLECTION, MANAGEMENT AND REPORTING 
9.1 
Clinical Center Responsibility 
9.1.1 
General Instructions on Recording and Sending Data to GenePOC 
An Electronic Data Capture (EDC) system will be used by all Clinical Centers. 
Individual instructions for completing paper source documents, eCRFs and other forms will be 
provided by GenePOC in the Study Site Manual. 
Electronic media (USB key) containing instrument data should kept on site. Data obtained from 
GenePOC instrument will be forwarded to GenePOC through the EDC system. 
Test results should be entered in the eCRF promptly i.e. within 2 business days of the test results 
are confirmed. 
The following paper forms, but not limited to (refer to Appendix A), will be completed as needed 
and kept on site during the study with a copy at GenePOC. The original will be kept at GenePOC 
at the end of the study with copies kept at the Clinical Center: 
 
Site Signature and Delegation of Authority Log (All persons authorized to complete, review 
and/or sign study documentation, including CRFs, will sign this Log. 
 
Study Visit Log; 
 
Reference method external control forms for culture media will be completed and copies 
will be sent to GenePOC with originals kept at the Clinical Center at the end of the study. 
 
Site Contact Log forms will be completed and maintained at the Clinical Center. 
 
Paper source documents will be completed first then the data will be transferred to the 
eCRF. 
 
 
Electronic Data Capture (EDC) 
Electronic CRFs (eCRF) will have to be completed immediately (usually within 2 business days 
of specimen enrollment) following completion of the testing procedure. 
The Principal Investigator must designate, in writing, any individuals authorized to complete and 
review the eCRFs. Only the Principal Investigator will have the right to sign the eCRFs. 
 
9.1.2 
Final Report 
The Principal Investigator, with input from the laboratory personnel, will be asked to provide 
GenePOC with a final report of special study issues, findings, assessment of ease-of-use and 
workflow, and any problems or recommendations, within 30 days of completion or termination 
of the study. This final report may include the convenience (ergonomics, performance, utility, 
rapidity, etc.) of the GenePOC CDiff system for integration into routine laboratory use and 
potential use near the subject. 
 
9.2 
GenePOC Responsibility 
A termination letter or notice will be sent by GenePOC to the Principal Investigator notifying the 
Clinical Center of the successful completion of the study terms by the Clinical Center. Terms 
and notifications for other causes of study termination will be addressed in the Clinical Trial 
Agreement. 
 

 
 
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9.3 
Data Confidentiality 
GenePOC will maintain the security and confidentiality of all trial data sent to GenePOC. 
GenePOC and the Clinical Center may be required to provide regulatory agencies access to 
trial data and records. GenePOC trial databases will not be shared with any third party. 
GenePOC provides an assurance that the de-identified data obtained in this study will be 
safeguarded and not used for unauthorized purposes. All other agreements by GenePOC, the 
Principal Investigator, and the Clinical Center in regards to confidentiality may be found in the 
Confidential Disclosure Agreement and the Clinical Trial Agreement. 
 
9.4 
Data Verification and Validation Rules 
Data captured will be entered into the database through the EDC system. Data related to eCRF 
and accountability logs will be transferred from the source documents to the eCRFs. Data 
related to the Reference Method, the discrepancy testing and EC will be transferred directly from 
the laboratory worksheets (considered as source documents) to the eCRFs. 
Data will be managed and controlled following GenePOC Quality Procedures and stored in a 
secure database with limited access and with electronic audit trails. 
Data validation (confirming the correctness, completeness, and compliance of the data) will be 
performed both during and after data entry. Validation during data entry will be performed using 
both visual inspection and programming incorporated into the forms.  

 
 
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10 
CLINICAL TRIAL INCIDENTS, RISK MANAGEMENT AND ADVERSE 
EVENTS 
10.1 
Clinical Trial Incidents 
A Clinical Trial Incident (CTI) is defined as any problem involving the investigational device, 
Reference Method, procedures, human subjects, or operators as a result of execution of this 
Study Protocol. CTIs may adversely (or potentially adversely) affect human safety, the integrity 
of the evaluation data, or the operation of devices. 
All serious occurrences which affect the health or safety of human subjects or operators involved 
in this evaluation are considered a Clinical Trial Incident, and may also be determined to be an 
Adverse Event (AE). AEs are addressed specifically in Section 10.4 below. Since subjects are 
not directly affected by the diagnostic device under evaluation and results are not used for 
clinical decisions, virtually all CTIs are not considered AEs. 
The Clinical Trials Incident Report Form is used to capture problems or observations arising 
during the use of the investigational product or in the execution of this Study Protocol and should 
be reported to the GenePOC Study Manager. The form should be filled out in the eCRF with a 
full description of the incident, and notification of the incident form may be sent by email to the 
GenePOC Study Manager. Incidents might include but are not limited to such occurrences as: 
instrument failure (IND or other), run incomplete, damage or deterioration of the GenePOC CDiff 
system, damage to devices or packaging caused by shipping or handling, or other incidents 
deemed to be failures or problems with the product or the execution of this Study Protocol. 
 
10.2 
Reporting of Incidents 
Any incidents which occur during the use of the GenePOC CDiff system or execution of this 
Study Protocol must be reported immediately to GenePOC. 
 
The primary contact will be the Study Manager. 
Catherine Lippe
Phone
(418) 650-3535 #269
Study Manager 
Cell Phone 
(418) 925-8597 
 
e-mail 
catherine.lippe@genepoc.ca 
 
 
clinical_trial@genepoc.ca 
 
In case of a problem with the GenePOC™ instrument, the second line of support will be: 
 
The Clinical Center must identify itself as a GenePOC CDiff clinical trial site and by providing it 
site number 
ln case of a problem with the EDC System, contact EDC System support line (phone # 
888.500.4247). If this support line does not provide a satisfactory response, contact the first line 
of support listed above who will either address the problem or dispatch the problem, as needed. 
All incidents must be documented on a Clinical Trial Incident report form. 
Sébastien Chapdelaine
Phone 
(418) 650-3535 #221 
Vice President Research & 
Development 
Cell Phone 
(418) 803-0650 
e-mail
sebastien.chapdelaine@genepoc.ca 
 
 
 

 
 
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•
 
10.3 
Risk Management 
10.3.1 
Potential Risks to the Subject 
There are no risks to the subject inherent to the execution of this evaluation; the investigational 
testing will: 
a) Be performed on excess de-identified specimens only; and, 
b) Include parallel clinical routine testing by an approved and established method for reporting 
subject results. 
 
10.3.2 
Potential Risks to the Personnel operating the Product 
To reduce the risk of exposed personnel, all processing, testing, and culturing of potentially 
infectious specimens must always be performed according to Standard Precautions, CDC 
Guidelines, Standard Guidelines, and the Clinical Center's own Laboratory Safety procedures 
and policies. 
 
10.4 
Adverse Events 
 
An Adverse Event (AE) is defined as any untoward medical occurrence, unintended 
disease or injury or any untoward clinical signs (including an abnormal laboratory finding) 
in subjects, users or other persons (investigational devices only) which is associated with 
the use of an investigational product or participation in an investigation, whether or not 
related to the investigational medical device. This includes event not seen at baseline and 
event that if present at baseline have worsened in intensity. 
 
Anticipated Adverse Events are defined as adverse events that are already known to 
occur from past experience. However, as cited in Section 10.1 above, there are no 
anticipated adverse events associated with this Study Protocol. 
 
An Adverse Device Effect (ADE) is defined as an adverse event related to the use of an 
investigational medical device. 
 
A Serious Adverse Device Effect (SADE) is defined as any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a 
device. 
 
An Unanticipated Serious Adverse Device Effect is a Serious Adverse Device Effect for 
which the effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan, or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects. If an 
Unanticipated Serious Adverse Device Effect occurs, it must be reported immediately by 
the Principal investigator to GenePOC and to the IEC (when required). GenePOC may 
additionally be required to report the occurrence to regulatory authorities. 
 
Medical Device Reporting (MDR) - Any commercially marketed device used in the trial 
which causes or contributes to a death or serious injury must be additionally reported to the 
commercial manufacturer as an MDR reportable event, under US federal regulations and 
Health Canada. An occurrence of serious injury during the trial that resulted from the use of 
a marketed device may require reporting as both an Adverse Event (to the IEC and Sponsor 
of the trial) and as an MDR (to the commercial manufacturer of the device). 

 
 
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11 
REGULATORY AND ADMINISTRATIVE INFORMATION 
11.1 
Institutional Requirements 
The Study Protocol must be submitted for review to the Clinical Center's IEC prior to the start of 
the study. In addition, this committee will inform the Principal investigator and the sponsor as to 
whether a waiver of informed consent has been granted. 
This must be done in accordance with Part 56 (Institutional Review Boards) of the Code of 
Federal Regulations Title 21 (USA) and Section 81(k) of the Canadian Medical Device 
Regulations. 
A copy of the IEC acknowledgment of review or approval from each institution must be forwarded 
to the study sponsor, GenePOC. 
 
11.2 
Ethical Conduct and Good Clinical Practice 
The procedures set forth in this Study Protocol are designed to ensure that GenePOC and the 
clinical investigators abide by the principles of Parts 50 and 56 of the Code of Federal 
Regulations Title 21 (USA), the Tri-Council's Code of Ethical Conduct for Research involving 
Humans (1998) and Part 3 of the Medical Devices Regulations (Canada), the Declaration of 
Helsinki (USA and Canada), and the Good Clinical Practices (ICH: USA, Canada and Europe), 
in the conduct, evaluation and documentation of this study. 
 
11.3 
Investigator Responsibilities 
The investigator responsibilities are defined in the present Study Protocol. The Financial 
Disclosure certification must be filled out in accordance with Part 54 of the Code of Federal 
Regulations, Title 21. 
 
11.4 
Subject Information Confidentiality 
All information will be treated with the utmost confidentiality by the hospital and the study 
sponsor, GenePOC. Only de-identified data will be obtained. Subject names or medical record 
numbers will not be transferred to the study sponsor.  
The specimens will be used strictly for isolation of C. difficile strain bearing the tcdB gene, and 
for no other purposes. Results from this study may be used by GenePOC to fulfill regulatory 
requirements of Health Canada, the US Food and Drug Administration (FDA), the European 
Parliament (providing the CE marking) and rest of the world. 
 
11.5 
Data Maintenance and Disclosure 
Study binder(s) will be provided to each Clinical Center to organize the required study 
documentation. Each Clinical Center is directly responsible for the maintenance and 
organization of the study documentation. 
Any corrections and/or changes made to entries on paper forms or logs, by the Principal 
Investigator or designees, must be crossed out with a single line leaving the initial entry legible. 
The correction must be dated and initialed. Incorrect entries must not be covered with correction 
fluid, obliterated, or made illegible in any way. If the reason for the change is not obvious, an 
explanation for the change must be written next to the modification. 

 
 
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Any change performed on an electronic form will be audited by the system and, when required, 
justified before electronic signature. 
The investigator is obligated to provide the study sponsor with complete test results and all data 
derived from the study. Any information that is unclear will be brought to the attention of the 
Principal Investigator and/or laboratory contact for prompt resolution. 
 
11.6 
Clinical Center Compliance 
11.6.1 
Investigator Responsibility 
Data generated from this evaluation will be used to support regulatory submissions. The 
Principal Investigator is expected to ensure that the Clinical Center and its personnel comply 
with Good Clinical Practices and pertinent regulations governing clinical research. 
 
11.6.2 
Accountability of Materials 
All materials will be handled and disposed of according to manufacturer's instructions. All 
investigational devices and their use and disposal will be accounted for in writing. Upon 
completion of the study, all remaining devices provided by GenePOC will be returned to 
GenePOC unless otherwise directed by the GenePOC Study Manager in writing. 
 
11.6.3 
Retention of Records 
The Principal Investigator will retain trial related documents as required by the applicable 
regulatory requirements or by an agreement with GenePOC. The Principal Investigator should 
take measures to prevent accidental or premature destruction of these documents. Essential 
documents should be retained for: 
 
A period of five years after the last approval or a marketing application to regulatory 
agencies. 
 
A period of five years has elapsed since the formal discontinuation of development of the 
investigational product. 
 
11.7 
Trial management 
11.7.1 
Study Initiation 
The Clinical study is anticipated to start in June 2016 at the earliest. Specimen enrollment will 
begin upon signed approval of all contract trial agreements, receipt of written IEC 
acknowledgment of review of this Study Protocol and demonstration of proficiency. The study is 
expected to be conducted over a period of three months depending upon the enrollment rate of 
diagnostic specimens and the prevalence of C. difficile strain bearing the tcdB gene. 
 
11.7.2 
Study Extension 
The evaluation may be extended beyond the estimated duration under terms agreed upon by 
the Clinical Center and GenePOC if more data are required for product development, or if the 
study is redirected or re-initiated. Any redirection of the study or re-initiation after a period of 
suspension would be subject to the re-negotiation of terms between GenePOC and the Clinical 
Center. 

 
 
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11.7.3 
Rules for Discontinuation 
GenePOC retains the right to terminate or curtail the study if this study protocol is not followed, 
or if the device under evaluation requires further development to meet the intended clinical 
objectives. 
The Clinical Center shall terminate the study upon any of the following conditions: 
 
Completion of the agreed maximum number of positive results or the agreed maximum 
number of total specimens;  
 
Reaching the date of maximum study duration;  
 
Withdrawal of approval from the Clinical Center Administration or IEC. 
 
Other reasons and conditions for study termination could be addressed in the Clinical Trial 
Agreement. 
 
 
 

 
 
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12 
REFERENCES 
Bagdasarian N, Rao K and Malani PN Diagnosis and treatment of Clostridium difficile in adults: 
a systematic review [Article] // JAMA 33. - 2015. - pp. 398-408. 
Barbut F [et al.] Does a rapid diagnosis of Clostridium difficile infestion impact on quality of 
patient management? [Article] // Clin Microbiol Infect 20. - 2014. - pp. 136-144. 
Bouza E Consequences of clostridium difficile infection: understanding the healtcare burden 
[Article] // Clin Microbiol Infect 18 suppl.6. - 2012. - pp. 5-12. 
Ghantoji SS [et al.] Economic healthcare costs of Clostridium difficile infection: a systematic 
review [Article] // J Hosp Infec 74. - 2010. - pp. 309-318. 
Goldenberg SD [et al.] Point-of-care testing for clostridium difficile infection: a real-world 
feasibility study of a rapid molecular test in two hospital settings. [Article] // Infect Dis Ther DOI 
10.1007/s40121-014-0038-6. - 2014. 
Goudarzi Mehdi [et al.] Clostridium difficile Infection: Epidemiology, Pathogenesis, Risk 
Factors, and Therapeutic Options [Article] // Hindawi Publishing Corporation. - 2014. - Vol. 214. 
Le Guern R et Wallet F Diagnostic de l'infection à Clostridium difficile au laboratoire [Article] // 
Ann Biol CLin. - 2013. - 71. - pp. 395-400. 
Lessa FC [et al.] Burden of Clostridium difficile infection in the United States [Article] // New 
England Journal of Medicine 372. - 2015. - pp. 825-834. 
Sewell B [et al.] Cost and impact on patient length of stay of rapid molecular resting for 
Clostridium difficile [Article] // Infect Dis Ther. - 2014. - 3. - pp. 281-293. 
Shroeder LF [et al.] Economic evaluation of laboratory testing strategies for hospital-associated 
Clostridium difficile infection [Article] // J Clin Microbiol 52. - 2014. - pp. 489-496. 
Surawicz CM [et al.] Guidelines for diagnosis, treatment, and prevention of Clostridium difficile 
infections [Article] // Am J Gastroenterol 108. - 2013. - pp. 478-498. 
 
 
 
 

 
 
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13 
APPENDIX 
13.1 
APPENDIX A: Regulatory Documents Requirements  
Trial Requirements
Investigator
Sponsor
Confidential Disclosure 
Agreement: (CDA) 
Original (signed and dated) 
Original (signed and dated) 
Curriculum vitae of principal 
investigator, co-investigators 
and other key site personnel 
Copy  
Copy  
Study training records 
Copy  
Original 
Laboratory Certification 
Copy  
Copy  
Protocol, including any 
revisions and changes 
Original (signed and dated) 
Original (signed and dated) 
CTA and Financial 
Agreement 
Original (signed and dated) 
Original (signed and dated) 
IEC composition, 
correspondence 
Or IEC acknowledgment of 
review 
Original 
Copy 
Financial Disclosure 
Agreement and Updates 
Original (signed and dated) 
Original (signed and dated) 
Site Contact Log  
No Copy 
Original 
Site Signature and 
Delegation of Authority Log 
and Study Visit Log 
Original (during the study) 
Copy (at the end of the 
study) 
Copy (during the study) 
Original (at the end of the 
study) 
Clinical Trial Incident Report 
form 
Original (signed and dated) 
Copy 
Laboratory Worksheets 
Copy 
Original 
Reference method external 
control forms 
Original 
Copy 
Investigational Material 
Accountability Log 
Copy 
Original 
Relevant Communications 
Copy (printed or electronic) 
Copy (printed or electronic) 
USB Keys for runs 
Make1 copy daily of runs 
from the GenePOC 
instrument. Keep the copy at 
site for all Instrument 
backups. Transfer instrument 
data to sponsor through EDC 
database 
Transfer electronically onto 
server and keep on a CD 
after. 
 
 
 

 
 
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13.2 
APPENDIX B: Testing Algorithm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Centralized) 

 
 
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13.3 
APPENDIX C: Discrepant Testing Algorithm 
 
 
 
Discrepant results
GenePOC    
Culture
+                      -
-
+
Retest on GenePOC 
CDiff test
(may be done onsite)
Retest on another 
test
Frozen SBT
Frozen broths
Isolated strains
Send to GenePOC
(only when requested)
Repeat testing at Clinical Center (once)