Multicenter, Prospective, Study Comparing PillCam® Crohn's Capsule Endoscopy (CE) to Ileocolonoscopy (IC) Plus MRE for Detection of Active Crohn's Disease (CD) in the Small Bowel and Colon in Subjects With Known CD and Mucosal Disease
Phase: NA
Conditions: Crohn Disease
Sponsor: Medtronic - MITG

BLINK Study Protocol (COVSBCC0549) 
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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title 
Multicenter, prospective study comparing 
PillCam® Crohn’s capsule endoscopy (CE) to 
ileocolonoscopy (IC) plus MRE for detection of 
active Crohn’s Disease (CD) in the small bowel 
and colon in subjects with known CD and mucosal 
disease (the BLINK study)
Clinical Investigation Plan Identifier
COVSBCC0549
Study Product Name 
PillCam® Crohn’s capsule endoscopy system
NCT 
NCT03241368
Document Version / Date
6.0 / 16November2018

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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title 
Multicenter, prospective study comparing 
PillCam® Crohn’s capsule endoscopy (CE) to 
ileocolonoscopy (IC) plus MRE for detection of 
active Crohn’s Disease (CD) in the small bowel 
and colon in subjects with known CD and mucosal 
disease (the BLINK study) 
Clinical Investigation Plan Identifier 
COVSBCC0549 
Study Product Name 
PillCam® Crohn’s capsule endoscopy system 
Sponsor/Local Sponsor 
United States: 
Medtronic MITG Early Technologies GI Solutions 
A Medtronic company (“Medtronic”) 
555 Long Wharf Dr, 
New Haven, CT 06511 
Phone: +(1)(203)562-1620 
Europe: 
Medtronic MITG Early Technologies GI Solutions 
A Medtronic company (“Medtronic”) 
Covidien Services Europe, Ltd.,  
Block G, First Floor 
Cherrywood Business & Technology Park 
Loughlinstown, Dublin 18, Ireland 
Phone: +(353)-(1)-4393000 
Israel: 
Medtronic MITG Early Technologies GI Solutions 
(Given Imaging Ltd.) 
A Medtronic company (“Medtronic”) 
2 Hacarmel St. New Industrial Park 
POB 258, 20692 Yoqneam, Israel 
Phone: +(972)-(4)-909-7700 
Document Version 
6.0 / 16November2018 

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Lead Principal Investigator(s) 
David H. Bruining, MD 
Division of Gastroenterology and Hepatology,   
Mayo Clinic College of Medicine,                            
200 1st St SW,                                        
Rochester, MN 55905,                                     
USA 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization of 
Medtronic is strictly prohibited. Persons to whom the information is disclosed must know that it is 
confidential and that it may not be further disclosed by them. 
 
 

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1. Investigator Statement 
Study product Name 
PillCam® Crohn’s capsule endoscopy system 
Sponsor 
United States: 
Medtronic MITG Early Technologies GI Solutions 
A Medtronic company (“Medtronic”) 
555 Long Wharf Dr, 
New Haven, CT 06511 
Phone: +(1)-(203)-562-1620 
Europe: 
Medtronic MITG Early Technologies GI Solutions 
A Medtronic company (“Medtronic”) 
Covidien Services Europe, Ltd.,  
Block G, First Floor 
Cherrywood Business & Technology Park 
Loughlinstown, Dublin 18, Ireland 
Phone: +(353)-(1)-439300 
Israel: 
Medtronic MITG Early Technologies GI Solutions 
(Given Imaging Ltd.) 
A Medtronic company (“Medtronic”) 
2 Hacarmel St. New Industrial Park 
POB 258, 20692 Yoqneam, Israel 
Phone: +(972)-(4)-909-7700 
Clinical Investigation Plan Identifier 
COVSBCC0549 
Version Number/Date  
Version 6.0 - 16November2018 
I have read the protocol, including all appendices, and I agree that it contains all necessary details for me 
and my staff to conduct this study as described. I will conduct this study as outlined herein and will make a 
reasonable effort to complete the study within the time designated. 
I agree to comply with United Stated Food and Drug Administration abbreviated requirements as defined in 
21CFR812.2(b)(US) or local laws and regulations as required for post-market clinical trials (Outside of the 
US). I agree to ensure that the confidential information contained in this document will not be used for any 
purpose other than the evaluation and conduct of the clinical investigation without the prior written consent 
of Medtronic. 
I will provide all study personnel under my supervision copies of the protocol and access to all information 
provided by Medtronic. I will discuss this material with them to ensure that they are fully informed about the 
products and the study. 
Investigator’s Signature: 
 
Investigator’s Name: 
 
Institution: 
 
Date:  
 

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Table of Contents  
 
1. 
Investigator Statement ...................................................................................................... 3 
Table of Contents ...................................................................................................................... 4 
2. 
Glossary .............................................................................................................................. 9 
3. 
Synopsis ........................................................................................................................... 12 
4. 
Introduction ..................................................................................................................... 15 
4.1. Background ........................................................................................................................... 15 
4.2. Purpose ................................................................................................................................. 16 
5. 
Objectives and Endpoints ................................................................................................. 17 
5.1. Objectives ............................................................................................................................. 17 
5.1.1. 
Primary Objective(s) .............................................................................................................. 17 
5.1.2. 
Secondary Objective(s).......................................................................................................... 17 
5.2    Endpoints ............................................................................................................................. 17 
5.2.1 Primary Endpoint ....................................................................................................................... 17 
5.2.2 Secondary Endpoints ................................................................................................................. 17 
5.2.3 Safety Endpoints ........................................................................................................................ 18 
6. 
Study Design .................................................................................................................... 18 
6.1. Duration ................................................................................................................................ 18 
6.2. Rationale ............................................................................................................................... 19 
7. 
Product Description.......................................................................................................... 19 
7.1. General ................................................................................................................................. 19 
7.2. Dosage Form and Route of Administration ............................................................................... 20 
7.3. Manufacturer ......................................................................................................................... 20 
7.4. Packaging .............................................................................................................................. 20 
7.5. Intended Population ............................................................................................................... 20 
7.6. Equipment ............................................................................................................................. 21 
7.6.1 
PillCam® Crohn’s Capsule ...................................................................................................... 21 

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7.6.2 
PillCam Recorder (DR3) ......................................................................................................... 21 
7.6.3 
PillCam Workstation .............................................................................................................. 21 
7.7. Product Use ........................................................................................................................... 22 
7.8. Product Training Requirements ............................................................................................... 22 
7.9. Product Receipt and Tracking ................................................................................................. 22 
7.10. 
Product Storage ............................................................................................................... 22 
7.11. 
Product Return ................................................................................................................. 23 
7.12. 
Product Accountability ...................................................................................................... 23 
8. 
Selection of Subjects ........................................................................................................ 24 
8.1. Study Population .................................................................................................................... 24 
8.2. Subject Enrollment ................................................................................................................. 24 
8.3. Inclusion Criteria .................................................................................................................... 24 
8.4. Exclusion Criteria ................................................................................................................... 24 
9. 
Study Procedures ............................................................................................................. 25 
9.1. Schedule of Events ................................................................................................................. 25 
9.2. Subject Consent ..................................................................................................................... 26 
9.3. Subject Screening .................................................................................................................. 28 
9.4. Baseline ................................................................................................................................ 29 
9.5. Medication Compliance ........................................................................................................... 30 
9.6. Magnetic Resonance Enterography .......................................................................................... 30 
9.7. PillCam Patency Study ............................................................................................................ 30 
9.8. Capsule Endoscopy Procedure ................................................................................................ 30 
9.9. Ileocolonoscopy ..................................................................................................................... 31 
9.10. 
Central Reader Image/Video Reading ................................................................................ 31 
9.10.1 
Imaging Scores for Central Reading ................................................................................... 32 
9.11. 
Assessment of Efficacy ..................................................................................................... 33 
9.12. 
Assessment of Safety ....................................................................................................... 33 
9.13. 
Recording Data ................................................................................................................ 34 
9.14. 
Deviation Handling ........................................................................................................... 34 
9.15. 
Subject Withdrawal or Discontinuation ............................................................................... 35 
10. Risks and Benefits ............................................................................................................ 36 

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10.1. 
Potential Risks .................................................................................................................. 36 
10.1.1 
PillCam® Crohn’s Capsule .................................................................................................. 36 
10.1.2 
MRE .................................................................................................................................... 36 
10.1.3 
Ileocolonoscopy ................................................................................................................. 37 
10.2. 
Potential Benefits ............................................................................................................. 37 
10.3. 
Risk-Benefit Rationale ....................................................................................................... 38 
11. Adverse Events and Device Deficiencies .......................................................................... 38 
11.1. 
Definitions/Classifications .................................................................................................. 38 
11.1.1 
Adverse Event (AE) ............................................................................................................ 39 
11.1.2 
Serious Adverse Event (SAE) .............................................................................................. 39 
11.1.3 
Customer Complaint .......................................................................................................... 40 
11.1.4 
Device Deficiency ............................................................................................................... 40 
11.1.5 
Adverse Event Severity Classification ................................................................................ 40 
11.1.6 
Adverse Event Relationship Classification ......................................................................... 40 
11.1.7 
Adverse Event Outcome Classification .............................................................................. 42 
11.2. 
Recording of Adverse Events ............................................................................................. 43 
11.3. 
Reporting of Adverse Events ............................................................................................. 43 
11.4. 
Notification to Authorities.................................................................................................. 44 
11.5. 
Device Deficiencies ........................................................................................................... 44 
12. Data Review Committees ................................................................................................. 44 
12.1 Medical Advisor ...................................................................................................................... 45 
12.2 Steering Committee ............................................................................................................... 45 
13. Statistical Design and Methods ........................................................................................ 45 
13.1 Sample Size Determination ..................................................................................................... 45 
13.2 Effectiveness Analyses ............................................................................................................ 45 
13.3 Safety Analysis....................................................................................................................... 45 
13.4 Analysis Populations ............................................................................................................... 45 
13.5 Interim Analyses .................................................................................................................... 46 
13.6 Handling of Missing Data ........................................................................................................ 46 
14. Ethics ................................................................................................................................ 46 
14.1. 
Statement(s) of Compliance .............................................................................................. 46 

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15. Study Administration ....................................................................................................... 47 
15.1. 
Monitoring ....................................................................................................................... 47 
15.2. 
Data Management ............................................................................................................ 48 
15.2.1 
Data Collection .................................................................................................................. 48 
15.2.2 
Data Access ........................................................................................................................ 48 
15.2.3 
Electronic Case Report Form Guidelines ........................................................................... 48 
15.2.4 
Data Queries ...................................................................................................................... 48 
15.2.5 
Audits and Inspections ...................................................................................................... 49 
15.2.6 
Close Out ........................................................................................................................... 49 
15.3. 
Direct Access to Source Data/Documents ........................................................................... 49 
15.4. 
Confidentiality .................................................................................................................. 49 
15.5. 
Liability ............................................................................................................................ 50 
15.6. 
CIP Amendments ............................................................................................................. 50 
15.7. 
Record Retention ............................................................................................................. 50 
15.8. 
Publication and Use of Information .................................................................................... 51 
15.9. 
Suspension or Early Termination ....................................................................................... 51 
16. References ....................................................................................................................... 52 
17. Appendices ....................................................................................................................... 55 
17.1 Appendix A – Montreal Classification ....................................................................................... 56 
17.2 Appendix B - Study Schedule for Clinical Laboratory and Pregnancy Tests ................................. 57 
17.3 Appendix C - MRE Procedure Instructions ................................................................................ 59 
17.3.1 Appendix C1 - MRE Subject Instructions .................................................................................. 60 
17.4 Appendix D – PillCam® Patency Study .................................................................................... 61 
17.5 Appendix E – CE and IC Procedure Instructions ....................................................................... 62 
17.5.1 
Appendix E1 – CE and IC Bowel Preparation Instructions ................................................. 63 
17.5.2 
Appendix E2 – CE and IC Subject Instructions Form .......................................................... 65 
17.5.3 
Appendix E3 – CE Procedure Instructions ......................................................................... 66 
17.5.4 Appendix E4 – CE and IC Bowel Cleansing Scale ...................................................................... 68 
17.7 Appendix F – Accuracy for Active Crohn’s Disease in Overall and Designated Bowel Segments .... 69 
17.8 Appendix G – Scores for Capsule endoscopy, Ileocolonoscopy, and MRE ................................... 70 
17.8.1 
Appendix G1 – Lewis Score ................................................................................................ 71 

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17.8.2 
Appendix G2 – Simple Endoscopic Score for Crohn’s Disease Index (SES-CD) Score ........ 72 
17.8.3 
Appendix G3 - Magnetic Resonance Index of Activity (MaRIA) Score ............................... 73 
17.9 Appendix H – Patient Satisfaction Questionnaire ...................................................................... 74 
18. Version History ................................................................................................................. 76 
 
 
 

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2. Glossary 
Term
Definition
ADL
Activities of Daily Living
AE
Adverse Event
BUN
Blood Urea Nitrogen
CBC
Complete Blood Cell Count
CD
Crohn’s Disease
CE
Capsule Endoscopy
CFR
Code of Federal Regulations
CIP
Clinical Investigation Plan
CRP
C-reactive Protein
CTE
Computed Tomography Enterography
Device deficiency
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
DMC
Data Monitoring Committee
DR
Data Recorder
eCRF
Electronic Case Report Form
eGFR
Estimated Glomerular Filtration Rate
EC
Ethics Committee
ED
Emergency Department
EMA
European Medicines Agency
FDA
United States Food and Drug Administration

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Term
Definition
FISP
Fast Imaging with Steady-state Free Precession 
GCP
Good Clinical Practice
GRE
Gradient-Recalled Echo
GI
Gastrointestinal
HIPAA
Health Insurance Portability and Accountability Act
IBD
Inflammatory Bowel Disease
IC
Ileocolonoscopy
ICF
Informed Consent Form
ICMJE
International Committee of Medical Journal Editors
IDE
Investigational Device Exceptions
IFU
Instructions for Use; a manual or document accompanying a technical device 
that describes the directions by which the device should be used
Investigative site
An approved, participating study center/institution
Investigator
Individual member of the investigation site team designated and supervised 
by the principal investigator at an investigation site to perform critical 
clinical-investigation-related procedures or to make important clinical 
investigation-related decisions.
NOTE An individual member of the investigation site team can also be 
called “sub-investigator” or “coinvestigator”.
IRB
Institutional Review Board
ISO
International Organization for Standardization
IV
Intravenous
MaRIA
Magnetic Resonance Index of Activity
MITG
Minimally Invasive Therapies Group
mITT
Modified Intent-To-Treat

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Term
Definition
MRE
Magnetic Resonance Enterography 
MRI
Magnetic Resonance Imaging
NPO
Nothing by mouth – no food or liquids
NPV
Negative Predictive Value
OC-RDC
Oracle Remote Data Capture
PEG
Polyethylene Glycol
PPV 
Positive Predictive Value
RDC
Remote Data Capture
RCE
Relative Contrast Enhancement
SAE
Serious Adverse Event 
SB
Small Bowel
SES-CD
Simple Endoscopic Score for Crohn’s Disease
SF-ELS
Sulfate-Free Polyethylene Glycol Electrolyte Lavage Solution
SSFSE
Single-Shot Fast Spin Echo
WSI
Wall Signal Intensity
WT
Wall Thickness
 
 

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3. Synopsis 
Title 
Multicenter, prospective study comparing PillCam® Crohn’s capsule endoscopy 
(CE) to ileocolonoscopy (IC) plus MRE for detection of active Crohn’s disease 
(CD) in the small bowel and colon in subjects with known CD and mucosal 
disease (the BLINK study) 
Clinical Study Type 
Multicenter, Prospective, Study 
Product Name 
PillCam® Crohn’s Capsule Endoscopy System 
Sponsor  
United States: 
Medtronic MITG Early Technologies GI Solutions 
A Medtronic company (“Medtronic”) 
555 Long Wharf Dr, 
New Haven, CT 06511 
Phone: +(1)-(203)-562-1620 
 
Europe: 
Medtronic MITG Early Technologies GI Solutions 
A Medtronic company (“Medtronic”) 
Covidien Services Europe, Ltd.,  
Block G, First Floor 
Cherrywood Business & Technology Park 
Loughlinstown, Dublin 18, Ireland 
Phone: +(353)-(1)-439300 
 
Israel: 
Medtronic MITG Early Technologies GI Solutions 
(Given Imaging Ltd.) 
A Medtronic company (“Medtronic”) 
2 Hacarmel St. New Industrial Park 
POB 258, 20692 Yoqneam, Israel 
Phone: +(972)-(4)-909-7700 
Investigation 
Purpose 
This study will evaluate the efficacy of PillCam Crohn’s capsule endoscopy (CE) 
versus IC with MRE for detection of active Crohn’s disease (CD) in the small 
bowel and colon in subjects with known CD and mucosal disease.   
Product Status 
Post-market 
Primary 
Objective(s) 
The primary objective of study is to assess the accuracy of CE versus IC plus 
MRE for detecting active CD, by visualizing the small bowel and colon in subjects 
with known CD and mucosal disease. 

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Secondary 
Objective(s) 
x
Specificity, negative predictive value (NPV), and positive predictive (PPV) 
value for active CD in the small bowel and colon by CE as compared to IC 
plus MRE.  
x
Sensitivity, specificity, NPV, and PPV for active CD in designated bowel 
segments (proximal small bowel, terminal ileum, and colon) by CE as 
compared to IC plus MRE. 
x
 
x
Patient satisfaction  
x
 
x
Concomitant medication  
Other Planned 
Analyses 
  
  
 
Study Design 
At baseline, subjects with known CD on routine clinical evaluation (e.g. history, 
physical exam, labs) and a history (within last 2 years) of mucosal disease 
(diagnosis based on radiologic, endoscopic, histologic, or other clinical evidence) 
will undergo MRE, CE, and IC, to assess presence or absence of CD in the small 
bowel and colon.  
Study Location 
United States, Israel, and Austria. Sites in the United States will include a 
minimum of 70% of total subjects; sites outside the US will be limited to 30% of 
subjects. 
Sample Size 
Up to 352 subjects. 
Planned study 
duration 
Based on the number of sites and enrollment rate, study duration is expected to 
be up to approximately 1.5 years. The expected duration of each subject’s 
participation is approximately 3 months.  
Planned # of Sites 
Up to 40 investigational sites.  
Video/Image 
Reading 
Central readers will be used to read all videos/images and analyses will be based 
on these results. A consensus panel will be used if there are discrepancies in 
results between modalities at baseline. Capsule endoscopy and IC results will be 
read by gastroenterologists and MRE results will be read by radiologists.  
Inclusion/Exclusion 
Criteria 
Inclusion Criteria: 
1.
Subject has provided informed consent. 
2.
Subject is ≥ 18 years of age. 
3.
Subject is willing and able to comply with all aspects of the treatment and 
evaluation schedule.  
4.
Subject has known CD and a recent history (within last 2 years) of mucosal 
disease (based on radiologic, endoscopic, or histologic evidence) OR known 
CD and active disease, based on clinical judgment based on symptoms, 
laboratory data or other clinical information. 

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Exclusion Criteria: 
1.
Subject has indeterminate, ulcerative, or antibiotic-associated colitis. 
2.
Subject has stool positive for ova and parasite or for Clostridium difficile 
toxins within 3 months prior to enrollment. 
3.
Subject with other known infectious cause of abdominal symptoms. 
4.
Subject with clinical evidence of renal disease within the past 6 months, 
defined as estimated glomerular filtration rate (GFR) outside of the normal 
reference range.  
5.
Subject with known history of intestinal obstruction or current obstructive 
symptoms, such as severe abdominal pain with accompanying nausea or 
vomiting, based on investigator judgment. 
6.
Subject with a diagnosis of gastroparesis or small bowel or large bowel 
dysmotility. 
7.
Subject with suspected or known bowel obstruction, stricture (defined as 
unequivocal proximal upstream dilation ≥ 2.5 cm), or fistula. 
8.
Subject has used non-steroidal anti-inflammatory drugs including aspirin, 
two times or more per week, during the 4 weeks preceding enrollment. Low 
dose aspirin regimens (≤ 100 mg daily) are acceptable and not exclusionary. 
9.
Subject suffers from any condition, such as swallowing problems, that 
precludes compliance with study and/or device instructions. 
10. Subject with cardiac pacemaker or other implanted electromedical device.  
11. Subject has any allergy or other known contraindication to the medications 
used in the study. 
12. Subject is pregnant (documented by a positive pregnancy test) or is actively 
breast-feeding. 
13. Subject is considered to be part of a vulnerable population (e.g. prisoners or 
those without sufficient mental capacity). 
14. Subject has known contraindication to MRE or IC. 
15. Subject has participated in a drug or device research study within 30 days of 
enrollment that may interfere with the subject’s safety or ability to 
participate in the study. 
16. Subject has any medical condition that would make it unsafe for them to 
participate, per the Investigator’s discretion 
17. Subject with ileostomy or colostomy, history of total or subtotal colectomy 
(including those with ileosigmoidostomy, and ileorectostomy 
 

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4. Introduction  
4.1.
Background  
Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) that has been a focus of attention 
due to its increasing incidence and prevalence around the world (1, 2). It involves any site of the 
gastrointestinal (GI) tract, but is most frequently localized to the terminal ileum and the proximal colon 
(3). Inflammation of the GI tract may ultimately lead to stricturing or perforating complications (4). 
Symptoms of CD include abdominal pain, diarrhea, weight loss, nausea, and vomiting. Long-term 
management of CD can be achieved with immunosuppressive or anti-inflammatory therapy, however 
most patients undergo repeated relapses and remission (5). 
Video capsule endoscopy was first approved for clinical use in 2001 for the evaluation of the small bowel 
and has served to be an effective, noninvasive technique for imaging of the entire small-bowel mucosa 
(6). Contraindications for use of capsule endoscopy include history of bowel obstruction and known bowel 
strictures or swallowing disorders; and recent abdominal surgery (7). The Capsule Endoscopy System, 
PillCam® SB, PillCam® Crohn’s, PillCam® Patency System and PillCam® COLON 2, are all FDA cleared 
for the US market in patients aged ≥ 18 years and carry the CE mark for the European market in patients 
aged ≥ 8 years. The PillCam® Crohn’s Platform includes 1) the ingestible Crohn’s capsule, 2) Data 
Recorder (DR3), PillCam® Software, and 4) Given® Workstation. The Crohn’s capsule is specifically 
designed to image the small and large bowels. The Crohn’s capsule is a two-headed video capsule with a 
field of view of 172 degrees in each head and has a frame of rate up to 35 frames per second.  
The PillCam® Crohn’s capsules and the COLON 2 capsules share hardware design, components and 
assembly and differ only in programming and operation mode, since the COLON 2 is designed to visualize 
the colonic mucosa while the Crohn’s capsule is intended for expanded visualization of the small bowel 
and the colon. The COLON 2 system has proven to be safe and effective in previous clinical studies (8-10) 
(ClinicalTrials.gov: NCT01087528, NCT01269372). Pre-clinical studies for the Crohn’s capsule have not 
been conducted, however clinical studies have been performed. To-date, there have been three 
performance studies that have assessed the Crohn’s capsule. One study included CD subjects 
(ClinicalTrial.gov: NCT01631435), another study included ulcerative colitis subjects (Clinical Trial.gov: 
NCT02025777), and a third which included suspected or established IBD patients (Clinical Trial.gov: 
NCT02742714). NCT01631435 study was a multi-center, prospective, controlled study, designed to 
establish the effectiveness of the PillCam® Crohn’s endoscopy platform as demonstrated by visualizing 
the small bowel and colon in subjects with active symptoms associated with CD. The primary objective 
was to evaluate the diagnostic yield of the Crohn’s capsule in the colon and terminal ileum compared to 
ileocolonoscopy (IC) (11). A total of 66 subjects with signs and symptoms of CD completed the study 
procedures and were included in the efficacy analysis.  The per-subject diagnostic yield rate was 83.3% 
for capsule endoscopy (CE) and 69.7% for IC. The yield difference was 13.6% (95% CI 2.6%-24.7%), 
with CE having a higher diagnostic yield rate for detection of active CD. The Crohn’s capsule was also 
able to evaluate and detect active CD in the more proximal small bowel, which cannot be reached by IC. 
There was only one device-related serious adverse event (bowel obstruction) reported, however the 
event resolved without sequelae. Since the comparison of the two modalities in this study was limited 

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only to the terminal ileum and the colon, there is a need to evaluate the performance of the Crohn’s 
capsule in the entire small bowel and colon compared to a gold standard.   
Clinical management of patients with known CD involves monitoring of disease activity for maintenance 
of clinical remission, early detection of relapse, and prevention of complications associated with the 
disease or treatment (12). Both the best measure of disease activity in CD and the measurement method 
are in question. Recent studies have shown that inflammation of the intestinal mucosa is not firmly 
correlated with laboratory inflammatory markers and patients’ symptoms (12-16). Mucosal healing, which 
is defined as restoration of normal mucosal appearance and complete absence of ulceration and 
inflammation, is now considered an accepted measure of disease activity in CD (12, 17). Evidence show 
that mucosal healing and deep remission are associated with improved long-term outcomes including 
reduced need for corticosteroid treatment, improved quality of life, and reduction in complications 
requiring hospitalization or surgery (12, 18, 19).  
Ileocolonoscopy is currently the gold standard for mucosal disease evaluation in CD patients (20). There 
are limitations to this technique due to its invasive nature and possible requirement of analgesia and 
sedation (17). Ileocolonoscopy reaches only to the terminal ileum, thus eliminating evaluation of the 
more proximal small bowel. Even though the terminal ileum is the most commonly affected area in the 
small bowel in CD, approximately half of the patients with CD have lesions detected in the jejunum (21). 
The prevalence of jejunal lesions is higher in patients with terminal ileum disease and associated with 
increased risk of relapse; therefore evaluation of the entire small bowel is necessary for monitoring 
patients with CD. 
If proximal small bowel involvement is suspected, patients may receive examination with small bowel 
capsule endoscopy and/or balloon-assisted enteroscopy in addition to IC (20). Cross-sectional imaging 
techniques including magnetic resonance enterography (MRE) and computed tomography enterography 
(CTE) may also be used to evaluate the small bowel, however these techniques have some 
disadvantages. Magnetic resonance enterography is costly and CTE involves exposure to radiation; both 
techniques require intravenous (IV) contrast medium and bowel distension with oral and/or rectal 
contrast. Since the PillCam® Crohn’s capsule is designed to evaluate both the small bowel and colon, the 
device would eliminate the need of using two different techniques for evaluation of both segments in 
patients with CD (11). Capsule endoscopy is safe, noninvasive, and does not involve radiation exposure, 
therefore making it a preferable alternative modality for assessment of CD activity and evaluation of 
mucosal healing in patients with CD. 
4.2.
Purpose  
This purpose of this study is to evaluate performance of the PillCam Crohn’s capsule [referred to as 
capsule endoscopy (CE)] as compared to IC with MRE. 

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5. Objectives and Endpoints 
5.1.
Objectives 
5.1.1.
Primary Objective(s) 
The primary objective of this multicenter, prospective study is to assess the accuracy of CE versus IC plus 
MRE for detecting active CD, by visualizing the small bowel and colon in subjects with known CD and 
mucosal disease.  
5.1.2.
Secondary Objective(s)  
Secondary objectives include: 
1.
Specificity, negative predictive value (NPV), and positive predictive (PPV) value for active CD in 
the small bowel and colon by CE as compared to IC plus MRE.  
2.
Sensitivity, specificity, NPV, and PPV for active CD in designated bowel segments (proximal small 
bowel, terminal ileum, and colon) by CE as compared to IC plus MRE. 
3.
Patient satisfaction 
5.2    Endpoints 
 
5.2.1 Primary Endpoint 
The primary endpoint is the sensitivity for detecting active CD in the small bowel and colon by CE as 
compared to IC plus MRE. 
 
5.2.2 Secondary Endpoints 
 
The following secondary endpoints will be assessed: 
 
1.
Specificity, negative predictive value (NPV), and positive predictive (PPV) value for active CD in the 
small bowel and colon by CE as compared to IC plus MRE (see Section 11.12.1).  
2.
Sensitivity, specificity, NPV, and PPV for active CD in designated bowel segments (proximal small 
bowel, terminal ileum, and colon) by CE as compared to IC plus MRE (see Section 11.12.1). 
3.
Patient satisfaction (see Appendix I). 
 

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5.2.3 Safety Endpoints 
Adverse events (AEs) will be reported by number, severity, and relationship to the study procedures 
(imaging modality, colonoscopy), as described in Section 11. The recording of AEs for all enrolled 
subjects will begin with the start of baseline imaging procedures (MRE) and end 14 days following 
completion of the final baseline imaging procedure (IC). Subjects with AEs at  14 days following the IC 
procedure will be followed for 30 days or until event resolves, whichever comes first.  
 
6. Study Design  
This is a multicenter, prospective study, evaluating the efficacy of CE versus IC with MRE for detecting 
active CD in the small bowel and colon in subjects with known CD and a recent history (within last 2 
years) of mucosal disease (based on radiologic, endoscopic, or histologic evidence) OR subjects with 
known CD and active disease based on clinical judgment based on symptoms, laboratory data or other 
clinical information. Subject population will include adult subjects (age ≥18 years). 
 
At baseline, subjects with known CD on routine clinical evaluation (e.g. history, physical exam, labs) and 
a recent history of mucosal disease (within last 2 years and diagnosis based on radiologic, endoscopic, or 
histologic findings) OR subjects with known CD and active disease based on clinical judgment based on 
symptoms, laboratory data or other clinical information will undergo MRE, CE, and IC, to assess presence 
or absence of CD across the small and large bowel.  
All CE and IC videos and MRE images will be evaluated by central readers. CE and IC videos and MRE 
images will be randomly distributed among the central readers. 
The planned number of subjects is up to 352. A total of approximately 352 Crohn’s capsules will be 
utilized in this study.  
There are no procedures for the replacement of subjects.  
Other than known contraindications and precautions of the PillCam® Crohn’s system, described in the 
PillCam User Manual, there are no foreseeable factors that may compromise the outcome of the clinical 
investigation or the interpretation of results (e.g. baseline characteristics, concomitant medication, the 
use of other study products, or subject-related factors such as age, gender or lifestyle). If any adverse 
occurrences are identified, they will be assessed, reported and documented.  
6.1.
Duration 
Subjects will be enrolled at up to 40 clinical sites in the United States, Israel, and Austria. United States 
sites will include a minimum of 70% of total subjects; sites outside the United States will be limited to 
30% of subjects. The minimum number of subjects enrolled at each site participating in the study will be 
0 as enrollment is expected to be challenging and there is a possibility that an individual site will be 
unable to enroll any subjects. The maximum number of subjects at each site will be 70 so that no more 
than 20% of the total study population will be enrolled at any individual site. Expected enrollment is 1 
subject per site per month. 
 

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The planned number of subjects is up to 352. Based on the number of sites and enrollment rate, study 
duration is expected to be up to approximately 1.5 year. The expected duration of each subject’s 
participation is approximately 3 months. 
6.2.
Rationale  
This clinical study design was formulated in order to capture performance of the Crohn’s capsule as 
compared to IC with MRE. 
The combination of the two procedures (IC plus MRE) will allow evaluation of the entire colon and small 
bowel and can be compared to the single procedure with CE.  
To-date, there have been few performance studies that have assessed the Crohn’s capsule. One study 
included CD subjects (ClinicalTrial.gov: NCT01631435),another study included ulcerative colitis subjects 
(Clinical Trial.gov: NCT02025777) and a third included suspected or established IBD patients (Clinical 
Trial.gov: NCT02742714). Results from NCT01631435 study demonstrated that the diagnostic yield rate 
for active CD in the terminal ileum and colon was higher with CE compared to ileocolonoscopy. However, 
due to the small sample size (66 subjects in efficacy analysis), further studies are warranted to confirm 
these findings (11). Additionally, since the comparison of the two modalities in this study was limited only 
to the terminal ileum and the colon, there is a need to evaluate the performance of the Crohn’s capsule 
in the entire small bowel and colon compared to a gold standard. 
7. Product Description 
7.1.
General 
The PillCam® Crohn’s capsule endoscopy platform is comprised of four main subsystems: (1) an 
ingestible PillCam® Crohn’s capsule; (2) PillCam® Recorder (DR); (3) PillCam® Software (Version 9.0); 
and (4) Given® Workstation. The PillCam® Crohn’s capsule endoscopy platform includes the PillCam® 
Software, which is designed to focus on targeted pathologies detected with the capsule, and an audio-
visual guidance platform integrated into the PillCam® Recorder that is intended to help guide the subject 
through the procedure. The PillCam® Crohn’s capsule platform is fully compliant with all safety and radio 
standards and regulations similar to the currently marketed capsule Endoscopy Systems. PillCam®  
Crohn’s has been approved for use in the US, Europe and Israel. 
The device does not incorporate any medicinal product, human blood derivative or tissues of animal 
origin. 
The PillCam® Crohn’s capsule, specifically the capsule outer envelope, will be in contact with human 
tissues or body fluids after ingestion.  
 

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7.2.
Dosage Form and Route of Administration 
The PillCam® Crohn’s capsule is intended to be swallowed by the patient (after appropriate bowel 
preparation and fasting) with a sip of water. Only one capsule will be ingested per endoscopy procedure. 
The device is intended to travel through the patient’s gastrointestinal tract and be excreted naturally. 
 
7.3.
Manufacturer 
PillCam® Crohn’s capsule endoscopy system is manufactured by Medtronic Minimally Invasive Therapies 
Group (MITG) Early Technologies GI Solutions (formerly GIVEN Imaging). 
7.4.
Packaging 
All equipment associated with the clinical study will be identified with visible markings stating, “For clinical 
trial use only.” Labeling of devices will be provided in accordance with local language requirements. 
7.5.
Intended Population 
The PillCam® Crohn’s capsule indications for use in US are:  
 
The PillCam® Crohn’s capsule is intended for visualization of the small bowel and colonic mucosa.  
 
• It may be used in the visualization and monitoring of lesions in the small bowel that may 
indicate Crohn’s disease not detected by upper and lower endoscopy, and for visualization of 
inflammation of the colon in patients with colonoscopy-diagnosed Crohn’s disease. 
 
• It may be used in the visualization and monitoring in the small bowel of lesions that may be a 
 
source of obscure bleeding (either overt or occult) or that may be potential causes of iron 
 
deficiency anemia (IDA) not detected by initial upper and lower endoscopy.  
 
• The PillCam® Crohn’s capsule may be used as a tool in the detection of abnormalities of the 
 
small bowel and colon. It is intended for use in adults 
 
 
The PillCam® Crohn’s capsule indications for use in Europe and Israel are:  
 
The PillCam® Crohn’s capsule is intended for visualization of the small bowel and colonic mucosa.  
 
 
• It may be used in the visualization and monitoring of lesions that may indicate Crohn’s disease.  
 
 
• It may be used in the visualization and monitoring of lesions that may be a source of obscure 
 
bleeding (either overt or occult).  
 
 
 
• It may be used in the visualization and monitoring of lesions that may be potential causes of  
 
iron deficiency anemia (IDA).   
 

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• The PillCam® Crohn’s capsule may be used as a tool in the detection of abnormalities of the 
 
small bowel and colon. It is intended for use in adults and children from 8 years of age
 
7.6.
Equipment 
7.6.1
PillCam® Crohn’s Capsule 
PillCam® Crohn’s capsule has been designed to achieve more complete coverage of the small bowel and 
colonic mucosa, so its adaptive frame rate is set to ensure that images of both anatomical regions are 
captured for analysis. Features include: 
 
x
Optics with super wide field of view (172 degrees for each imaging head). 
x
Higher and adaptive frame rate (up to 35 frames per second). High frame rate is activated when 
the capsule enters the small bowel. 
 
The PillCam® Crohn’s capsule is provided as a single use disposable product. PillCam® Crohn’s capsule is 
ingested by the subject after bowel preparation, with a sip of water. The capsule will be ingested a 
maximum of three times for the entire duration of the study (ingestion at baseline and 6- and 12-month 
follow-ups for subjects randomized to CE arm; ingestion at baseline only for subjects randomized to IC 
with or without MRE arm. The capsule will be ingested at baseline to evaluate presence/absence of active 
CD in the small bowel and colon. At 6- and 12-month follow-ups, the capsule will be ingested to evaluate 
mucosal healing.  
7.6.2
PillCam Recorder (DR3) 
The new generation of PillCam® Recorder used in this study has enhanced communication features, 
computing power, and incorporates a Real-Time Viewing screen. These modifications are detailed in the 
PillCam User Manual.  
7.6.3
PillCam Workstation 
The Workstation is a modified standard personal computer that is intended for reviewing the Pillcam® 
Software (Version 9.0) videos generated from the images acquired by the capsule, interpretation and 
analysis of the acquired data, and for generating reports. 
 
The software program used for video creation and interpretation has several useful features incorporated 
that aid the physician during the video review. 
The PillCam® Crohn’s capsule is contraindicated for use under the following conditions: 
x
In patients with known or suspected gastrointestinal obstruction, strictures, or fistulas based on 
the clinical picture or pre-procedure pre-ingestion testing and profile. 
x
In patients with cardiac pacemakers or other implanted electromedical devices. 
In patients with dysphagia or other swallowing disorders. 

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7.7.
Product Use 
A member of the Medtronic Technical Support team will install the PillCam Workstation at each 
participating research site and ensure all equipment is fully functional.  Information regarding Instructions 
for Installation and Use can be found in the provided PillCam Endoscopy User Manual (US PillCam User 
Manual for sites in the US and International PillCam User Manual for sites outside of the US). Specific 
instructions for Site Investigators for transferring video images to the Core Imaging Lab will be provided 
separately. 
7.8.
Product Training Requirements 
Gastroenterologists selected as Principal Investigators participating in the clinical study and the 
associated clinical study staff will receive training on the device and system (including procedural use, 
device characteristics, shelf life and storage requirements, warnings, precautions, and contraindications).  
It is the responsibility of the Principal Investigator at each participating site to assure any staff performing 
tasks related to the clinical trial (Study Coordinators, Study Nurses, Radiologists, Gastroenterologist Sub-
Investigators, etc) have been properly trained, training documented, and included on the Delegation of 
Authority Log. 
 
For CE videos, central readers will be experienced gastroenterologists trained to read PillCam® Software 
videos. Experience and training are required in order to accurately interpret capsule endoscopy videos. 
The central readers will be trained by the Sponsor on reading PillCam® Software videos. The training will 
include PillCam® version 9.0 software and PillCam® Software videos evaluation training.  
 
Central readers will be experienced gastroenterologists for IC videos and radiologists for MRE images.  
 
7.9.
Product Receipt and Tracking 
The Sponsor will initiate shipment of equipment to the site upon receipt of all required documents (e.g., 
Site Qualification Report, fully executed Clinical Trial Agreement). The site may not use the 
equipment/product or begin subject enrollment until IRB/EC approval is received and the Sponsor 
provides notification of Site Activation.  The Sponsor will maintain tracking for all shipment 
documentation. Prior to any shipment, the site will be informed by the Sponsor on the upcoming 
shipment, expected arrival date, and content of the shipment. The site should confirm receipt of the 
shipment and maintain shipping receipts.  
For each capsule, the appropriate Device Tracking and Device Identification electronic Case Report Forms 
(eCRFs) should be completed upon receipt and upon dispensing, respectively, by the site.  
 
7.10. Product Storage 
PillCam® Crohn’s capsule should be stored in an area where the temperature is controlled between 0-
25°C. As storage is at ambient temperature and PillCam Crohn’s capsule is a readily marketed product, 
temperature logs are not required for BLINK; however storage area should be locked/secure with access 
limited only to approved study staff to avoid use of the study device on non-trial patients. 

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To avoid accidental activation (blinking) of the capsule while in its box:  
 
 
• Keep the PillCam capsules in their box until use.  
 
• Store the PillCam capsules only in the packaging supplied with the product.  
 
• Do not use a PillCam capsule if the packaging is damaged.  
 
• Keep the capsule package away from strong magnetic fields (such as magnetic resonance 
 
imaging [MRI] devices).  
 
• Stack PillCam capsule boxes with the clear lid facing up only; never stack capsule boxes lid  
 
to lid.  
 
• Keep metal objects away from the lid of the capsule box.  
 
• After ingesting the PillCam capsule, instruct the patient not to sit on bare metal 
 
surfaces, such as chairs with a metal sitting area, during the procedure. 
7.11. Product Return 
At the termination of the study, all unused study material must be returned with the corresponding 
documentation as directed by Medtronic. Any capsule that reaches its expiration date before it has been 
dispensed should be returned to the Sponsor or destroyed on site; with proper documentation in either 
scenario.  The Device Tracking eCRF should be completed once a capsule is dispensed, returned or 
destroyed.  
 
7.12. Product Accountability  
Good clinical research practice requires that investigators and research teams ensure accurate 
accountability for any device used in a research study. It is expected that all devices will be used in the 
manner intended during the study, that they will be stored under appropriately controlled conditions and 
that they will be used only by (on) subjects who have consented to participate in the research study. 
Access should be limited to designated study staff only. Device accountability should be managed 
through the site’s completion of the Device Tracking and Device Identification eCRFs. 
 
Any device being used in clinical research must be strictly accounted for and will not be shipped to any 
site unless all of the necessary approvals (e.g. Regulatory, IRB/EC) have been received.  
 
This includes keeping records of:  
 
1. Site receipt and inventory management  
2. Storage  
3. Subject Disbursement  
4. Return (by Subjects and Center) and/or disposal  
It is the site’s responsibility to return the PillCam Workstation and Recorder to Medtronic within 30 days 
of the End of Study. 
 

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8. Selection of Subjects 
8.1.
Study Population 
Subjects aged ≥18 years with known CD and mucosal disease. 
8.2.
Subject Enrollment 
After being informed of the nature of the study, the subject will sign a written informed consent form 
(ICF) that has been approved by the Sponsor and the appropriate IRB/ EC of the respective clinical site 
or the central IRB/EC during the screening visit. A subject is considered enrolled in the study when the 
ICF is signed and it is determined that all inclusion/exclusion criteria are met. Inclusion/Exclusion may 
only be determined once screening lab results (C. Dificile, Stool O&P) and pregnancy test (as required) 
are reviewed.  Documented ICF will be collected prior to any data collection. See Section 11.4 for details 
on subject informed consent procedure. 
8.3.
Inclusion Criteria 
1.
Subject has provided informed consent. 
2.
Subject is ≥ 18 years of age. 
3.
Subject is willing and able to comply with all aspects of the treatment and evaluation schedule.  
4.
Subject has known CD and a recent history (within last 2 years) of mucosal disease (based on 
radiologic, endoscopic, or histologic evidence) OR known CD and active disease, based on clinical 
judgment based on symptoms, laboratory data or other clinical information. 
 
8.4.
Exclusion Criteria 
1.
Subject has indeterminate, ulcerative, or antibiotic-associated colitis. 
2.
Subject has stool positive for ova and parasite or for Clostridium difficile toxins within 3 months prior 
to enrollment. 
3.
Subject with other known infectious cause of abdominal symptoms. 
4.
Subject with clinical evidence of renal disease within the past 6 months, defined as estimated 
glomerular filtration rate (GFR) outside of the normal reference range.  
5.
Subject with known history of intestinal obstruction or current obstructive symptoms, such as severe 
abdominal pain with accompanying nausea or vomiting, based on investigator judgment. 
6.
Subject with a diagnosis of gastroparesis or small bowel or large bowel dysmotility. 
7.
Subject with suspected or known bowel obstruction, stricture (defined as unequivocal proximal 
upstream dilation ≥ 2.5 cm), or fistula. 

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8.
Subject has used non-steroidal anti-inflammatory drugs including aspirin, two times or more per 
week, during the 4 weeks preceding enrollment. Low dose aspirin regimens (≤100 mg daily) are 
acceptable and not exclusionary. 
9.
Subject suffers from any condition, such as swallowing problems, that precludes compliance with 
study and/or device instructions. 
10. Subject with cardiac pacemaker or other implanted electromedical device.  
11. Subject has any allergy or other known contraindication to the medications used in the study. 
12. Subject is pregnant (documented by a positive pregnancy test) or is actively breast-feeding. 
13. Subject is considered to be part of a vulnerable population (e.g. prisoners or those without sufficient 
mental capacity). 
14. Subject has known contraindication to MRE or IC. 
15. Subject has participated in a drug or device research study within 30 days of enrollment that may 
interfere with the subject’s safety or ability to participate in the study. 
16. Subject has any medical condition that would make it unsafe for them to participate, per the 
Investigator’s discretion 
17. Subject with ileostomy or colostomy, history of total or subtotal colectomy (including those with 
ileosigmoidostomy, and ileorectostomy 
 
9. Study Procedures  
9.1.
Schedule of Events 
Table 1: Study schedule and Site Collection Data 
 
 
Screening 
(No more than 30 days prior to first 
Baseline Procedure - MRE) 
Baseline Procedures  
1, 2 
Informed consent1 
X 
 
Eligibility criteria 
X 
 
Demographics  
X 
 
Montreal classification3 
X 
 
Medical history 
X 
 
Previous GI procedures 
X 
 
Surgical history 
X 
 

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Laboratory tests4, 5 
X 
X 
Pregnancy test4, 5 
X 
 
Concomitant medications 
 
X 
PillCam® patency test 
 
X 
IC, MRE AND PillCam® Crohn’s1 
 
X 
Patient satisfaction6 
 
X 
Adverse events 
 
X 
Study deviations 
X 
X 
Study exit 
 
X 
1. Informed consent may be collected more than 30 days prior to first baseline imaging procedure – MRE. 
2. All baseline imaging procedures (MRE, patency capsule [if needed], CE, and IC) need to be performed within 4 weeks. If 
MRE demonstrates a stricture with unequivocal upstream dilatation of at least 2.5cm, then the subject must be exited from 
further study participation. If any other stricture is identified on MRE, or there is clinical suspicion that the PillCam Crohn’s 
capsule will not be excreted naturally, then a patency capsule procedure needs to be performed. IC will take place on the same 
or following day after CE.                                                                               
3. See Appendix A for more details.                                                                                                                                   
4. See Appendix B for a complete listing of tests to be performed.   
5. Please note that Screening Laboratory results for Stool O&P, C.Difficile and pregnancy test are required to determine subject 
inclusion/exclusion.  Screening Laboratory results MUST be evaluated prior to enrolling a subject in the trial.  Baseline labs 
must be collected and results reviewed within 14 days prior to MRE.                                                                      
6. The patient satisfaction questionnaire will be completed by subjects after the last baseline procedure (IC) in person or via 
phone on the same or next business day of IC procedure completion.        
 
9.2.
Subject Consent 
Informed consent will be obtained before any study-specific procedures are initiated or data collected. 
Principal Investigator or his/her authorized designee will conduct the informed consent process. 
 
At the screening visit, subjects will be approached to obtain written informed consent prior to any data 
collection. Once the ICF is collected, screening of subject will follow. The purpose of the study and the 
benefits and risks of the procedures will be explained to the subject and the consent process must be 
documented accordingly in the medical record. Subjects who agree to study participation must sign a 
Sponsor and IRB/EC-approved ICF. Consent to participate in this study must be given in writing. Subjects 
that are unable to give consent will not be included in study. 
 
Informed Consent will be obtained in accordance with the CFR Title 21, Part 50 (US) or ISO14155:2011 
(Austria and Israel) as well as the Declaration of Helsinki. The Investigator or designee must obtain 
written informed consent before any clinical study related activity takes place. Prior to entry into the 
study, the IRB/EC and Medtronic-approved ICF form, and the Health Insurance Portability and 

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Accountability Act (HIPAA) Authorization Form (US only) will be given to each subject. The Investigator or 
designee will fully inform the subject of all aspects of the clinical study that are relevant to the subject’s 
decision to participate in the clinical study (e.g. purpose and duration of the study, requirements of the 
subject during the study, potential risks and possible benefits associated with participation in this study). 
All items addressed in the Informed Consent Form must be explained. The language used shall be as 
non-technical as possible and must be understandable to the subjects. 
 
The subject must have ample time and opportunity to read and understand the Informed Consent Form, 
to inquire about details of the clinical study, and to decide whether or not to participate in the clinical 
study. All questions about the clinical study should be answered to the satisfaction of the subject.  In the 
case that a subject is unable to read, an impartial witness must also be present and sign the informed 
consent to confirm that the research has been clearly explained and all of the subject’s questions have 
been answered. 
 
Neither the Investigator, nor the investigation site staff shall coerce or unduly influence a subject to 
participate or to continue to participate in the clinical study. The informed consent process shall not waive 
or appear to waive the subject’s rights. 
 
When the subject decides to participate in the clinical study, the HIPAA Form (US only) and the Informed 
Consent Form must be personally signed and dated by the subject 
 
After all persons have signed and dated the Informed Consent Form, the Investigator must provide the 
subject with a copy. 
 
Medtronic will inform the Investigators whenever information becomes available that may be relevant to 
the subject’s confirmed participation in the clinical study. The Investigator or his/her authorized designee 
should inform the subject in a timely manner. 
 
Medtronic will revise the written Informed Consent Form whenever new information becomes available 
that may be relevant to the subject’s confirmed participation in the clinical study. The revised information 
will be sent to the Investigator for approval by the IRB/EC. After approval by the IRB/EC, a copy of this 
information must be provided to the participating subjects, and the informed consent process as 
described above needs to be repeated. 
 
If the ICF is amended during the course of the study, the IRB/EC will determine: 
 
 
• Whether or not active subjects should be re-consented at their next visit and 
 
• Whether or not subjects who have completed the study at the time of the amendment should 
 
repeat the informed consent process. 
 
Subjects will be informed that qualified personnel from the investigational center, the Sponsor 
(Medtronic), agencies such as the FDA/local regulatory authority in Europe (Austria) and Israel and/or the 
IRB/EC may have access to clinic records that reveal their identity. 
 
The investigational center must report the following violations to their IRB/EC: 
 
 
• Failure to obtain informed consent from subject. 
 
• Failure to obtain informed consent prior to performing one or more study procedures. 
 
• Failure to maintain ICFs on file for all subjects who have provided informed consent. 

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• Use of an ICF that has not received approval from the IRB/EC.             
 
• Use of an incorrect version of the ICF. 
9.3.
Subject Screening  
All subjects must be properly consented prior to any screening and/or baseline procedures.  Once 
consented, a screening visit will be performed within 30 days prior to baseline procedures to assess pre-
procedure eligibility. In the event that the screening and eligibility assessment takes place more than 30 
days prior to the planned procedure date, the Investigator should contact the subject prior to the 
procedure date to assure there is no change in the subject’s medical condition.  
 
Screening visit (No more than 30 days prior to first Baseline Procedure - MRE) - the following 
assessment will be performed at screening and the results will be recorded on the appropriate subject 
eCRFs:  
 
x
Informed consent (may be completed >30 days prior to MRE) 
x
Inclusion/Exclusion criteria 
o
Please note evaluation of results of several Screening Laboratory tests (Stool O&P, C. 
Difficile, pregnancy) is required to assess Inclusion/Exclusion criteria.   
x
Demographics – including gender, year of birth, height, and weight.  
x
Montreal classification – see Appendix A. 
x
Medical history – relevant (related to inclusion/exclusion criteria) medical historywithin the last 2 
years will be assessed including recent history of mucosal disease, history of swallowing 
problems, history of intestinal stricture, presence of implanted electromedical device, any known 
allergies, current GI symptoms (e.g. obstructive symptoms, history of gastroparesis) or other GI 
motility disorder, contraindication to MRE or IC, and enrollment in any other drug/device study 
within 30 days.  
x
Previous GI procedures – all previous IBD–related procedures within the last 5 years (including 
but not limited to IC, MRE, CTE, capsule endoscopy, esophagogastroduodenoscopy), including 
date and results from the last procedure will be documented. 
x
Surgical history – other GI-related surgical procedures not captured under ‘previous GI 
procedures.’ 
x
Prior and concomitant medications – All current medications, including type and dose, need to be 
reported. Subject will be excluded from the study if he/she has used non-steroidal anti-
inflammatory drugs including aspirin, two times or more per week, during the 4 weeks preceding 
enrollment. Low dose aspirin regimens (≤100 mg daily) are acceptable and not exclusionary.  
Additionally, subjects must not use NSAIDs including aspirin, two times or more per week, from 
the time of enrollment until completion of the IC procedure.   
x
Laboratory tests – See Appendix B. 
x
Pregnancy test – see Appendix B. 
x
Study deviations 

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A subject is considered enrolled in the study when the ICF is signed (See Section 11.4 for details) and it 
is determined that all inclusion/exclusion criteria are met. Documented ICF will be collected prior to any 
data collection. Subjects who provide study consent, but then are determined to be ineligible prior to the 
MRE procedure at baseline will be considered a screen failure and will not require additional study follow-
up visits. The reason for the screen failure will be clearly captured on the applicable eCRFs. 
9.4.
Baseline 
All baseline procedures must be completed within 4 weeks (completion of MRE to completion of IC).  All 
baseline labs must be completed prior to, but no more than 14 days before, MRE. Subjects will first 
undergo MRE evaluation as outlined in Appendix C. If MRE shows evidence of a stricture with unequivocal 
proximal upstream dilation ≥ 2.5 cm, based on local reading results, then the subject will be exitedfrom 
the study. If any other stricture is identified on MRE, based on local reading, or if there is clinical 
suspicion that the PillCam Crohn’s capsule will not be excreted naturally, then 
the subject must  undergo a Patency procedure before proceeding with the CE procedure and then the IC 
procedure, all within 4 weeks after the MRE..  
 
Subjects whose patency cannot be confirmed through either the baseline MRE procedure or capsule 
patency study will be discontinued from the study. 
 
Prior to the CE procedure, subjects will be instructed to perform the bowel preparation procedure and 
follow a detailed dietary regimen. All sites and subjects will follow the same preparation procedure as 
outlined in Appendix E1 for the CE procedure.  
 
Following completion of the CE procedure (either the same or following day), the subjects will undergo 
an IC procedure with intubation of the terminal ileum, if possible. In case the IC procedure follows the CE 
procedure on the same day, it is recommended to start the CE procedure early in the morning. If the IC 
procedure is done the following morning, the subject will stay on clear liquid diet (or NPO, if required per 
physician’s discretion for sedation) and receive additional preparation per physician discretion. Day 0 will 
be in reference to the last day of baseline procedures, which will be the day of completion of IC.  
 
Baseline visit - the following assessment will be performed at baseline and the results will be recorded 
on the appropriate subject eCRFs: 
x
Laboratory tests– see Appendix B 
x
Concomitant medications: 
At baseline subjects must not use NSAIDs including aspirin, two times or more per week, 
during the 4 weeks preceding CE, IC and MRE procedures. Low dose aspirin (<100 mg 
daily) regimens are acceptable and not exclusionary. 
 
 
All current medications, including type and dose, need to be reported 
 
 
Need to specify related/non-related medication for CD 
x
Patient satisfaction – see Appendix I. At baseline, questionnaires will be completed by subjects 
after IC. If subjects are unable to complete the questionnaires immediately following IC due to 
sedation, appropriately delegated research staff may interview the subject by phone the following 
day in order to obtain the subject’s responses. 

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x
Adverse events 
x
Study deviations  
9.5.
Medication Compliance 
Subjects will take a preparation for CE, IC, and MRE. The CE system has a regimen alert system to 
remind subjects to take the prescribed preparation materials. There will also be medications taken by 
subjects as prescribed by their respective physicians to treat Crohn’s disease. The medication usage will 
be tracked in appropriate eCRFs. 
9.6.
Magnetic Resonance Enterography 
Sites may be asked to submit sample imaging studies to the Imaging Core Lab. The sample cases 
demonstrate that local site can follow the study protocol for the MRE procedure before subject 
recruitment begins. If there are errors in the sample imaging studies, corrections need to be made before 
enrollment begins.  
 
MRE will be performed by local radiologists with experience in conventional and GI MRI who have been 
properly trained to the study protocol and included on the Delegation of Authority Log. MRE procedure 
must be performed in alignment with Appendix C and the BLINK Imaging Manual.  A 1.5T or 3T whole-
body MRI unit will be used. All sites and all subjects will follow the same procedure as outlined in 
Appendix C for MRE.   
 
The MRE images must be uploaded and transferred to the Imaging Core Lab (ICON) within 48 hours of 
completion of the procedure, based on instructions provided.  
9.7.
PillCam Patency Study 
If a stricture with unequivocal upstream dilation of at least 2.5cm is evident on baseline MRE (based on 
local read), then the subject must be exited from further participation in the study.  If any other stricture is 
evident on baseline MRE, or there is clinical suspicion that the PillCam Crohn’s capsule will not be excreted 
naturally, then a PillCam Patency procedure (Appendix D) should be performed prior to the baseline CE 
procedure.  
9.8.
Capsule Endoscopy Procedure 
Subjects will be instructed to perform a preparation procedure and follow a detailed dietary regimen prior 
to and during the CE procedure. All preparation products will be standard GI cleansing products approved 
by FDA and European Medicines Agency (EMA). All sites and all subjects will follow the same preparation 
procedure as outlined in Appendix E1 for the CE procedure.  
 
CE procedure must be performed per instruction provided in Appendix E1 and the BLINK Imaging 
Manual.  During the CE procedure, subjects will be asked to use a Subject Instructions Form (Appendix 
E2) to document their activities. This form will be used to document the subject’s adherence to the 
procedure steps. The Subject Instructions Form will also serve as source data for eCRF entries. Trained 

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Medtronic personnel may be present at the capsule ingestion and at study follow-up visits. The role of the 
Medtronic person is to give technical support only. 
 
All CE videos and raw data files will be downloaded to the PillCam work station and then saved in a digital 
format on the provided external hard drive. The CE video files must be uploaded and transferred to the 
Imaging Core Lab (ICON) within 48 hours of the completion of the procedure, based on instructions 
provided in the BLINK Imaging Manual.  The raw data files should be maintained on the external hard 
drive and will be collected by Medtronic personnel.   
9.9.
Ileocolonoscopy 
The IC will be performed on the same or following day after the CE procedure. To avoid repetitive bowel 
preparation for subsequent colonoscopy, the CE bowel preparation (Appendix E1) is to be followed at 
baseline. If IC is done the following day, the subject will stay on clear liquid diet (or NPO, based on 
physician’s discretion for sedation) and receive additional preparation per physician discretion. 
 
Prior to discharge, the subject will be instructed to notify study staff in case of any abdominal pain, 
vomiting or other GI problems. 
 
The IC examination will be recorded in digital format. The site number and subject number (NOT name) 
should appear in the recorded video either by inserting the information to the recording or by taking a 
video recording at the beginning of the procedure video with the endoscope of the site and subject 
number written on a piece of paper.  
 
All IC videos will be saved in a digital format (an external hard drive will be provided, if necessary). The 
IC videos must be sent to the Imaging Core Lab (ICON) within 48 hours, based on instructions provided. 
9.10. Central Reader Image/Video Reading 
All CE and IC videos and MRE images will be randomly distributed to and evaluated by central readers at 
an Imaging Core Lab.  Central readers will be blinded to the site and subject from which the 
videos/images they are assigned originate. 
 
All study analyses will be based on the results of the central readers. A consensus panel will be used if 
there are discrepancies in results between modalities at baseline.  
In cases when an imaging modality is not available for a given segment (small bowel, TI, and/or colon), 
that modality will be considered “null” for the segment and will not be used to assess modality agreement 
or disease activity for the segment.  The available modality or modalities will be reviewed by central 
readers and (if necessary) the Consensus Panel and used to assess disease activity in these cases.  
 
Detailed instructions will be provided to sites for transferring videos/images to the Imaging Core Lab via 
the BLINK Imaging Manual.  Detailed reader instructions will be provided to the central readers via the 
Imaging Core Lab. All central readers must read each video or image independently without input from 

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other readers, investigators, or other site staff. Each reader will produce an independent report (CE 
Readers) and complete appropriate eCRFs for each video or image assigned to them. 
 
9.10.1
Imaging Scores for Central Reading 
Active CD, and subtle (defined as ulcers ≤ 5mm) lesions will be assessed with central reader results 
across the three modalities.  
 
Presence of active CD in the proximal small bowel, terminal ileum, and colon will be assessed at baseline 
(see Appendix G for more details). The scores detailed below will be used to compare the accuracy 
(sensitivity, specificity, NPV, PPV) of CE and IC plus MRE in the identification of active CD in the small 
bowel and colon. The combination of all three procedures (MRE, CE, and IC) will serve as the gold 
standard.  
 
Additionally, subgroup analyses will be performed to compare the accuracy of CE and IC plus MRE in the 
following designated bowel segments: proximal small bowel, terminal ileum, and colon. The following 
procedures will serve as the gold standard in the designated bowel segments: MRE+CE in the proximal 
small bowel, MRE+CE+IC in the terminal ileum, and CE+IC in the colon. 
 
Capsule Endoscopy Scores: 
 
The scores used for identification of active CD will be the Lewis score (Appendix H1) and Simple 
Endoscopic Score for Crohn’s Disease Index (SES-CD) (Appendix H2) for CE. The Lewis score will be used 
to evaluate active CD in the proximal small bowel and the SES-CD will be used for the terminal ileum and 
colon.  
 
Ileocolonoscopy Score: 
 
The score used for identification of active CD will be the SES-CD (Appendix H2) score for IC. SES-CD 
score will be used to evaluate active CD in the terminal ileum and colon.  
 
MRE Score: 
 
The score used for identification of active CD will be the Magnetic Resonance Index of Activity (MaRIA) 
score for MRE (Appendix H3). The MaRIA score will be used to evaluate active CD in the small bowel 
(proximal and terminal ileum). 
 
 
 
 
 
 
 
 

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Table 2: Central Reader Collection Data  
 
 
Screening 
 
Baseline 
Procedures  
 
Presence of Active CD1 
 
X 
Subtle lesion 
 
X 
Bowel cleansing level 
scale2 
 
X 
1. Presence of active CD will be used to calculate accuracy 
measures comparing CE to IC plus MRE. Active CD will be 
assessed based on the following scores: the Lewis score (see 
Appendix H1) will be used to evaluate the proximal small bowel 
with CE; the SES-CD scores (see Appendix H2) will be used to 
evaluate both the terminal ileum and colon with CE and IC; and 
the MaRIA (see Appendix H3) score will be used to evaluate the 
small bowel (proximal and terminal ileum) with MRE.                      
2. Following bowel preparation, the bowel cleansing level scale as 
detected with CE (see Appendix E4)/IC (see Appendix F3) will be 
collected. 
 
9.11. Assessment of Efficacy 
Data for accuracy of CE versus IC plus MRE for detecting active CD will be collected and evaluated by 
central readers after all baseline procedures (MRE, CE, and IC) have been completed.  All CE and IC 
videos and MRE images will be randomly distributed to and evaluated by central readers. Presence of 
active CD will be used to calculate accuracy measures comparing CE to IC plus MRE. Active CD will be 
assessed based on the following scores: the Lewis score (see Appendix H1) will be used to evaluate the 
proximal small bowel with CE; the SES-CD scores (see Appendix H2) will be used to evaluate both the 
terminal ileum and colon with CE and IC; and the MaRIA (see Appendix H3) score will be used to 
evaluate the small bowel (proximal and terminal ileum) with MRE. See Section 9.13.1 for details on 
imaging scores for central reading.  
 
Each reader will produce an independent report (CE readers only) and complete appropriate eCRFs for 
each video or image assigned to them.  
 
9.12. Assessment of Safety 
Type, incidence, severity, duration, and procedure/device relationship of adverse events (AEs) will be 
collected. AEs for all enrolled subjects will be collected from the start of baseline imaging procedures 
(MRE) and end 14 days after completion of the last imaging procedure (IC).  Subjects with AEs at 14 

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days after the IC procedure will be followed for 30 days or until event resolves, whichever comes first. 
Adverse event data will be collected and reported on eCRFs.  
For safety analyses, adverse events will be summarized using frequency counts and percentages. 
Descriptive statistics will be provided by study arm and by severity and relationship, according to the 
definitions in Section 11. Between groups comparison will be performed by Chi-square test or Fisher’s 
exact test as appropriate. Individual listings of adverse events, (including modifications and deleted 
events), including event type, start date, duration, severity, and device-relatedness will be provided as 
appropriate. 
9.13. Recording Data 
This study will utilize an electronic database and eCRF. All data requested on the eCRF are considered 
required. Data points not collected and/or recorded will be considered deviations unless otherwise 
specified. Procedures used for data review, database cleaning, and issuing/resolving data queries will be 
included in the Data Management Plan.  
 
The Principal Investigator must ensure the accuracy and completeness of the recorded data and then 
provide his/her signature on the appropriate eCRFs. The Investigator’s electronic signature for specific 
eCRFs will be documented in compliance with local regulations. Changes to data previously submitted to 
the Sponsor will be reviewed for potential AE and complaint data and will require a new signature by the 
Investigator to acknowledge/approve the changes. 
 
Visual and/or computer data review will be performed to identify possible data discrepancies. Manual 
and/or automatic queries will be created in the Oracle Remote Data Capture (OC-RDC) system and will be 
issued to the site for appropriate response. The site staff will be responsible for resolving all queries in 
the database. 
 
This study will be using a 21 CFR Part 11 compliant electronic data capture system. All system level 
validation documentation is retained within the Information Systems group. 
9.14. Deviation Handling 
No changes to the protocol will be permitted without the written approval from Medtronic, the IRB/EC, 
and Competent Authority. The investigator is not allowed to deviate from the Clinical Investigation Plan 
(CIP), except under emergency circumstances to protect the rights, safety and well-being of human 
subjects. The investigator must notify Medtronic and the reviewing IRB/EC of any deviation, which will be 
recorded in the eCRF, from the CIP when specific to the protection of the life or physical well-being of a 
subject in an emergency. Such notice must be given as soon as possible, but in no event later than 5 
working days after the emergency has occurred. Except in such an emergency, prior written approval by 
Medtronic is required for changes in or deviations from the CIP. If these changes or deviations affect the 
scientific soundness of the CIP or the rights, safety, or welfare of human subjects the IRB/EC will also be 
notified. All other deviations will be reported per the site’s IRB/EC deviation policy. Should any deviations 
from the CIP occur, these will be reviewed by Medtronic for their clinical significance. If the event is 
performed without written approval from all parties, the investigator may be terminated from the study. 
Corrective and preventive actions and principal investigator disqualification will be included in the Clinical 
Study Management Plan and/or Monitoring Plan. If further escalation is needed, it may result in 

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Corrective and Preventive Action (CAPA), suspension, or termination. If it is determined that there is 
investigator fraud, or strong evidence of fraud, the course of action may include, but is not limited to: 
potential exclusion from analyses, site closure, notification of the responsible IRB/EC of the actions to be 
taken, notification of key stakeholders and/or study team of the actions to be taken, notification of 
appropriate regulatory authority(ies) and/or restrictions on future participation in clinical studies. 
9.15. Subject Withdrawal or Discontinuation  
The reason for study exit, including screen failure, will be documented on the applicable eCRF and in the 
subject file. The Sponsor must be informed of each withdrawal case.  
 
In the event the subject withdraws consent during the study, the date of withdrawal will be documented. 
Individual subjects will not be replaced.  
 
If the Investigator voluntarily removes a subject from further study participation, supporting 
documentation must be in place for the rationale and date of removal. The Investigator may withdraw a 
subject from the study at any time for the following reasons: 
 
x
Severe side effects clearly related to the study procedures 
x
Presence or appearance of exclusion criteria 
x
Appearance of accompanying diseases rendering further participation in the study impossible 
x
A significant protocol violation, as determined either by the Sponsor or the Investigator 
x
Subject noncompliant with procedures 
x
Subject noncompliant with visits 
x
At the specific reasonable request of the study Sponsor 
 
For Austria and Israel only: If patient withdrawal is due to problems related to the device safety or 
performance, the Investigator shall ask for the subject's permission to follow his/her status/condition 
outside the clinical investigation. 
Every attempt will be made to contact subjects that are noncompliant with study visits Subjects will be 
considered lost to follow-up once the following steps have been taken: 
x
Two phone calls should be made to the subject.  Each attempt should be clearly documented in 
the source documents and the response or lack thereof should be captured.   
x
If there is no response to the phone calls, then an official, certified letter should be written to the 
subject.  A copy of the letter and return or delivery receipts should be retained in the subject’s 
source document. 
 
When all due diligence attempts to contact have been made, after a period of two (2) weeks, the subject 
will be considered Lost to Follow-up. The Sponsor should be notified and the End of Study (EOS) form 
should be completed. 

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10. Risks and Benefits 
10.1. Potential Risks 
For female subjects that are pregnant or have childbearing potential, there may be risks to the subject or 
unborn child that are not yet known. 
There may be additional risks related to this study (other than those listed here) that are not yet known. 
Risks must be continuously monitored, assessed and documented by the Investigator. 
 
10.1.1
PillCam® Crohn’s Capsule 
Possible Risks associated with use of the PillCam® Crohn’s capsule, include but are not limited to the 
following: 
x
Nausea 
x
Vomiting 
x
Diarrhea 
x
Abdominal pain 
x
Headache 
x
Vertigo 
x
Difficulty or inability to swallow the capsule 
x
Asymptomatic capsule retention 
x
Fatigue 
x
Capsule aspiration 
x
Capsule retention or delayed excretion 
x
Physical intervention, which could include surgery, to remove the capsule 
x
Obstruction 
x
Perforation 
x
Mucosal injury or bleeding 
x
Small bowel obstruction  
 
Implanted electronic devices such as, but not limited to, pacemakers, neurostimulators, implantable 
cardioverter defibrillators, ventricular assist devices, spinal cord stimulators, cochlear implants, infusion pumps, 
and bone growth stimulators may be influenced by interference produced by PillCam® Crohn’s.  
 
10.1.2
MRE 
Although the MRE examination poses almost no risk to the average patient when appropriate safety 
guidelines are followed; there are still risks which include, but are not limited to the following: 
x
Possibility of excessive sedation, if used. 
x
Nephrogenic systemic fibrosis (thickening and scarring of connective tissue in the skin, joints, eyes, 
and internal organs)  
x
Allergic reaction if contrast material is injected. If subject experience allergic symptoms, a radiologist 
or other doctor will be available for immediate assistance. 
x
Nausea 

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x
Vomiting  
x
Abdominal pain 
x
Blurry vision 
x
Dry mouth 
x
Tachycardia 
x
Electrolyte disturbance 
x
Dehydration 
x
Kidney injury 
x
Fluid retention 
x
Hypotension, hypertension or vasovagal reaction 
 
10.1.3
Ileocolonoscopy 
 
Possible risks associated with Ileocolonoscopy, include but are not limited to the following: 
x
Cramping  
x
Pain 
x
Bloating 
x
Diarrhea 
x
Nausea 
x
Vomiting  
x
Abdominal swelling  
x
Perforation, infection, or bleeding to the intestinal wall 
x
Postpolypectomy syndrome 
x
Undetected abnormalities 
x
Allergic reaction to sedation 
x
Respiratory depression, hypoxia, chest pain, cardiac arrhythmias 
x
Hypotension or hypertension, and vasovagal reactions 
x
Fluid retention  
x
Kidney injury 
10.2. Potential Benefits 
Professional guidelines for the management of Crohn’s disease have recommended ongoing monitoring of 
disease activity with tools such as those used in this study (22). A “treat to target” strategy is increasingly 
recommended to tailor therapy based on mucosal evidence of disease (23). Thus, subjects may benefit 
from results of diagnostic tests performed during the study as treating physicians may be able to make 
more informed decisions in the care of subjects based on results of study procedures.  
The information from this study may benefit other subjects with CD in the future. 

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10.3. Risk-Benefit Rationale 
This study will include up to 352 subjects, aged 18 years and older, that have known CD and mucosal disease. 
Subject may be female or male. All study procedures are part of the standard medical management of 
patients with Crohn’s disease. The risks to subjects would be similar to the expected risks to Crohn’s disease 
patients in standard medical practice. MR enterography has been advocated to be very useful in the 
assessment of mucosal disease without endoscopy but its utility is limited to the small bowel. The PillCam® 
Crohn’s capsule has the advantage of being able to assess both the small bowel and colonic mucosa in a 
single examination, which has the potential to reduce time, expense and inconvenience to the subject. This 
study is designed to evaluate the ability of the Crohn’s capsule to assess mucosal disease with MRE and 
ileocolonoscopy.  
 
The risks for MRE, as noted, will be minimized by excluding subjects who have evidence of renal insufficiency. 
This should service to greatly reduce the potential for nephrogenic systemic fibrosis. In addition, subjects with 
sensitivity to substances used in the course of the MRE, or during the preparation for the CE and IC 
procedures will be excluded.  Sedation will be performed only in accredited facilities by qualified personnel and 
the ileocolonoscopy will be performed by board certified gastroenterologists to decrease the risk to study 
subjects.  
 
Retention of the Crohn’s capsule will be minimized since capsule will be administered only to those subjects 
who have demonstrated patency of the gastrointestinal tract by MRE.  MRE has shown to be an effective 
predictor of safe passage of the video capsule (24). Also, investigators have the option of using the Patency 
capsule to determine whether the video capsule will be excreted. Patency capsule is useful in identifying 
patients that can undergo capsule enteroscopy without risks of capsule retention (25).  
 
Subjects with swallowing disorders are excluded to avoid the risk of capsule aspiration or inability to 
swallow the capsule. Known side effects of the purgatives used for the preparation for capsule endoscopy 
and colonoscopy will be minimized by allowing both procedures to be performed with a single 
preparation. 
11. Adverse Events and Device Deficiencies 
11.1. Definitions/Classifications 
Adverse event definitions used in this study are based on ISO 14155:2011 (Clinical Investigation of 
Medical Devices for Human Subjects -- Good Clinical Practice), which is aligned with MEDDEV 2.7/3 
Revision 3, May 2015 (Guidelines on Medical Devices, Clinical Investigations: Serious Adverse Event 
Reporting).  
 
 Events will be collected for all enrolled subjects with the start of baseline imaging procedures (MRE) and 
end  14 days following completion of the IC procedure. Subjects with AEs  14 days following the IC 
procedure will be followed for 30 days or until event resolves, whichever comes first.  During the course 
of the study, the following AEs will be collected and reported on the eCRF: 
 
x
All AEs related to PillCam® Crohn’s  
x
All AEs related to IC 

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All AEs related to MRE 
x
All AEs related to bowel preparation 
x
All device deficiencies  
x
All SAEs 
 
The following should not be considered an AE: 
 
x
A condition requiring a preplanned procedure unless the condition worsened since screening. 
x
A preexisting condition found as a result of screening, unless the condition has worsened since 
enrollment. 
 
 
For purposes of this protocol, the following occurrences are considered to be expected 
observations and will not be considered AEs, as long as the event is not associated with significant 
sequelae, does not prolong hospitalization, and responds to standard medical therapy:  
 
x
Transient nausea, diarrhea, vomiting, headache or abdominal pain that is determined to be 
related to one of the study procedures (including the preparation) and that resolves within 48 
hours without extended hospitalization (>24 hours). 
 
All responses to the above events that require treatment beyond the institution’s standard 
procedures will be reported as AEs. 
 
11.1.1
Adverse Event (AE) 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not related to the 
medical device.  
 
Note 1: This definition includes events related to the medical device or the comparator. 
 
Note 2: This definition includes events related to the procedures involved. 
 
Note 3: For users or other persons, this definition is restricted to events related to medical devices. 
 
Documented pre-existing conditions are not considered to be reportable AEs unless there is a change in the 
nature or severity of the condition 
OR 
A condition requiring a preplanned procedure unless the condition worsened since screening 
11.1.2
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is any untoward medical occurrence in a subject that meets the criteria of 
“serious.”  A SAE is one that: 
x
led to death, 

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led to serious deterioration in the health of the subject that either resulted in 
x
a life-threatening illness or injury, or 
x
a permanent impairment of a body structure or a body function, or 
x
an in-patient or prolonged hospitalization, or 
x
medical or surgical intervention to prevent life threatening illness or injury or permanent 
impairment to a body structure or a body function, or 
x
led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
 
NOTE: Planned hospitalization for a pre-existing condition or a procedure required by the clinical 
investigation plan, without serious deterioration in health, is not considered an SAE. 
11.1.3
Customer Complaint 
Any written, electronic, or verbal communication indicating a deficiency in the identity, quality, durability, 
reliability, safety, effectiveness, or performance of any product after it is released for distribution. 
 
11.1.4
Device Deficiency 
A device deficiency is an inadequacy of a medical device related to its identity, quality, durability, 
reliability, safety, or performance. This may include malfunctions, misuse or use error and inadequate 
labeling. 
11.1.5
Adverse Event Severity Classification 
Severity will be defined according to the following criteria: 
 
Mild 
Awareness of event, but easily tolerated 
Moderate 
Discomfort enough to cause some interference with activities of daily living (ADL) 
Severe 
Incapacitating, with an inability to perform ADL 
 
An AE can be classified as severe and not deemed an SAE. Similarly, an SAE is not automatically severe in 
nature. 
11.1.6
Adverse Event Relationship Classification 
Causality assessments define the relationship between the use of the medical device (including the 
medical-surgical procedure) and the occurrence of each adverse event. During causality assessment 
activity, clinical judgment shall be used and the relevant documents, such as the Clinical Evaluation 
Report and the Risk Management Report shall be consulted, as all the foreseeable serious adverse events 
and the potential risks are listed and assessed there. The presence of confounding factors, such as 
concomitant medication/treatment, the natural history of the underlying disease, other concurrent illness 
or risk factors shall also be considered. 
 
Each AE will be classified according to five different levels of causality. The Sponsor and the Investigators 
will use the following definitions to assess the relationship of the serious adverse event to the medical 
device or procedures: 

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Relationship to study product administration will be determined as follows: 
x
Not related: relationship to the device or procedures can be excluded when: 
o
the event is not a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
o
the event has no temporal relationship with the use of the device or the procedures; 
o
the serious event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
o
the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or increase 
of the level of activation/exposure), do not impact on the serious event; 
o
the event involves a body-site or an organ not expected to be affected by the device or 
procedure; 
o
the serious event can be attributed to another cause (e.g. an underlying or concurrent 
illness/ clinical condition, an effect of another device, drug, treatment or other risk 
factors); 
o
the event does not depend on a false result given by the device used for diagnosis, when 
applicable; 
o
harms to the subject are not clearly due to use error; 
o
In order to establish the non-relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the serious event. 
 
x
Unlikely: the relationship with the use of the device seems not relevant and/or the event can be 
reasonably explained by another cause, but additional information may be obtained. 
 
x
Possible:  the relationship with the use of the device is weak but cannot be ruled out completely. 
Alternative causes are also possible (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment). Cases were relatedness cannot be 
assessed or no information has been obtained should also be classified as possible. 
 
x
Probable:  the relationship with the use of the device seems relevant and/or the event cannot 
reasonably explained by another cause, but additional information may be obtained. 
 
x
Causal relationship: the serious event is associated with the device or with procedures beyond 
reasonable doubt when: 
o
the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
o
the event has a temporal relationship with device use/application or procedures; 
o
the event involves a body-site or organ that 

the device or procedures are applied to; 

the device or procedures have an effect on; 

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o
the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
o
the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
o
other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and 
an effect of another device, drug or treatment) have been adequately ruled out; 
o
harm to the subject is due to error in use; 
o
the event depends on a false result given by the device used for diagnosis, when 
applicable; 
o
In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious event. 
 
The Sponsor and the Investigators will distinguish between the AEs related to the device and those 
related to the procedures (any procedure specific to the clinical investigation). An adverse event can be 
related both to procedures and the device. Complications of procedures are considered not related if the 
said procedures would have been applied to the subjects also in the absence of  device use/application. 
 
In some particular cases the event may be not adequately assessed because information is insufficient or 
contradictory and/or the data cannot be verified or supplemented. The Sponsor and the Investigators will 
make the maximum effort to define and categorize the event and avoid these situations. Where the 
Sponsor remains uncertain about classifying the serious event, it should not exclude the relatedness and 
classify the event as “possible”.  
 
11.1.7
Adverse Event Outcome Classification 
Outcome of the event will be defined according to the following: 
 
x
Fatal: This event is determined to be the cause of death. 
 
x
Not Recovered/Not Resolved: The event has not fully resolved at the end of the study. 
 
x
Recovered/Resolved: The event has fully resolved at the end of the study. 
 
x
Recovered/Resolved with sequelae: The event has resolved, but retained pathological conditions 
resulting from the prior disease or injury. 
 
x
Recovering/Resolving: The event is ongoing at the end of the study. 
 
x
Unknown 
 

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11.2. Recording of Adverse Events 
Assessment of the occurrence of an AE will be based on changes in the subject’s physical examination, 
laboratory results and/or signs and symptoms. The recording of AEs for all enrolled subjects will begin at 
the start of baseline imaging procedures (MRE) and end  14 days after completion of the IC procedure. 
Subjects with AEs at  14 days after the IC procedure will be followed for 30 days or until event resolves, 
whichever comes first. Medical care will be provided, as defined in the informed consent, for any AE 
related to study participation. Adverse events will be collected on an AE eCRF and applicable source 
documentation. To the extent possible, the event to be recorded and reported is the event diagnosis as 
opposed to event symptoms (e.g., fever, chills, nausea and vomiting in the presence of a clinically 
diagnosed infection is to be reported as infection only). 
11.3. Reporting of Adverse Events 
Please refer to Table 3 for a list of the minimum AE reporting requirements for Investigators.  If local 
regulations or IRB/EC require faster reporting, then the Investigator will adhere to those requirements.  
Reporting of all safety events to the Sponsor will be completed through Investigator submission of the AE 
eCRF in the remote data capture (RDC) system.  In case of emergency only for SAEs (ex. RDC system is 
unavailable), the Clinical Safety Specialist may be contacted directly at rs.mstsafetymitg@medtronic.com ; 
this will not serve as a substitute for proper reporting on the appropriate eCRF.  
 
Table 3: Investigator AE Reporting Requirements 
 
Type 
Report to 
Reporting Timeframe (from time of learning of 
event) 
Adverse Event (AE) 
IRB/EC 
Per IRB/EC reporting requirements 
Sponsor 
Within 10 working days 
Serious Adverse 
Event (SAE) 
Sponsor 
Within 24 hours 
IRB/EC 
Per IRB/EC reporting requirements 
 
Device Deficiency 
Sponsor (technical 
support) 
Within 48 hours  
IRB/EC 
If SAE occurs due to the device deficiency, within 24 
hours of learning of the event and per IRB/EC reporting 
requirements 
Device Related 
AE/SAE 
Sponsor 
Within 24 hours 
 

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Events will be reviewed by the Sponsor to determine any reporting obligations to the FDA or National 
Competent Authorities as well as IRB/EC. Reporting will occur within the timelines per local regulations 
and requirements. 
11.4. Notification to Authorities 
The following events are generally considered reportable during the course of this study and should be 
reported to the Sponsor: 
 
x
any SAE 
x
any Device Deficiency that might have led to an SAE if  
o
suitable action had not been taken or  
o
intervention had not been made or  
o
if circumstances had been less fortunate  
x
new findings/updates in relation to already reported events.  
x
deaths 
 
Events will be reviewed by the Sponsor for reporting obligations to National Competent Authorities. 
Reporting to National Competent Authorities will occur within the timelines described in the study Safety 
Plan by the Sponsor.  
11.5. Device Deficiencies 
 
All device deficiencies will be documented on the appropriate Device malfunction eCRF and the device 
should be returned to the Sponsor for analysis, if possible. Instructions for returning the device will be 
provided.  Device deficiencies should also be documented in the subject’s medical record. 
 
Device deficiencies are NOT to be reported as AEs. However, if there is an AE that results from a device 
deficiency, that specific event would be recorded on the appropriate eCRF. 
 
A device deficiency must be reported to Medtronic (technical support) within 48 hours after the 
investigator is made aware of the event.  
 
12. Data Review Committees  
A Medical Advisor and Steering Committee will be utilized in this study. This study will not have a Data 
Monitoring Committee (DMC) or an Adverse Events Advisory Committee (AEAC).  
 

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12.1 Medical Advisor 
The Sponsor will utilize a Medical Advisor to provide an independent medical review according to the 
study safety plan. The Medical Advisor will not be affiliated with an investigative center. 
 
12.2 Steering Committee 
The Steering Committee will consist of Investigators participating in this study, expert 
gastroenterologists, as well as appropriate members of Medtronic Clinical and Medical Affairs. The role of 
the Steering Committee is to make recommendations on the design and conduct of the study, the 
analysis of data, and the communication of results in alignment with the Medtronic Publication and 
Authorship Policy. The Steering Committee will also review aggregate adverse event data on an as 
needed basis, as described in the Steering Committee Charter. 
 
13. Statistical Design and Methods 
13.1 Sample Size Determination 
The sample size for this study will be comprised of subjects enrolled by April 30, 2019 forming a 
convenient sample.  Therefore, the study is not powered to make statistical inference. 
13.2 Effectiveness Analyses 
Sensitivity, Specificity, PPV and NPV will be estimated for each treatment group, along with the 95% 
confidence interval. The difference between treatment groups in Sensitivity and Specificity will be 
compared.     
13.3 Safety Analysis 
Individual listings of AEs, including type of device, AEs (reported term) start date, duration, severity, and 
procedure-relatedness will be provided. Procedure relatedness will be assessed separately relative to the 
imaging modality and colonoscopy, as described in Section 13.1.9. The recording of AEs for all enrolled 
subjects will begin with the start of baseline imaging procedures (MRE) and 2 weeks following the final 
imaging procedure, IC. Adverse events will be summarized using frequency counts and percentages. 
Descriptive statistics will be provided by treatment group and by severity and relationship, according to 
the definitions in Section 13.1.9.   
13.4 Analysis Populations 
The effectiveness and safety analyses will be based on all subjects who go through procedures MRE, CE, 
and IC modalities and can be evaluated for overall active CDat baseline (i.e., a modified intent-to-treat 
(mITT) population).  
 
The effectiveness analyses will also be conducted on the per protocol population, which includes all 
subjects in the mITT population who have no major protocol deviations (defined to be protocol violations 
that may have a significant impact on subject outcomes) and who do not meet any of the following 
criteria: 
 

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x
Subject withdraws 
x
Capsules remained in the stomach or small bowel during the entire procedure 
x
System technical failure 
 
Subgroup analyses will be performed on following designated bowel segments: proximal small bowel, 
terminal ileum, and colon. Additional analyses may also be explored and will be specified in the Statistical 
Analysis Plan (SAP). 
 
The SAP will include procedures for reporting any deviation(s) from the original statistical plan, 
specifications for subgroup analysis, and criteria for the termination on statistical grounds. Changes to 
the planned statistical analysis as defined in the protocol will be documented in the SAP.  
13.5 Interim Analyses 
No interim analysis is planned for this study.   
13.6 Handling of Missing Data 
All practical monitoring and follow-up steps will be taken to ensure complete and accurate data collection. 
No data imputation for missing data will be performed for the primary analysis.  As sensitivity analysis, 
missing data strategies such as multiple imputations may be used to assess the robustness of study 
results.   
14. Ethics 
14.1. Statement(s) of Compliance  
This clinical investigation will be conducted in accordance with the protocol and ethical principles that 
have their origin in the Declaration of Helsinki (2013 version). In Austria and Israel, local laws and 
regulations for the execution of a post-market, non-regulatory clinical trial will be followed. In the US, the 
study will be conducted in compliance with the abbreviated requirements for a non-significant risk IDE as 
defined in 21 CFR 812.2(b). All principles of the Declaration of Helsinki have been implemented in this 
clinical study by means of the patient informed consent process, IRB/EC approval, clinical study training, 
clinical study registration, publication policy.  
 
The clinical investigation will not begin at a given site until the required approvals/favorable opinions from 
the IRB/EC and/or notification/approvals from a regulatory authority have been obtained, as appropriate 
and a Site Activation Letter has been provided by the Sponsor. Should an IRB/EC or regulatory authority 
impose any additional requirements, they will be followed. PillCam® Crohn’s has been approved for use 
in the US (K170210), Israel and Europe.  
 
Information regarding the study and study data will be made available via publication on clinicaltrials.gov 
(NCT03241368).  Additionally, the results of this study will be submitted for publication in an appropriate 
journal. 
 

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15. Study Administration 
15.1. Monitoring  
Monitoring will be conducted to ensure the protection and safety of human subjects, the quality and 
integrity of the clinical data, and compliance with the protocol. The Monitoring Plan will give details on 
how and when data review will be conducted by clinical monitors. It will be updated and revised as 
needed due to changes in documents or processes. 
 
Employees of the Sponsor, or its designees, who have received appropriate training, will serve as the 
Study Monitor(s). Monitoring visits will be conducted based on Medtronic’s Standard Operating 
Procedures and the needs of the study. Quality documents will be followed for the conduct of all activities 
related to monitoring for this study. 
 
Site Qualification and Initiation Visits will be completed at each site prior to enrollment of the first 
subject. On Site study monitoring activities will include an inspection of completed study documents, 
source document verification and reporting, verification of database accuracy and completeness. All 
subjects enrolled in the study will be monitored and the eCRF data verified against the subjects’ original 
source documents. Following each monitoring visit, a report will be prepared by the Monitor. From 
initiation of study to close out visit, the Study Monitor(s) and Clinical Research Specialist(s) will share 
responsibility for communications between the Study Investigators and the Sponsor. 
 
Site visits will be conducted by an authorized Medtronic representative to inspect study data, subjects’ 
medical records, and eCRFs in accordance with appropriate FDA regulations (US only) and the respective 
local and national government regulations and guidelines (if applicable). The Study Investigator and the 
investigating site will permit authorized clinical research personnel and clinical monitors from Medtronic 
and/or designee(s) employed by Medtronic to review completed eCRFs, IRB/EC decisions, and clinical site 
records, and facilities relevant to this study at regular intervals throughout the study per the monitoring 
plan. Additionally, subject charts and clinical records will be requested and reviewed so that protocol 
adherence and source documentation can be verified. In instances where data protection regulations 
prohibit the direct examination of hospital records by the study Sponsor or designee(s), the Investigator 
will cooperate in a system of source data verification with the Sponsor. Monitoring may be performed with 
in person visits or remotely, when applicable. 
 
All monitoring visits to the investigational center will be recorded using the Monitoring Visit Log. The log 
will be kept in the site regulatory binder and a copy will be collected and submitted to the Sponsor. 
 
To ensure the rights, safety, and welfare of study subjects are being maintained, the monitor will review 
training records to ensure all study staff are adequately trained on the study protocol and use of the 
study devices. If the monitor discovers that an Investigator is not complying with the signed Investigator 
Agreement, the investigational plan, applicable laws, or any conditions of approval imposed by the 
reviewing IRB/EC, the monitor will report to the Sponsor and take such steps necessary to promptly 
secure compliance. If compliance cannot be secured, device shipments to the Investigator may be 
discontinued and the Investigator’s participation in the investigation terminated. The monitor shall also 
require such an Investigator to dispose of or return the device, unless this action would jeopardize the 
rights, safety, or welfare of a subject.  

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15.2. Data Management 
The Sponsor will oversee and/or perform all data management functions. Data management functions 
include database development, system maintenance, data queries, and report generation. This study will 
utilize Oracle to manage data via RDC. The RDC system is a validated technology system, compliant with 
21 CFR Part 11, and adheres to all applicable federal regulations.  
 
15.2.1
Data Collection 
 
All data required for analysis will be collected and entered on standardized eCRFs using OC-RDC module.  
 
Required data will be recorded on eCRFs by authorized site personnel as indicated on the Delegation of 
Authority Log. The Investigator will ensure that all eCRFs are completed promptly, completely, and 
accurately. Information on case report forms must conform to the information in the source documents.  
 
Investigators must ensure that clinical records clearly indicate that the subject has been enrolled in a 
clinical investigation. Regulations require that Investigators maintain information in the study subject’s 
medical records to corroborate data collected on the eCRF. In order to comply with these regulatory 
requirements, the study site will manage the following information, and retain/manage it as required to 
make it available to monitors, auditors and/or regulatory bodies. Complete hospital and clinical medical 
records for all study subjects should include all study required procedures, labs and assessments as noted 
in Study schedule and Site Collection Data.  
 
15.2.2
Data Access 
 
Secure access to the RDC system will be maintained. Users will be given appropriate levels of access for 
their delegated responsibilities in the study. An audit trail is maintained in OC-RDC to capture any 
corrections or changes of the eCRFs.  If a person is only authorized to complete CRFs or to make changes 
to an already signed CRF, the Investigator shall re-sign this CRF. Training will be provided to users of the 
eCRF electronic data capture system. The RDC system maintains an audit trail on entries, changes or 
corrections in the eCRFs. System backups for data stored in the OC-RDC system will be consistent with 
Medtronic standard procedures.  
 
15.2.3
 Electronic Case Report Form Guidelines 
 
Medtronic will provide detailed instructions to assist with eCRF completion.  
 
15.2.4
Data Queries 
 
During monitoring visits, the Monitor will perform a source verification of required data points that comprise 
the eCRF for each subject. 
 
Discrepancies will be queried by Medtronic and must be resolved by the investigational site staff and PI in 
a timely manner, and as requested by Medtronic. 
 

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Manual and/or automatic queries will be created in the OC-RDC system and will be issued to the site for 
appropriate response. The site staff will be responsible for responding to all queries in the database.  
x
Manual discrepancies will be issued in accordance with the Data Review Guidelines 
x
Automatic discrepancies will be issued in accordance with the Edit Check Document and the eCRF 
Database Question Specifications 
 
In the event of data discrepancies, investigational centers will be asked to resolve queries electronically in 
the RDC system; otherwise, irresolvable data-related issues will be routed to the Sponsor for review and 
final disposition.  
 
Imaging discrepancies will be issued by the Imaging Core Lab, ICON PLC, in SQUARE.  For information on 
accessing and responding to imaging queries, please refer to the BLINK Imaging Manual. 
 
15.2.5
Audits and Inspections 
 
Medtronic-initiated audits or regulatory authority-initiated inspections at the investigational sites may 
occur during the course of or after completion of the study.  In the event that an audit is initiated by 
Medtronic or a designee, the investigator shall allow access to the original medical records and provide all 
requested information.  In the event that an inspection is initiated by a regulatory authority, the 
investigator shall immediately notify Medtronic of the impending inspection and allow the regulatory body 
access to the medical records and other information as required by applicable laws and regulations. 
 
15.2.6
Close Out  
 
Medtronic will only consider eCRFs to be complete when all discrepancies have been resolved by the site 
and reviewed and closed by Medtronic. In addition, specific eCRFs must also be reviewed and electronically 
signed by the Investigator, indicating his/her agreement with the accuracy of all recorded data. It is 
expected that the Investigator and his/her staff will cooperate with the monitoring team and provide any 
missing data in a timely manner. 
 
15.3. Direct Access to Source Data/Documents  
The investigator(s)/institution(s) will permit study-related monitoring, audits, IRB/EC review, and 
regulatory inspection(s) and provide direct access to source data/documents as per local policies and 
regulations. 
15.4. Confidentiality 
All records identifying the subject will be kept confidential and will not be made publicly available. 
 
Subject names will be kept confidential. Only the subject number will be recorded in the eCRF, and if the 
subject name appears on any other document, it must be obliterated. In cases where the local law does 
not allow using the subject initials, for example in Europe, serial number will be appointed (e.g. AAA, 

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BBB). Study findings stored on a computer will be stored in accordance with local data protection laws. 
The subjects will be informed in writing that representatives of the Sponsor, IRB or Regulatory Authorities 
may inspect their medical records to verify the information collected, and that all personal information 
made available for inspection will be handled in strictest confidence and in accordance with local data 
protection laws. 
 
Subjects will also be informed that information regarding the study that does not include subject identifiers 
will be posted on clinicaltrials.gov. 
 
If the results of the study are published, the subject’s identity will remain confidential. The Investigator will 
maintain a list to enable subjects’ records to be identified. 
15.5. Liability 
Given Imaging Ltd, is a wholly owned subsidiary of Medtronic, which as the parent company of such 
entity maintains appropriate clinical study liability insurance coverage as required under applicable laws 
and regulations and will comply with applicable local law and custom concerning specific insurance 
coverage. If required, a clinical study insurance statement/certificate will be provided to the IRB/EC. 
15.6. CIP Amendments 
A CIP amendment will be prepared when there are revisions that are significant changes or corrections, 
or modifications that impact subject safety, ethical conduct, data integrity or study design. CIP 
amendments must undergo review by IRB/EC and any appropriate regulatory authority and will be logged 
in the document version history (Section 1). IRB/EC approval, site training and a new Acknowledgement 
form will be signed and returned before any new procedures take place. 
15.7. Record Retention 
The Investigator and the Sponsor will maintain the records of the study including all pertinent 
correspondence, the study protocol with any/all amendments, all correspondence with and approval from 
the IRB/EC, the clinical study agreement, the Investigator Agreement, device accountability records, 
individual subject records, and signed ICFs. In addition, the Investigator will retain the source documents 
from which the information entered on the eCRF was derived. Original source data that supports the 
eCRF entry must be maintained by the Investigator in compliance with national regulations. Investigator 
records are subject to inspection and copying by regulatory authorities and Medtronic 
 
Subject files and other source data must be kept for a period of not less than 2 years after the latter of 
the following two dates: the date on which this investigation is terminated or completed, or the date that 
the records are no longer required for purposes of supporting a premarket application. Records may need 
to be maintained by the Investigator for a longer duration if national regulations require or if agreed to in 
writing with Medtronic. The Investigator should not dispose of these records without the approval of the 
Sponsor. The Investigator should take measures to prevent accidental or early destruction of the clinical 
study related material. Should the Investigator wish to assign the study records to another party or move 
them to another location, advance written notice should be given to the Sponsor. 
 
All data and documents should be made available if requested by relevant authorities. 

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15.8. Publication and Use of Information 
The Medtronic Publication and Authorship Policy is aligned with the International Committee of Medical 
Journal Editors (ICMJE) recommendations (www.icmje.org). Medtronic will seek to publish, in appropriate 
peer-reviewed journals and scientific conferences, results of clinical studies where human subjects are 
involved, regardless of outcome. Information regarding the study and study data will be made available 
via publication on clinicaltrials.gov. Additionally, the results of this study will be submitted for publication 
in an appropriate journal. While study results are owned by Medtronic, all data on which a publication is 
based will be made available to all authors as required for their participation in the publication process. 
Furthermore, data may be published or used by study investigators provided that such publication or use 
is in accordance with this this protocol, the Medtronic-MITG Publication and Authorship Policy, and the 
Clinical Investigation Agreement. Investigators must submit a copy of all manuscripts and/or abstracts to 
Medtronic for review and comment 30 days prior to planned submission. Medtronic acknowledges that its 
right to review and comment shall relate solely to the proprietary, licensing, and/or confidential rights 
Medtronic may have in such proposed publication, rather than whether such results and/or opinions are 
favorable to Medtronic.  
 
The publication of substudies, post-hoc analyses, regional results, or single-center experiences based on 
multicenter clinical studies should not precede that of the primary multicenter publication, and should cite 
the primary publication whenever possible, as required by specific journal and scientific meeting 
guidelines.  
 
Medtronic involvement in a publication (e.g., funding of the study; sponsor of the study; collection, 
analysis, and interpretation of data; professional writing assistance) must be disclosed according to 
journal-specific policies, submission requirements, and prevailing editorial standards, in addition to those 
specified by ICMJE. Authors must ensure that an acknowledgement/disclosure statement is included in 
the body of the manuscript for Medtronic to review for accuracy. All authors must also disclose financial 
or personal affiliations that could be considered conflicts of interest as per journal/conference 
requirements. 
 
To enable health care providers, payers, and patients access to the wealth of Medtronic’s research, 
Medtronic will report its scientific data in accordance with the principles outlined in the Guidance 
Document on Registration and Reporting Results of Company-Sponsored Clinical Trials Under FDAAA 
2007 (Title VIII).   
15.9. Suspension or Early Termination 
Medtronic reserves the right to discontinue the study at any stage, with suitable written notice to all 
investigators, all reviewing IRB/ECs, FDA and Competent Authorities. The appropriate ethics committees 
will be notified of discontinuation of the study for any reason no later than 5 working days after the 
Sponsor makes this determination.  In addition, local ethics committee and/or regulatory authority can 
decide whether the study is to be terminated and will notify the Sponsor. 
 
Similarly, investigators may withdraw from the study at any time, subject to providing written notification 
to Medtronic 30 days prior to the date they intend to withdraw. However, Medtronic and investigators will 

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be bound by their obligation to complete the follow-up of subjects already participating in the study. The 
subjects must be followed according to the clinical protocol, and information obtained during subject 
follow-up shall be reported to Medtronic on the appropriate eCRF. 
Suspension or termination of a site may include but is not limited to: 
x
Ethics Board approval expiration 
x
Consistent non-compliance to the protocol (e.g. failure to follow subjects, etc.) 
x
Lack of enrollment 
x
Non-compliance to regulations and the terms of the Agreement with Medtronic  
x
Ethics Board suspension of the site 
 
If the site terminates or suspends participation without prior agreement of Medtronic: 
x
The site must promptly inform Medtronic and provide a detailed written explanation of the termination 
or suspension 
x
The site must promptly inform the institution (where required per regulatory requirements) 
x
The site must promptly inform the Ethics Board, if applicable       
                                                       
If the Ethics Board terminates or suspends its approval:  
 
x
The site must promptly inform Medtronic and provide a detailed written explanation of the termination 
or suspension within 5 working days. 
x
Patient enrollment must stop until the Ethics Board suspension is lifted 
x
Subjects already enrolled should continue to be followed in accordance with the Ethics 
x
Board policy or its determination that an overriding safety concern or ethical issue is involved 
x
The site must inform his/her institution (where required per local requirements) 
x
The site must promptly inform the patients, if applicable 
 
16. References 
1.
Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing 
incidence and prevalence of the inflammatory bowel diseases with time, based on systematic 
review. Gastroenterology. 2012;142(1):46-54 e42; quiz e30. doi: 10.1053/j.gastro.2011.10.001. 
PubMed PMID: 22001864.
2.
de Mattos BR, Garcia MP, Nogueira JB, Paiatto LN, Albuquerque CG, Souza CL, et al. 
Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments. 
Mediators of inflammation. 2015;2015:493012. doi: 10.1155/2015/493012. PubMed PMID: 
26339135; PubMed Central PMCID: PMC4539174.

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3.
Kefalas CH. Gastroduodenal Crohn's disease. Proceedings. 2003;16(2):147-51. PubMed 
PMID: 16278730; PubMed Central PMCID: PMC1201000.
4.
Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, et al. Long-term 
evolution of disease behavior of Crohn's disease. Inflamm Bowel Dis. 2002;8(4):244-50.
PubMed PMID: 12131607.
5.
Lee SM, Han EC, Ryoo SB, Oh HK, Choe EK, Moon SH, et al. Long-term Outcomes 
and Risk Factors for Reoperation After Surgical Treatment for Gastrointestinal Crohn Disease 
According to Anti-tumor Necrosis Factor-alpha Antibody Use: 35 Years of Experience at a 
Single Institute in Korea. Annals of coloproctology. 2015;31(4):144-52. doi: 
10.3393/ac.2015.31.4.144. PubMed PMID: 26361616; PubMed Central PMCID: PMC4564666.
6.
Ladas SD, Triantafyllou K, Spada C, Riccioni ME, Rey JF, Niv Y, et al. European 
Society of Gastrointestinal Endoscopy (ESGE): recommendations (2009) on clinical use of video 
capsule endoscopy to investigate small-bowel, esophageal and colonic diseases. Endoscopy. 
2010;42(3):220-7. doi: 10.1055/s-0029-1243968. PubMed PMID: 20195992.
7.
Kopylov U, Seidman EG. Clinical applications of small bowel capsule endoscopy. 
Clinical and experimental gastroenterology. 2013;6:129-37. doi: 10.2147/CEG.S48005. PubMed 
PMID: 23983481; PubMed Central PMCID: PMC3751460.
8.
Eliakim R, Yassin K, Niv Y, Metzger Y, Lachter J, Gal E, et al. Prospective multicenter 
performance evaluation of the second-generation colon capsule compared with colonoscopy. 
Endoscopy. 2009;41(12):1026-31. doi: 10.1055/s-0029-1215360. PubMed PMID: 19967618.
9.
Spada C, Hassan C, Munoz-Navas M, Neuhaus H, Deviere J, Fockens P, et al. Second-
generation colon capsule endoscopy compared with colonoscopy. Gastrointest Endosc. 
2011;74(3):581-9 e1. doi: 10.1016/j.gie.2011.03.1125. PubMed PMID: 21601200.
10.
Rex DK, Adler SN, Aisenberg J, Burch WC, Jr., Carretero C, Chowers Y, et al. Accuracy 
of capsule colonoscopy in detecting colorectal polyps in a screening population. 
Gastroenterology. 2015;148(5):948-57 e2. doi: 10.1053/j.gastro.2015.01.025. PubMed PMID: 
25620668.
11.
Leighton JA, Helper DJ, Gralnek IM, Dotan I, Fernandez-Urien I, Lahat A, et al. 
Comparing diagnostic yield of a novel pan-enteric video capsule endoscope with 
ileocolonoscopy in patients with active Crohn's disease: a feasibility study. Gastrointest Endosc. 
2016. doi: 10.1016/j.gie.2016.09.009. PubMed PMID: 27658907.
12.
Mitselos IV, Christodoulou DK, Katsanos KH, Tsianos EV. Role of wireless capsule 
endoscopy in the follow-up of inflammatory bowel disease. World J Gastrointest Endosc. 
2015;7(6):643-51. doi: 10.4253/wjge.v7.i6.643. PubMed PMID: 26078832; PubMed Central 
PMCID: PMC4461938.
13.
Efthymiou A, Viazis N, Mantzaris G, Papadimitriou N, Tzourmakliotis D, Raptis S, et al. 
Does clinical response correlate with mucosal healing in patients with Crohn's disease of the 
small bowel? A prospective, case-series study using wireless capsule endoscopy. Inflamm Bowel 
Dis. 2008;14(11):1542-7. doi: 10.1002/ibd.20509. PubMed PMID: 18521929.
14.
Hall BJ, Holleran GE, Smith SM, Mahmud N, McNamara DA. A prospective 12-week 
mucosal healing assessment of small bowel Crohn's disease as detected by capsule endoscopy. 
Eur J Gastroenterol Hepatol. 2014;26(11):1253-9. doi: 10.1097/MEG.0000000000000194. 
PubMed PMID: 25264865.

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15.
Niv E, Fishman S, Kachman H, Arnon R, Dotan I. Sequential capsule endoscopy of the 
small bowel for follow-up of patients with known Crohn's disease. Journal of Crohn's & colitis. 
2014;8(12):1616-23. doi: 10.1016/j.crohns.2014.03.003. PubMed PMID: 24666976.
16.
Peyrin-Biroulet L, Reinisch W, Colombel JF, Mantzaris GJ, Kornbluth A, Diamond R, et 
al. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's 
disease in the SONIC trial. Gut. 2014;63(1):88-95. doi: 10.1136/gutjnl-2013-304984. PubMed 
PMID: 23974954.
17.
Boal Carvalho P, Rosa B, Dias de Castro F, Moreira MJ, Cotter J. PillCam COLON 2 in 
Crohn's disease: A new concept of pan-enteric mucosal healing assessment. World J 
Gastroenterol. 2015;21(23):7233-41. doi: 10.3748/wjg.v21.i23.7233. PubMed PMID: 26109810; 
PubMed Central PMCID: PMC4476885.
18.
Dave M, Loftus EV, Jr. Mucosal healing in inflammatory bowel disease-a true paradigm 
of success? Gastroenterology & hepatology. 2012;8(1):29-38. PubMed PMID: 22347830; 
PubMed Central PMCID: PMC3277196.
19.
Orlando A, Guglielmi FW, Cottone M, Orlando E, Romano C, Sinagra E. Clinical 
implications of mucosal healing in the management of patients with inflammatory bowel disease. 
Dig Liver Dis. 2013;45(12):986-91. doi: 10.1016/j.dld.2013.07.005. PubMed PMID: 23993738.
20.
D'Inca R, Caccaro R. Measuring disease activity in Crohn's disease: what is currently 
available to the clinician. Clinical and experimental gastroenterology. 2014;7:151-61. doi: 
10.2147/CEG.S41413. PubMed PMID: 24876789; PubMed Central PMCID: PMC4035027.
21.
Flamant M, Trang C, Maillard O, Sacher-Huvelin S, Le Rhun M, Galmiche JP, et al. The 
prevalence and outcome of jejunal lesions visualized by small bowel capsule endoscopy in 
Crohn's disease. Inflamm Bowel Dis. 2013;19(7):1390-6. doi: 10.1097/MIB.0b013e31828133c1. 
PubMed PMID: 23552764.
22.
Papay P, Ignjatovic A, Karmiris K, Amarante H, Milheller P, Feagan B, et al. Optimising 
monitoring in the management of Crohn's disease: a physician's perspective. Journal of Crohn's 
& colitis. 2013;7(8):653-69. doi: 10.1016/j.crohns.2013.02.005. PubMed PMID: 23562672.
23.
Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. 
Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining 
Therapeutic Goals for Treat-to-Target. Am J Gastroenterol. 2015;110(9):1324-38. doi: 
10.1038/ajg.2015.233. PubMed PMID: 26303131.
24.
Rozendorn N, Klang E, Lahat A, Yablecovitch D, Kopylov U, Eliakim A, et al. 
Prediction of patency capsule retention in known Crohn's disease patients by using magnetic 
resonance imaging. Gastrointest Endosc. 2016;83(1):182-7. doi: 10.1016/j.gie.2015.05.048.
PubMed PMID: 26142554.
25. 
Signorelli C, Rondonotti E, Villa F, Abbiati C, Beccari G, Avesani EC, et al. Use of the Given 
Patency System for the screening of patients at high risk for capsule retention. Dig Liver Dis. 
2006;38(5):326-30. doi: 10.1016/j.dld.2006.01.010. PubMed PMID: 16527556. 
 
 

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17. Appendices  
17.1 Appendix A – Montreal Classification 
17.2 Appendix B - Study Schedule for Clinical Laboratory and Pregnancy Tests 
17.3 Appendix C - MRE Procedure Instructions 
17.4 Appendix D – PillCam® Patency Study 
17.5 Appendix E – CE Procedure Instructions 
 
17.5.1 Appendix E1 – CE Bowel Preparation Instructions 
 
17.5.2 Appendix E2 – CE Subject Instructions Form 
 
17.5.3 Appendix E3 – CE Procedure Instructions 
 
17.5.4 Appendix E4 – CE Bowel Cleansing Scale 
17.6 Appendix F – Ileocolonoscopy Procedure Instructions 
 
17.6.1 Appendix F1 - Ileocolonoscopy Bowel Preparation 
 
17.6.2 Appendix F2 - Ileocolonoscopy Subject Instructions Form 
 
17.6.3 Appendix F3 - Ileocolonoscopy Bowel Cleansing Scale 
17.7 Appendix G – Accuracy for Active Crohn’s Disease in Overall and Designated Bowel Segments 
17.8 Appendix H – Scores for Capsule endoscopy, Ileocolonoscopy, and MRE 
 
17.8.1 Appendix H1 – Lewis Score 
17.8.2 Appendix H2 – Simple Endoscopic Score for Crohn’s Disease Index (SES-CD) Score 
 
17.8.3 Appendix H3 - Magnetic Resonance Index of Activity (MaRIA) Score 
17.9 Appendix I – Patient Satisfaction Questionnaire 
 
 

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17.1 Appendix A – Montreal Classification 
Data for Montreal classification will be captured at screening.  
 
Montreal classification: 
 
i. Age at diagnosis (years) 
a.
< 16, A1 
b.
16-40, A2 
c.
> 40, A3 
ii.  Disease behavior 
a.
Inflammatory, B1 
b.
Stricturing, B2 
c.
Penetrating, B3 
iii.  Disease location 
a.
Ileum, L1 
b.
Colon, L2 
c.
Ileocolon, L3 
 
 
 

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17.2 Appendix B - Study Schedule for Clinical Laboratory and 
Pregnancy Tests 
 
1. Stool Clostridium difficile (if not done within previous 3 months). 
2.  Stool ova/parasites OR stool PCR microorganism panel (if not done within previous 3 months). 
3. Clinical Chemistry  
 
Blood urea nitrogen (BUN) 
 
Serum creatinine 
 
Serum albumin  
 
Fecal calprotectin 
 
C-reactive protein (CRP) 
4. Complete blood count (CBC): 
 
Hemoglobin 
 
Hematocrit 
 
Erythrocyte count (RBC) 
 
Leukocytes (WBC) 
 
Absolute Neutrophils 
 
Platelets  
5. Pregnancy Test - Female subjects will be assessed for childbearing potential, and if they do have 
childbearing potential, they will undergo a pregnancy blood or urine test. If the test is positive, they will 
be withdrawn from the study. If the pregnancy test is negative, these subjects should practice 
contraceptive methods through the course of the study. s.  
 
 
Screening 
(No more 
than 30 
days prior to 
first Baseline 
Procedure - 
MRE) 
Baseline 
Procedure 
(Day 0)5 
 
 
 
 
Stool Clostridium 
difficile1 
X 
 
 
 
 
 
Stool 
ova/parasites OR 
stool PCR 
microorganism 
panel1 
X 
 
 
 
 
 
BUN2 
X 
 
 
 
 
 
Serum 
creatinine2,3 
X 
 
 
 
 
 
Serum albumin 
 
X 
 
 
 
 

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Fecal calprotectin4 
 
X 
 
 
 
 
CRP 
 
X 
 
 
 
 
CBC w differential 
 
X 
 
 
 
 
Pregnancy test 
X 
 
 
 
 
 
1. Prior standard of care C.difficile and stool O&P/PCR microorganism panel results may be leveraged for the screening visit 
once informed consent has been collected and provided that the date of results is no more than 3 months prior to informed 
consent date.  These lab results, along with pregnancy test, must be evaluated as part of inclusion/exclusion criteria prior to 
subject enrollment.   
2. BUN and serum creatinine data will be collected to evaluate renal function and results must be evaluated prior to MRE.          
3. Serum creatinine measurement will be used to estimate the glomerular filtration rate (eGFR) and results must be evaluated 
prior to MRE.                                              
4. A central laboratory will be used for analysis of fecal calprotectin. Please see Laboratory Manual for additional information. 
5. Baseline labs may be collected on the day of the MRE procedure, prior to the procedure. 
 
 
 

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17.3 Appendix C - MRE Procedure Instructions 
The MRE procedure will be in accordance with Coimbra et al., Aliment Pharmacol Ther 2016; 43: 61–72.  
Instructions for subjects can be found in Appendix C1. 
All deviations from prep and procedural requirements should be appropriately documented and reported. 
1.
Subjects will fast for 4 hours and drink up to 1000-1800 mL of an oral non-absorbable bowel 
preparation solution (Breeza® [Beekley Medical, Bristol, CT, USA], or VoLumen® [Bracco 
Diagnostics Inc., Princeton, NJ, USA] or 5% mannitol solution). Non-proprietary oral contrasts 
containing sugar alcohols (e.g., 3% sorbitol solution) are also permissible, but should be cleared 
with Medtronic prior to study initiation. 
2.
An intravenous (IV) catheter will be placed into a peripheral vein.  
3.
An IV or subcutaneous injection of an anti-peristaltic agent (0.5 mg glucagon [Lilly, Indianapolis, 
IN, USA] in the US or 10 mg buscopan [Boehringer Ingelheim, Sant Cugat, Spain] in Europe) will 
be administered prior to scanning.  The anti-peristaltic agent can be administered in a split dose 
(prior to scanning and immediately prior gadolinium administration) or as a single dose prior to 
administration of gadolinium (step 5 below). 
4.
Following a fast scout series and a succession of breath holds, T2-weighted true fast imaging 
with steady-state free precession (FISP) and T2-weighted single-shot fast spin echo (SSFSE) 
series will be acquired, with and without fat suppression, using coronal and axial images, as 
described in Table 2 of the BLINK Imaging Manual. The field of view will be adjusted to cover the 
digestive tract from the fundus of the stomach to the anus. It is appropriate to move the field of 
view inferiorly to not image the liver dome and stomach so that the anus is within the imaged 
volume.  The number of slices for each series will be adjusted to keep the series duration within 
approximately 25 seconds and to allow for acceptable breath hold periods. Multiple staggered 
series will be allowed to fulfil the prescribed coverage.  Prone positioning is preferred by not 
mandatory.  Supine positioning is preferred for patients with end ileostomies. 
 
*Optional – it is optional for sites to acquire axial images using either types of pre-contrast pulse 
sequence instead of coronal images.  At least one precontrast series should be acquired in the 
axial plane. 
5.
A fast breath-hold 3D gradient-recalled echo (GRE) coronal T1-weighted, fat-suppressed series 
will be acquired prior to and approximately 45 seconds and 180 seconds following the IV 
administration of an extracellular gadolinium-based contrast agent (such as 0.1 mmol/kg 
MultiHance [Bracco Diagnostics Inc., Princeton, NJ, USA], 0.1 mmol/kg Omniscan [GE Healthcare 
Inc., Oslo, Norway] or 0.1 mmol/kg Dotarem [Guerbet LLC., Bloomington, IN, USA]). The small 
bowel (including duodenum), colon, rectum, and anus need to be imaged.  Required and 
suggested parameters are listed in Table 2 of the BLINK Imaging Manual*.  Slice thicknesses can 
be interpolated. 
* Optional - For large patients, the coronal slice thickness can be increased to 4 mm and the axial 
slice thickness can be increased to 5 mm to permit for coverage and appropriate signal, if 
needed. 
6.
Finally, one final breath-hold series of axial T1-weighted GRE with fat suppression will be 
acquired. 
 

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17.3.1 Appendix C1 - MRE Subject Instructions 
See attached document “Appendix C1_BLINK_MRE Subject Instructions” 
 
 
 

Subject Code:
Page 1 of 3
Subject Instructions
MRE Procedure
BLINK Clinical Trial (COVSBCC0549)
Thank you for your participation in this study. The preparation for your examination is a very 
important part of your exam. Please follow all instructions carefully to ensure a successful 
procedure.
• After completion of each step, check box (9) and specify time in the column on the right,        
otherwise detail why step was not followed in Comments section.
• Both you and the Research Staff Member should sign and date Page 3 of this form
On the day of the examination:
• Bring these instructions with you to the clinic
• Dress in comfortable 2-piece clothing
To be completed by research staff:
Subject #:                                                     Site #:
Please arrive at the clinic on _____________ at __________ for your 
procedure.
Your MRE is scheduled to begin at ____________
Contact for questions:
Name: ___________________   Phone: ________________
Date
Time
Time
COVSBCC0549 MRE Subject Instructions v3

Subject Code:
Page 2 of 3
Time
Action 
"
The Day of the Examination
Day of the week:__________, Date:____/____/___
Start: 4 hours 
prior to 
procedure
(see top of 
Page 1)
• Drink water only. No solid foods or other beverages.
As defined by 
Radiologist
• Ingest 1000-1800mL of the bowel preparation solution provided to 
you.
Start Time:
Finish Time:
As Scheduled
• MRE Procedure
COVSBCC0549 MRE Subject Instructions  v3
Subject #:

Subject Code:
Page 3 of 3
Time
Comments
Additional Information and Comments
COVSBCC0549 MRE Subject Instructions v3
Subject #:
Research Staff Signature
Patient Signature
Date
Date

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17.4 Appendix D – PillCam® Patency Study 
In all subjects with evidence of stricture on MRE, or according to investigator’s discretion, a PillCam® 
patency study must be performed prior to the PillCam® procedure. 
 
During the PillCam® patency study, if the patency capsule is excreted structurally whole or located 
structurally whole in the colon at any time, then this confirms patency of the GI tract of the subject for 
objects the size of the capsule. The capsule is designed to dissolve starting 30 hours following ingestion, 
during a period of approximately 12 hours. If any time before 30 hours after capsule ingestion the 
patency capsule cannot be detected in the subject's body, it indicates the following: 
 
x
The PillCam® patency capsule was excreted naturally and structurally whole 
x
Patency of the GI tract for objects the size of the capsule is confirmed 
 
The PillCam® patency scanner is used to detect the presence of the patency capsule in the subject’s 
body. If desired, fluoroscopy or X-ray may be used.  The subject should return to the clinic as close to, 
but no more than, 30 hours after ingestion of the patency capsule to be evaluated – suggest scheduling 
subject appointment for 28 hours after initial ingestion. 
 
If the PillCam® patency scanner or x-ray does not detect the patency capsule in the GI tract any time 
prior to 30 hours post-ingestion, this implies that it has been excreted structurally whole, and patency of 
the GI tract can be confirmed.  
 
 
 
 

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17.5 Appendix E – CE and IC Procedure Instructions 
This appendix includes instructions for the capsule endoscopy (CE) and IC procedures in 4 parts: 
 
x
Appendix E1 – CE Capsule and IC Bowel Preparation Instructions 
x
Appendix E2 – CE Capsule and IC Subject Instructions Form 
x
Appendix E3 – CE Procedure Instructions 
x
Appendix E4 – CE and IC Bowel Cleansing Scale 
 
 
 
 

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17.5.1 Appendix E1 – CE and IC Bowel Preparation Instructions 
Subjects will be instructed to follow a detailed dietary and colon preparation regimen prior to and during 
the CE procedure day. All colon preparation products will be standard colon cleansing products approved 
by the FDA and/or EMA.    Additional bowel prep after capsule endoscopy, prior to ileocolonoscopy is at 
the discretion of the investigator. 
 
Subjects will keep a timed diary of key preparation steps and bowel activity, including capsule excretion, 
located in Appendix E2.  CE Procedure Instructions can be located in Appendix E3.  
 
Preparation Procedure 
The Day Before the Procedure Day 
All Day 
Clear liquid diet. 
15 hours prior to capsule ingestion 
Begin ingestion of 2L PEG  (such as ELS; NuLYTELY, Braintree 
Laboratories, Braintree, MA), one 8-10 oz. cup every 10-15 minutes. 
13 hours prior to capsule ingestion 
Complete ingestion of 2L PEG 
Procedure Day 
3 hours prior to capsule ingestion 
Begin ingestion of remaining 2L PEG, one 8-10 oz. cup every 10-15 
minutes. 
1 hour (±15 minutes) prior to 
capsule ingestion 
Complete ingestion of remaining 2L PEG1,2. Subject should remain NPO 
until capsule ingestion.  Strongly suggest requiring subject to finish 
morning PEG in clinic to assure capsule ingestion occurs within 1 hour 
(±15 minutes) of completion. 
As scheduled  
Capsule Ingestion with a sip of water then resume NPO until Alert 1.  
Capsule MUST be ingested within 1 hour (±15 minutes) after completing 
ingestion of PEG. 
Alert 0 (1 hour after capsule 
ingestion) 
10 mg Metoclopramide or 250mg oral Erythromycin 
Please note, not all subjects will receive Alert 0 
Alert 1 (Upon SB Detection) 
3 oz. (half bottle) SUPREP® (US), Eziclen®/Izinova® (EU) diluted per 
package insert instructions + drink 1L water 
Alert 2 (3 hrs later) 
3 oz. (half bottle) SUPREP® (US), Eziclen®/Izinova® (EU) diluted per 
package insert instructions + drink 1L water 
Alert 3 (2 hrs later) 
10 mg Bisacodyl suppository. 
1 Any subject ingesting <2.5L of PEG (combined between evening and morning dose) should not proceed with CE 
procedure and should be discontinued from the trial. 
2 Any subject requiring >3 hours to ingest the morning PEG dosage (2L) should not proceed with CE procedure and 
should be exited from the trial. 
 
Following capsule endoscopy procedure, physician must instruct subject regarding clear liquid diet and/or 
NPO status until completion of IC procedure.  Physician may administer additional prep following 
completion of the CE procedure, prior to the IC procedure at his/her discretion. 
 
EXAMPLE Subject Schedule for 8am capsule ingestion: 
The Day Before the Procedure Day 
All Day 
Clear liquid diet. 
5pm (15 hrs prior to scheduled 
ingestion) ) 
Begin ingestion of 2L PEG  

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7pm (13 hrs prior to scheduled 
ingestion) 
Complete ingestion of 2L PEG 
Procedure Day 
5am (3 hrs prior to scheduled 
capsule ingestion) 
Begin ingestion of remaining 2L PEG 
7am (±15 minutes) (1 hour prior to 
scheduled capsule ingestion) 
Complete ingestion of remaining 2L PEG. Subject should remain NPO 
until capsule ingestion. 
8am (08:00) 
Capsule Ingestion with a sip of water then resume NPO until Alert 1. 
 
 

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17.5.2 Appendix E2 – CE and IC Subject Instructions Form 
During the CE procedure, subjects will be asked to use a Subject Instructions Form to document their 
activities during the bowel preparation and capsule examination. This form will be used to document the 
subject’s adherence to the procedure steps. The Subject Instructions Form will also serve as source data 
for eCRF entries. Site staff must complete the instructed “start” and “finish” times in the left-hand column 
of the CE Subject Instruction Form to inform the patient when they should start and finish each step of 
the bowel prep, based on the timelines set in Appendix E1, CE Bowel Preparation Instructions. 
 
See attached document, “BLINK_CE and IC Subject Instructions Form” 
 
 
 

Subject Code:
Page 1 of 4
Thank you for your participation in this study. The preparation for your examinations are very important part of 
your exam. Please follow all instructions carefully to ensure adequate cleansing of the bowel for your 
procedure. The Research Staff will complete the information in the left hand column, to indicate when you 
should start and finish each step of the procedures.  You must complete the column on the right, indicating the 
exact time you started and finished each step.  BOTH the Research Staff and Patient must sign and date Page 4.
• Important: After the capsule endoscopy, you must follow your physician’s instructions on what you can eat or 
drink until your ileocolonoscopy procedure (IC) is complete; either directly following the PillCam® Crohn’s 
procedure or the next morning.
• After completion of each step, check box (9) and specify time in the column on the right, otherwise detail 
deviation in comments
• During the preparation period do not take any iron supplements or vitamin supplements containing iron
• If you take anti-coagulants (Warfarin, Aspirin) or antibiotics as a preventive treatment for heart disease, please 
consult your physician first
• It is recommended to use moist baby wipes instead of toilet paper
On the day of the Capsule Endoscopy procedure:
• Bring these instructions and the remaining 2L of PEG (SF-ELS) with you to the clinic
• Dress in comfortable 2-piece clothing and bring any reading material or electronic personal entertainment you 
with to use during the capsule endoscopy procedure.
During your capsule endoscopy procedure:
•Try to remain active and take short walks, this can speed up the transit of the capsule through your body. No 
sleeping.  
•Do not lean on or sit in metal chairs during the procedure as this can cause interference.
•Avoid intense sunlight during procedure
COVSBCC0549 PillCam Crohn’s and IC Subject Instructions v4
To be completed by research staff:
Subject #:                                                    Site #:
Please arrive at the clinic on:
____________ at __________ for your capsule endoscopy procedure AND
____________ at __________ for your ileocolonoscopy procedure.
Contact for questions:
Name: __________________________  Phone: ___________________
Research Staff: Please complete the blank information in the left hand column of Pages 2 and 3 to 
indicate when the subject should start and finish each step of the procedure based on the 
requirements in Appendix E1.  Remember to sign and date Page 4, along with the patient.
Time
Time
Date
Subject Instructions
Capsule Endoscopy (PillCam® Crohn’s) and Ileocolonoscopy 
Procedure
BLINK Clinical Trial (COVSBCC0549)
Date

Subject Code:
Page 2 of 4
Action 
"
The Day Before the Procedure
Day of the week:__________, Date:____/____/___
All day
• Drink clear fluids only, see description below,  No solid foods.
• It is recommended to drink a lot of sugared clear drink of your 
choice through the day (e.g. carbonated soda, apple juice, energy  
drinks etc.)
Afternoon
• Prepare PEG solution according to the instructions on the package. 
Shake well until all the powder is dissolved and keep refrigerated
To be 
completed by 
Study 
Coordinator:
Expected 
Start:
____________
Expected 
Finish: 
____________
_
• Document the time you actually Start and Finish each step in the 
column to the right 
• Drink ½ gallon (2 liters) of PEG (SF-ELS) solution, one
200-250ml cup every 10-15 minutes, for up to 2 hrs.  Do not ingest 
too quickly in order to avoid stomach discomfort. During this time, 
you should avoid drinking other fluids.
• Document the Start and End times of drinking the solution
• Keep the remaining volume (1/2 gallon) of the PEG (SF-ELS) 
solution refrigerated and bring it with you on the day of the 
examination
• Contact the study coordinator in case you are having trouble 
completing the entire volume
Clear Liquid Diet
COVSBCC0549 PillCam Crohn’s and IC Subject Instructions  v4
Subject #:
Actual Start:
Actual Finish:
Total PEG 
intake:
liters
•
Water
•
Apple, white cranberry, white grape juices
•
Tea or black coffee (no milk or cream)
•
Clear sports drinks or carbonated soft drinks (no red or purple colored)
•
Popsicles or jello (any color except red or purple)
•
Bubble gum or hard candy (lemon or mint flavored) 
AVOID: Juices with pulp, milk, cream, soup or broth, alcoholic beverages and solid foods

Subject Code:
Page 3 of 4
Day of the Examination
(Day of the week:_________, Date:____/____/____)
Action
"
All Day
•Only clear fluids are allowed. No solid foods
To be completed 
by Study 
Coordinator:
Expected Start:
_____________
Expected Finish: 
_____________
• May start morning PEG at home depending on scheduled 
capsule ingestion time (see top of Page 1 for scheduled time)
•Drink ½ gallon (2 liters) of PEG (SF-ELS) solution,
one 200-250ml cup every 10-15 minutes, for up to 2 hours.
• It is recommended that you bring a small amount of remaining 
PEG with you to the clinic to finish at the clinic. This will help 
ensure you ingest the PillCam capsule within 1hr of completing 
your PEG ingestion
• Try to avoid consumption of any other liquid during PEG 
ingestion
• When finished, maintain a complete fast until instructed 
otherwise by the study staff. 
Actual Start:
Actual Finish:
Total PEG intake:
liters
1 hour (t15min) 
after finishing 
PEG
•Ingest PillCam® Crohn’s capsule with a cup of water
Action
Alert Number 
& Time
Prokinetics
10mg Metoclopromide or 250mg Erythromycin
*Not all patients will receive Alert 0
0 ________________
1st Boost
•Drink SuPrep solution (0.5 bottle (88ml)  diluted to
240ml) 
•Drink at least 1 liter (Four 8 oz cups) of water
1 ________________
2nd Boost*
(3 hrs after 1st Boost)
•Drink SuPrep solution (0.5 bottle (88ml)  diluted to
240ml) 
•Drink at least 1 liter (Four 8 oz cups) of water
2* ______________
Suppository
(2 hrs after 2nd Boost)
Insert suppository (10mg Bisacodyl) as described in the 
package insert
3 ________________
End of 
Procedure* 
Capsule was naturally excreted                   -- or --
Recorder (DR3) alert “End of Procedure”                     
End of Procedure
________________
COVSBCC0549 PillCam Crohn’s and IC Subject Instructions v4
*Subjects are allowed to leave the clinic (at the physician’s discretion) after Alert 2 is received and all associated actions 
completed, if the capsule is not yet excreted. If subject leaves before excretion they must insert the suppository when Alert 3 
is received and document the time.  They must also document the time the capsule is excreted or “End of Procedure” alert is 
received.  They may disconnect the recorder at excretion or battery failure (whichever comes first). 
Subject #:

Subject Code:
Page 4 of 4
•Research Staff Signature
Time
Comments
Additional Information and Comments
COVSBCC0549 PillCam Crohn’s and IC Subject Instructions v4
Subject #:
Research Staff Signature
Patient Signature
Date
Date

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17.5.3 Appendix E3 – CE Procedure Instructions 
On the day of the examination, the arrival time of the subject at the clinic will be documented on the 
Subject Instructions Form (see Appendix E2) and the subject will complete the bowel preparation 
procedure as detailed in Appendix E1.  All deviations from bowel prep and procedural requirements 
should be appropriately documented and reported. 
 
The subject’s last bowel movement should be clear to yellow effluent prior to the CE exam.  Any subject 
ingesting <2.5L of PEG should not proceed with CE procedure and should be discontinued from the trial. 
 
After the final PEG ingestion, subjects should remain NPO until capsule ingestion.  Within 1 hour (±15 
minutes) of the final PEG ingestion, the subject will swallow the PillCam® Crohn’s capsule with a cup of 
water.  The subject will then resume their NPO status until they receive an alert. The subject will follow 
the instructions for any alert they receive until the capsule is excreted. The subject will be instructed to 
notify the staff upon exit of the capsule from the body and to record the time on the subject instruction 
form.  After the baseline capsule endoscopy procedure, the subject should be instructed to follow the 
anesthesiologist’s instruction in regard to NPO status until the completion of the baseline IC procedure. 
 
Throughout the CE procedure, the subject will be instructed to verify when the capsule has exited the 
body and to inform the physician or the clinical coordinator of the time of exit. The time of exit should be 
documented on the Subject Instructions Form and in the eCRF.  
 
Throughout the CE procedure, the subjects will be instructed to notify the study physician if experiencing 
abdominal pain, headache, vomiting, bloating, and nausea which are anticipated symptoms that could be 
related to the procedure.  
 
The system may be disconnected upon one of the following: capsule excretion (“End of Procedure” alert) 
or until battery failure, whichever comes first. The PillCam® Recorder may also be removed in case of 
procedure failure. 
 
Subjects will be allowed to leave the clinic once the capsule is excreted (“end of procedure” alert) OR 
once Alert 2 has been received and all associated instruction for Alert 2 is completed by the subject, 
approximately 8 hours after ingestion.  Subjects leaving before excretion must be instructed and agree to 
the following; the importance of complying with these instructions should be stressed: 
 
x
Insert the biscodyl suppository at home upon notification of Alert 3
x
Document the time of Alert 3 on the CE Subject Instructions (Appendix E2).  
x
Evaluate bowel movements for capsule excretion and document the time of excretion on the CE 
Subject Instructions (Appendix E2).  If the capsule is not excreted prior to returning to the clinic, 
the “End of Procedure” alert time or the time the battery failed should be recorded on the 
Subject Instructions, whichever occurs first.
x
The subject may disconnect the recorder at excretion (“End of Procedure” alert) or battery failure 
(whichever comes first) and return the equipment to the clinic the next day.
 
  
 
 

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Site staff must continue to follow the subject until the capsule is excreted.  If the capsule is not 
confirmed to have been excreted by 14 days after ingestion, then a plain abdominal film will be 
performed to verify the capsule exit. 
 
Since the capsule endoscopy and ileocolonoscopy share a single bowel prep, the physician may 
administer additional bowel prep at his/her discretion if the ileocolonoscopy is to be conducted the day 
after completion of the capsule endoscopy.  The physician must also instruct the subject whether they 
may have a meal or must maintain clear liquid diet or NPO between the 2 procedures.  If the capsule has 
not been excreted by the time the IC is conducted, and the battery has already failed, the colonoscopist 
may remove the capsule during IC. 
 
 
 
 

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17.5.4 Appendix E4 – CE and IC Bowel Cleansing Scale 
 
 Cleansing Level Scale for Capsule Endoscopy 
Rating 
Description 
Poor 
Inadequate 
Large amount of fecal residue precludes a complete examination 
Fair 
Inadequate, but examination completed 
Enough feces or turbid fluid to prevent a reliable examination 
Good 
Adequate 
Small amount of feces or turbid fluid not interfering with examination 
Excellent 
Adequate 
No more than small bits of adherent feces 
Adapted from Leighton JA et al. Endoscopy 2011;43:123-7. 
 
 
 
 

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17.7 Appendix F – Accuracy for Active Crohn’s Disease in Overall 
and Designated Bowel Segments 
 
Accuracy of CE versus IC plus MRE for detection of active CD in the small bowel and colon will be 
assessed.  
 
Accuracy measures (sensitivity, specificity, negative predictive value, positive predictive value) will be 
calculated for the overall bowels (small bowel and colon) as well as for the designated bowel segments 
(proximal small bowel, terminal ileum, and colon).  
Accuracy for active CD needs to be first be measured for each designated bowel segment. The gold 
standard for each segment will vary:  
x
MRE+CE in the proximal small bowel 
x
MRE+CE+IC in the terminal ileum 
x
CE+IC in the colon 
Once accuracy is defined for each segment, the data will be aggregated to measure accuracy for the 
overall bowels. If there is any positive finding of active CD in any of the three designated segments 
(proximal small bowel, terminal ileum, colon), it will be counted as positive for overall accuracy.  
 
 
 

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17.8 Appendix G – Scores for Capsule endoscopy, 
Ileocolonoscopy, and MRE 
 
This appendix includes scores that will be used by central readers for assessment of active CD and 
mucosal disease activity using CE, IC, and MRE.  
 
x
Appendix G1 – Lewis Score 
x
Appendix G2 – Simple Endoscopic Score for Crohn’s Disease Index (SES-CD) Score 
x
Appendix G3 – Magnetic Resonance Index of Activity (MaRIA) Score 
 
 
 
 

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17.8.1
Appendix G1 – Lewis Score 
The Lewis Score will be used to evaluate the more proximal small bowel for CE.  
 
 
Number 
Extent 
Descriptors 
Villous appearance 
(worst-affected tertile) 
Normal – 0 
Edematous – 1 
≤10% – 8 
11-50% – 12 
>50% – 20 
Single – 1  
Patchy – 14 
Diffuse – 17 
Ulcer (worst-affected 
tertile) 
None – 0 
Single – 3 
2-7 – 5 
≥ 8 – 10 
≤10% – 5 
11-50% – 10 
>50% – 15 
<1/4 – 9 
1/4-1/2 – 12 
>1/2 – 18 
Stenosis (whole study) 
None – 0 
Single – 14 
Multiple – 20  
Non- ulcerated – 2 
Ulcerated – 24 
Traversed – 7 
Not traversed – 10  
 
Total score will be calculated based on the most severe tertile plus the stenosis score. On central reading, 
a Lewis score of ≥ 135 will be considered active disease. 
 
 
 
 

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17.8.2
Appendix G2 – Simple Endoscopic Score for Crohn’s Disease Index 
(SES-CD) Score 
 
The Simple Endoscopic Score for Crohn’s Disease Index (SES-CD) will be used to evaluate the terminal 
ileum and colon for CE and IC. On central reading, a SES-CD score of ≥ 3 will be considered active 
disease. 
 
Variable 
0 
1 
2 
3 
Size of ulcers 
(cm) 
None 
Aphthous ulcers 
(diameter 0.1-0.5) 
Large ulcers 
(diameter 0.5-2) 
Very large ulcers 
(diameter > 2) 
Ulcerated surface 
None 
< 10% 
 
10-30% 
> 30% 
Affected surface 
Unaffected  
segment 
< 50% 
50-75% 
> 75% 
Presence of 
narrowings  
None 
Single, can be 
passed 
Multiple, can be 
passed 
Cannot be passed 
 
 
 
 
 

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17.8.3
Appendix G3 - Magnetic Resonance Index of Activity (MaRIA) Score 
 
The Magnetic Resonance Index of Activity (MaRIA) Score will be used to evaluate the small bowel for 
MRE in accordance with Coimbra et al., Aliment Pharmacol Ther 2016; 43: 61–72 .  
 
The per segment MaRIA score is defined as: 
 
 
 
 
 
 
 
WT = wall thickness of bowel in mm, measured at thickest point in the segment 
 
RCE = relative contrast enhancement  
 
 
Edema and ulcer are each assigned a value of 1 if there is evidence of either in the segment; 0 if 
 
there is no evidence.  
 
 
RCE is measured at areas with the largest enhancement in a bowel wall segment after IV contrast 
administration: 
 
 
 
 
 
 
 
 
 
 
Gd = gadolinium 
 
WSIpost-Gd = mean bowel wall signal intensity after Gd 
 
WSIpre-Gd = mean bowel wall signal intensity before Gd 
 
SDnoisepost-GD = standard deviation of MRE image in air after Gd 
 
SDnoisepre-GD = standard deviation of MRE image in air before Gd 
 
The MaRIA score for the small bowel and TI will be computed separately per the formula above. On 
central reading, a MaRIA score of ≥ 7 will be considered active disease. 
 
 
 
MaRIAseg = 1.5 × WT + 0.02 × RCE + 5 × edema + 10 × ulcer  
 
 
    WSIpost-Gd – WSIpre-Gd                 SDnoisepre-Gd 
                                        WSIpre-Gd                                   SDnoisepost-Gd 
× 
RCE = 100  × 

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17.9 Appendix H – Patient Satisfaction Questionnaire 
The questionnaire will be completed by subjects after the last baseline procedure (IC).  If the subject is 
unable to complete the questionnaire on the same day following completion of imaging procedures due 
to sedation, the questionnaire may be completed by phone the following day. 
 
BLINK Patient Satisfaction Questionnaire 
 
Subject #: _______________ 
 
Baseline Visit: 
Which procedure would you prefer to have in the future? 
o
PillCam Crohn’s capsule 
o
MRE + colonoscopy 
o
Colonoscopy 
 
Why do you prefer this procedure? (choose all that apply) 
o
less invasive 
o
less discomfort 
o
safer  
o
less embarrassing 
o
no need to be put to sleep 
o
no time off of work/school 
o
no need for someone to drive me 
o
cutting edge technology 
o
single procedure to look at all of intestines 
o
no need to be in a small space 
o
can collect tissue (biopsy) at same time 
o
more familiar with it 
o
standard procedure 
o
more accurate 

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o
less bowel prep 
o
finds disease outside of intestines 
o
no need for an IV 
o
can move around during procedure 
o
no need to drink chalky solution 
o
other: provide comment ___________________________________________________________ 
 
How likely are you to recommend the procedure you chose to others with your condition?  
o
not likely 
o
likely 
o
very likely 
 
Name of Research Staff Obtaining Responses from Subject: 
 
_________________________________________________________________ 
 
Research Staff Signature:  _____________________________________________________ 
 
Date: ______________________________           
 
 

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18. Version History 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
x
N/A 
Mamata Thapa, PhD; 
Medical Writer 
2.0 
x
Transferred to new CIP template (056-F275, Version 2.0) per 
Medtronic policy. Sections were added and/or revised to meet 
global Medtronic CIP template and checklist requirements. 
x
Changed “PillCam SBC” to “PillCam Crohn’s” due to renaming of 
product. 
x
Added “diagnosis based on radiological, endoscopic, or 
histological evidence” in inclusion criteria for subjects with 
known Crohn’s disease.    
x
Excluded pediatric subjects. Removed procedure details and 
supporting documents (pediatric patient satisfaction and quality 
of life questionnaires) pertaining to pediatric population. 
x
Excluded vulnerable subjects.  
x
Updated study status for ClinicalTrial.gov: NCT01631435 and 
NCT02025777. 
x
Added “terminal ileum” to bowel segments that will be evaluated 
with the Lewis score.  
x
Removed “sub-investigator” designation for radiologist. 
x
Added information as required by Medtronic checklist in 
following sections: Study Design, Product Description, Study 
Procedures, Risks and Benefits, Statistical Design and Methods, 
Study Administration, Data Management, and Study Contact and 
Information.  
x
Deleted “standard of care” since “IC plus  MRE” is not 
considered standard of care for monitoring CD in the small 
bowel and colon. Reported comparator group procedure/s at 
baseline (IC plus MRE) and 6- and 12- month follow-ups (IC 
with or without MRE).  
x
Modified protocol to reflect that the study will be a post-market, 
off-label trial in the US (NSR IDE) and post-market, on-label, 
non-regulatory trial in EMEA. 
x
Added statement that the study will begin in Europe; and the 
study will begin in the US and Israel only after the product has 
been approved for use in these countries.  
x
Updated proposed indication for the US, Europe, and Israel.  
x
Minor updates and minor clarifications were made throughout 
the protocol. These minor changes did not affect the purpose or 
requirements of the study.   
Mamata Thapa, PhD; 
Medical Writer 

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3.0 
x
Updated version number and date 
x
Removed ADE, UADE, USADE definitions from glossary 
x
Updated Section 4 and Section 10.4 to include the exclusion 
criteria “Subject has any medical condition that would make it 
unsafe for them to participate, per the Investigator’s discretion” 
x
Updated Section 11.2 to include collection of subject’s birth year 
in demographics 
x
Updated Section 11.4 to note an impartial witness must also 
sign the ICF if the subject is unable to read 
x
Updated Section 11.10 to indicate Medtronic personnel may be 
present during capsule endoscopy procedure to provide 
technical support 
x
Updated Sections 11.8, 11.10, 11.11 to include requirement of 
transfer of imaging to Imaging Core Lab within 48 hours of 
completion of procedure 
x
Updated Section 13 to remove definitions and reporting 
timelines for ADEs, UADEs and USADEs as this will be a post-
market study. Country-specific requirements will be captured in 
Safety Plan 
x
Updated Appendix B to allow for stool PCR microorganism panel 
as an alternative to stool ova/parasite 
x
Updated Appendix C to remove administration of remaining dose 
of anti-peristaltic agent 
x
Updated Appendix E1 to clarify that subjects are required to 
remain at the endoscopy clinic until excretion of the capsule or 
battery failure of the device (whichever comes first) 
x
Updated Appendix E3 to clarify subjects must remain in clinic for 
duration of the procedure 
Jessica Carlson, 
Principal Clinical 
Research Specialist 
4.0 
x
Moved to v3.0 of CIP Template 
x
Added definition of stricture to Section 3 Protocol Synopsis, 
Section 8.4 Exclusion Criteria, and Section 9.5 Baseline 
x
Corrected typo in Section 3 Protocol Synopsis and Section 8.4 
Exclusion Criteria #2 to change “and” to “or” 
x
Removed exclusion criteria #7 from Section 3 and Section 8.4 
x
Added Belgium to Section 3 Study Locations and throughout 
document 
x
Updated Section 4.1 to indicate PillCam Crohn’s capsule has 
received FDA clearance in the US 
x
Updated Section 5.2.1 Primary Endpoint to “IC with or without 
MRE” 
x
Updated Section 5.2.3 Safety Endpoints to correct references in 
Section 11 
x
Removed Lewis Score as CE scoring mechanism for terminal 
ileum throughout document 
x
Removed collection of age from Section 9.2 Subject Screening 
x
Updated Section 9.3 Prior and Concomitant Medications to 
clarify restriction on use of NSAIDs 
Jessica Carlson, Clinical 
Research Specialist 

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x
Updated Section 9.4 Baseline to allow responses to 
questionnaires by phone 
x
Updated Section 9.5 Randomization and Treatment Assignments 
to clarify randomization procedures. 
x
Removed requirement for withdrawal time of IC endoscope to 
be at least 6 minutes from Section 9.12 
x
Added definition of subtle lesions to Section 9.13.1 
x
Removed reference to USADEs from Section 11 as this does not 
apply to a post-market trial 
x
Reference to “Medical Advisor Charter” removed from Section 
12.1 
x
Updated Section 13.5 to indicate subjects Subject ingesting 
<2.5L of PEG bowel preparation prior to CE or IC procedure will 
be excluded from analysis 
x
Added clinicaltrials.gov study identifier to Section 14.1 
Statement of Compliance 
x
Updated Appendix C “MRE Procedure Instructions” to clarify 
choice of Breeza or Volumen as oral non-absorbable bowel 
preparation solution 
x
Added Appendix C1 “MRE Subject Instructions” 
x
Updated Appendix E3 “CE Procedure Instructions” to align with 
Appendix E2 “CE Subject Instructions” and to allow subjects to 
leave the clinic if procedure is not complete at 10 hours 
x
Appendix E2 “CE Subject Instructions” updated to provide more 
clear instruction 
x
Appendix F1 “IC Bowel Preparation” to indicate clear liquid diet 
only on day of procedure 
x
Updated Appendix H3 to clarify calculation of MaRIA score.  
x
Updated Appendices I and J to reflect that questionnaires may 
be completed via phone call with subject  
x
Appendix I “Patient Satisfaction Questionnaire” updated to 
include information regarding research staff collecting subject 
responses. 
x
Appendix J attachments “EQ-5D-3L” and “Inflammatory Bowel 
Disease Questionnaire” updated to include information regarding 
research staff collecting subject responses. 
5.0 
x
Updated document version number to version 5 in Header, 
Footer, Title page and Investigator Statement 
x
Added term NPO and definition to Section 2 – Glossary 
x
Removed Germany as a participating country throughout 
document 
x
Updated Primary Objective, Secondary Objectives #1 and #2, 
Primary Endpoint, and Secondary Endpoints #1 and #2 to 
indicate “CE as compared to IC plus MRE” instead of “IC with or 
without MRE” as these outcomes are determined by baseline 
data when all subjects will undergo all imaging procedures. 
Jessica Carlson, 
Principal Clinical 
Research Specialist 

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x
Section 5.2.3 – Safety Endpoints: Removed “All AEs will be 
captured, regardless of severity or relationship to the procedure” 
as only the adverse events defined in Section 11.1 are being 
collected. 
x
Updated Section 7.9 – Product Receipt and Tracking to clarify 
study equipment and device will be sent to site upon execution 
of Clinical Trial Agreement to allow adequate time for shipment 
and installation but site is not allowed to use product or begin 
enrollment until the Sponsor provides notification of Site 
Activation.  
x
Updated Section 9.1 – Schedule of Events and Appendix B – 
Study Schedule for Clinical Laboratory and Pregnancy Tests to 
clarify Screening Procedures should occur no more than 30 days 
prior to baseline MRE, not 30 days prior to baseline IC as 
previously stated.  Removed requirement for Baseline pregnancy 
test as deemed not clinically necessary given timing of screening 
pregnancy test.   
x
Updated Section 9.1, Footnote #3 to indicate all required labs 
should take place no more than 14 days prior to the first 
imaging procedure at any given visit timepoint to remain within 
required visit windows. 
x
Updated Section 9.5 – Baseline and 9.12 - Ileocolonoscopy to 
indicate physician may instruct subject to be NPO after 
completion of baseline CE Procedure to prepare for IC procedure 
and associated sedation. 
x
Updated Section 11 – Adverse Events and Device Deficiencies 
for clarity.  
x
Updated Section 11.1 – Definitions/Classifications to clarify all 
AEs related to subject’s Crohn’s disease, all device deficiencies 
and all SAEs should be reported 
x
Updated Section 11.1.2 – Serious Adverse Event (SAE) to 
remove “that is not related to the device comparator or study 
procedure” from the definition 
x
Changed Emergency Safety contact to Safety Representative 
email in Section 11.3 – Reporting of Adverse Events 
x
Updated Section 13 “Statistical Design and Methods” to correct 
analysis population to align with primary endpoint and provide 
additional clarifications. 
x
Section 15.2.4 – Data Queries - Added clarification that queries 
related to imaging will be issued by ICON through the SQUARE 
system. 
x
Appendix C – MRE Procedure Instructions updated to clarify 
procedural requirements per Lead Radiologist 
x
Appendix C1 – MRE Subject Instructions updated to correct a 
page numbering error 
x
Appendix E1 – CE Bowel Prep Instructions and Appendix E2 – 
CE Subject Instructions updated to be easier to understand and 
follow for research staff and study subjects.  Additionally, 

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250mg oral Erythromycin has been added as an acceptable 
substitute for 10mg Metoclopramide at Alert 0. 
x
Appendix E3- CE Procedure Instructions updated to be easier to 
understand and follow.   
x
Appendix F1 – Ileocolonoscopy Bowel Preparation and Appendix 
F2 – Ileocolonoscopy Subject Instructions updated to be easier 
to understand and follow for research staff and study subjects. 
Removed Bowel Prep requirements for 2 days prior to the 
procedure, including removal of requirement for subject to take 
4 Senna tablets.  Provided clarification, that as required, 
subjects should be instructed to be NPO prior to any sedation 
for the ileocolonoscopy per standard care. 
6.0 
x
Updated entire document to remove 3, 6, 9, and 12 month 
follow-up visits (and associated procedures) throughout.  
x
Removed Appendices J1 EQ-5D-3L and J2 Short IBD 
Questionnaire 
x
Combined Appendices E1 CE Bowel Preparation Instructions and 
F1 Ileocolonoscopy Bowel Preparation Instructions 
x
Combined Appendices E2 CE Subject Instruction Form and F2 IC 
subject Instruction Form.   
x
Added lines for Subject and Study Coordinator signature and 
date to Appendix C1 MRE Subject Instructions and Appendix E2 
CE and IC Subject Instructions for verification of source 
documents 
x
Updated document to version 6 in Header, Footer, Title page 
and Investigator Statement 
x
Added “or other clinical evidence” to Study Design section of 
Synopsis 
x
Removed other European countries throughout, leaving Austria 
x
Updated Inclusion Criteria #4 to include subjects with known CD 
and active disease, based on clinical judgment based on 
symptoms, laboratory data or other clinical information. 
x
Removed “any current condition believed to have an increased 
risk of capsule retention such as” from Exclusion Criteria #7 for 
clarity and to reduce redundancy. 
x
Added Exclusion Criteria #17, “Subject with ileostomy or 
colostomy, history of total or subtotal colectomy (including those 
with ileosigmoidostomy, and ileorectostomy” 
x
Clarified AE reporting requirements in Sections 5.2.3, 11.1, 11.2, 
13.4 to specify that reporting of AEs should start beginning with 
first baseline imaging procedure (MRE). 
x
Updated language in Section 6 Study Design in alignment with 
Inclusion Criteria #4 to allow enrollment of subjects with current 
active disease based on symptoms, laboratory data, or other 
clinical information 
x
Increased maximum number of enrolled subjects from a single 
site to 70 (20%) in Section 6.1 Duration 
Jessica Carlson, Clinical 
Research Manager 

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x
Updated Section 7.10 Product Storage to indicate Temperature 
Logs are not required for BLINK as storage is expected at 
ambient temperature 
x
Updated footnotes in Table 1 Schedule of Events to provide 
additional clarity 
x
Added clarification to Section 9.2 Screening Visit that Medical 
History should include any history within the last 2 years related 
to the study inclusion/exclusion criteria; Previous GI Procedures 
should be captured for the last 5 years; and Surgical History 
should include only GI-related surgeries 
x
Clarified Section 9.5 Baseline to include: completion of MRE to 
completion of IC should be no more than 4 weeks, all baseline 
labs must be completed no more than 14 days prior to baseline 
MRE, and instruction regarding determination of patency prior to 
capsule endoscopy 
x
Removed “pregnancy test” from Section 9.5 Baseline in 
alignment with Baseline Laboratory requirements 
x
Clarified Section 9.10 PillCam Patency Study to designate when 
subjects should be exited from trial due to stricture and when 
patency procedure should be completed 
x
Added additional detail to Section 9.13 Central Reader 
Image/Video Reading to indicate procedures for assessing 
disease activity in cases where an imaging modality is not 
available for evaluation 
x
Added detail of specific PillCam Crohn’s procedure-related AEs 
that must be reported 
x
Clarification added to Section 13.5 Analysis Populations for 
handing of subjects with missing imaging 
x
Removed all interim analyses in Section 13.6 Interim Analyses 
due to enrollment ending in April 2019 
x
Added footnote to Appendix B Study Schedule for Clinical 
Laboratory and Pregnancy Tests to clarify that standard of care 
C. Difficile and Stool O&P lab results may be used for trial 
purposes provided the date of results is no more than 90 days 
prior informed consent date 
x
Appendix C MRE Procedure Instructions updated to include 
allowance of split does of anti-peristaltic agent and increased 
imaging thickness for larger patients 
x
Corrected typo in Appendix C1 MRE Subject Instructions 
x
Added additional clarification to Appendix D PillCam Patency 
Procedure to make instructions easier to follow 
x
Added additional clarification to Appendix E1 CE Bowel 
Preparation Instructions to make them easier to follow 
x
Added additional clarification to Appendix E2 CE Subject 
Instructions Form to make it easier to follow 
x
Added additional clarification to Appendix F1 Ileocolonoscopy 
Bowel Preparation Instructions to make them easier to follow 

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x
Added active disease scoring thresholds to Appendix G1 Lewis 
Score, Appendix G2 SES-CD Score, and Appendix G3 MaRIA 
Score for transparency