Contour Neurovascular System - European Pre-Market Unruptured Aneurysm Study (CERUS)
Phase: NA
Conditions: Intracranial Aneurysm
Sponsor: Cerus Endovascular, Inc.

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 1 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Contour Neurovascular SystemTM   
European Pre-Market Unruptured Aneurysm Study (CERUS)  
February 5, 2019 
NCT Number 03680742 
Study Sponsor:  
Cerus Endovascular, Ltd  
John Eccles House  
Oxford Science Park  
Oxford, OX4 4G  
United Kingdom   
Telephone: +44 7968 548773  
Study Responsibility and 
Contact:  
L. Carol Holt, MS, RN  
Vice President, Clinical Affairs Cerus 
Endovascular, Inc.  
A subsidiary of Cerus Endovascular, Ltd  
47757 Fremont Blvd  
Fremont, CA 94538 Telephone: 1-
510-641-4000 
carol.holt@cerusendo.com  
Principal Investigators:  
  
Univ.-Prof. Dr. Thomas Liebig  
Leiter Institut für Neuroradiologie  
Klinikum der Universität München  
Campus Großhadern  
Marchioninistraße 15  
81337 München  
TEL: +49-89-440072501 FAX: 
+49.89-440072509  
thomas.liebig@med.uni-muenchen.de  
 
 
Confidentiality Statement  
This study is considered confidential in nature. All information related to this study is considered proprietary and should not be 
made available to those not directly involved with this study. Authorized recipients of this information include investigators and 
co-investigators, other study and health care personnel necessary to conduct the study, Ethics  
Committees and Institutional Review Boards, and regulatory agencies with oversight of this study.  The personnel provided with 
this protocol and data from this study are hereby informed of its confidential and proprietary nature.  Release of the protocol 
and these data to individuals other than those listed above requires the prior written permission of Cerus Endovascular Limited.  
 
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 2 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Study Information  
Protocol Name  
Contour Neurovascular SystemTM European Pre-Market Unruptured 
Aneurysm Study (CERUS)  
Protocol Number  
DNX099-01   
Device Name  
Contour Neurovascular SystemTM  
Manufacturer  
Cerus Endovascular, Inc.   
47757 Fremont Blvd   
Fremont, CA 94538  
United States  
Core Lab   
Eppdata GmbH  
Lokstedter Steindamm 18  
22391 Hamburg, Germany  
Web-Based Image System  
CIMAR  
Cimar UK Ltd   
Kemp House 152-160 City Road London EC1V 2NX Telephone 0800 
0930913 Email info@cimar.co.uk   
Electronic-Data Capture 
System  
Simplified  Clinical  
100 Market St., Suite 401  
Portsmouth, NH  03801  
  
  
List of principal investigators and investigation sites will be maintained separately and is available upon 
request.  
  
  
TABLE OF CONTENTS  
1  Overview ............................................................................................................................................ 4 
2  Clinical Study Synopsis ...................................................................................................................... 5 
3  Acronyms .........................................................................................................................................20 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 3 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
4  Introduction .....................................................................................................................................21 
5  Investigational Device Description ....................................................................................................23 
5.1 Implant and Delivery system........................................................................................................................................................................................ 23 
5.2 Indications for Use and Intended Use .......................................................................................................................................................................... 24 
5.3 Training ........................................................................................................................................................................................................................ 24 
5.4 Device Manufacturing Overview ................................................................................................................................................................................. 25 
5.5 Device Evaluation and Testing .................................................................................................................................................................................... 25 
6  Risks and Benefits ............................................................................................................................25 
6.1 Potential Risks .............................................................................................................................................................................................................. 25 
6.2 Potential Benefits ......................................................................................................................................................................................................... 29 
6.3 Risk-to-Benefit Rationale ............................................................................................................................................................................................. 30 
7  Investigational Protocol ....................................................................................................................30 
7.1 Design........................................................................................................................................................................................................................... 30 
7.2 Objective ...................................................................................................................................................................................................................... 30 
7.3 Target Patient Population ............................................................................................................................................................................................. 30 
7.4 Screening ...................................................................................................................................................................................................................... 30 
7.5 Eligibility ...................................................................................................................................................................................................................... 30 
7.6 Baseline Evaluation ...................................................................................................................................................................................................... 33 
7.7 Implant Procedure ........................................................................................................................................................................................................ 34 
7.8 Hospital Discharge ....................................................................................................................................................................................................... 34 
7.9 Follow-Up .................................................................................................................................................................................................................... 34 
7.10 Early Withdrawal ....................................................................................................................................................................................................... 36 
7.11 Study Termination ...................................................................................................................................................................................................... 36 
7.12 Premature termination ................................................................................................................................................................................................ 36 
8  Adverse Events .................................................................................................................................37 
8.1 Adverse Event Definitions ........................................................................................................................................................................................... 37 
8.2 Adverse Event Classification ....................................................................................................................................................................................... 38 
8.3 Adverse Event Reporting/Analysis .............................................................................................................................................................................. 40 
9  Study Oversight ................................................................................................................................40 
9.1 Clinical Events Committee (CEC) ............................................................................................................................................................................... 40 
9.2 Data Safety and Monitoring Board (DSMB) ............................................................................................................................................................... 40 
9.3 Patient Selection Committee ........................................................................................................................................................................................ 41 
10 Statistical Analysis ...........................................................................................................................41 
10.1 Justification of Methodology ..................................................................................................................................................................................... 41 
10.2 Patient Population ...................................................................................................................................................................................................... 42 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 4 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
10.3 General Principles ...................................................................................................................................................................................................... 42 
10.4 Multi-center Trial Considerations .............................................................................................................................................................................. 42 
10.5 Endpoints .................................................................................................................................................................................................................... 42 
10.6 Interim Analysis ......................................................................................................................................................................................................... 44 
10.7 Sample Size Rationale ................................................................................................................................................................................................ 44 
11 Additional Trial Characteristics ......................................................................................................44 
11.1 Measures Taken to Avoid Bias .................................................................................................................................................................................. 44 
11.2 Special Equipment for Investigation .......................................................................................................................................................................... 44 
11.3 Procedure for Replacing Withdrawn Subjects ........................................................................................................................................................... 44 
11.4 Other Devices Used During Study ............................................................................................................................................................................. 45 
11.5 Total Expected Trial Duration.................................................................................................................................................................................... 45 
12 Study Management ..........................................................................................................................45 
12.1 Investigator Responsibilities ...................................................................................................................................................................................... 45 
12.2 Sponsor Responsibilities ............................................................................................................................................................................................ 50 
13 Publications .....................................................................................................................................57 
14 References .......................................................................................................................................58 
15 Revision History ..............................................................................................................................60 
16 APPENDIX A - Statement of Compliance and Signature Page ........................................................60 
17 APPENDIX B - Sponsor Approval Page ..........................................................................................62 
18 APPENDIX C - German Medical Devices (MPG) ...........................................................................64 
19 APPENDIX D – Report of Prior Investigations ...............................................................................73 
19.1 First-In-Human Clinical Study – Contour Compassionate Use ................................................................................................................................. 73 
19.2 Study INCA: Intracranial Aneurysm Treatment with NeXsys .................................................................................................................................. 76 
19.3 European Pilot Clinical Study – Contour ................................................................................................................................................................... 81 
19.4 Compassionate Use - Contour .................................................................................................................................................................................... 83 
19.5 Compassionate Use - Neqstent ................................................................................................................................................................................... 83 
19.6 Summary of Animal Studies - Contour ...................................................................................................................................................................... 83 
20 APPENDIX E – Case Report Form CRF Samples ...........................................................................85 
 
  
1 Overview  
 
This document provides a detailed plan for the Contour Neurovascular SystemTM European Pre-Market 
Unruptured Aneurysm Study (CERUS).   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 5 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
2 Clinical Study Synopsis  
 
Study Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm Study 
(CERUS)  
Study 
Purpose  
Cerus Endovascular, Ltd., is sponsoring a prospective, multi-center trial to document the safety and 
performance of the Contour Neurovascular System™ (“Contour”).   
The purpose of the study is to document safety and performance of the Contour in treatment for 
patients with intracranial aneurysms (IA). The data from the study will be reported as a Pre-Market 
study to the Notified Body to support CE Mark approval.   
Indications 
for Use and  
Intended  
Use  
The Contour is intended for the endovascular embolization of intracranial aneurysms. The device 
should only be used by physicians licensed and credentialed to perform endovascular embolization 
catheterization procedures. Physicians must be thoroughly familiar and experienced with standard 
vascular embolization techniques and trained on the Contour Neurovascular System™ before using 
the device.   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 6 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Contour 
Training   
Cerus Endovascular will provide training using flow models, didactic slide presentation and 
implant simulation using a vascular simulation 3-D replicator. Physician proctoring will occur for 
the first three implants and a patient selection committee will provide guidance over the 
identification of all the study patient aneurysms at each site to facilitate successful patient 
identification and implantation.  A web-based image system called CIMAR will be used to view 
and store angiographic images of patient aneuryms.    
  
  
  
  
  
  
  
  
  
  
  
  
Study 
Design  
Prospective, single arm, multi-center study.  
  
  
  
  
  
  
  
  
  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 7 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Study Size 
and 
Duration  
Study Size:  The study population will include 30 subjects enrolled and implanted at up to 10 
centers in Europe.  
Study Duration:  It is expected that the study will take 9 months to enroll 30 patients.  Follow-up 
for the primary endpoint is the 6-month visit.  Total duration of enrollment (9 months), follow-up 
duration for primary endpoint (6 months), 12 months follow up and reporting (3 months) will take 
approximately 24 months.     
Any patient for whom a failed implant attempt is performed will be followed for 1 month, or until 
resolution of any potential device or implanted related adverse events, whichever occurs last.   
Any patient who is consented but has no implant attempt will be study exited.  
 
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 8 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Device  
Description  
The Contour device works by providing a physical barrier between the parent vessel and the 
intracranial aneurysm neck (as demonstrated by the Contour clinical investigations as well as the 
pre-clinical research) thereby excluding the aneurysm from the parent artery blood flow. The 
Contour implant is sized to provide a proper fit and position across the neck of the aneurysm. 
Therefore, blood flow is diverted away from entering at the neck, leading to reduction in flow into 
the aneurysm cavity with subsequent stasis followed by the formation of thrombus within the 
confines of the aneurysm. As wound healing progresses and fibrosis occurs over the ensuing days 
and months, it serves to strengthen the physical barrier between the parent vessel and the aneurysm 
cavity. The weakened vascular tissue of the aneurysm cavity, in particular the dome, is thus 
protected from the shear wall stresses generated by the previous blood flow.  
 
The Contour Neurovascular System™ (CNS) (CNS05, CNS07, CNS09, CNS11) is an 
intrasaccular, self-expanding, embolization device intended for the treatment of unruptured 
intracranial aneurysms. The CNS is shown in Figure 1 and comprises an:   
Implant  
The implant is a self-expanding concave shaped device comprised of a double layer nickel-titanium 
and platinum wire mesh, and a platinum marker. The implant is packaged unconstrained in a 
protective dispenser hoop with an Introducer preloaded onto the DPW shaft just proximal to the 
implant.   
Detachable Pusher Wire (DPW)  
The DPW functions as a guidewire for implant delivery. The pre-attached DPW has a composite 
stainless steel and polymer construction, and a platinum marker. The DPW has a white fluorosaver 
mark on its proximal shaft that provides a visual indication of when the implant is approaching, but 
not exiting the distal end of the micro-catheter (MC).  
Introducer  
The Introducer is a single lumen polymer tube that is used to constrain the implant during 
introduction into the micro-catheter hub. The implant body and proximal marker can be visualized 
under fluoroscopy.   
All devices are provided sterile and nonpyrogenic and are for single patient use only. The device is 
not an active device and does not incorporate any software/firmware.   
  
Figure  1   -   Contour Neurovascular System™   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 9 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
The Contour Neurovascular System™ is offered in four sizes, suitable for embolization of 
intracranial aneurysm. Table 1 details the selection guideline for these four sizes:  
The Contour Neurovascular System should only be used by operators who have received 
appropriate training in neurointerventional techniques. The operator delivers the implant to the 
aneurysm under fluoroscopic guidance using standard endovascular techniques and a commercially 
available 0.027” inner diameter MC1. The implant is electrolytically detached from the DPW using 
a commercially available detachable coil power supply2,3.  
Due to its unique placement across the neck of the aneurysm, the device acts as both a flow 
disrupter and diverter. The Contour only requires the neck and equatorial diameter to be taken into 
consideration when sizing the implant to the aneurysm (please see figure below). The height is not 
a requirement as the dome of the aneurysm is not required to stabilize the device.   The device mesh 
provides a uniform scaffold distributed across the neck of the aneurysm for the establishment of 
neointimal development and unlike devices placed in the parent vessel, is not dependent on the use 
of dual antiplatelet therapy.   
Table 1 - Implant Size Selection Guide  
  
REF (Catalog Number) – 
Diameter  
Aneurysm   
Neck (mm)  
Aneurysm  Width 
(mm)  
 
CNS05 – 5 mm  
2.0 - 3.0  
2.0 - 3.5  
CNS07 – 7 mm  
3.0 - 5.0  
3.0 - 5.5  
CNS09 – 9 mm  
4.0 - 6.0  
5.0 - 7.5  
CNS11– 11 mm  
5.0 - 8.0  
7.0 - 8.5  
 
1 Stryker Neurovascular Excelsior® XT-27® (0.027” ID, 2.9F/2.7F OD, 150cm Length)  
2 Detachable Coil Power Supply: Stryker Neurovascular InZone® Detachment System, REF M00345100940  
3 Power Supply Detachment Cable: Stryker Neurovascular IZDS Connecting Cable, REF 00345110250  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 10 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 
  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 11 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Objective 
and 
Endpoints  
The primary objective of this study is to document the safety and performance of the Contour 
Neurovascular System.  The data from the study will be reported as a Pre-Market study to the 
Notified Body to support CE Mark approval.  In addition, the data may be used to support US 
approval by the Food and Drug Administration (FDA) to market the Contour device in the United 
States.  
1. Primary Safety Endpoint:    
The proportion of subjects with death of any non-accidental cause or any major disabling stroke 
within the first 30 days after treatment or major disabling stroke or death due to neurological cause 
from day 31 to 6 months after treatment.  
Note: Major Disabling Stroke is defined as an episode of neurological signs or symptoms that 
persist beyond 24 hours accompanied with evidence of ischemia/infarction on imaging that results 
in an increase of NIHSS from baseline by ³ 4 points and/or an increase from mRS baseline by >2.   
2. Primary Performance Endpoint:    
To demonstrate the occlusion rate on the 6 month angiogram as adjudicated by a core laboratory. 
Success will be defined as complete occlusion demonstrated by a Grade 1 using the Raymond Roy 
Scale.   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 12 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Secondary 
Measures  
Additional measures will be summarized:  
Secondary Safety:  
• 
Serious Adverse Events (SAE) associated with the procedure or device   
• 
All serious neurological adverse events Secondary Performance:   
• 
Detailed assessment of aneurysm occlusion from post procedure to 6-months provided by 
the core lab review of the angiogram (DSA) including the following:  
- 
Raymond Roy scale  
- 
Modified Web Occlusion Scale  
- 
Percent Occlusion   
- 
Device Stability   
• 
Rate of retreatment   
• 
Summary of device performance including the following:  
- 
Time required for implantation of the Contour   
- 
Device sizes used  
- 
Number of attempts to deploy the device  
- 
Number of failed implant attempts  
- 
Any reports of device deficiencies  
Sample Size  A maximum of 35 subjects will be enrolled to obtain follow-up data for the primary analysis for 30 
subjects while allowing for attrition to be submitted for CE Mark application.    
Number of  
Sites  
A maximum of 10 European investigational sites will participate.   
Study Visits  Baseline, procedure, discharge, one (1) month, six (6) months and twelve (12) months.    

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 13 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Enrollment 
and  
Eligibility  
Enrollment   
To participate, patients must meet all inclusion criteria and no exclusion criteria listed below.All 
patients must sign a study-specific consent form prior to the study procedure. Final qualification 
will occur during the study procedure due to the need for confirmation of IA appropriateness with 
cerebral angiography. The patient is enrolled at the time of consent and is considered a study 
subject in the reporting analysis group only when the patient is fully qualified and at least one 
Contour device has been placed into the patient’s body. The following listing provides examples of 
patient enrollment scenarios for the study:    
• 
The patient is not considered enrolled but not included in the primary analysis group in the 
study: if at the onset of the procedure in the initial DSA, the investigator determines the 
patient’s IA was not suitable for treatment with the device, thus, no attempt was made by 
the investigator to place the device. The patient will be treated outside of the study per the 
investigator’s usual practices. The reason for not treating the patient must be documented 
on a study exit form. The patient is not included in the primary analysis group because the 
Contour was never opened or deployed inside the patient. All patients will be listed in the 
final report.  
• 
The patient is considered enrolled but not included in the primary analysis group in the 
study: at the onset of the procedure, the investigator determines the subject’s IA was 
suitable for treatment with the device. The investigator attempted but was unable to place 
the device within the IA and the subject required alternative treatment. The subject is 
considered enrolled for the purposes of the study but will only be followed through the 1 
month visit. All failed implant attempts will be reported in the final report.  
• 
The patient is considered enrolled and included in the primary analysis group in the study: 
if at the onset of the procedure, the investigator determines the subject’s IA was suitable 
for treatment with the device. The investigator successfully placed the device within the 
IA. The subject is considered enrolled for the purposes of the study and will be followed 
for the duration of the study.  
• 
The patient is considered enrolled and included in the primary analysis group in the study: 
if at the onset of the procedure, the investigator determines the subject’s IA was suitable 
for treatment with the device. The investigator successfully placed the device within the 
IA. In addition, the subject required and received further treatment with another 
endovascular device(s). The subject is considered enrolled for the purposes of the study 
and will be followed for the duration of the study.  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 14 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Eligibility 
Criteria  
Patients of all genders who meet all indications and contraindications will proceed to implantation.  
Inclusion criteria  
1. Patient’s indication for treatment of unruptured aneurysm is according to the 
national/international guidelines.  
2. Age 18-80 years at screening  
3. Patients who are suitable for non-emergency endovascular embolization of saccular IAs  
4. IA located at a bifurcation in the anterior or posterior circulation with dimensions consistent 
with implant size selection guidelines included in the IFU  
5. Patient has the necessary mental capacity to participate and is willing and able to participate in 
the study for the duration of the study follow-up and is able to comply with study requirements  
6. Patient able to able to give their informed consent can be included in this study.  This must be 
demonstrated by means of a personally signed and dated informed consent document indicating 
that the subject has been informed of and understood all pertinent aspects of the study.   
Exclusion criteria  
The presence of condition that may create unacceptable risk during the aneurysm embolization 
procedure, such as patients with:  
1. Ruptured aneurysm  
2. Patient anatomy or physiology considered unsuitable for endovascular treatment  
3. Contraindication for arterial access  
4. Largest measured IA equatorial diameter >8.5 mm or <2 mm  
5. Largest measured IA neck diameter >8 mm or <2 mm  
6. Target IA contains other devices/implants (e.g., coils)  
7. Known allergy to platinum, nickel or titanium  
8. Known allergy to contrast agents  
9. Contraindication to anticoagulants or platelet inhibitor medication  
10. Stenosis of the target IA’s parent vessel >50%   
11. Anticoagulation medications such as warfarin that cannot be discontinued  
12. Pregnant, breastfeeding or planning pregnancy in the next 2 years  
13. Acute / chronic renal failure (including dialysis); Creatinine > 2.00 mg/dl or > 182 μmol/L  
14. Myocardial Infarction, Stroke or TIA within the last 6 months   
15. Any other medical issue within the brain that precludes the device implantation such as brain 
surgery, radiation in the target area of intervention, acute traumatic craniocerebral injury, etc.  
16. Other medical conditions that cause an inability to comply with study requirements and/or that 
could increase the risk of neurovascular procedures or death within 2 years (e.g., liver failure, 
cancer, heart failure, chronic obstructive pulmonary disease, immunosuppression, neural 
disease, and hematologic disorders etc.)  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 15 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
17. Participating in another study with investigational devices or drugs that would confound the 
effects of the study outcomes  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 16 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Follow-Up 
and 
Required  
Assessments  
All implanted subjects will complete the scheduled follow-up assessments. Adverse events will be 
collected from device implantation through study duration. Table 2 highlights the required 
assessments:  
Table 2. Schedule of Assessments  
  
 
 
 
 
 
 
Medical history and medications  
X  
  
  
  
  
X  
Neurologic Exam  
X  
  
X  
X  
X  
X  
NIH Stroke Scale  
X  
X*  
X*  
X*  
X*  
X  
Modified Rankin Scale (mRS)  
X  
  
X**  
X**  
X**  
X  
Pregnancy test (pre-menopausal 
female)  
X  
  
  
  
  
  
CT angiography (CTA) ^  
X#  
  
  
  
  
  
Magnetic Resonance Angiogram 
(MRA) ^   
X#  
  
  
  
  
  
Cerebral Angiogram (DSA) ^  
X# 
w/3D  
X 
w/3D  
  
  
X  
w/3D  
  
Adverse Event assessment  
  
X  
X  
X  
X  
X  
Procedure Information  
  
X  
  
  
  
  
Aneurysm Occlusion Status – 
Raymond Roy and general 
assessment on study form##  
  
X  
  
  
X  
  
^Baseline image aneurysm assessment can be made with either CTA, MRA OR DSA, upon MD 
discretion.  
# Baseline image screening can be completed within 3 months prior to enrollment.  Imaging will 
always be performed on the day of the procedure which will be used for core laboratory baseline for 
comparison at 6 months.   
* The NIH Stroke Scale score should be obtained within 24 hours after stroke in the event a subject is 
diagnosed with a stroke.   
** mRS will be obtained at all scheduled visits.  
## Aneurysm occlusion status and Raymond Roy completed when cerebral angiograms are performed.  
Background  The most commonly provided endovascular therapy for intracranial aneuryms (IA) is coil 
embolization. Endovascular coiling and neurosurgical clipping are therapeutic options, and the 
outcome in terms of survival free of disability at 1 year is significantly better with endovascular  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 17 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 
coiling.4  Despite the high prevalence of its use, coil embolization success in wide necked 
bifurcated/side wall aneurysms is limited due to geometric considerations and target intracranial 
aneurysm access. Coils can become compacted and regress into the dome of the IA due to water 
hammer effect resulting in further filling at the IA neck.  
Two other technologies to support coiling in wide neck aneurysms have emerged; Balloon assisted 
coiling (BAC) and stent assisted coiling (SAC) which also have their own set of issues.5  
Balloon assisted coiling is a technique where a balloon is inflated at the neck to create a temporary 
wall so coils can be deployed to fill the aneurysm without the need for dual antiplatelet. However, 
this technique has its own challenges as there is a need to completely close the aneurysm but at the 
same time protect different branches of the bifurcation.  Risk factors including procedure-related 
complications leading to death or dependency were significantly higher in BAC (14.1%) compared 
with those in conventional coiling (3%).6  
Stent assisted coiling consists of two techniques; Y stenting and waffle cone, both of which consist 
of creating a permanent scaffold in the parent vessel to support coils inside the aneurysm sac. 
Unfortunately, both of these techniques can only be used in unruptured or recanalized aneurysms as 
dual antiplatelet therapy is required to avoid stent thrombosis.  Risk factors were associated with a 
significant decrease of angiographic recurrences, but they were associated with more lethal 
complications compared with coiling without stents.7    
More recently, new devices for IA treatment that retard the flow of blood from the parent artery into 
the IA, have become available. Flow diverters are high mesh density stents placed in the parent 
artery across the neck of the IA. Stasis of blood in the IA induces thrombosis which helps achieve 
the goal of preventing pulsatile flow into the IA. The mesh component of flow diverters has also 
 
4 Molyneux AJ, Birks J, Clarke A, Sneade M, Kerr RS. The durability of endovascular coiling versus neurosurgical 
clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid 
Aneurysm Trial (ISAT). The Lancet. 2015 Feb 27;385(9969):691-7.  
5 L Pierot. A Biondi  (2006) Endovascular techniques for the management of wide-neck intracranial aneurysms:  A 
critical review of the literature. J Neuroradiology. 2016 Jun;43(3): 167-75. Doi: 10.1016/j.neurad.2016.02.001.Epub 
2016 Mar 11.  
6 Sluzewski M, van Rooij WJ, Beute GN, Nukssen PC. Balloon-assisted coil embolization of intracranial aneurysms: 
incidence, complications, and angiography results. J Neurosurgery. Sep; 105(3):396-9.  
7 Piotin M, Blanc R, Spelle L, Mounayer C, Piantino R, Schmidt PJ, Moret J. (20xx)  Stent-Assisted Coiling of 
Intracranial Aneurysms Clinical and Angiographic Results in 216 Consecutive Aneurysms. Stroke. 2010 
Jan;41(1):110-5. Doi:10.1161/STROKEAHA.109.558114.Epub 2009 Dec 3.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 18 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
been shown to serve as a scaffold for endothelial growth8, which can promote permanent occlusion 
of the target IA. These two components (flow disruption and scaffolding for re-endothelialization) 
distinguish flow diverters from standard coil embolization used with or without adjunctive devices.  
Published data demonstrates high occlusion rates for aneurysms treated with flow diverters, 
irrespective of aneurysm size, with the complete occlusion rate reaching >50% at 6 months and >  
80% at 1 year. Morbidity, thromboembolic complications, and mortality associated with the  
  
 
8 Kallmes, D. F., et al. (2009) A second-generation, endoluminal, flow-disrupting device for treatment of saccular 
aneurysms. AJNR Am. 30(6):1153-8   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 19 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 
treatment of unruptured aneurysms with flow diversion have been comparable with that reported in 
stent-assisted coiling literature. In addition, recent cost-effectiveness analyses have favored flow 
diversion over alternative endovascular treatments, particularly for large or giant aneurysms.9  
An attempt to establish a faster procedure, which would not require anticoagulation and 
antiaggregation and to improve the stability of aneurysm occlusion prompted the recent 
development of intrasaccular flow disruptors.10  The Contour is a flow diverter designed to be 
placed in the IA sac. Like other flow diverters, the device is designed to disrupt blood flow into the 
IA and to provide a stablea scaffold for the establishment where endothelial cells can grow. These 
two mechanisms of action may increase the likelihood of complete IA occlusion compared to 
embolization coils.   
Two intrasaccular flow diverters have received CE-mark, but only one is available for clinical use 
in Europe. The WEB is a mesh device in a spherical shape. It works by mechanisms similar to 
Contour in that 1) it is an intrasaccular flow diverter, and 2) its mesh can serve as a scaffold upon 
which endothelial cells can grow, however, difficulty in accurate sizing and resulting compaction 
of the device may limit long term success rates.11 Significant clinical experience is already 
available for WEB. The device in its first version with two mesh layers (“dual layer”) is no longer 
available. A single layer version with a more spherical shape comes with a lower profile, enhanced 
visibility, better navigation and is offered in diameters of 4–11 mm. WEB can be used with a high 
level of procedural safety. Early aneurysm occlusion is achieved in the majority of aneurysms. The 
 
9 Fargen, K. M. and B. L. Hoh (2015). "Flow Diversion Technologies in Evolution: A Review of the First Two  
Generations of Flow Diversion Devices." World Neurosurg 84(2): 254-256  
10 Mine, B., et al. (2014). "Intrasaccular flow-diversion for treatment of intracranial aneurysms: the Woven 
EndoBridge." Expert Rev Med Devices 11(3): 315-325  
11 Cognard, C. & Januel, A. C. (2015). Remnants and Recurrences After the Use of the WEB Intrasaccular Device in 
Large-Neck Bifurcation Aneurysms. Neurosurgery 76, 522–530  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 20 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
issue of aneurysm recurrence, however, is not solved with this implant as it appears that the device 
can experience changes in shape and configuration leading to aneurysm recanalization.12  
Another intrasaccular flow diverter, Artisse, also consists of a double layer of nitinol wire mesh 
held together by two radiopaque markers. It was primarily designed to treat small-necked 
aneurysms, and the only available shape is oval. The device is currently under clinical evaluation 
and no clinical and anatomical results have been published to date.  
The Contour Neurovascular System™ provides improvements and several advantages in the field 
of vascular occlusion devices because it provides aneurysm treatment and/or amelioration, 
particularly for neurovascular aneurysms, via the use of a minimum amount of fully-retrievable 
deployable material. Its configuration eliminates the need for additional material for pinning the 
aneurysm neck and/or for an anchoring mechanism in the parent vessel adjacent to the aneurysm 
and/or for spherical, radial expansion of the body portion of the device into the sac of the 
aneurysm.  
  
3 Acronyms  
 
The following list provides acronyms used in this document and their meaning:  
 
12 Williamson, R. W., et al. (2015). "Intrasaccular Flow Diversion for Wide-Neck Bifurcation Aneurysms: Should the 
Bar Be Set Higher?" World Neurosurg 84(2): 207-208  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 21 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
AE   
Adverse event   
ADE   
Adverse device effect  
CA  
Competent Authority  
CIP   
Clinical Investigation Plan  
CRF   
Case report form  
CRO   
Contract Research Organization  
CT   
Computed Tomography  
CTA   
Computed Tomography Angiography  
CTA   
Clinical Trial Agreement  
CVA  
Cerebrovascular accident  
DPW   
Detachable Pusher Wire  
EC  DSA  
Ethics Committee  
Digital Subtraction Angiography  
GCP   
Good Clinical Practice  
IA   
Intracranial Aneurysm  
IC  
Informed consent  
ICF  
Informed consent form  
ID   
Identification  
LTF  
Lost to Follow-up  
MC   
Microcatheter  
MR   
Magnetic resonance  
MRI  
Magnetic resonance imaging  
MRA  
Magnetic resonance angiogram  
mRS   
Modified Rankin Scale  
NIH  
National Institutes of Health  
PI   
Principal Investigator  
SADE  
Serious adverse device effect  
SAE   
Serious adverse event  
SAH   
Subarachnoid haemorrhage  
TOF  
Time-of-flight  
USADE   
Unanticipated Serious Adverse Device Effect  
4  Introduction  
 
Intracranial aneurysms (IA) are an important medical condition that can lead to substantial morbidity and 
mortality. An IA is caused by a weakness in the wall of a cerebral artery, which leads to dilation or expanding of 
the blood vessel. Untreated, IAs can rupture, a condition known as subarachnoid haemorrhage (SAH). Roughly 
30% of patients with SAH due to IA rupture die; of survivors, roughly 30% are left with significant neurological 
deficits.1 When large, IAs may also cause neurological symptoms resulting from “mass effect.” Common 
symptoms include double vision, loss of visual fields, headache and other cranial nerve problems.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 22 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Current treatment for IAs is provided in two settings: ruptured and unruptured IAs. When ruptured, the clinical 
goal is to stabilize the patient and reduce the risk of rebleeding from the IA. Surgical treatment involves opening 
the skull and placing clips or other devices over the offending IA. Endovascular treatment typically involves 
placement of coils into the target aneurysm through a catheter.   
Coil embolization of IAs is a well-established therapy. In ISAT, a large randomized comparison of surgical and 
endovascular treatment of IAs, endovascular treatment was shown to have a lower rate of death or dependence at 
one year compared to surgical treatment.2 Ten-year follow-up from ISAT showed that rebleeding from the target 
IA was uncommon but slightly higher in the endovascular group (p=.02). However, the rate of death or 
dependence was lower in those treated with the endovascular approach.3   
Incomplete occlusion of the target IA is associated with increased risks of aneurysmal bleeding. In CARAT, a 
large US clinical trial, in comparison to patients with complete IA occlusion, patients with 91-99% occlusion had 
a 2.9-fold increased risk of aneurysmal bleeding; relative risks of rebleeding with residual neck (70-90% 
occlusion) and partial occlusion (<70%) were 2.9 and 21.7, respectively.4 For this reason, clinicians attempt to 
occlude the target IA as completely as possible.  
Currently, the most commonly provided endovascular therapy for IAs is coil embolization. Despite the high 
prevalence of its use, coil embolization is substantially restricted due to geometric limitations and target IA 
access. Moreover, complete occlusion of the target IA is relatively uncommon; in a large randomized trial of coil 
embolization, complete occlusion of the target IA at 6-month follow-up was seen in only about 30% of cases.5     
It is commonly accepted that large IAs or those with a neck size >4 mm are more difficult to completely occlude 
with embolization coils. Wide-necked IAs are especially difficult to treat, as the geometry of the IA does not 
allow coils to stay in place. Adjunctive devices to improve coil embolization in wide-necked IAs are available. 
Balloon catheters may aid the clinician in packing the IA with coils and several intravascular stents are now 
commercially available. These stents are placed in the parent artery adjacent to the target IA; stent struts help to 
hold coils in place inside the target IA. Unfortunately, few studies are available to estimate the relative increase 
in complete occlusion rate provided by these adjunctive devices. Even more challenging is the treatment of 
widenecked IAs located at arterial bifurcations. Placement of intracranial stents in a variety of configurations has 
been associated with a significantly higher risk 6,7.  
Incomplete occlusion has additional risks, including growth of the IA and reopening related to continued 
pulsatile blood flow into the IA. Moreover, coils can become compacted and regress into the dome of the IA, 
resulting in further filling at the IA neck. In addition to exposing patients to bleeding risk, incomplete IA 
occlusion is also associated with the need for surveillance, which is stressful for patients. More importantly, 
these patients may need another embolization. Retreatment procedures can be complex and not always 
successful, thereby exposing the patient to further risk.  
Recently, a new set of devices for IA treatment have become available. These devices, called flow diverters, are 
stents placed in the parent artery. Flow diverters have a mesh component that retards the flow of blood from the 
parent artery into the IA fundus. Stasis of blood in the fundus induces IA thrombosis, which achieves the goal of 
preventing pulsatile flow into the IA. The mesh component of flow diverters has also been shown to serve as a 
scaffold for endothelial growth,8 which can promote permanent occlusion of the target IA. These two 
components (flow disruption and scaffolding for re-endothelialisation) distinguish flow diverters from standard 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 23 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
coils embolization. For large (>10 mm in maximum dimension) and giant (>25 mm) IAs, flow diverters have 
been shown to have high complete occlusion rates.9  Most flow diverting devices are placed into the parent 
artery, requiring the patient to take antiplatelet agents (aspirin and clopidogrel) for prolonged periods.  This can 
be a significant limitation, which precludes their use in the acute setting of aneurysm treatment.   
Another group of devices used in endovascular treatment of IAs, intra-saccular flow disrupters, do not require 
antiplatelet therapy as a prerequisite. These devices are placed in the IA and their mechanism of action is to 
disrupt the intra-aneurysmal blood flow and subsequently create intra-aneurysmal (and intra-device) thrombosis. 
The Contour Neurovascular SystemTM device (Cerus Endovascular Limited, Oxford, UK) is designed to be a 
flow disruptor that is placed into the IA sac, and does not require the use of antiplatelet therapy.  The Contour 
Neurovascular SystemTM device is composed of a double layer of 72-wire platinum core Nitinol braid mesh 
heatset into a concave shape. The device is delivered through a 0.027” microcatheter into the IA fundus and is 
placed at the IA neck. It is designed to disrupt blood flow into the IA and to act as a scaffold upon which 
endothelialization  can occur. These two mechanisms of action may increase the likelihood of complete IA 
occlusion compared to embolization coils.  
Other intra-saccular flow disruptors, such as the WEB™ Aneurysm Embolization System (Sequent Medical, 
Aliso Viejo, CA) and LUNA Aneurysm Embolization System (Medtronic, Inc., Irvine, CA), have been 
developed and have CE mark approval. Despite working in principle in the same way as the Contour 
Neurovascular SystemTM, these other devices have demonstrated certain limitations in their use 10, 11. For 
example, certain inherit properties of the WEB necessitates selected geometric “matching” of the device to the 
overall aneurysm shape. Failure to do so has led the device to migrate distally in the aneurysm or to 
compacting/foreshortening of the device with subsequent neck recanalization. Migration of the device is 
associated with movement out of the aneurysm sac, whereas movement refers to movement distally into the sac.  
It has become increasingly clear that accurate correlation of the shape of the WEB to the aneurysm is of critical 
importance and may not always be possible. Accordingly, there is a need to address these limitations and further 
improve the performance of intra-saccular flow disruptors.    
This study was designed in accordance with International Organization for Standardization (ISO) 14155:2011, 
the World Medical Association (WMA), Declaration of Helsinki in its current version and MEDDEVs from the 
European Commission.12-19  
5  
Investigational Device Description  
 
5.1 Implant and Delivery system  
The Contour Neurovascular SystemTM is comprised of the Contour Neurovascular System implant  
(hereafter called “Contour”), which is pre-attached to a detachable pusher wire (DPW), and an Introducer. 
The DPW facilitates the delivery of the Contour implant through a microcatheter (MC) and into the 
aneurysm. All devices are provided sterile and non-pyrogenic, and are for single patient use only.  
The Contour Neurovascular System consists of a self-expanding, concave shaped device (implant) 
comprised of a double layer mesh made from nickel-titanium with a platinum core. See Figure 2 below. 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 24 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
The implant also has a platinum marker for additional visualization during the procedure.  The preattached 
DPW has a composite stainless steel and polymer construction. The Introducer is a single lumen polymer 
tube that is used to constrain the Contour implant during introduction into the MC hub. The Contour 
implant body and proximal marker can be visualized under fluoroscopy.  
Given the platinum core of the device’s mesh and the platinum marker, the Contour implant is radiopaque 
and delivered into the target IA under fluoroscopic guidance using standard endovascular techniques and a 
commercially available microcatheter. The implant is electrolytically detached from the DPW using a 
commercially available detachable coil power supply.   
The Contour Neurovascular System is provided sterile with an Introducer preloaded onto the DPW shaft 
just proximal to the implant. Refer to the Instructions for Use (IFU) for additional information.  
  
Figure 2. Contour Neurovascular SystemTM Implant  
5.2 Indications for Use and Intended Use  
The Contour is intended for the endovascular embolization of unruptured intracranial aneurysms.  The 
device should only be used by physicians licensed and credentialed to perform endovascular embolization 
catheterization procedures. Physicians must be thoroughly familiar and experienced with standard vascular 
embolization techniques and the Contour Neurovascular System™ before using the device.  
The Contour is placed across the neck of the aneurysm and acts as both a flow disrupter and a flow 
diverter. The device mesh provides a scaffold distributed across the neck of the aneurysm for the 
establishment of neointimal development resulting in aneurysm occlusion.   
5.3 Training  
Cerus Endovascular will provide training to all participating investigators using a variety of the following:  
• 
flow models  
• 
didactic slide presentation  
• 
implant simulation using a vascular simulation 3-D replicator   
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 25 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
A patient selection committee will provide guidance over the identification of all suitable aneurysms in all 
eligible patients at each site to facilitate successful patient identification and implantation. The patient 
selection committee consists of 3 or more implanting physicians from around the world who are trained 
and/or experienced with Contour and have previous experience with embolization devices used in 
aneurysm treatment.  The committee will have access to the patient images submitted by the investigator 
during the screening process.  The selection committee will individually review and cast opinion on 
whether the proposed anuerym is treatable with a Contour device per product specification guidelines.  
The web-based image system called CIMAR will be used to view and store images and patient committee 
member opinions on aneurysm suitability for treatment based on the Contour sizing guidelines.   
Physician proctoring by a consulting clinician will occur for the first three implants at a newly implanting 
center. The proctor will provide feedback and guidance for the implantation of the Contour after the 
selection committee determines the aneurysm is treatable.  A sponsor representative will also be available 
for at least the initial six implantation procedures.  
5.4 Device Manufacturing Overview  
The Contour Neurovascular System is manufactured by Cerus Endovascular, Ltd., which is ISO 13485 
certified.  Components are supplied and  sterilization is performed by suppliers of Cerus Endovascular.  
The approved suppliers are managed by Cerus personnel in accordance with Cerus quality system 
procedures and component/device specifications. Ethylene oxide sterilization processing is performed by 
an ISO 13485 registered contract sterilizer. The sterilization process is performed in conformance with 
applicable standards.  
5.5 Device Evaluation and Testing  
5.5.1  Biocompatibility and Biological Safety  
A biological risk assessment of the Contour Neurovascular System has been performed. This 
assessmentfocused on the requirements of EN ISO 10993-1:2009, EN ISO 14971:2012, and the 
European Union (EU)Medical Device Directive (MDD) 93/42/EEC. The assessment examined the 
components used in the device, information on device materials from the literature, results of in vitro 
biocompatibility testing and in vivo studies on the device, and the history of safe and effective use of the 
device materials in humans. The assessment concluded that Contour Neurovascular System poses a low 
to rare risk of discernible toxicity to the patient.   
6  
Risks and Benefits  
 
6.1 Potential Risks  
The potential risks and complications of the device will be explained to the patients receiving the 
implanted device. The risks similar to the risks of other devices approved for endovascular aneurysm 
treatment are well known.   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 26 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
These risks may cause significant neurologic complications such as a cerebrovascular accident (CVA)  
and possibly death, and include but are not limited to the following: infection, abnormal bleeding or 
clotting, pain, injury to the groin site, injury to the aneurysm including bleeding and/or rupture, decreased 
blood flow to the brain or other parts of the body, inability of the device to totally prevent blood from 
flowing inside it, movement of the device within the aneurysms or to another location in the body.   
Anticipated Risk 
by  
Clinical Category  
Percent  
Anticipated Risk  
Occurence  
Specific Anticipated Risks  
Neurovascular 
Sequelae  
Rarely (< 5%)  
CVA – ischemic  
Rarely (< 5%)  
CVA – hemorrhagic  
Rarely (< 5%)  
Aneurysm rupture   
Anticipated Risk 
by  
Clinical Category  
Percent  
Anticipated Risk  
Occurence  
Specific Anticipated Risks  
 
Rarely (< 5%)  
Blood vessel dissection  
Rarely (< 5%)  
Blood vessel perforation/rupture   
Rarely (< 5%)  
Subarachnoid hemorrhage  
Rarely (< 5%)  
Parenchymatous hematoma  
Rarely (< 5%)  
Intraventricular hemorrhage  
Rarely (< 5%)  
Thrombosis with resultant occlusion of aneurysm 
parent artery of other blood vessel  
Rarely (< 5%)  
Embolism with resultant occlusion of blood vessel  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 27 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Less Likely (5-15%)  
Device migration – from the aneurysm to a distal 
site  
Likely (>15%)  
Headache  
Rarely (< 5%)  
Cranial nerve palsy  
Rarely (< 5%)  
Intra-cranial hypertension  
Less Likely (5-15%)  
Recanalization of the aneurysm  
Vascular Access 
Site Sequelae  
Less Likely (5-15%)  
Bleeding/Hematoma   
Very Rarely (< 3%)  
Local infection  
Less Likely (5-15%)  
Pseudoaneurysm  
Rarely (< 5%)  
Thrombosis with resultant occlusion of access 
artery  
Rarely (< 5%)  
Embolism with resultant occlusion of blood vessel  
Rarely (< 5%)  
Arterio-venous fistula  
Anticipated Risk 
by  
Clinical Category  
Percent  
Anticipated Risk  
Occurence  
Specific Anticipated Risks  
Angiogram- 
related Sequelae  
Less Likely (5-15%)  
Allergic reaction to contrast media  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 28 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
Less Likely (5-15%)  
Radiation exposure – the radiation dose of a 
cerebral angiogram is equivalent to about 2 years of 
background radiation and increases the risk of 
inducing cancer to 0.025% (1 in 4,000). Exposure 
of the fetus to radiation can harm the fetus and shall 
be avoided.  In addition, if the subject is of 
childbearing age, the doctor will ask the subject to 
undergo urine or blood pregnancy tests at the time 
of the procedure or angiograms to ensure that the 
subject is not pregnant.  
Less Likely (5-15%)  
Renal dysfunction secondary to contrast media  
Other Risks  
Less Likely (5-15%)  
Non-allergic drug reaction (local or systemic)  
Less Likely (5-15%)  
Allergic drug reaction  
Rarely (< 5%)  
Bleeding event – non-intracranial, non-access  
Rarely (< 5%)  
Cardiovascular events  
Rarely (< 5%)  
Peripheral vascular events  
Rarely (< 5%)  
Gastrointestinal events  
6.1.1 Risk Mitigation  
The manners in which risks shall be minimized for the device procedure include the following:  
1. The PI and clinical site staff were chosen because of their expertise in the field of neurovascular 
procedures.   
2. The physician(s) performing device-related procedures have received the appropriate training in the 
use of the device.  
3. Subjects are being monitored/observed throughout the study by multiple-disciplinary site staff, 
trained in the management of patients with IAs.  
4. Extensive pre-clinical, bench and in vivo testing was performed in order to optimize the device 
safety and function.  
5. Sponsor Clinical Personnel shall provide oversight throughout the Study.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 29 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
There may be unknown risks.Experienced Clinical Monitors will perform on-site and remote Monitoring 
throughout the trial to ensure protocol compliance and compliance with ISO 14155:2011 and all 
applicable EC and competent authority (CA) regulations.  
6.2 Potential Benefits  
There may be no direct benefit for subjects participating in this study. Subjects may indirectly benefit from 
their participation in this study by helping researchers improve their understanding of the Contour 
Neurovascular System. This study allows the Sponsor and Investigators to help other patients indicated for 
similar procedures.  
As previously described, recent results from the use of existing intra-saccular flow disruptor devices have 
shown a risk of compaction and neck regrowth. The Contour Neurovascular System device is designed to 
increase the likelihood of complete IA occlusion. Therefore, subjects may potential show a benefit if they 
have complete IA occlusion from the Contour Neurovascular System. This may reduce the risk of 
subsequent IA rupture.   
In addition, potential benefits that may be associated with endovascular treatment of IAs include:    
• 
Less invasive approach to treatment compared to surgery   
• 
No surgical incisions required, avoiding complications associated with surgical clipping   
• 
Decrease in post-operative morbidity caused by surgical procedures performed under general 
anesthesia  
• 
Less operative discomfort  
• 
Reduced total procedure time compared to surgical clipping  
• 
Shorter hospital stay  
Possible benefits of the Contour Neurovascular System vs. standard endovascular aneurysm coiling:    
• 
Simplified sizing approach  
• 
Reduced operative time  
• 
Reduced risk of rupture since the device does not engagre with the vulnerable aneurysm dome 
during the procedure  
• 
Ability to stabilize device in optimal placement with the visualization feature on the  DPW which 
can visually confirm separation of implant from device after detachment   
• 
Controlled deployment and placement with the ability to be deployed and re-sheathed multiple 
times in a safe and controlled manner until optimal placement is achieved •  
Reduced 
exposure to radiation   
• 
Improved durability of embolization by creating a stable scaffold across the aneurysm neck to 
permit establishment of stable endothelium.   
• 
Ability to confirm device stability upon implant by device oversizing to the aneurysm and 
employing a ‘push’ technique with the DPW prior to final detachment   
• 
Lower total mass of implanted material thus reducing the “mass effect” on adjacent structures in 
the brain.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 30 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
6.3 Risk-to-Benefit Rationale   
The Contour Neurovascular System has been implanted in first-in-human, pilot studies and compassionate 
use patients.  The device has been proven to be suitable for its intended purpose. There are no 
unacceptable residual risks/intolerable risks beyond the need to evaluate the safety and performance 
within this protocol. All applicable anticipated risks have been addressed through the provision of the 
appropriate IFU. Evaluation of the risks and benefits that are expected to be associated with the use of the 
Contour Neurovascular System demonstrate that when used under the conditions intended, the benefits 
associated with the use of the Contour Neurovascular System should outweigh the risks.  
7  Investigational Protocol  
 
7.1 Design   
Prospective, single arm, multi-center study.   Details are provided in Section 10 – Statistical Analysis.  
7.2 Objective  
The primary objective of this study is to document the safety and performance of the Contour  
Neurovascular System™.  The data from the study will be reported as a Pre-Market study to the Notified 
Body to support CE Mark approval.  In addition, the data may be used to support US approval by the Food 
and Drug Administration (FDA) to market the Contour device in the United States.  
7.3 Target Patient Population  
The target patient population is patients with unruptured intracranial aneuryms requiring endovascular 
treatment.   
7.4 Screening  
Patients shall be screened for participation through standard methods. Typically, patients with IAs are 
referred to neurovascular clinicians for evaluation and treatment of IAs discovered routinely or because of 
an IA rupture.  Only unruptured IAs will be included in the study.  A detailed list of the eligibility criteria 
is included in the Eligibility Section.  
Screening includes a clinical evaluation and a review of appropriate imaging which typically includes a 
computed tomography angiography (CTA), magnetic resonance angiogram (MRA) and/or a cerebral 
angiogram (DSA), which are all standard of care for patients who have been diagnosed with or are 
suspected to have an IA. It is recommended that the baseline screening angiogram include the acquisition 
of a 3D rotational angiogram of the aneurysm and parent vessel for proper evaluation of the anatomy. The 
angiogram completed at the time of procedure can be used for the Baseline Angiogram.    
7.5 Eligibility  
To participate, patients must meet all inclusion criteria and no exclusion criteria listed in Table 3.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 31 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Table 3. Study Eligibility Criteria  
Inclusion Criteria  
Patients of all genders who meet all indications 
and contraindications will proceed to 
implantation.  
1. Patient’s indication for treatment of 
unruptured aneurysm is according to the 
national/international guidelines.  
2. Age 18-80 years at screening  
3. Patients who are suitable for 
nonemergency endovascular embolization 
of saccular IAs  
4. IA located at a bifurcaton in the anterior or 
posterior circulation with dimensions 
consistent with implant size selection 
guidelines included in the IFU  
5. Patient has the necessary mental capacity 
to participate and is willing and able to 
participate in the study for the duration of 
the study follow-up and is able to comply 
with study requirements  
6. Patient able to able to give their informed 
consent can be included in this study.  This 
must be demonstrated by means of a 
personally signed and dated informed 
consent document indicating that the 
subject has been informed of and 
understood all pertinent aspects of the 
study.    
Exclusion Criteria  
The presence of condition that may create 
unacceptable risk during the aneurysm 
embolization procedure, such as patients with:  
1. Ruptured aneurysm  
2. Patient anatomy or physiology considered unsuitable 
for endovascular treatment  
3. Contraindication for arterial access  
4. Largest measured IA equatorial diameter >8.5 mm or 
<2 mm  
5. Largest measured IA neck diameter >8 mm or <2 mm  
6. Target IA contains other devices/implants (e.g., coils)  
7. Known allergy to platinum, nickel or titanium  
8. Known allergy to contrast agents  
9. Contraindication to anticoagulants or platelet inhibitor 
medication  
10. Stenosis of the target IA’s parent vessel >50%   
11. Anticoagulation medications such as warfarin that 
cannot be discontinued.  
12. Pregnant, breastfeeding or planning pregnancy in the 
next 2 years  
13. Acute / chronic renal failure (including dialysis); 
Creatinine > 2.00 mg/dl or > 182 μmol/L  
14. Myocardial Infarction, Stroke or TIA within the last 6 
months   
15. Any other medical issue within the brain that precludes 
the device implantation such as brain surgery, radiation 
in the target area of intervention, acute traumatic 
craniocerebral injury, etc.  
16. Other medical conditions that cause an inability to 
comply with study requirements and/or that could 
increase the risk of neurovascular procedures or death 
within 2 years (e.g., liver failure, cancer, heart failure, 
chronic obstructive pulmonary disease, 
immunosuppression, neural disease, and hematologic 
disorders etc.)  
17. Participating in another study with investigational 
devices or drugs that would confound the effects of the 
study outcomes  
All patients must sign a study-specific consent form prior to the commencement of any protocol-specific 
assessments and/or procedures. Final qualification will occur during the implant procedure due to the need 
for confirmation of IA appropriateness with cerebral angiography.   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 32 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
The patient is enrolled at the time of consent and is considered a study subject in the reporting analysis 
group only when the patient is fully qualified and at least one Contour device has been placed into the 
patient’s body. The following listing provides examples of patient enrollment scenarios for the study:  
o The patient is not considered enrolled but not included in the primary analysis group in the 
study:  if at the onset of the procedure in the initial DSA, the investigator determined the 
patient’s IA was not suitable for treatment with the device, thus, no attempt was made by the 
investigator to place the device. The patient will be treated outside of the study per the 
investigator’s usual practices.  The reason for not treating the patient must be documented on a 
study exit form.  The patient is not included in the primary analysis group because the Contour 
was never opened or deployed inside the patient.  All patients will be listed in the final report. o 
The patient is considered enrolled but not included in the primary analysis group in the study:  at 
the onset of the procedure, the investigator determined the subject’s IA was suitable for 
treatment with the device. The investigator attempted but was unable to place the device within 
the IA and the subject required alternative treatment.  The subject is considered enrolled for the 
purposes of the study but will only be followed through the 1-month visit.  All failed implant 
attempts will be reported in the final report.  
o The patient is considered enrolled and included in the primary analysis group in the study: if at 
the onset of the procedure, the investigator determined the subject’s IA was suitable for 
treatment with the device. The investigator successfully placed the device within the IA.  The 
subject is considered enrolled for the purposes of the study and will be followed for the duration 
of the study.  
o The patient is considered enrolled and included in the primary analysis group in the study:  if at 
the onset of the procedure, the investigator determined the subject’s IA was suitable for 
treatment with the device. The investigator successfully placed the device within the IA. In 
addition, the subject required and received further treatment with another endovascular 
device(s).  The subject is considered enrolled for the purposes of the study and will be followed 
for the duration of the study.  
The available sizes of the Contour implant along with coordinating aneurysm dimensions and definitions 
are provided in Figure 3.  
REF (Catalog Number) – 
Diameter  
Aneurysm   
Neck (mm)  
Aneurysm  Width 
(mm)  
CNS05 – 5 mm  
2.0 - 3.0  
2.0 - 3.5  
CNS07 – 7 mm  
3.0 - 5.0  
3.0 - 5.5  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 33 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
CNS09 – 9 mm  
4.0 - 6.0  
5.0 - 7.5  
CNS11– 11 mm  
5.0 - 8.0  
7.0 - 8.5  
 
Figure 3 – Contour Sizing and Aneurysm Dimension Definitions  
7.6 Baseline Evaluation   
The baseline evaluation is performed after signing the consent form and prior to the implant procedure. 
During the baseline evaluation, the investigator and/or coordinator will record basic medical information 
on the study case report form (CRF), including known diagnoses and daily medication use. Any relevant 
neurologic findings will be recorded on the CRF. A modified Rankin Scale (mRS) will be performed at 
baseline.  The mRS is a widely used scale for measuring the degree of disability or dependence in the 
daily activities of people who have suffered a stroke or other causes of neurological disability.   
All images obtained at screening or from images obtained prior to screening as standard, including the 3D 
angiogram, MRA and/or CTA are to be submitted for review to the patient selection committee to confirm 
the subject’s eligibility for use of the Contour Neurovascular System.  The Contour Neurovascular System 
procedure may be scheduled following confirmation from the committee. Additionally, the images 
obtained at baseline shall be submitted to the independent core laboratory.   
7.6.1 Angiogram  
A cerebral angiogram that includes a 3D rotational angiogram shall be performed prior to the Contour 
Neurovascular System implant placement procedure to allow proper assessment of the target IA being 
treated.  The angiogram will include the acquisition of a 3D rotational angiogram of the aneurysm and 
parent vessel.  Imaging will always be performed on the day of the procedure which will be used for core 
laboratory baseline for comparison at 6 months. All imaging must be submitted to the independent core 
lab for analysis.   
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 34 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
7.7 Implant Procedure  
7.7.1 Preoperative Preparation  
The subject undergoes standard preoperative preparation. The device implant procedure must be 
performed under general anaesthesia.   
7.7.2 Arterial Access  
Standard methods are used to gain access to the femoral artery. Standard methods are used (e.g., sheaths 
and guide catheters, distal support guides) to obtain access to the IA. Tri-axial approach, although not 
mandatory, is highly recommended.  
7.7.3 Angiogram  
A cerebral angiogram of the target IA and the parent artery at the beginning of the procedure will be 
performed to confirm final eligibility for the study.   
7.7.4 Contour Neurovascular SystemTM Procedure  
Contour Neurovascular System placement is described in detail in the Instructions for Use (IFU).  
Briefly, the target IA is accessed via standard methods. A 0.027” microcatheter is placed into the target 
IA. The Contour Neurovascular SystemTM device is introduced into the microcatheter and slowly 
delivered into the target IA. Once the Contour implant is in the appropriate location, the device 
positioning and stability is confirmed via a gentle push forward on the DPW, then is detached via a 
standard electrolytic mechanism.   
A final post-placement angiogram, which includes a 3D angiogram of the aneurysm and parent vessel, 
will be performed and all devices are removed from the body. All relevant radiographic images should 
be saved. Specifically, the investigator should document flow disruption compared to pre-placement 
flow. Any device deficiencies, technical complications or adverse events occurring during the procedure 
should be noted in the CRF.  
All images captured during the procedure, including the 3D angiogram, shall be submitted to the 
independent core laboratory.   
Pre and Peri-operative anti-platelet use is not excluded and may be used at the discretion of the operator.  
7.8 Hospital Discharge  
The subject will be discharged from the hospital as per standard practices. Prior to discharge, the 
investigator should evaluate the subject for any adverse events and perform a neurologic examination.  
7.9 Follow-Up  
Following discharge, the subject will have a follow-up visit at 1 month, 6 months and 12 months after the 
implant procedure. At each study visit, the subject shall be assessed for any new adverse events (AEs). A 
standard neurologic examination should be performed to evaluate for any new adverse events. A modified 
Rankin Scale (mRS) will be recorded at each follow-up visit. It is expected that most target IAs will be 
asymptomatic and the likelihood of post-placement neurologic changes is very low. The NIH Stroke Scale 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 35 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
assessment should be obtained within 24 hour after a stroke in the event a subject is diagnosed with a 
stroke. Cerebral angiography will be repeated at 6 months. The cerebral angiography will include a 3D 
angiogram. The investigator should ensure that follow-up angiography is done with identical views to 
maximize the ability to compare baseline and post-treatment views. All angiographic images should be 
submitted to the independent core laboratory. The target IA status shall be evaluated by an independent 
core laboratory.   
The study’s schedule of assessments and post-treatment visit windows are shown in Table 4.  
Table 4. Schedule of Assessments  
  
 
 
 
 
 
 
Medical history and medications  
X  
  
  
  
  
X  
Neurologic Exam  
X  
  
X  
X  
X  
X  
NIH Stroke Scale  
X  
X*  
X*  
X*  
X*  
X  
Modified Rankin Scale (mRS)  
X  
  
X**  
X**  
X**  
X  
Pregnancy test (pre-menopausal 
female)  
X  
  
  
  
  
  
CT angiography (CTA) ^  
X#  
  
  
  
  
  
Magnetic Resonance Angiogram 
(MRA) ^   
X#  
  
  
  
  
  
Cerebral Angiogram (DSA) ^  
X# 
w/3D  
X 
w/3D  
  
  
X  
w/3D  
  
Adverse Event assessment  
  
X  
X  
X  
X  
X  
Procedure Information  
  
X  
  
  
  
  
Aneurysm Occlusion Status – 
Raymond Roy and general 
assessment on study form##  
  
X  
  
  
X  
  
  
^Baseline image aneurysm assessment can be made with either CTA, MRA OR DSA, upon MD discretion.  
# Baseline image screening can be completed within 3 months prior to enrollment.  Imaging will always be 
performed on the day of the procedure which will be used for core laboratory baseline for comparison at 6 months.  * 
The NIH Stroke Scale score should be obtained within 24 hours after stroke in the event a subject is diagnosed with a 
stroke.   
** mRS will be obtained at all scheduled visits.  
## Aneurysm occlusion status and Raymond Roy completed when cerebral angiograms are performed.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 36 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
7.10 Early Withdrawal  
Reasons for subject withdrawal prior to study completion shall be documented. Valid reasons for early 
study withdrawal include:  
• 
Death  
• 
AE or other medical condition that prevents study participation  
• 
Withdrawal of voluntary consent  
• 
Lost to follow-up (LTF)  
• 
Termination of Study   
At least three documented attempts shall be made to contact any subject who is LTF.  
7.11 Study Termination  
The Sponsor has the right to terminate the Study. Reasons for Study termination shall be documented in 
the Clinical Investigation Report and Close-Out Monitoring Report. Valid reasons for study termination 
include:  
• 
Administrative issues mandate termination  
• 
Interim data analyses warrant study termination  
• 
Regulatory action mandates termination  
If the study is terminated for any reason, the governing Competent Authority and Ethics Committee shall 
be notified as applicable.  If the study is terminated, all patients will remain in follow-up per the standard 
of care.  
7.12 Premature termination  
The Sponsor reserves the right to discontinue the clinical trial/investigation at any stage (e.g. for safety 
reasons) or reduce the follow-up period with suitable written notice to the Investigator.  
Possible reason(s) include:  
Sponsor makes a final decision for the early termination of the clinical trial, or per DSMB recommendation 
Further product development is cancelled.  
Should the clinical trial be discontinued by the Sponsor, subjects will be followed up as per routine 
hospital practice.  
In this case, the Investigator shall return all clinical trial/investigation materials (including devices) to the 
Sponsor and provide a written statement as to why the premature termination has taken place to the EC (if 
applicable) and inform subjects still participating to the trial. All applicable Clinical Investigation 
documents shall be subject to the same retention policy (the Investigators and/or designee(s) will be 
instructed to retain all study records required by the Sponsor and regulatory authorities in a secure and safe 
facility, with limited access.  All study material shall be stored for at least 10 years or as based on national 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 37 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
regulations. The Investigator must request authorization from the Sponsor prior to destroying study 
records).  Sponsor or designee will inform the CA about premature termination of Clinical Trial as per 
regulatory requirements Study discontinuation:  
The Study Completion/Discontinuation Form must be completed when:   
• 
the subject is considered lost to follow-up (per the above definition) before the 12 months 
follow-up time point has been reached or   
• 
the subject withdraws from the study or   
• 
the Investigator withdraws the subject from the study or  
• 
the subject has completed the study (at last Follow up visit per protocol, the 12 months follow up 
visit).  
  
The Sponsor shall be notified of the reason for subject discontinuation. The site will provide this 
information on the Study Completion/Discontinuation Form (e-CRF) and on source documents. 
Investigators must also report this to their EC if defined by their institution’s procedure.  
  
8 Adverse Events  
 
8.1 Adverse Event Definitions  
Definitions of Adverse Event subtypes are provided in Table 5. All AEs and device deficiencies shall be 
reported by the clinical site investigator on a specific case report form (CRF).  
Table 5. AE Definitions per ISO 14155:2011  
Adverse Event 
(AE)  
An AE is:   
Any untoward medical occurrence in a subject, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device.  
Note 1: This definition includes events related to the investigational medical device or the 
comparator.  
Note 2:  This definition includes events ralted to the procedures involved.  
Note 3:  For users or other persons, this definition is restricted to events related to 
investigational medical devices.  
Adverse device 
effect (ADE)  
An ADE is:  
AE related to the use of a medical device.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 38 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Note 1: This definition includes events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
medical device.   
Note 2: This definition includes any event resulting from use error or from intentional misuse 
of the medical device.  
Serious adverse 
event (SAE)  
An SAE is:  an 
AE that • 
led to 
death,  
• 
led to serious deterioration in the health of the subject that either resulted in o a 
life-threatening illness or injury, or  
o 
a permanent impairment of a body structure or a body function, 
or o in-patient or prolongation hospitalization, or  
o 
medical or surgical intervention to prevent life-threatening illness 
or  o injury or permanent impairment to body structure or body function,  
• 
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 investigational plan, without serious deterioration in health, is not considered to be 
an SAE.  
Serious adverse  
device effect  
(SADE)  
An SADE is:  
ADE that has resulted in any of the consequences characteristic of an SAE.  
Unanticipated 
serious adverse  
device effect  
(USADE)  
A USADE is:  
a SADE which by its nature, incidence, severity or outcome has not been identified in the 
current version of the risk analysis report.  
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report.  
8.2 Adverse Event Classification  
8.2.1 AE Severity:  
The severity of an AE is a qualitative judgment of the degree of intensity, as determined by the 
Investigator or as reported by the subject.  The severity of the AE shall be evaluated according to the 
following scale:  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 39 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
Mild - no limitation of usual activities, no therapy or only symptomatic therapy required to treat the 
injury or illness.  
• 
Moderate - some limitation of usual activities or specific therapy is required.  
• 
Severe - inability to carry out usual activities, hospitalization, emergency treatment, life threatening 
events, or death.  
The assessment of severity shall be made independent of the relationship to the device and therapy or the 
seriousness of the event.  
8.2.2 AE causality:   
Each AE shall be assessed by the Investigator for its relationship to the use of the study device or study 
procedure as outlined below.   
Device Related: Restricted to the study device.   
Procedure Related: Restricted to the implant procedure and any procedure associated directly with 
placement of the device.   
Definitely related: An AE is definitely related to a specific category if it is obvious, certain or there is 
little doubt regarding the relationship.   
Possible related: An AE is possibly related to a specific category if it is capable of being  related but 
relatively unlikely.   
Not related: An AE is not related to a specific category if it is determined that there is no plausible 
association.  
Subjects experiencing AEs shall be offered comprehensive medical care for conditions associated with 
the implant procedures and followed until their medical outcomes are resolved.  
Table 6. AE Categorization  
AEs  
Non-
DeviceRelated  
Device-Related   
 
Device Deficiencies*  
Non-Serious  AE  
ADE  
 
Without SADE potential  
Serious  
  
SAE  
  
SADE  
 
With SADE potential  
Anticipated  
Unanticipated  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 40 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
  
ASADE  
USADE  
  
* Device deficiency is the inadequacy of a medical device related to its identity, quality, durability, reliability, safety 
or performance. This may include malfunctions, misuse, errors, inadequate labeling  
8.3 Adverse Event Reporting/Analysis  
The timely and complete reporting of AEs is essential for the risk management process. Monitoring and 
documentation of all AEs will allow the Sponsor to identify potential ADEs and to adhere to regulatory 
requirements.  
The Investigative Site shall report all SAEs including USADEs and device deficiencies to the study 
sponsor or the sponsor’s designee within 48 hours of occurrence.   
All AEs shall be documented in the patient’s medical record by the PI and reported by the PI using the AE  
CRFs. AE definitions and categories are described in Section (8), the Monitors shall confirm that the AEs  
are correctly categorized and entered onto the AE CRFs. The Monitor shall confirm that the AEs are 
consistent with the source documents.   
The sponsor is responsible for submitting reports to the Competent Authority as required by the applicable 
regulations and guidelines.  The investigator is responsible for reporting safety information to the ECs 
according to the ECs requirements.  
9  Study Oversight  
 
9.1 Clinical Events Committee (CEC)  
A CEC will be established by Cerus Endovascular or designee to assess, review and classify all 
neurologic, device-related and procedure-related SAEs to ensure they are reported accurately. The CEC 
member(s) appointed for the study will be qualified by background, training and expertise in 
neurovascular treatment of IAs. The member(s) will not be an investigator on the study. The CEC will 
regularly review and adjudicate the adverse events and any deaths. Classification of the events will include 
device and procedure relatedness and seriousness.  Member(s) will be provided data summaries and 
source documentation for review.  
9.2 Data Safety and Monitoring Board (DSMB)  
A DSMB will convene of member(s) experienced in an associated disclipline.  The DSMB will review the 
study data after enrollment of the first five patients. Enrollment of further patients will occur as the DSMB 
reviews the data.  The DSMB will provide a report following the review and advise Cerus Endovascular 
for any modifications or concerns that may be necessary.  The DSMB will provide further evaluation at 
least twice per year and after the first 5 patients are enrolled.  If slow enrollment occurs, the DSMB may 
meet less frequently. The CEC and DSMB will meet as a combined committee.   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 41 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
9.3 Patient Selection Committee  
A patient selection committee will provide guidance over the identification of all aneurysms in all eligible 
patients at each site to facilitate successful patient identification and implantation. The patient selection 
committee consists of 3 or more implanting physicians from around the world who are trained and/or 
experienced with Contour and have previous experience with embolization devices used in aneurysm 
treatment.  The committee will have access to the patient images submitted by the investigator during the 
screening process.  The selection committee will individually review and cast opinion on whether the 
proposed anuerym is treatable with a Contour device per product specification guidelines.  The web-based 
image system called CIMAR will be used to view and store images and patient committee member 
opinions on aneurysm suitability for treatment based on the Contour sizing guidelines.   
10 Statistical Analysis  
 
This study intends to examine the safety and performance of the Contour Neurovascular System TM used 
for the treatment for embolization of intracranial anueryms.  The data from the study will be reported as a 
Pre-CE Mark study to the Notified Body to support CE Mark approval.  In addition, the data may be used 
to support US approval by the Food and Drug Administration (FDA) to market the Contour device in the 
United States.  The study is not powered to detect statistical significance.  As such, clinical judgement is 
required to assess device safety and performance from the data collected during this study. Clinical 
judgement will be provided throughout the study by the DSMB. In addition, under future review of the 
Clinical Section of the regulatory submission for CE Mark, clinical review will be included from the  
Notified Body to ensure adequate documentation of safety and performance required for the CE Mark.  
10.1 Justification of Methodology  
This study is designed as a single arm study to develop further understanding of the Contour  
Neurovascular System. It will provide safety and performance information for subjects from the Contour 
implantation to six month follow-up.  
At one month post procedure, the subjects will provide an adverse event profile related to the placement of 
the device.  At six months of the study there will be additional information related to the adverse event 
profile including any device related instability or deficiency.  
Similarly, the subjects will provide a performance profile.  At six months post procedure, the information 
will provide how well the aneurysm has healed or embolized through the analysis of imaging performed 
by the independent core lab for accuracy and removal of bias.  
The totality of the data will represent the data necessary for submission to the Notified Body for the 
assessment of CE Mark application.  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 42 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
10.2 Patient Population   
Two patient populations will be considered in the analyses, an Intent-to-Treat (ITT) population and a Per 
Protocol population (PP).  The ITT population includes all patients.  The PP population will include 
subjects who complete 6 months of follow-up, die prior to their 6-month clinic visit, or are study failure 
(withdrawal from study to obtain alternate treatment).  The PP will exclude patients with any major 
protocol violation that affects proper study inclusion or significant outcomes. Endpoints will be evaluated 
in the PP and ITT populations.  
  
10.3  General Principles  
The analysis for all primary and secondary study endpoints and baseline, procedural and follow-up 
characteristics will be performed on an intent-to-treat analysis population which will include all available 
data for all enrolled subjects. Standard summary statistics will be calculated for all study variables.  
The primary safety endpoint will be calculated as the proportion of subjects with death of any 
nonaccidental cause or any major stroke within the first 30 days after treatment or major stroke or death 
due to neurological case from day 31 to 6 months after treatment.    
The primary performance endpoint will be calculated as the proportion of subjects with complete 
occlusion demonstrated with a Grade 1 on the Raymond Roy Scale at 6 months.  
For AE reporting, both subject counts and event counts will be presented in tabular summaries of results.  
A summary of subjects with protocol deviations will be reported but those subjects will be included in all 
analyses although endpoints may be summarized without the subjects (per-protocol analysis group) to 
provide additional information but not for the primary analysis.  
For continuous variables, statistics will include means, standard deviations, medians and ranges.  
Categorical variables will be summarized in frequency distributions. Missing data will not be imputed. 
The number of data values available for each analysis will be reported so that the impact of missing data 
can be seen.   
Statistical analyses will be conducted in SAS version 9.4 or above (SAS Institute, Cary, N.C.).  
10.4  Multi-center Trial Considerations  
Up to 10 clinical sites will participate in the study.  The maximum enrollment at any one site will be 20 
subjects.  
This is a multi-center clinical study with standardization of subject enrollment, data entry and AE 
reporting.  
10.5 Endpoints  
10.5.1 Primary Endpoints  
Primary Safety Endpoint:  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 43 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
The proportion of subjects with death of any non-accidental cause or any major disabling stroke within 
the first 30 days after treatment or major disabling stroke or death due to neurological cause from day 31 
to 6 months after treatment.  
Note: Major Disabling Stroke is defined as an episode of neurological signs or symptoms that persist 
beyond 24 hours accompanied with evidence of ischemia/infarction on imaging that results in an 
increase of NIHSS from baseline by ³ 4 points and/or an increase from mRS baseline by >2.   
   
Primary Performance Endpoint:  
To demonstrate the occlusion rate on the 6 month angiogram as adjudicated by a core laboratory.  
Success will be defined as complete occlusion demonstrated by a Grade 1 using the Raymond Roy Scale.   
  
10.5.2 Secondary Endpoints  
Additional measures will be summarized:  
Secondary Safety Endpoint:  
• 
Serious Adverse Events (SAE) associated with the procedure or device   
• 
All serious neurological adverse events Secondary Performance Endpoint:   
• 
Detailed assessment of aneurysm occlusion from Post Procedure to 6-months provided by the core 
lab review of the angiogram (DSA) including the following:  
- 
Raymond Roy scale  
- 
Modified Web Occlusion Scale  
- 
Percent Occlusion   
- 
Device Stability   
• 
Rate of retreatment   
• 
Summary of device performance including the following:  
- 
Time required for implantation of the Contour   
- 
Device sizes used  
- 
Number of attempts to deploy the device  
- 
Number of failed implant attempts  
- 
Any reports of device deficiencies  
10.5.3 Independent Analysis of Imaging  
Follow-up imaging (i.e., cerebral angiograms) angiographic assessments of the aneurysm shall be 
completed by an independent core laboratory with experience in neurovascular imaging of IAs. 
Clinicians responsible for imaging analyses at the core laboratory will not have any financial conflict 
with the study sponsor and shall not be affiliated with a clinical study site.    

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 44 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
10.6   Interim Analysis  
No interim data analysis will be performed.  
10.7   Sample Size Rationale  
This is a single arm study designed to provide adequate data for the purpose of CE Mark.  It is expected 
the 30 patients with evaluable data at 6 month follow-up will show adequate evidence of safety and 
performance for the application for CE Mark of the device.  No formal hypothesis testing of the study 
endpoints will be performed, therefore no formal sample size was calculated.    
11  Additional Trial Characteristics  
 
11.1 Measures Taken to Avoid Bias  
The study has been designed to ensure treatment and follow-up of subjects are consistent with current 
medical practice.  
The study will be approved by the central Ethics Committees (ECs) prior to initiation and will undergo 
continuing review by the ECs as the study progresses.  Additionally, each clinical site will provide further 
oversight and approval of the study.   
All investigators must disclose potential conflicts of interest, including financial interests, to the study 
sponsor prior to participation in the study.  
Data from all investigative sites will be monitored throughout the study.    
A CEC/DSMB will adjudicate all neurological, device related and procedure related serious adverse 
events.  
A CEC/DSMB will regulatory review the study data to provide oversight and necessary input for any trial 
modifications.  
Imaging obtained during the procedure and follow-up period will be reviewed by an independent Core 
Laboratory to verify the status of the Contour implant and the surrounding vasculature.    
11.2 Special Equipment for Investigation  
Apart from the study device, all equipment used in the trial will be maintained and calibrated in 
accordance with the clinical site institution’s policies and procedures.  
11.3 Procedure for Replacing Withdrawn Subjects  
Subjects who withdraw from the study shall not be replaced.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 45 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
11.4 Other Devices Used During Study  
Several devices are standardly used during endovascular procedures to treat IAs. Other than the 
investigational implant and implant delivery system, no special devices are required for this study.      
11.5 Total Expected Trial Duration  
The enrollment period is expected to take 9 months and the follow-up duration is expected to be 6 months 
to obtain data for the primary analysis.  The study population will include 30 subjects enrolled and 
implanted at up to 10 centers in Europe with evaluable data at 6 months for the analysis for CE Mark.  It is 
expected that the study will take 9 months to enroll the first 30 patients and continue up to 9 months for 
the initial report for CE Mark.    
All patients must be consented prior to performing study related procedures. All patients that provide 
consent and are implanted will be followed according to the follow-up schedule. Any patient for whom a 
failed implant attempt is performed will be followed for 1-month or until resolution of any potential 
device or implanted related adverse events, whichever occurs last.   
12  Study Management  
 
This study will be managed according to ISO 14155:2011, the Declaration of Helsinki in its current revision, 
conditions imposed by local ethics committees (ECs), and any applicable regulatory requirements. For this study, 
the sponsor will have certain direct responsibilities and may delegate other responsibilities to appropriate 
consultants and/or contract research organizations (CROs). Together, the sponsor and all related participants will 
ensure that the study is conducted according to the above standards and all applicable regulations. All personnel 
to participate in the conduct of this clinical trial will be qualified by training, education and/or experience to 
perform his or her respective tasks.   
12.1 Investigator Responsibilities  
This section highlights responsibilities of the principal investigator (PI) at each site regarding this 
investigation. The PI, i.e., the main investigator at each study site, is responsible for managing day-to-day 
aspects of the study. The PI will take steps to ensure compliance with the CIP and associated documents 
and processes. The PI also protects data integrity and the rights, safety and well-being of clinical study 
subjects.  
12.1.1 Disclosure  
All investigators must disclose potential conflicts of interest, including financial interests, to the study 
sponsor, both before and during conduct of the clinical study as well as up to 1 year after the study has 
completed.   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 46 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
12.1.2 Additional Site Team Members  
The site may add new members to the investigational team. Training of new personnel will be 
documented before new personnel participate in the study. New investigators should disclose potential 
conflicts, as described in Section 12.1.1.   
12.1.3 Communications with EC  
The site Principal Investigator (PI) and the site clinical study team are responsible for communication 
with site ethics committee if required. The Sponsor and/or designee is responsible for communication 
with central ethics committees if required. The PI will:  
• 
provide the sponsor with copies of any relevant EC communications regarding this CIP  
• 
comply with requirements from the EC regarding the CIP  
• 
obtain written/dated approval/favourable opinion from the site EC, before starting the study or 
recruiting subjects  
• 
obtain written/dated approval from the site EC before implementing any changes in a CIP 
amendment  
• 
ensure the timeliness of safety reporting to the site EC  
• 
promptly report deviations from the CIP to the EC that affect the rights, safety or well-being of 
the subject or the scientific integrity of the CIP  
• 
keep all EC communications in its study file  
12.1.4 Informed Consent  
The PI is responsible for the informed consent (IC) process in this CIP. The PI will ensure that:  
• 
the IC used for the consent process is the most current IC, has been approved by the EC and is 
consistent with any requirements imposed by the EC   
• 
the IC process occurs consistent with ISO 14155:2011, and importantly, prior to any procedure 
specific to the clinical investigation is applied to the subject.  
• 
a copy of the signed/dated IC form is kept in the subject’s records  
• 
either he/she or an authorized designee conducts the consent process consistent with ISO 14155  
12.1.5 Subject Identification Log  
The PI or designee will maintain a log of all subjects enrolled in the study. The log links study 
identification (ID) numbers to identifying patient information (name, contact information). The log will 
be housed securely on site.  
12.1.6 Compliance with CIP  
The PI is responsible for ensuring that his/her site complies with the CIP. The PI will:  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 47 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
maintain oversight of the study at the clinical site  
• 
sign an investigator agreement form  
• 
conduct the investigation in compliance with this CIP, applicable sections of ISO 14155:2011, 
and requirements of the EC to ensure the safety and well- being of study subjects  
• 
create, maintain and make available source documents for study subjects  
• 
not implement any change to the CIP without prior approval from the sponsor, local EC, and (if 
required) regulatory bodies if required  
• 
not deviate from the CIP, except to maintain the subject’s rights, protect the life and physical 
well-being of a subject in an emergency, or the scientific integrity of the investigation  
• 
document all deviations from the CIP13  
• 
ensure that the site has adequate staff and capabilities  
• 
ensure that site equipment used in the study is maintained and calibrated  
• 
ensure the accuracy, completeness and timeliness of study data in CRFs and reports  
• 
allow and support sponsor monitoring and auditing activities  
• 
be available to monitors and the sponsor to address questions during study visits  
• 
be available and support regulatory authorities during audits  
• 
respond in a timely manner to sponsor inquiries  
• 
make reasonable efforts to prevent early withdrawal  
• 
make reasonable efforts to ascertain the reason for early withdrawal  
12.1.7 Subject Records   
The Investigator will maintain original source documents from which study-related data are derived, 
which include, but are not limited to:  
• 
Clinic progress notes recording subject’s medical history and medications  
• 
Medical charts with operative reports and condition of subject upon discharge  
• 
Medical records regarding AEs, including treatment and clinical outcome   
• 
Results of diagnostic examinations  
  
 
13 The sponsor may also document deviations from the CIP  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 48 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
Results of subject questionnaires  
• 
Imaging (such as x-rays, angiograms, CTs, MRIs) as well as any existing reading or interpretation 
of diagnostic imaging  
• 
Notes of phone calls and/or correspondence indicating investigational site’s attempts to follow 
study subjects at the required follow-up visits until subject’s participation in the study is complete 
or terminated  
• 
Records relating to patient death (e.g., death certificate, autopsy report/terminal medical records)  
• 
Printouts of source data generated by technical equipment (e.g., x-rays, angiograms) must be filed 
with the patient’s records  
12.1.8 Subject Accountability  
The PI will make reasonable efforts to account for all study subjects, especially those who withdrew. If 
withdrawal is due to problems with study device safety or performance, the PI will obtain the subject’s 
permission to follow his/her status/condition outside the clinical investigation, if possible.  
12.1.9 Device Deficiencies and Malfunctions  
Throughout the study, the PI or designee and sponsor will report and document all device deficiencies 
and malfunctions related to the identity, quality, durability, reliability, safety or performance of the 
device. This includes reporting of device deficiencies/malfunctions that did not lead to an AE but could 
have if: 1) suitable action had not been taken, 2) intervention had not been made, or 3) circumstances 
had been less fortunate.  
The PI should make every effort to return devices suspected of deficiency or malfunction to the sponsor 
for analysis.  
12.1.10 Medical Care  
The PI will provide standard medical care to study subjects, including:  
• 
Informing the subject of a plan for further treatment including the treatment if the device is not 
implanted  
• 
informing the subject of the nature and possible cause of any AEs experienced  
• 
informing the subject of any new significant findings occurring during the clinical investigation, 
including the need for additional medical care that may be required  
• 
providing the subject with medical care required for possible emergency situations related to the 
clinical investigation  
• 
ensuring that clinical records are clearly marked to indicate that the subject is enrolled in this 
study  
• 
providing, if required, the subject with documentation that the subject is enrolled in this study  
• 
informing the subject’s personal physician about the subject’s participation in the study  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 49 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
12.1.11 Safety Reporting  
The PI will make reasonable and consistent efforts to document all adverse events (AEs). The PI will:  
• 
record every AE and observed device deficiency or malfunction  
• 
report all SAEs and device deficiencies to the sponsor within 48 hours of occurrence   
• 
provide sponsor-requested details for AEs and device deficiencies/malfunctions in a timely 
manner  
• 
report SAEs to the EC   
• 
submit a summary of the progress of the study to the involved ethics committee once a year or 
according to the national/local requirements  
12.1.12 Device Accountability   
Device accountability records must be maintained at the study site. All investigational devices will be 
traced by part number, lot number, and if applicable, serial number. The investigator is responsible for 
accounting for all devices transferred to his position. The investigator will ensure that any devices stored 
at the site are in a secure location.  
The sponsor will ensure that investigational devices are tracked carefully from the time of provision to 
the site to disposition.  
12.1.13 Recording Data on Electronic CRFs  
The data will be entered via electronic interface through an Electronic Data Capture system (database), 
validated and secured with compliant requirements such as audit trail, secure log-in with the PI 
responsible for reviewing the electronic data and signing using the database system signature method.  
The study will use electronic case report forms that have been standardized for the study to collect data. 
Site personnel will be trained in use of the eCRFs before study initiation. The PI will ensure that data 
recorded in the eCRFs in a timely manner and are accurate, consistent with source documents, reliable 
and logically correct.   
Electronic CRF Form samples are in Appendix D20.  
12.1.14 Deviations  
The investigator is not allowed to deviate from the Clinical Investigational Plan, except to maintain the 
subject’s rights, protect the life and physical well-being of a subject in an emergency, or the scientific 
integrity of the investigation. All protocol deviations shall be documented on the Protocol Deviation 
Case Report Form.    
The sponsor (or delegate) is responsible for analyzing deviations, assessing their significance, and 
identifying any additional corrective and/or preventive actions (e.g. amend the Clinical Investigational 
Plan, conduct additional training, or terminate the investigation). Repetitive or serious investigator 
compliance issues may result in initiation of a corrective action plan with the investigator and site, and in 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 50 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
some cases, necessitate suspending enrollment until the problem is resolved or ultimately terminating the 
investigator's participation in the study.   
12.1.15 Final Report  
The sponsor will prepare a final report when the study is completed or if it is terminated. The sponsor 
will provide the report to the EC and regulatory authorities as required.   
12.1.16 Document Retention  
The PI will maintain documents related to this investigation until 2 years after the study is complete or in 
accordance to EU or individual site requirements. The PI may transfer custody of records to another 
person/party and document the transfer at the clinical site with notification to the sponsor or at the 
sponsor's facility. The PI and/or site personnel cannot destroy the study documents without first 
obtaining written approval from the sponsor. Required documents to retain are extensive and are listed in 
Annex E of ISO 14155:2011(E).  
12.1.17 Source Documents  
The PI will retain original source documents (or copies thereof) used to verify study data. The PI or site 
personnel will provide written confirmation with signature and date that copies of source documents are 
true reproductions of the original source document. The sponsor may have access to original source 
documents upon request.  
12.2 Sponsor Responsibilities  
12.2.1 Overall Conduct of Study  
Cerus Endovascular Ltd, the study sponsor, is responsible for the overall conduct of this investigation, 
including:  
• 
implementing written clinical quality procedures to ensure that the clinical investigation is 
designed, conducted and monitored, and that data are generated, documented, recorded and 
reported in compliance with Good Clinical Practice (GCP), the CIP and its amendments, and any 
other applicable standards and regulatory requirements  
• 
maintaining records to document the compliance of all parties involved in the clinical 
investigation  
• 
documenting significant/key correspondence with all parties involved in the clinical investigation  
• 
ensuring that the clinical investigation is appropriately monitored by determining the extent and 
nature of monitoring  
• 
reviewing monitoring reports and following up any required actions in those reports  
• 
taking prompt action to secure compliance with all clinical investigation requirements  
• 
submitting progress reports, including safety summary and deviations, when requested, to all 
reviewing ECs and the regulatory authorities  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 51 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
providing insurance, in accordance with national regulations, covering the costs of treatment of 
subjects in the event of the study related injuries.  
12.2.2 Clinical Personnel  
The sponsor will designate or appoint one or more study monitors and will ensure documentation of 
training of monitors sufficient to conduct the investigation.   
12.2.3 Study Preparation  
Before starting the study, the sponsor will:  
• 
define all roles and responsibilities related to this investigation  
• 
ensure that all required signatures are obtained  
• 
ensure the accuracy of translation, if required, of any aspect of the study prior to initiating the 
study at the selected site  
• 
develop a complete set of documents necessary to begin the study, including consent forms, case 
report forms (CRFs) and, if required, an investigator’s brochure   
• 
document any financial arrangements between the PI or investigation site and the sponsor  
• 
submit any required application(s) to begin the investigation to appropriate regulatory authorities 
for review, acceptance or permission, as required  
• 
ensure documented EC approval before the study is started  
• 
ensure documented ongoing EC approval of the study  
• 
ensure that the site’s ICF is consistent with requirements of ISO 14155:2011  
• 
ensure that any modifications required by the EC or regulatory authority are made and 
documented by the PI  
12.2.4 Study Documentation Amendment  
The IB, CIP, CRFs, informed consent form and other subject information, or other clinical investigation 
documents shall be amended as needed throughout the clinical investigation, and a justification 
statement shall be included with each amended section of a document. Proposed amendments to the CIP 
shall be agreed upon between the sponsor and principal investigator, or the coordinating investigator. 
The amendments to the CIP and the subject's informed consent form shall be notified to, or approved by, 
the EC and regulatory authorities. The version number and date of amendments shall be documented.  
For non-substantial changes [e.g. minor logistical or administrative changes, telephone numbers, renewal 
of insurance] not affecting the rights, safety and well-being of human subjects or not related to the 
clinical investigation objectives or endpoints, a simple notification to the EC and, where appropriate, 
regulatory authorities can be sufficient.  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 52 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
12.2.5 Investigational Site Qualification  
The sponsor will ensure that each investigational site:  
• 
has a qualified PI   
• 
has adequate staff, resources, including facilities, laboratories, equipment and a qualified 
investigation site team  
• 
has access to an adequate number of subjects on a timely basis Site qualification will be 
documented.  
12.2.6 Investigational Site Initiation  
The sponsor will ensure that the site does not begin the study until all of the following have been 
collected or performed and documented:  
• 
training in requirements and contents of this CIP and its associated documents (e.g., CRFs, IFU, 
IB, etc.)  
• 
written EC approval, including EC-approved IC form, if required  
• 
list of EC members or EC assurance number, if required  
• 
documentation of investigational team’s designated roles and responsibilities  
• 
documentation of investigator conflict of interest  
• 
signed investigator agreement  
• 
signed clinical trial agreement (CTA). The CTA is the legal agreement between the site, PI and 
sponsor that covers all activities related to the study. The agreement will indicate that, by 
participating in a clinical investigation, the parties may share some regulatory responsibilities 
with the sponsor.  
• 
current curriculum vitae of PI and any sub-investigators  
12.2.7 Monitoring  
Monitoring will be performed during the study according to the study Monitoring Plan.  
The sponsor is responsible for study monitoring. Monitoring is done to verify that the study has been 
performed consistent with this CIP (and its amendments), and any other local or national requirements. 
The sponsor will document a monitoring plan.  
12.2.8 Qualified Monitors  
The sponsor will ensure that study monitors:  
• understand requirements of this CIP  
• are knowledgeable on the use of the study device  
• are knowledgeable on the informed consent process  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 53 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• are trained on the applicable portion of the sponsor’s quality control system  
• are trained in any special procedures required for monitoring this CIP Training will be 
documented in the sponsor’s files.  
12.2.9 Remote Monitoring  
Data collected during the study will be systematically reviewed by the sponsor to identify 
inconsistencies, potential data errors or potentially unclear information. Statistical techniques may be 
used to identify outliers. Queries will be sent to the site for data that may represent errors or that require 
clarification.   
12.2.10 On-Site Monitoring  
The monitor will perform on-site monitoring visits to verify:  
• 
compliance with this CIP and its amendments  
• 
compliance with requirements, if any, of the governing /EC  
• 
compliance with local regulations pertaining to a clinical study  
• 
compliance with requirements, if any, of regulatory authorities  
• 
continued adequacy of investigation site resources, including laboratories, equipment and the 
investigation site team  
• 
continued access to a sufficient number of potential study subjects  
• 
compliance with the informed consent process  
• 
all CIP requirements are met before the study begins at the site  
• 
adequate storage, maintenance and accountability of investigational devices  
• 
adequate storage and maintenance of source documents and other related records  
• 
source documents are accurate, complete and up-to-date  
• 
CRFs and queries are completed adequately, in a timely manner, and consistent with source 
documents  
• 
all AEs, deviations and device deficiencies are documented and reported to the sponsor  
• 
any device deficiencies/malfunctions that could have led to an SAE are reported to the sponsor 
without unjustified delay  
• 
all SAEs are reported to the EC, if required  
• 
maintenance of required reports, notifications, applications, submissions and correspondence in 
the PI’s files  
• 
maintenance and calibration (and documentation thereof) of all equipment relevant to this CIP  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 54 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
maintenance and documentation of current laboratory normal values and certifications, if required  
• 
subject withdrawal and reasons for withdrawal have been documented  
• 
subject non-compliance with the requirements stated in the informed consent has been 
documented  
• 
any corrective and preventive actions, as needed, have been implemented and are effective  
The monitor will document site monitoring visits in a report that includes the site’s compliance with the 
CIP. The report will include:  
• 
date of monitoring  
• 
site identification  
• 
name of monitor and PI  
• 
summary of what was reviewed  
• 
summary of observations and findings  
• 
summary of recommendations   
The monitor will share all findings with the PI and the sponsor.  
12.2.11 Study Close Out  
When the investigation is complete, the sponsor will ensure that sites undergo closeout activities, to 
include:  
• 
all essential documents are available and present in the PI’s files  
• 
all CRFs are completed  
• 
all queries are resolved  
• 
the status of all ongoing AEs is documented  
• 
arrangements for record retention have been made  
• 
all documents needed for sponsor’s files are retrieved  
• 
unused study devices are accounted for and returned to the sponsor  
• 
local EC and regulatory authorities are notified, if applicable In addition, the sponsor will:  
• 
provide a clinical investigation report to sites  
• 
ensure that clinical investigational report is provided to EC, investigators and regulatory 
authorities (if required)  
12.2.12 Auditing  
At the discretion of the sponsor, any site may undergo audit by the sponsor or a sponsor-designated third 
party. Audits evaluate compliance with this CIP, ISO standards or other regulatory requirements.   

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 55 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
12.2.13 Safety Reporting  
The sponsor is responsible for ongoing safety evaluation in this CIP. Sponsor activities regarding safety 
include:  
• 
ensuring the CEC reviews all serious neurologic, device and procedure related adverse events to 
ensure they are reported accurately and in sufficient detail   
• 
review and classification of all AEs reported in the study  
• 
confirm site’s classification of AEs in terms of severity and relatedness to the study device  
• 
review of device deficiencies and malfunctions, including determination and documentation of 
whether deficiencies/malfunctions could have led to an SAE  
• 
ensuring the reporting of all SAEs and device deficiencies/malfunctions that could have led to an  
SAE to the EC and, if required, regulatory authorities in a timely fashion and informing all site 
PIs in writing of all SAEs at all sites in a timely fashion  
• 
ensuring that the EC and the regulatory authorities are informed of significant new information 
about the clinical investigation  
• 
updating the risk analysis and assessment of corrective or preventive actions potentially required 
as a result of new information obtained in the investigation  
The sponsor will evaluate all serious adverse events. The sponsor will investigate each SAE to determine 
whether the event represents an unanticipated serious adverse device effect (USADE). The sponsor will 
report any event to regulatory authorities, investigators and reviewing ECs as necessary. If an 
investigation shows that a USADE presents an unreasonable risk to subjects, the sponsor will terminate 
all investigations or parts of investigations presenting that risk as soon as possible. The sponsor will only 
resume a terminated investigation after corrective actions have taken place, site investigators are 
informed and ECs have been notified and given approval to resume the study.  
12.2.14 Device Deficiencies and Malfunctions  
A device deficiency is defined as inadequacy of a medical device related to its identity, quality, 
durability, reliability, safety or performance, such as malfunction, misuse or use error and inadequate 
labelling (ISO 14155:2011). A device malfunction is a failure of a medical device to perform in 
accordance with its intended purpose when used in accordance with the Instructions for Use or CIP (ISO 
14155:2011).   
The sponsor will conduct an analysis of any device deemed deficient or malfunctioning by the site and 
track underlying causes for failure.   
All deficiencies and malfunctions will be evaluated against applicable requirements for reporting.   
12.2.15 Suspension or Termination of Study  
The sponsor may temporarily suspend or terminate the study at any time at one or more sites for the 
following reasons:  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 56 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
Suspicion of risk to patients, including occurrence of high rate of known AEs or unexpectedly 
high rate of unexpected AEs  
• 
Poor site compliance with this CIP  
• 
Inadequate site enrolment  
• 
Obtaining new scientific knowledge that shows that the study is no longer valid or necessary  
• 
Persistent non-compliance with EC or regulatory requirements  
• 
Persistent failure to comply with obligations arising from the clinical trial agreement  
• 
Other business reasons (e.g., insolvencies or business entity liquidation)  
The sponsor will document reasons for study suspension and notify relevant site PIs. The sponsor will 
ensure that the EC and regulatory authorities (if required) are notified in a timely manner. If suspension 
occurred because of a safety issue, all site PIs will be notified. When terminating the study, the sponsor 
and investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.   
12.2.16 Resuming a Temporarily Suspended Study  
If the sponsor temporarily suspends the study and wishes to resume it, the sponsor will inform the site 
PIs, ECs and (if appropriate) regulatory authorities. The sponsor will provide a rationale for resuming 
the study. ECs must provide written approval before the study is resumed at the site.  
12.2.17 Suspension of Study Center  
The Sponsor may discontinue a study center if the center fails to recruit sufficient patients or if the centre 
is found to be in recurrent or continuous non-compliance with the Clinical Investigation Plan and/or ISO 
14155:2011 or other applicable requirements.  
12.2.18 Document Control  
The CIP may require updating during the study. Important sponsor documents related to this CIP will be 
controlled with version numbers to ensure traceability. Expired versions of documents will be archived 
by the study sponsor.  
The sponsor will ensure that amended documents (e.g., new versions) are, where required, approved by 
the EC before they are used in the study. Reasons for amendment will be justified and documented. The 
sponsor will ensure that the PI has acknowledged receipt of significant new documents.  
12.2.19 Clinical Investigation Report  
The sponsor will be responsible for ensuring that a clinical investigation report is prepared which 
summarizes study findings. The report will be prepared even if the investigation is terminated early.  
The report will:  
• 
be in written form  
• 
be completed even if the study is premature terminated  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 57 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
will include device identification and description  
• 
summarize clinical trial methodology  
• 
include a summary of deviations  
• 
provide adequate analysis with statistical analysis, where appropriate,  
• 
critically appraise the aims of the study and whether the aims were met  
• 
not provide personally identifying subject information  
• 
be made available to the study Principal Investigator prior to finalization for comment and review  
• 
signed by the study Principal Investigator  
• 
provided to ECs and regulatory authorities, as per applicable requirements  
12.2.20 Document Retention  
The sponsor will maintain documents related to this pre-market study as required by applicable 
regulatory standards and according to the applicable national or local law. Required documents to retain 
are extensive and are listed in Annex E of ISO 14155:2011.  
13  Publications  
 
The study will be publicly registered prior to first enrollment in accordance with the 2007 Food and Drug 
Administration Amendments Act (FDAAA) and Declaration of Helsinki on http://clinicaltrials.gov.  
In accordance with the sponsor’s Corporate Policy on the Conduct of Human Subject Research, the sponsor 
requires disclosure of its involvement as a sponsor or financial supporter in any publication or presentation 
relating to a sponsor’s study or its results. In accordance with the sponsor’s Corporate Policy for the Conduct of 
Human Subject Research, the sponsor will submit study results for publication (regardless of study outcome) 
following the conclusion or termination of the study. The sponsor adheres to the Contributorship Criteria set 
forth in the Uniform Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely manner, while 
maintaining an unbiased presentation of study outcomes, sponsor personnel may assist authors and investigators 
in publication preparation provided the following guidelines are followed:   
All authorship and contributorship requirements as described above must be followed.   
Sponsor involvement in the publication preparation and the sponsor Publication Policy should be discussed with 
the Principal Investigator(s) and/or Executive Committee at the onset of the project.   
The First and Senior authors are the primary drivers of decisions regarding publication content, review, approval, 
and submission.   
Publication status will be posted to the pertinent study listing on clinicaltrials.gov.  
  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 58 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
14 References  
 
1. Brisman JL, Song JK, Newell DW. Cerebral aneurysms. N Engl J Med 2006;355(9):928–39.   
2. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical 
clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised 
trial. Lancet 2002;360(9342):1267–74.   
3. Molyneux AJ, Birks J, Clarke A, Sneade M, Kerr RSC. The durability of endovascular coiling versus 
neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the 
International Subarachnoid Aneurysm Trial (ISAT). Lancet 2015;385(9969):691–7.   
4. Johnston SC, Dowd CF, Higashida RT, et al. Predictors of rehemorrhage after treatment of ruptured 
intracranial aneurysms: the Cerebral Aneurysm Rerupture After Treatment (CARAT) study. Stroke J Cereb 
Circ 2008;39(1):120–5.   
5. Molyneux AJ, Clarke A, Sneade M, et al. Cerecyte coil trial: angiographic outcomes of a prospective 
randomized trial comparing endovascular coiling of cerebral aneurysms with either cerecyte or bare 
platinum coils. Stroke J Cereb Circ 2012;43(10):2544–50.   
6. Ko JK, Han IH, Cho WH, et al. Crossing Y-stent technique with dual open-cell stents for coiling of 
widenecked bifurcation aneurysms. Clin Neurol Neurosurg 2015;132:54–60.   
7. Akgul E, Balli T, Aksungur EH. Hybrid, Y-configured, dual stent-assisted coil embolization in the treatment 
of wide-necked bifurcation aneurysms. Interv Neuroradiol J Peritherapeutic Neuroradiol Surg Proced Relat 
Neurosci 2015;21(1):29–39.   
8. Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A second-generation, endoluminal, 
flowdisrupting device for treatment of saccular aneurysms. AJNR Am J Neuroradiol 2009;30(6):1153–8.   
9. Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicentre 
clinical trial. Radiology 2013;267(3):858–68.  
10. Cognard C, Januel AC, Remnants and recurrences after the use of the WEB intrasaccular device in largeneck 
bifurcation aneurysms. Neurosurgery. 2015 May; 76(5):522-30; discussion 530. doi:  
10.1227/NEU.0000000000000669.  
11. Pierot L, Costalat V, Moret J, et al. Safety and efficacy of aneurysm treatment with WEB: results of the 
WEBCAST study. J Neurosurg. 2015 Sep 18:1-7. [Epub ahead of print]  
12. ISO 14155:2011, Clinical investigation of medical devices for human subjects – Good clinical practice.  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 59 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
13. Directive for Medical Devices (MDD): 93/42/EEC and Active Implantable Medical Devices (AIMD) 
90/385/EEC. Amended by Directive 2007/47 EC (European Council).  
14. Article 2.3.5 under Clinical Evaluation (Annex VII, 90/385/EEC and Annex X 93/42/EEC).  
15. MEDDEV 2.7/3 (2015) Guidelines: SAEs Reporting-Clinical Investigations.  
16. MEDDEV 2.12-1 rev7 (2012): Guidelines on a Medical Devices Vigilance System.  
17. MEDDEV 2.12-2 rev2 (2012): Guidelines on a Medical Devices, Post Market Clinical Follow-Up Studies.  
18. WMA Declaration of Helsinki. Ethical Principles of Medical Research Involving Human Subjects. JAMA. 
2013 Vol. 310 (20): 2191-2194.  
19. MEDDEV 2.7.1 rev3 (2009): Clinical evaluation. A guide for manufacturers and notified bodies.  
20. Hetts, S.W., Turk, A., el al., (2013) Stent-Assisted Coiling versus    
  
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 60 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
15 Revision History  
 
This section maintains the revision history for the document, including submission history.  
Revision A of the document was prepared for initial review for NCA and EC submission.    
Rev  
DCO  
Change Description  
Release Date  Submitted to Ethic 
Committees  
A  
0344  
Initial Release  
25 Jan 2018  
Feb 2018  
B  
0400  
Revisions based on BfArM and Kiel Ethics 
Committee responses  
03 Jul 2018  
4 July 2018  
C  
0412  
Revisions based on BfArM response  
15 Aug 2018  
NA  
C  
0415  
Correction Only:  correct header to be same for 
all pages.  Correct Sponsor signature page, #56  
16 Aug 2018  
17 Aug 2018  
D  
0422  
Added Core lab contact  
Revisions based on BfArM response  
10 Sep 2018  
Sept 2018  
E  
0560  
• Correct Sponsor and manufaturer from Cerus  
Endovascular, Inc., to Cerus Endovascular, 
Ltd  
• Remove Pr Laurent Spelle as PI  
• Change enrollment period from 6 months to 9 
months  
06 Dec 2019  
Dec 2019  
F  
0560  
• Update to new core lab contact  
06 Dec 2019  
Dec 2019  
  
 
  
  
16 APPENDIX A - Statement of Compliance and Signature Page  
 
Clinical Investigation Number: DNX099-01  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 61 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
The signature below signifies that I have read this Clinical Investigation Plan and agree to adhere to the 
requirements. I will provide copies of this Clinical Investigation Plan and all pertinent information to the study 
personnel under my supervision. I will discuss this material with them and ensure they are fully informed 
regarding the Plan’s requirements. I will ensure that the study is conducted in compliance with the Plan, ISO 
14155:2011, the Declaration of Helsinki, and the pertinent individual country laws/regulations and all applicable 
regulatory requirements including requirements imposed by Ethics Committee (EC).  
Site Name:  
  
  
Site Principal Investigator:  
(Print Name)  
  
  
  
  
  
Signed:    
  
  
Date:  
  
  
  
 
  
  

  
 
  
Document Number  
DNX099-01  
Rev  
F  
Page 62 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
17 APPENDIX B - Sponsor Approval Page  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 63 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
  
  
Study Title:  
  
CIP Document Number:  
  
CIP Revision:   
  
  
CIP Date:  
  
  
  
  
Signature:  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm  
Study (CERUS)  
DNX099-01  
F  
06 Dec 2019  
______________________________________________  
L. Carol Holt, MS, RN  
Vice President, Clinical Affairs  
Cerus Endovascular Inc  
47757 Fremont Blvd  
Fremont, CA  94538  
United States  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 64 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
18 APPENDIX C - German Medical Devices (MPG)   
 

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 65 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 66 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 67 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 68 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 69 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 70 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 71 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 72 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 73 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
19 APPENDIX D – Report of Prior Investigations  
 
19.1 First-In-Human Clinical Study – Contour Compassionate Use  
A total of 4 patients received the Contour implant under a Compassionate Use (expanded access) approval by the 
Clinica La Segrada Familia, Ethics Committee (EC). The rationale was that the Contour implant could 
potentially treat patients with difficult, complex, unruptured intracranial aneurysms (IA)s with less risk 
compared to other alternatives. The procedures were performed by neuro interventional radiologist, Pedro Lylyk, 
M.D., at Clinica La Sagrada Familia, Buenos Aires, Argentina.   
The patient baseline demographics are shown in Table 7.   
Interim Results (Update report is expected 31 July 2018)  
All 4 patients (4/4, 100.0%) were Caucasian females. The mean age was 65.8 years (yrs) old.   
Table 7 FIM Study: Baseline Demographics  
  
  
Gender   
  
Age (yrs)   
  
Ethnicity   
Patient 1   
  
Female   
  
65   
  
Caucasian   
Patient 2   
  
Female   
  
75   
  
Caucasian   
Patient 3   
  
Female   
  
  
58   
  
  
Caucasian   
  
Patient 4   
  
Female   
 
65   
 
Caucasian   
  
Three out of 4 patients (3/4, 75.0%) had multiple IAs. One out of 4 patients (1/4, 25.0%) had a history of 
bilateral carotid stenosis that required stenting and percutaneous transluminal angioplasty (PTA). Two out of 4 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 74 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
patients (2/4, 50.0%) were on dual anti-platelet (DAP) therapy for prior implants (carotid stent and flow diverter) 
in the parent artery.   
Detailed Clinical characteristics are shown in Table 8 below:   
Table 8 Clinical Characteristics  
  
IA Location   
  
Symptoms  
related to IA   
  
  
Neuro exam  
findings   
  
  
Medical History   
  
Patient 1   
Anterior  
Communicating  
Artery (ACom)   
None   
Rotatory horizontal 
nystagmus   
Arterial Hypertension   
Dilated Cardiomyopathy   
Right Middle Cerebral Artery (MCA) IA 
previously treated with Web device   
Left pericollosal IA previously treated with 
coils   
Patient 2   
Left MCA   
  
None   
  
Unable to evaluate 
neurologically   
  
Ruptured, Right Posterior communicating  
Artery (PCom) previously treated with coils   
Subarachnoid hemorrhage (SAH) secondary to 
ruptured PCom   
Arterial Hypertension   
Patient 3   
Hypophyseal   
  
Headache  
(HA)   
  
  
No abnormal 
findings   
  
  
Right carotid ophthalmic previously treated 
with Pipeline Embolization device (PED) – 
patient placed on DAP medications   
  
Patient 4   
Right MCA   
None   
  
No abnormal 
findings   
Hypertension   
Dyslipdemia   
Bilateral carotid stenosis requiring stent 
placement - patient placed DAP medications   

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 75 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Three out of 4 patients (3/4, 75.0%) have completed their 12 month follow-up visits. See  Table 9 for the details:  
Table 9 Procedure and Follow-Up  Visit  
  
Procedure   
  
30 Day FU   
  
6 Month FU   
  
12 month FU   
  
Patient 1   
Date: 2015-10-19  
No Adverse Events (AE)s, 
Adverse Device effects (ADE)s 
or Device Malfunctions   
Cerebral angiogram 
demonstrated immediate stasis 
of blood flow within IA after  
Contour was deployed   
Remained 
asymptomatic; Normal 
neuro exam; No AEs   
Cerebral angiogram 
demonstrated partial 
occlusion   
Remained 
asymptomatic; Normal 
neuro exam; No AEs; 
No device migration   
Cerebral angiogram 
demonstrated partial 
occlusion   
Remained 
asymptomatic; 
Normal neuro 
exam; No AEs;   
Patient 2   
Date: 2015-10-19  
No AEs, ADEs or Device  
Malfunctions   
Cerebral angiogram 
demonstrated immediate stasis 
of blood flow within IA after  
Contour was deployed   
  
Cerebral angiogram 
demonstrated 
aneurysm is smaller in 
size compared to 
baseline   
  
Patient has not returned 
for 6 month FU Patient 
deceased as a result of 
complications from 
initial stroke. SAE 
related to pre-existing 
condition.   
  
N/A   
  
Patient 3   
Date: 2015-10-20  
No AEs, ADEs or Device  
Malfunctions   
Cerebral angiogram 
demonstrated immediate stasis 
of blood flow within IA after  
Contour was deployed   
Asymptomatic; Normal 
neuro exam; No AEs   
Cerebral angiogram 
demonstrated 
decreased flow within 
the IA   
  
Remained 
asymptomatic; Normal 
neuro exam; No AEs; 
No device migration   
Cerebral angiogram 
demonstrated Contour in 
good position with 
partial occlusion   
Remained 
asymptomatic; 
Normal neuro 
exam; No AEs;   
Patient refused 
angiogram   
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 76 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Patient 4   
  
Date: 2015-10-26  
No intraprocedural Adverse 
Events (AE)s, Adverse Device 
effects (ADE)s or Device 
Malfunctions   
Two days post-procedure, 
patient had a transient right 
pseudo femoral aneurysm 
confirmed via echodoppler.  
Asymptomatic; Normal 
neuro exam; No AEs   
Cerebral angiogram 
demonstrated 
decreased flow within 
the IA   
Remained  
asymptomatic; Normal 
neuro exam; No AEs; No 
device migration   
Cerebral angiogram 
demonstrated Contour in 
good position with 
partial occlusion   
Remained 
asymptomatic; 
Normal neuro 
exam; No AEs;   
Physician rated it as mild in 
severity. No treatment was 
required for AE resolution. 
Physician rated it as related to 
the procedure but not the 
device.   
Cerebral angiogram 
demonstrated immediate stasis 
of blood flow within IA after  
Contour was deployed   
  
Overall, the Contour demonstrated an excellent safety profile with its initial clinical use on a complex set of 
patients.. There was 1 ADE in Patient #4 that was right femora pseudo aneurysm that resolved without treatment. 
It was rated as mild in severity by the PI. The second AE was a SAE in patient #2 who died as a result of a 
complication from a pre-existing condition. These AEs were anticipated and are similar to those expected for 
aneurysm embolisation procedures. The remaining 3 patients did not have any AEs at their 12 month follow-up 
visits.   
In its initial clinical use, the Contour demonstrated an excellent safety profile in all 4 patients and performed as 
intended. The physician reported that there was 100% technical success with all 4 cases. Follow-up angiograms 
demonstrated partial occlusion of the IA.   
19.2    Study INCA: Intracranial Aneurysm Treatment with NeXsys  
The INCA study includes 3 patients that was conducted at La Clinica Sagrada Familia, Buenoe Aires in 
accordance with good clinical practices as described in ISO 14155:2011, with the Helsinki Declaration 
adopted by the 18th World Medical Assembly in Helsinki, Finland in 1964, as amended by the World 
Medical Assembly, and under ethics committee approval and is approved by Administración Nacional 
de Medicamentos, Alimentos y Tecnología Médica (ANMAT).  
19.2.1 Interim Results  
The patient baseline demographics are shown below.  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 77 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Two out of 3 patients were female (2/3, 66.6%).  All 3 patients were Caucasian. The mean age was 67 
yrs old.  
Demographics  
  
Gender  
Age  
(yrs.)  
Ethnicity  
Patient 
001JIM  
Female  
77  
Caucasian  
Patient  
002- 
PEZ  
Male  
62  
Caucasian  
Patient 003- 
PAR  
Female  
62  
Caucasian  
Clinical Characteristics  
  
IA Location  
Symptoms  
related to IA  
Neuro exam 
findings  
Medical History  
Patient 
001-JIM  
Pericallosal  
None  
None  
Non (never) Smoker  
PComm aneurysm previously 
treated with coils  
  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 78 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Patient 
002-PEZ  
Rt. A1/2  
None  
None  
Current smoker  
Existing Lt MCA bifurcation 
aneurysm and Lt Cavernous 
Carotid aneurysm under watchful 
waiting  
Current history of Hypertension,  
Obesity, Dyslipidemia and 
Asthmatic  
Current medication, Carvelidol and 
Valsartan for Hypertension and 
Estatin for Dyslipidemia  
Pituitary Macroadenoma with 
previous Rt frontal craniotomy 
surgery.  
Long standing bilateral visual field 
defects (Rt temporal hemianopsia 
and Lt Temporal quadrantopsia)   
Patient  
003-PAR  
Rt. Carotid 
Bifurcation  
Headache 
(HA)  
None  
Non (Never) smoker  
No prior history aneurysm   
 
 
 
 
Hypothyroidism currently on 
Levothyroxine  
Procedure and Follow-Up Visits  
  
Procedure   
30 Day FU  
6 Month FU  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 79 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Patient 001JIM  
Date: 2016-May-09  
11mm device deployed 
which failed to open fully. 
Device retrieved without 
incident and replaced with 
9mm device  
Peri procedural slight 
vasospasm distal to A1 to 
ACCA bifurcation cleared 
using 10mg diluted to 30% 
Nimodipine intra-arterially  
Cerebral angiogram 
demonstrated slowed filling 
of the aneurysm with contrast 
media within IA after 
NeXsys was deployed  
Remained asymptomatic;  
Normal neuro exam; No 
AEs  
Device remained stable  
Cerebral angiogram 
demonstrated partial 
reduction of flow into the 
IA with poor device 
apposition   
AE: Patient remained 
hospitalized as a result of 
complications of SAH 
from ruptured Lt PComm 
aneurysm treated 6 days 
before NeXsys procedure. 
Patient developed  
Hyponatremia. Discharged  
32 days after index 
procedure.  
Remained asymptomatic;  
Normal neuro exam; No 
AEs;   
Cerebral angiogram 
demonstrated migration of 
the device distally into the 
aneurysm sac with blood 
flow into the aneurysm  
Patient 002-PEZ  
Date: 2016-Jun-08  
No AEs, ADEs or Device 
Malfunctions during the 
procedure or before 
discharge.  
Cerebral angiogram 
demonstrated immediate 
stasis of blood flow within 
IA after Contour was 
deployed.  
SAE 9 days post procedure, 
patient presented to 
emergency room with Lt. 
Hemiplegia. MRA showed 
distal thrombus formation in  
Patient refused 30-day 
angiogram  
Cerebral Angiography at 6 
months demonstrated 
complete aneurysm 
occlusion  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 80 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 
the ACA probably secondary 
to thrombus formation on the 
NeXsys device detachment 
marker in the parent vessel. 
The thrombus was treated 
with intra-arterial antiplatelet 
infusion. Resolved with no 
sequelae and patient 
discharged.  
Device stable at 11-day post 
implant imaging.  
 
 
Patient 3  
Date: 2016-Sep-02  
No AEs, ADEs   
Device Malfunction of 9mm 
device where the implant did 
not fully open. Device 
retrieved and returned for 
inspection where it was 
found to have fibrin elements 
constricting the distal edge 
which had resulted in failure 
to fully open. New device 
opened and deployed without 
incident.  
Cerebral angiogram 
demonstrated immediate 
stasis of blood flow within IA 
after NeXsys was deployed  
Asymptomatic; Normal 
neuro exam; No AEs  
Continues to be 
asymptomatic  
Patient refused cerebral 
angiogram and MRI 
performed.  
Cerebral Angiography at 3 
months demonstrated 
complete aneurysm 
occlusion  
Adverse Events  
Subject 
ID  
Onset 
Date  
Resolved 
Date  
Event 
Description  
SAE  
Relation  
Intervention,  if Any  
PEZ002  
17 June 
2016  
20 June 
2016  
Ischemic Stroke  
Yes  
Device 
Related  
Patient underwent intra-arterial 
infusion of anti-platelet agent  
(Agrastat) under cerebral 
angiography and MRA follow  
up. Patient discharged without 
sequelae.  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 81 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
JIM-001  
13 May 
2016  
11 June 
2016  
Hyponatremia   
Yes  
Not Device  
or  
Procedure 
Related  
Sodium Chloride replenishment  
JIM-001  
13 May 
2016  
11 June 
2016  
Urinary Tract 
Infection (UTI)  
No  
Not Device  
or  
Procedure 
Related  
Antibiotics  
There was 1 AE that was a UTI that developed in Patient JIM-001 during their ICU stay that required 
antibiotics for resolution.  
There was 1 ADE in Patient JIM-001 where the device was seen to have migrated into the aneurysm at 
6month follow up. This device was not fully opposed to the aneurysm wall as seen on 3-month follow up.    
In the patients enrolled to date, the Contour Neurovascular System™ continues to demonstrate a safety 
profile consistent with current practice. There were 2 SAEs, one related to the device which resulted in 
hemiparesis caused by thromboembolic complication. This resolved with the administration of intraarterial 
Agrestat and the patient was discharged with no sequelae on anti-platelet medication. A second SAE 
related to the patient’s stay in the intensive care unit (ICU) where they developed Hyponatremia. This was 
resolved with sodium chloride replenishment and is related to the initial aneurysm rupture for which the 
patient was admitted.   
  
19.3 European Pilot Clinical Study – Contour  
A synopsis for the EU Pilot study is included below.  The study includes 3 sites in the United Kingdom 
and one site in Hungary.    
Study Title  
Pilot Study of the Contour Neurovascular System™   
Device Name  
Contour Neurovascular SystemTM  
Primary Objective  
To collect and report the safety variables data of the Contour Neurovascular System™  
Secondary Objective  
To collect and report the efficacy variables data of the Contour Neurovascular 
System™  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 82 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Design  
Prospective, single arm, multi-centre study  
Assigned Intervention  
Endovascular treatment with the Contour Neurovascular System™ for an unruptured 
intracranial aneurysm (IA)  
Target Patient 
Population  
Patients with unruptured IAs suitable for treatment with the Contour Neurovascular 
System™ and who meet study eligibility criteria  
Primary Variables  
Safety:  Safety variables are the occurrence and frequency of adverse events (AE)s, 
adverse device effects (ADE)s, serious adverse events (SAE)s, serious adverse device 
effects (SADE)s and unanticipated serious adverse device effects (USADE)s  
Specific AEs associated with this procedure that shall be evaluated include but are not 
limited to: blood vessel perforation or rupture, unintended thrombosis, adverse tissue 
reaction, infection, and hematoma formation, and major ipsilateral stroke/subarachnoid 
hemorrhage (SAH) or death due to neurologic cause within six (6) months after 
treatment  
Secondary Variables  
Efficacy: Efficacy variables are related to the ability of the device to embolize the 
aneurysm and shall be analyzed relative to the baseline visit. The variables to be 
collected and reported shall include but are not limited to:  
Angiographic and/or magnetic resonance imaging (MRI)/MR angiogram (MRA) 
assessment of aneurysm occlusion including evaluation of occlusion grade, parent 
vessel patency, physical positioning, occlusion durability, and any device migration  
Sample Size  
A maximum of forty-five (45) subjects  
Number of Sites  
A maximum of five (5) clinical study sites   
Study Visits  
Baseline, procedure, six (6) weeks, six (6) months, and one (1), two (2), three (3), four  
(4), and five (5) years  
Study Duration   
Projected to be at least 5 ½ years, including enrolment (assumes 6 months for 
enrollment)  
  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 83 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
19.4 Compassionate Use - Contour  
The Contour Neurovascular System has been used under a compassionate use basis for 7 patients.  The 
patients were implanted outside of the studies and have no prospectively defined data collection or 
analysis.  To date, there have been 7 compassionate use implants worldwide for the Contour device, 4 in 
South America (see section 16.1), 2 in United Kingdom and 1in Denmark.    
19.5 Compassionate Use - Neqstent  
The Neqstent has been used under a compassionate/emergency use basis for 5 patients and all patients 
were in Denmark.  The patients were implanted outside of the studies and have no prospectively defined 
data collection or analysis.    
19.6 Summary of Animal Studies - Contour  
This summary will provide an overview of the early animal and clinical research, as well as the laboratory 
testing conducted by Cerus Endovascular to evaluate the Contour Neurovascular System and 
Neqstentevaluate  
19.6.1 Non-GLP Animal Studies  
During the development phase of the Contour device, a series of non-GLP animal studies were 
performed to evaluate the usability, deployment, sizing and materials used in the initial prototypes.  A 
total of 13 animals were evaluated in the first four animal protocols during development for these 
formative assessments of the device.  
The final non-GLP animal study in 12 animals was conducted to evaluate the deployment, device 
stability when deployed across the neck of the aneurysm and the degree of exclusion of the aneurysm 
from circulation at 30 and 90 days post implantation. The protocol and reports associated with the 
nonGLP are included for your reference in Attachment 4.  
19.6.2 GLP Animal Studies  
A formal GLP Animal Study was conducted in preparation for human clinical trials.  The study included 
treatment and analysis for 12 animals at 30- and 90-day time points.  The protocol and final report are 
included for your reference in Attachment 5.  A summary is provided below.  
19.6.2.1 CONTOUR: GLP ANIMAL STUDY – CHRONIC FEASIBILITY STUDY SUMMARY  
 
Report Document  
NPIMR CER277/15  
Objectives  
To assess the safety and efficacy of the Contour Neurovascular System™ to occlude blood flow in an 
experimental aneurysm animal model. Methods  
The study was performed in compliance with the Good Laboratory Practice Regulations 1999 (S.I. No.  
3106) as amended by the 2004 regulations (S.I. No. 994) which are based on the principles of Good  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 84 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
Laboratory Practice as adopted by the Organization for Economic Co-operation and Development 
(OECD), ENV/MC/CHEM (98) 17.   
An induced experimental aneurysm model was used to investigate the Contour Neurovascular System™ 
as a treatment for intracranial aneurysm. The rabbit model has evolved over recent years as the species 
of choice for endovascular intracranial aneurysm due to three main factors:  
• 
The rabbit model is similar to the coagulation system in humans.  
• 
The dimensions of the extracranial carotid arteries are similar to the intra-arterial cerebral artery 
dimensions in the human.  
• 
Elastase aneurysms in rabbits are similar in size and shape to those seen in humans.  
Twelve male rabbits were used in the study, with six rabbits in the 30-day group and 6 rabbits in the 
90day group. Group allocation was randomized. The study comprised of the following steps:  
• 
The surgical creation of an aneurysm using the elastase model, targeting an aneurysm neck size 
between 3 and 6 mm.  
• 
The placement of the test article in the aneurysm using fluoroscopic guidance.  
• 
The assessment of performance of the test article using fluoroscopy, immediately after placement 
as well as at sacrifice 30 or 90 days later.  
• 
The post-mortem harvest of test article with local vasculature for histology. The aneurysm neck 
was scored for platelet/fibrin thrombus, percent endothelialization, and neointimal formation, 
while the aneurysm sac was scored for sac organization, inflammation, and neoangiogenesis.  
Main Outcome Measures  
1. Test article detachment time, confirmed visually under angiography.  
2. Test article positioning in the neck of the aneurysm, confirmed visually under angiography and by 
histology.  
3. Test article stability in situ over 30 and 90 days, visually by angiography and by histology.  
4. Evidence of aneurysm thrombosis following implant of the test article over 30 and 90 days, 
visually by angiography and by histology. Results  
Twelve animals underwent device placement as per the protocol and angiographic results are available 
on 6 animals at 30 days and 6 animals at 90 days. All animals maintained healthy body weight 
throughout the duration of the study. Histology results are available on 5 animals at 30 days and 6 
animals at 90 days. One aneurysm in the 30-day follow-up group was exceptionally small and did not 
withstand the preparation process for histology evaluation.  
Safety results are as follows:  
• 
The device was successfully deployed with 100% technical success in 12/12 cases with no 
evidence of adverse events confirmed fluoroscopically by the implanting physician.  
Histopathology at 30 and 90 days demonstrated no wall laceration or tears due to the implant.  
• 
In 12/12 animals parent vessel flow was maintained with no evidence of thrombo-emboli.  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 85 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
• 
12 of 12 devices detached within the design specification time of less than 120 seconds average 
and less than 180 seconds maximum.  
Efficacy endpoints are as follows:  
1. Stasis of blood flow in the aneurysm was achieved in all cases within 15 minutes with most 
aneurysms, demonstrating stasis immediately post detachment.  
2. Intra-aneurysmal thrombus was assessed using both the angiography at follow-up (30/90 days) and 
histopathological assessment.  
a. Angiography at 30 days: four grade 0 (complete occlusion), one grade 1 (90%+ occlusion), and 
one grade 2 (70-89% occlusion).  
b. Angiography at 90 days: four grade 0 and two grade 1 (with minor flow at the neck of the 
aneurysm).  
c. Histopathology at 30 days:  
i. 
Five of five aneurysms showed marked sac thrombus organization.  
ii. 
Four of five aneurysms showed marked neointimal growth across the neck. In one animal, the 
aneurysm was exceptionally small, and a portion of the device was positioned in the parent 
vessel. This device had a minimal amount of surface thrombus deposition on one side of the 
neck and had remained open to blood flow, not obstructing the parent artery.  
d. Histopathology at 90 days:  
i. 
Six of six aneurysms showed marked sac thrombus organization.  
ii. 
Four of six aneurysms showed marked endothelial growth across the surface of the device and 
two of six showed moderate endothelial growth across the surface of the device.  
iii. Five of six aneurysms showed complete neointimal filling of the lumen.  
e. 12 of 12 devices remained stable in situ during the follow-up time period. Conclusions  
The animal study demonstrated excellent effectiveness and safety results with regards to the performance 
of the Contour Neurovascular System™ in the treatment of elastase aneurysms in the rabbit model. 
Specifically, endothelialization and neointimal coverage, combined with aneurysm occlusion was seen in 
all animals. No aneurysm or vessel perforations/damage and no device migration or movement were 
observed in the angiographic and histopathological analysis.  
20 APPENDIX E – Case Report Form CRF Samples  
 

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 86 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 87 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
Clinical Study of the   
Contour Neurovascular System™  PATIENT 
ELIGIBILITY   
Site 
Numb er   
Subject 
Number  
  
  
  
  
  
  
  
ENTRANCE CRITERIA  
Yes  No  
1. Did subject meet all general entrance criteria  
  
  
2. Did subject meet all intra-procedural entrance criteria  
  
  
3. Date Informed Consent Signed  
  
 
   
If Study Device placement was attempted, patient remains in the study.  
  
.  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  /  
  /  

  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.   
  
Document Number  
DNX099-01  
Rev  
F  
Page 88 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
  
  
  
  
  
  
  
PI SIGNATURE (IF SOURCE DOCUMENT)  
 
Name:  
  
  
Date (DD-MON-YY):  
  
  
Signature:  
  
  
  
  
  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page 1 of 42  
  

  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use.  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 89 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 90 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 91 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
Clinical Study of the   
Contour Neurovascular System™  
DEMOGRAPHICS   
Site 
Numb er   
Subject 
Number  
  
  
  
  
  
  
  
DEMOGRAPHICS  
 
1. Birth Date  
  
2. Gender  
 
 Male  
 Female  
3. Ethnicity  
N/A  
4. Race  
Check all that apply  
 American Indian or Alaska Native  
A person having origins in any of the original peoples of 
North and South America (including Central America), and 
who maintains tribal affiliation or community attachment  
Asian  
A person having origins in any of the original peoples 
of the Far East, Southeast Asia, or the Indian 
subcontinent   Black   
A person having origins in any of the black racial 
groups of Africa  
 Native Hawaiian or Other Pacific Islander  
A person having origins in any of the original peoples 
of  
Hawaii, Guam, Samoa, or other Pacific Islands  
 White  
A person having origins in any of the original peoples 
of  
Europe, the Middle East, or North Africa  
 Unknown   
 Subject refused  
VITAL SIGNS  
 
5. Weight  
 kg  
6. Height  
 cm  
  /  
  /  
  .  
  .  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 92 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
7. Blood Pressure  
 mmHg  
8. Temperature  
 ⁰C   
9. Pregnancy test result  
 Positive (note: study exclusion)  
 Negative  
 Not done  
 Not applicable (male or postmenopausal 
woman)  
  
2 
  /  
  .  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 93 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 94 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
Clinical Study of the   
Contour Neurovascular System™  
DEMOGRAPHICS   
Site  
Numb er   
Subject 
Number  
  
  
  
  
  
  
ANTI-THROMBOTIC MEDICATIONS  
10. Total number of antiplatelet medications used 
pre-procedure  
 record any on medication log  
11. Total number of anticoagulation medications 
used pre-procedure  
 record any on medication log  
MEDICAL HISTORY  
Does patient have history of:  
12. Arrhythmia, non-Atrial Fibrillation  
 Yes   
 No   
 Unknown   
13. Atrial Fibrillation  
 Yes   
 No   
 Unknown   
14. Cardiovascular Disease   
(documented CAD, Valvular Disease, CHF)  
 Yes   
 No   
 Unknown   
15. Connective Tissue Disorder  
(i.e. systemic lupus erythematosus, rheumatoid  
arthritis, scleroderma, polymyositis, 
dermatomyositis)  
 Yes   
 No   
 Unknown   
16. Diabetes Mellitus  
 Yes   
 No   
 Unknown   
17. Hyperlipidemia requiring medication  
 Yes   
 No   
 Unknown   
18. Peripheral Vascular Disease  
 Yes   
 No   
 Unknown   
19. Hypertension requiring medication  
 Yes   
 No   
 Unknown  
20. Renal Insufficiency (Creatinine > 2.5 mg/dL)  
 Yes   
 No   
 Unknown  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 95 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
21. Smoking   
 Never smoked  
 Current smoker  
 Previous smoker   
  
  
  
3 

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 96 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 97 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
Clinical Study of the   
Contour Neurovascular System™  
DEMOGRAPHICS   
Site  
Numb er   
Subject 
Number  
  
  
  
  
  
  
  
NEUROVASCULAR MEDICAL HISTORY  
 22. History of stroke  
 Yes   
 No   
 Unknown  
22.1 If Yes, date most recent stroke  
  
22.2 If Yes, type of stroke(s)  Ischemic   
 
 
 
Check all that apply  
Intracranial Hemorrhage  
 Subarachnoid Hemorrhage  
 23. History of serious head trauma  
 Yes   
 No   
 Unknown  
 24. History of Hydrocephalus  
 Yes   
 No   
 Unknown  
24.1 If Yes, date most recent  
Hydrocephalus   
 25. History of Seizure  
 Yes   
 No   
 Unknown  
25.1 If Yes, date most recent seizure  
  
 26. History of other cerebral aneurysm  
 Yes   
 No   
 Unknown  
26.1 If Yes, date most recent aneurysm  
  
SIGNS AND SYMPTOMS  
 27. Severe Headache  
 Yes   
 No   
 Unknown  
28. Proptosis or Exophthalmos  
 Yes   
 No   
 Unknown  
  /  
  /  
  /  
  /  
  /  
  /  
  /  
  /  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 98 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 29. Conjunctival chemosis  
 Yes   
 No   
 Unknown  
30. Ocular bruit  
 Yes   
 No   
 Unknown  
31. Visual Loss  
 Yes   
 No   
 Unknown  
32. Epistaxis  
 Yes   
 No   
 Unknown  
  
  
4 

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 99 of 106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
 

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 100 of 
106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 101 of 
106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
Clinical Study of the   
Contour Neurovascular System™  
NEUROLOGICAL TESTING - BASELINE  
Site 
Numb er   
Subject 
Number  
  
  
  
  
  
  
  
GLASCOW COMA SCALE (GCS)  
 
   Not done  
 
 
Exam Date  
  
Performed by  
 _________________________________________  
GCS Total Score   
 3 - 15  
MODIFIED RANKIN SCALE (MRS)  
 Not done  
Exam Date  
  
Performed by  
 _________________________________________  
mRS Grade  
 0 - 6  
NIH STROKE SCALE (NIHSS)  
 Not done  
Exam Date  
  
Performed by  
 _________________________________________  
NIHSS Total Score  
 0 - 42  
Subject sedated for exam  
 
 Yes   
 No  
Subject intubated and paralyzed for exam  
 
 Yes   
 No  
  /  
  /  
  /  
  /  
  /  
  /  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 102 of 
106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
  
6 

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 103 of 
106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 104 of 
106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
  
BASELINE ANGIOGRAM   
  Not Done  
 
An  angiogram of the target aneurysm and parent vessel must be performed within 3 months of Enrollment  
1. Date of Angiogram  
  
 2. Angiogram performed by  
 ______________________________________________    
3. Target IA Type  Sidewall   
 Bifurcation or Terminal  
 Other, specify:  
_______________________________   
4. Target IA Width  mm  
5. Target IA Neck  mm  
6. Target IA Height  mm  
 7. Evidence of ruptured IA  
 Yes   
 No  
  
Clinical Study of the   
Contour Neurovascular System™  
BASELINE ANGIOGRAM   
Site  
Numb er   
Subject 
Number  
  
  
  
  
  
  
  /  
  /  
  .  
  .  
  .  

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 105 of 
106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary  
8. Location of aneurysm  Anterior, 
Petrous, Cavernous, Paraclinoid – right  
 Anterior, Petrous, Cavernous, Paraclinoid – left  
 Anterior, ICA terminus – right  
 Anterior, ICA terminus – left  
 Anterior, MCA – right  
 Anterior, MCA – left, level:  _____________________   
 Anterior, ACA / AComm – right  
 Anterior, ACA / AComm - left  
 Anterior, ICA / PComm – right  
 Anterior, ICA / PComm - left  
 Posterior, Vertebral - right  
 Posterior, Vertebral – left  
 Posterior, Basilar Trunk  
 Posterior, Basilar Tip  
 Posterior, Basilar / PComm – right  
 Posterior, Basilar / PComm – left  
 Anterior, Other, location:  ______________________   
Posterior, Other, location:  ______________________   
  
  
7 

  
 
  
CERUS CONFIDENTIAL  
  
 
DNX099-F1.B  
04 May 2018  
Page  of 42  
  
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use .  
  
  
Document Number  
DNX099-01  
Rev  
F  
Page 106 of 
106  
Investigational Protocol  
Title  
Contour Neurovascular SystemTM European Pre-Market Unruptured Aneurysm 
Study (CERUS)  
Confidential & Proprietary