Coil Assisted Flow Diversion: A Prospective, Single Arm, Multi-center Study to Assess the Safety and Performance of Neqstent in Adjunctive Therapy (CAFI Study)
Phase: NA
Conditions: Intracranial Aneurysm
Sponsor: Cerus Endovascular, Inc.

Study Protocol and Statistical Analysis Plan  
Document Title: Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent in adjunctive therapy (CAFI Study) 
Document Date: 15-Jan-2020 
NCT Number: NCT04187573 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 1 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Coil Assisted Flow Diversion: A prospective, 
single arm, multi-center study to assess the safety 
and performance of Neqstent in adjunctive 
therapy (CAFI Study) 
 
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: 1-510-651-4000 
carol.holt@cerusendo.com 
Principal Investigator: 
 
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. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 2 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Study Information 
Protocol Name 
Coil Assisted Flow Diversion: A prospective, single arm, multi-
center study to assess the safety and performance of Neqstent in 
adjunctive therapy (CAFI Study) 
Protocol Number 
DNQS428-01  
Device Name 
Neqstent 
Manufacturer 
Cerus Endovascular, Ltd.  
John Eccles House 
Oxford Science Park 
Oxford, OX4 4G 
United Kingdom 
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 Data Systems, LLC 
100 Market St., Suite 401 
Portsmouth, NH  03801 
 
List of principal investigators and investigation sites will be maintained separately and is available upon 
request. 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 3 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
TABLE OF CONTENTS 
1 
Overview.............................................................................................................................. 5 
2 
Clinical Study Synopsis ......................................................................................................... 5 
3 
Acronyms ........................................................................................................................... 16 
4 
Introduction ....................................................................................................................... 17 
5 
Investigational Device Description....................................................................................... 24 
5.1 
Implant and Delivery system .................................................................................................................................................................. 24 
5.2 
Indications for Use and Intended Use ..................................................................................................................................................... 25 
5.3 
Training .................................................................................................................................................................................................. 25 
5.4 
Device Manufacturing Overview ............................................................................................................................................................ 25 
5.5 
Device Evaluation and Testing ............................................................................................................................................................... 26 
6 
Risks and Benefits .............................................................................................................. 26 
6.1 
Potential Risks ........................................................................................................................................................................................ 26 
6.2 
Potential Benefits .................................................................................................................................................................................... 28 
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 ................................................................................................................................................................................................ 31 
7.5 
Eligibility ................................................................................................................................................................................................ 31 
7.6 
Baseline Evaluation ................................................................................................................................................................................ 34 
7.7 
Implant Procedure ................................................................................................................................................................................... 35 
7.8 
Hospital Discharge.................................................................................................................................................................................. 35 
7.9 
Follow-Up .............................................................................................................................................................................................. 36 
7.10 Early Withdrawal .................................................................................................................................................................................... 38 
7.11 Study Termination .................................................................................................................................................................................. 38 
7.12 Premature termination............................................................................................................................................................................. 38 
8 
Adverse Events ................................................................................................................... 39 
8.1 
Adverse Event Definitions ...................................................................................................................................................................... 39 
8.2 
Adverse Event Classification .................................................................................................................................................................. 41 
8.3 
Adverse Event Reporting ........................................................................................................................................................................ 42 
9 
Study Oversight ................................................................................................................. 42 
9.1 
Clinical Events Committee (CEC) .......................................................................................................................................................... 42 
9.2 
Data Safety and Monitoring Board (DSMB)........................................................................................................................................... 43 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 4 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
9.3 
Patient Selection Committee ................................................................................................................................................................... 43 
10 Statistical Analysis.............................................................................................................. 43 
10.1 Justification of Methodology .................................................................................................................................................................. 43 
10.2 Patient Population ................................................................................................................................................................................... 44 
10.3 Multi-center Trial Considerations ........................................................................................................................................................... 44 
10.4 Endpoints ................................................................................................................................................................................................ 44 
10.5 Interim Analysis ..................................................................................................................................................................................... 45 
10.6 Sample Size Rationale and Statistical Considerations ............................................................................................................................. 45 
11 Additional Trial Characteristics .......................................................................................... 46 
11.1 Measures Taken to Avoid Bias ............................................................................................................................................................... 46 
11.2 Special Equipment for Investigation ....................................................................................................................................................... 47 
11.3 Procedure for Replacing Withdrawn Subjects ........................................................................................................................................ 47 
11.4 Other Devices Used During Study .......................................................................................................................................................... 47 
11.5 Total Expected Trial Duration ................................................................................................................................................................ 47 
12 Study Management............................................................................................................. 47 
12.1 Investigator Responsibilities ................................................................................................................................................................... 47 
12.2 Sponsor Responsibilities ......................................................................................................................................................................... 53 
13 Publications ....................................................................................................................... 60 
14 References .......................................................................................................................... 61 
15 Revision History ................................................................................................................. 63 
16 APPENDIX A - Statement of Compliance and Signature Page ............................................. 64 
17 APPENDIX B - Sponsor Approval Page .............................................................................. 65 
18 APPENDIX C -  Report of Prior Investigations ............................................................... 66 
18.1 Human Use for Neqstent (Subject device) .............................................................................................................................................. 66 
18.2 Human Use for Contour (First generation device) .................................................................................................................................. 66 
18.3 Pre-Clinical Evaluation and Testing ....................................................................................................................................................... 67 
18.4 Conclusion .............................................................................................................................................................................................. 70 
19 APPENDIX E – Data Management Plan ............................................................................. 71 
20 APPENDIX F – Case Report Form CRF ............................................................................. 72 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 5 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
1 
Overview 
This document provides a detailed plan for Neqstent: Coil Assisted Flow Diversion: A 
prospective, single arm, multi-center study to assess the safety and performance of Neqstent in 
adjunctive therapy (CAFI Study) 
2 
Clinical Study Synopsis 
 
Study Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center study to assess the 
safety and performance of Neqstent in adjunctive therapy (CAFI Study) 
Study 
Purpose 
Cerus Endovascular is sponsoring a prospective, single arm, multi-center study to 
document the safety and performance of Neqstent in adjunctive therapy.  
The purpose of the study is to document safety and performance of the Neqstent in 
adjunctive therapy in treatment for patients with intracranial aneurysms (IA).  
Indications 
for Use and 
Intended 
Use 
Neqstent is intended for use in conjunction with embolization coils for endovascular 
embolization of saccular 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 Neqstent before using the 
device.  
Neqstent 
Training  
Cerus Endovascular will provide training using flow models and didactic slide 
presentation. Physician proctoring will occur for the first three implants and an 
experienced Neqstent implanter 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 aneurysms or images will be viewed as forwarded by the 
treating physician. 
Study 
Design 
Prospective, single arm, multi-center study. 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 6 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Study Size 
and 
Duration 
Study Size: The study population will include 51 subjects enrolled and implanted at up 
to 11 centers. 
Study Duration: It is expected that the study will take 6 months to enroll a minimum of 
51 patients.  Follow-ups for the primary endpoint are the 6-month visit and 12-month 
visit, depending on the Raymond Roy score at the 6-month visit. Total duration of 
enrollment approximately 6 months, follow-up duration for primary endpoint (6-12 
months), 24 months follow-up and reporting (3 months) will take approximately 33 
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. 
Device 
Description 
The Neqstent device works by providing a physical barrier between the parent vessel and 
the intracranial aneurysm neck (as demonstrated by the Neqstent clinical investigations 
as well as the pre-clinical research) thereby excluding the aneurysm from the parent 
artery blood flow. The Neqstent 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. 
 
Figure 1 - Neqstent 
The Neqstent (NQS) (NQS407-XX, NQS409-XX, NQS411-XX) is an intrasaccular, self-
expanding, embolization device intended for the treatment of intracranial aneurysms. 
The NQS 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.  
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 7 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Device 
Description 
(continued) 
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 fluoro-saver 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. 
The Neqstent is offered in three sizes, suitable for embolization of intracranial aneurysm. 
Table 1 details the selection guideline for these three sizes: 
The Neqstent 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 Neqstent only requires the neck 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) 
NQS407-XX – 7 mm 
3.0 - 5.0 
NQS409-XX – 9 mm 
4.0 - 6.0 
NQS411-XX – 11 mm 
5.0 - 8.0 
 
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 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 8 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Objective 
and 
Endpoints 
The primary objective of this study is to document the safety and performance of the 
Neqstent.   
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 ≥ 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. 
Note: In the event of a Grade 2 or more using the Raymond Roy Scale, a second 
assessment will be made at 12 month follow-up to re-assess for remnant stability and/or 
complete occlusion and will be reported as a secondary efficacy endpoint. 
Sample 
Size 
51 subjects will be enrolled to obtain adequate follow-up data for the study to complete 
sponsor obligation to the notified body.  
Number of 
Sites 
Up to 11 sites will enroll in the study.  
Study 
Visits 
Baseline, procedure, discharge, one (1) month, six (6) months, twelve (12) months and 
twenty-four (24) months.   
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 9 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 a Neqstent 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 Neqstent 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. 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 10 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 IAs 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. Any patient anatomy, physiology, existing implants with failed aneurysm 
embolization that would interfere with the ability for Neqstent to seal at the neck of 
the aneurysm. (i.e., compacted coils in close proximity to the neck that prevent good 
apposition of the Neqstent to the wall of the aneurysm, stent and/or stent-like devices 
whose struts span the aneurysm neck to retain the coil mass that inhibit access and/or 
successful Neqstent seating at the aneurysm neck, and/or any aneurysm that has a 
failed device and confirmed thrombus-burden inside the aneurysm sac)  
4. Contraindication for arterial access 
5. Largest measured IA neck diameter >8 mm or <3 mm 
6. Target IA contains other devices/implants (e.g., coils) that will prevent complete 
expansion of Neqstent 
7. Known allergy to platinum, nickel or titanium 
8. Known allergy to contrast agents 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 11 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 women of childbearing potential not on adequate birth 
control (only women with a highly effective method of contraception [oral 
contraception or intra-uterine device] or sterile women can be enrolled to the study) 
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  
18. The presence of condition that may create unacceptable risk during the aneurysm 
embolization procedure 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 12 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 
 
Baseline# 
Procedure 
Discharge 
1-month 
(± 1 weeks) 
6 months 
(± 1 month) 
12 months 
(± 1 month) 
24 months 
(± 1 month) 
Medical history and medications 
X 
 
 
 
 
X 
 
Neurologic Exam 
X 
 
X 
X 
X 
X 
X 
NIH Stroke Scale 
X 
X* 
X* 
X* 
X* 
X 
X* 
Modified Rankin Scale (mRS) 
X 
 
X** 
X** 
X** 
X** 
X** 
Medical history and medications 
X 
 
 
 
 
X 
 
Neurologic Exam 
X 
 
X 
X 
X 
X 
X 
NIH Stroke Scale 
X 
X* 
X* 
X* 
X* 
X 
X* 
Modified Rankin Scale (mRS) 
X 
 
X** 
X** 
X** 
X** 
X** 
Pregnancy test (pre-menopausal 
female) 
X 
 
 
 
 
 
 
CT angiography (CTA) ^ 
X# 
 
 
 
X 
X**** 
 
Magnetic Resonance Angiogram 
(MRA) ^  
X# 
 
 
 
 
 
 
Cerebral Angiogram (DSA) ^ 
X# 
w/3D 
X 
w/3D 
 
 
X 
w/3D 
X*** 
w/3D 
 
Adverse Event assessment 
 
X 
X 
X 
X 
X 
X 
Procedure Information 
 
X 
 
 
 
 
 
Aneurysm Occlusion Status – 
Raymond Roy and general 
assessment on study form## 
 
X 
 
 
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. 
*** 
Cerebral angiogram is required at 6 months only; in the event of a Grade 2 or more using the 
Raymond Roy Scale at 6 months, a second cerebral angiogram assessment will be made at 12-
month follow-up to re-assess for complete occlusion and will be reported as secondary efficacy. 
**** CTA is required at 6 months only; in the event of a Grade 2 or more using the Raymond Roy Scale 
at 6 months, a second cerebral angiogram assessment will be made at 12-month follow-up to re-
assess for complete occlusion and will be reported as secondary efficacy. 
 ## 
Aneurysm occlusion status and Raymond Roy completed when cerebral angiograms are 
performed. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 13 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Background 
and Study 
Rationale 
The most commonly provided endovascular therapy for intracranial aneurysms (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 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, aided by the water hammer effect, 
resulting in increased filling and re-growth of at the aneurysm from the neck.  This 
creates a need for further intervention due to the lack of embolization of the aneurysm.  
Neqstent was designed to fulfill this clinical unmet need.  Physicians’ only course of 
available intervention is to continue to fill the aneurysm without the ability to seal and 
stabilize the wide neck.  Neqstent is positioned at the neck of the aneurysm with the 
ability to leave in existing endovascular technology and also add more as needed to fully 
fill and close the aneurysm with the goal of complete occlusion or embolization.  
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 
 
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. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 14 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 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 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, first generation device by 
the sponsor, is an intrasaccular 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 stable scaffold for the establishment of endothelial cells, across the neck and 
ultimately isolate the aneurysm from the parent artery blood flow. These two 
mechanisms of action may increase the likelihood of complete IA occlusion compared to 
embolization coils alone.  
One intrasaccular flow diverter has received CE-mark and FDA approval.  The WEB 
(Woven Endobridge Device, Sequent Medical, Terumo, Aliso Viejo, California) is a 
mesh device in a spherical shape. It works by mechanisms similar to Neqstent 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 
 
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. 
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  
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 

 
Document Number 
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Rev.  
F 
Page 15 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 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 
Contour 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. 
Neqstent is a derivative device and subject device for this study. It was designed as 
adjunctive therapy in patients where failed attempts at aneurysm embolization have 
occurred.  Neqstent can be positioned at the neck of an aneurysm with existing coils and 
other embolization products.  And, more adjunctive therapies can be added to fill the 
aneurysm after placement of Neqstent.   
 
 
 
 
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 
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 

 
Document Number 
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Rev.  
F 
Page 16 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
3 
Acronyms 
The following list provides acronyms used in this document and their meaning: 
AE  
Adverse event  
ADE  
Adverse device effect 
CA 
Competent Authority 
CERUS 
Contour Neurovascular System(TM) European Pre-Market Study 
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 (Cerebral) 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 
PMCF 
Post market clinical follow-up 
PI  
Principal Investigator 
SADE 
Serious adverse device effect 
SAE  
Serious adverse event 
SAH  
Subarachnoid haemorrhage 
SoC 
Standard of Care 
USADE  
Unanticipated Serious Adverse Device Effect 
 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 17 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
4 
Introduction 
The Neqstent Implant is designed for endovascular treatment of intracranial aneurysms (IAs).  The device 
is designed to be placed into the sac of an intracranial aneurysm through a standard endovascular 
procedure. Neqstent is a design derivative of the first generation Cerus intrasaccular Contour device 
implant.  Neqstent is designed to be an adjunctive therapy to coil embolization which permits treatment of 
a broader range of aneurysm morphologies.   
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. 
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 decreased 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. Multiple studies are available 
to estimate the relative increase in complete occlusion rate provided by these adjunctive devices. Even 
more challenging is the treatment of wide-necked IAs located at arterial bifurcations. Placement of 
intracranial stents in a variety of configurations has been associated with a significantly higher risk 6,7. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 18 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Incomplete occlusion has additional risks. Incomplete occlusion of IAs can lead to IA growth 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 
cerebral angiography and retreatment. 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 placed either in the parent artery or in the IA itself. 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,11 which 
can promote permanent occlusion of the target IA. These two components (flow disruption and 
scaffolding for re-endothelialization) distinguish flow diverters from standard 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.12  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.  
Most flow diverting devices are placed into the parent artery; this requires the patient to take antiplatelet 
agents (aspirin and clopidogrel) for prolonged periods. The Neqstent device (Cerus Endovascular, Oxford, 
UK) is designed to be a flow diverter that is placed instead into the IA sac. Like other flow diverters, the 
device is designed to disrupt blood flow into the IA and to act as a scaffold upon which endothelial cells 
can grow. These two mechanisms of action may increase the likelihood of complete IA occlusion 
compared to embolization coils.  Because the device is placed into the IA sac, antiplatelet therapy is not 
required.  Use of antiplatelet and/or anticoagulation is at the discretion of the treating physician. 
Neqstent is the design derivative flow diverting device manufactured by Cerus Endovascular.  The 
Contour Neurovascular System (“Contour”) is the first generation flow diverting device.  The following 
are the differences between Contour and Neqstent: 
  
 
 

 
Document Number 
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Rev.  
F 
Page 19 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Table 3. Contour and Neqstent Comparison 
Features/Benefits 
Neqstent 
Contour 
Comments 
Simplified sizing approach taking only the aneurysm 
neck diameter into consideration when sizing 
Yes 
Yes 
None 
No parent artery stabilizing component unlike other 
adjunctive devices used in a coiling procedure. These 
benefits include; 
• 
eliminating the need to take the dimensions of the 
parent artery into consideration when sizing 
device 
• 
reduce or eliminate the need for anticoagulation 
therapy post procedurally. 
Yes 
Yes 
None 
Reduced risk of rupture since the device does not 
engage with the vulnerable aneurysm dome during the 
procedure 
Yes 
Yes 
None 
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  
Yes 
Yes 
None 
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 
Yes 
Yes 
None 
Improved durability of embolization by creating a 
stable scaffold across the aneurysm neck to permit 
establishment of stable endothelium.  
Yes 
Yes 
None 
Increased scaffold coverage across the neck 
permitting the physician to pack more coils without 
the risk of coil herniation or migration into the parent 
artery 
Yes 
No 
Neqstent offers ability 
to be adjunctive 
therapy  
Ability to retreat the more challenging failed or 
recurrent aneurysm which have previously been 
embolized and have left little room in the neck region 
to accommodate other adjunctive devices such as 
pCONUS or PulseRider. Additionally, branching 
vessels at the base of the aneurysm may be too small 
to accommodate parent vessel stenting or flow 
diversion to retreat aneurysms in these locations 
Yes 
No 
Neqstent offers the 
ability for retreatment 
since it can be used 
adjunctively with 
coils/stents. 

 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Features/Benefits 
Neqstent 
Contour 
Comments 
Ability for access by the coiling microcatheter 
either/both around or through the mesh of the implant 
giving the physician the flexibility to best embolize 
the aneurysm with the coiling microcatheter  
Yes 
No 
Neqstent provides new 
way of closing 
aneurysm with the 
ability to use in 
conjunction with 
coils/stents. 
Flow diversion from the implant can stabilize coil 
mass within the aneurysm sac and permit the 
establishment of thrombus 
Yes 
No 
Neqstent can be used 
with coils/stents. 
 
Other intrasaccular flow diverters are commercially available in Europe. As reviewed below, Sequent’s 
WEB (Woven Endobridge) is a mesh device in a barrel shape. It works by mechanisms similar to 
Neqstent in that 1) it is a flow diverter, and 2) its mesh can serve as a scaffold upon which endothelial 
cells can grow. Published information regarding WEB is provided below.  
Flow diverters have been commercially available since 2008. The first flow diverter was Pipeline 
Embolization Device (Covidien). A PubMed search for “Pipeline Embolization Device” on May 29, 2015 
revealed 250 hits. A full summary of the Pipeline literature is beyond the scope of this review.  
Many case reports of Pipeline use for large and giant or fusiform IAs have been reported (e.g., the first 
report in a giant fusiform IA13) but will not be summarized here.  The device has been the subject of a 
number of large studies including: 
• 
PITA, a prospective multicenter single-arm clinical trial of wide-necked or other difficult-to-treat 
or failed IAs.14 The study showed a high rate of complete occlusion of the target IA with a good 
safety profile. The study enabled CE marking of the device.  
• 
PUFS was a prospective, international multicenter single-arm clinical trial of large and giant 
IAs.12  The trial showed a high rate of complete occlusion of the target IA and a good safety 
profile. The IAs in this study were particularly challenging and, in most cases, no other device 
was available to treat these IAs. 
• 
INTREPED was a post-market retrospective assessment of use of this device in 793 patients in 17 
centers worldwide.15 The device was used in IAs throughout the brain arterial circulation. The 
neurologic morbidity and mortality rate was 8.4%. Subgroup analyses were used to examine 
predictors of adverse events. The target IA population was different (more complex) than the 
population proposed in the INCA study. 
Other parent artery flow diverter devices are in clinical use, including FRED, LVIS (MicroVention 
Terumo), Surpass (Stryker), Silk (Balt), p64 (Phenox), Derivo (Acandis), and BRAVO (Cerenovus). All 
devices are made from metallic meshes similar to Neqstent. The published literature on these devices is 
less extensive compared to Pipeline Embolization Device but shows similar findings.  

 
Document Number 
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Rev.  
F 
Page 21 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
The published literature is very clear that flow diverters such as Pipeline Embolization Device, are now 
playing an increasing role in the treatment of wide-neck, large and giant, complex IAs. Their use in 
smaller IAs has been explored but is not accepted as standard treatment. 
WEB (Woven Endobridge, Sequent Medical, Terumo, Aliso Viejo, California) is an intrasaccular flow 
diverter that shares characteristics with Neqstent and has both CE Mark and FDA approval. Because of 
the similarities, the published literature on WEB use is highly relevant. 
• 
Ding16 reported use of WEB in an animal study similar to those done to support Neqstent.  The 
study showed complete occlusion in 33% of cases. 
• 
Behme17 reported a retrospective assessment of use of WEB in 52 patients (55 IAs), including 15 
ruptured IAs. The device was deployed in all patients and implanted in 93%. Procedure 
complications occurred in 12%, including 2 thromboembolic events, 2 thrombus formations, 1 
high-grade posterior cerebral artery stenosis, and 1 aneurysm rupture. None of these had clinical 
sequelae. Favorable angiographic results were seen in 29 (53%).  
• 
Pierot18 reported use of WEB in 21 IAs at 3 centers in the EU. All IAs were treated with the 
device and adjunctive treatment (coiling and/or stent placement) was used in 24% of patients. 
One patient (4.8%) has a symptomatic thrombotic event. Inadvertent detachment of WEB 
occurred in 1 patient. Complete occlusion of the target IA was seen in 7 (33%) IAs. 
• 
Colla19 reported use of WEB in 4 wide-necked basilar tip bifurcation IAs at a single Italian 
hospital. There were no perioperative adverse events and satisfactory occlusion was seen in all 
cases. 
• 
Wallner20 reported a patient treated with WEB who had IA recurrence requiring retreatment. 
• 
Pierot21 reported a prospective multicenter French study of use of WEB in 62 patients (63 IAs). 
Two versions of WEB were used. Morbidity was low (3.2% overall). Angiographic occlusion was 
not reported. 
• 
Lubicz reported a multicenter experience with WEB use in 45 patients with 45 IAs treated with 
WEB.22 Good clinical outcome was observed in 93%. Complete occlusion was observed in 30 
(67%) patients in the short term (median 6 months) and 26 patients (58%) in the long term 
(median 13 months). 
• 
Cognard23 reported experience with WEB in 15 patients (15 IAs). Worsening of IA occlusion 
status was seen in 10 (67%) of cases, with compression of the implant. Complete occlusion at last 
follow-up was seen in only 1 case (6.7% of all patients).  
• 
Papagiannaki24 reported multicenter French retrospective WEB use to treat 83 patients with 85 
IAs. Periprocedural complications were seen in 10.8%, with permanent neurologic deficits in 
3.9%. Complete IA occlusion was seen in 37 (44%) of IAs at a median of 5.3 months of follow-
up. 
• 
Fiorella25 reported interobserver agreement when judging IA occlusion with use of WEB. The 
degree of agreement was high. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 22 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
The published literature on WEB is promising: it shows that intrasaccular flow diverters can be useful in a 
subset of IAs (primarily wide-necked IAs at arterial bifurcations). Periprocedural safety was good; 
complete occlusion of the target IA was often observed. However, compaction of the device may limit 
overall success rates. 
In addition, there are also braided and laser-cut intra-arterial dwelling stents, such as, Solitaire AB 
(Medtronic), Enterprise 2, PulseRider (Cerenovus), LVIS Jr (Microvention Terumo), Baby LEO (Balt), 
ATLAS, Neuroform (Stryker), ACCLINO Flex Plus (Acandis) and pCONUS (Phenox). Substantial 
literature exists to support these various braided and laser-cut intra-arterial dwelling stents. Please see 
literature samples in Table 4. . 
Table 4. Literature Samples 
Title 
Authors 
Device(s) 
Citation 
Update on flow diverters for the endovascular 
management of cerebral aneurysms  
Gary Rajah, MD, Sandra 
Narayanan, MD, and Leonardo 
Rangel-Castilla, MD  
Various 
Neurosurg Focus 42 (6):E2, 
2017  
How safe and effective are existing treatments 
for wide-necked bifurcation aneurysms? 
Literature- based objective performance 
criteria for safety and effectiveness  
David Fiorella, Adam S Arthur, 
Richard Chiacchierini, Evelyne 
Emery, Andy Molyneux, 
Laurent Pierot 
Various 
Fiorella D, et al. J 
NeuroIntervent Surg 
2017;0:1–5. 
doi:10.1136/neurintsurg-
2017-013223  
Endovascular techniques for the management 
of wide-neck intracranial bifurcation 
aneurysms: A critical review of the literature  
Laurent Pierot, Alessandra 
Biondi  
Various 
Journal of Neuroradiology 
(2016) 43, 167—175  
Results of the ANSWER Trial Using the 
PulseRider for the Treatment of Broad-
Necked, Bifurcation Aneurysms  
Alejandro M. Spiotta, MD et al 
PulseRider 
Neurosurgery 00:1–10, 2017  
The pCONUS device for the endovascular 
treatment of wide neck bifurcation aneurysms. 
Lubicz B, Morais R, Alghamdi 
F, Mine B, Collignon L, Eker 
OF. 
pCONUS 
Lubicz B, et al. J 
Neurointerv Surg. 2016. 
Coil occlusion of wide-neck bifurcation 
aneurysms assisted by a novel intra- to extra-
aneurysmatic neck-bridging device 
(pCONUS): initial experience. 
Aguilar-Pérez M, Kurre 
W, Fischer S, Bäzner H, Henkes 
H. 
pCONUS 
Aguilar-Pérez M, et al. 
AJNR Am J Neuroradiol. 
2014. 
Assisted coiling using LEO Baby or LVIS Jr 
stents: Report of six cases 
Matías Negrotto, Roberto Crosa, 
and  Walter Casagrande 
Various 
Interv Neuroradiol. 2015 
Oct; 21(5): 566–574. 
The LVIS/LVIS Jr. stents in the treatment of 
wide-neck intracranial aneurysms: multicentre 
registry. 
Poncyljusz W, Biliński 
P, Safranow K, Baron 
J, Zbroszczyk M, Jaworski 
M, Bereza S, Burke TH. 
LVIS 
J Neurointerv Surg. 2015 
Jul;7(7):524-9. doi: 
10.1136/neurintsurg-2014-
011229. Epub 2014 May 14. 
Y-Stent-Assisted Coiling of Wide-Neck 
Bifurcation Intracranial Aneurysms: A Meta-
Analysis. 
Cagnazzo F, Limbucci 
N, Nappini S, Renieri L, Rosi 
A, Laiso A, Tiziano di Carlo 
D, Perrini P, Mangiafico S 
Meta-
analysis 
Cagnazzo F, et al. AJNR Am 
J Neuroradiol. 2018. 

 
Document Number 
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Rev.  
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Page 23 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Title 
Authors 
Device(s) 
Citation 
The Use of Solitaire AB Stents in Coil 
Embolization of Wide-Necked Cerebral 
Aneurysms 
Teng-Fei Li et al 
Solitaire 
AB 
PLoS One. 2015; 10(10): 
e0139714 
Safety and Efficacy of Low-Profile, Self-
Expandable Stents for Treatment of 
Intracranial Aneurysms: Initial and Midterm 
Results - A Systematic Review and Meta-
Analysis 
Park S.-Y et al 
Meta-
analysis 
Intervent Neurol 
2017;6:170-182 
In summary, parent artery flow diverters and stents are a widely accepted therapy options for treating 
wide-necked, large and giant IAs. Intrasaccular flow diverters are promising but present some difficulties 
in terms of placement and IA recurrence. Fiorella25 concluded that “conventional therapies for WNBAs 
are associated with relatively low rates of complete occlusion and peri-procedural complications are not 
uncommon. Newer therapies are needed for the treatment of these aneurysms.”  Neqstent is an alternative 
to WEB that might be easier to place and, due to its design, result in better long-term angiographic 
outcomes.   
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 
 
 

 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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5 
Investigational Device Description 
5.1 
Implant and Delivery system 
The Neqstent is comprised of the Neqstent implant (hereafter called “Neqstent”), which is pre-
attached to a detachable pusher wire (DPW), and an Introducer. The DPW facilitates the delivery 
of the Neqstent 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 Neqstent 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. The 
implant also has a platinum marker for additional visualization during the procedure.  The pre-
attached DPW has a composite stainless steel and polymer construction. The Introducer is a 
single lumen polymer tube that is used to constrain the Neqstent implant during introduction into 
the MC hub. The Neqstent implant body and proximal marker can be visualized under 
fluoroscopy. 
Given the platinum core of the device’s mesh and the platinum marker, the Neqstent 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 Neqstent 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. Neqstent Implant 
 
 

 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
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 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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5.2 
Indications for Use and Intended Use 
Neqstent is intended for use in conjunction with embolization coils for endovascular embolization 
of saccular 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 
Neqstent before using the device. 
The Neqstent is placed across the neck of the aneurysm to offer flow diversion as well as wire 
scaffolds spanning the neck of the aneurysm to support the retaintion of the coil mass inside the 
aneurysm sac. The device mesh also provides support for the establishment of neointimal cells 
across the aneurysm neck opening, providing long term stability of the neck and isolation of the 
aneurysm sac from the parent artery blood flow.  
5.3 
Training 
Cerus Endovascular will provide training to all participating investigators using a variety of the 
following: 
• 
flow models 
• 
didactic slide presentation 
At least one patient selection committee will have access to the patient aneurysm images 
submitted by the treating physician during the screening process.  The patient selection committee 
will individually review and cast opinion on whether the proposed aneurysm is treatable with a 
Neqstent device per product specification guidelines.  Either a web-based image system called 
CIMAR will be used to view and store images along with the patient selection committee’s 
opinion on aneurysm suitability for treatment based on the Neqstent sizing guidelines or images 
will be viewed as forwarded by the treating physician.  
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 
Neqstent after the patient selection committee has deemed 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 Neqstent 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. 

 
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Rev.  
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Page 26 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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5.5 
Device Evaluation and Testing 
5.5.1 
Biocompatibility and Biological Safety 
A biological risk assessment of the Neqstent has been performed. This assessment focused 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 Neqstent 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.  
 
Table 5. Risks of Endovascular Aneurysm Treatment 
Anticipated Risk  
Percent 
Anticipated Risk 
Occurrence 
Specified Risks 
Neurovascular procedure 
related 
Rarely (< 5%) 
CVA – ischemic 
Rarely (< 5%) 
CVA – hemorrhagic 
Rarely (< 5%) 
Aneurysm rupture 
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 
Less Likely (5-15%) 
Device migration – from the aneurysm to a distal site 
Likely (>15%) 
Headache 
Rarely (< 5%) 
Cranial nerve palsy 

 
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 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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Anticipated Risk  
Percent 
Anticipated Risk 
Occurrence 
Specified Risks 
Rarely (< 5%) 
Intra-cranial hypertension 
Less Likely (5-15%) 
Recanalization of the aneurysm 
Vascular Access Site 
procedure related 
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 
Assessment (SoC) related 
procedure: Angiogram 
Less Likely (5-15%) 
 
 
Allergic reaction to contrast media and Renal dysfunction 
secondary to contrast media. 
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 child-bearing 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. 
Other Risks related to 
general anesthesia and 
medication therapy 
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. 

 
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Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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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. 
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.  Neqstent is being designed and developed in accordance 
with a risk management process that conforms with EN ISO 14971:2012.  This process serves to 
identify hazards associated with the subject devices and accessories, estimate and evaluate the 
risks associated with those hazards, control (reduce) those risks, and monitor the effectiveness of 
that control. Risk management ensures that risks to the patient, users and third parties are 
minimized and determined to be acceptable. The risk management results are crosschecked 
against applicable risk reduction documentation to ensure the risk reduction measures are 
implemented.  
The Cerus Endovascular design review process ensures that all identified risk reduction measures 
have been implemented. Residual risks, the risks remaining after risk control (i.e. risk reduction) 
measures have been taken, are addressed in the “Contraindications” and “Adverse Events” 
sections of the Instructions For Use as well as listed in Table 5. 
Potential adverse events associated with use of Neqstent, some of which could be fatal or cause 
severe neurologic deficits, include:  
• 
Aneurysm rupture causing intracranial hemorrhage  
• 
Injury to parent artery causing thrombosis or hemorrhage  
• 
Distal embolization of particles or blood clot causing stroke  
• 
Parent artery vasospasm  
• 
Parent artery dissection  
• 
Aneurysm recanalization  
• 
Infection  
• 
Device migration causing incomplete occlusion, hemorrhage or ischemic stroke 
Contraindications:  
• 
Allergy to platinum, nickel or titanium 
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 Neqstent. This study allows the Sponsor and Investigators to help other patients indicated 
for similar procedures  
The Neqstent device is designed with materials and processes commonly used in medical devices 
used for IA treatment. The device is designed for easy placement and to increase the likelihood of 

 
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Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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complete IA occlusion. Complete IA occlusion may reduce the risk of subsequent IA rupture, 
recanalization and requirement for retreatment. 
As previously described, recent results from the use of existing intra-saccular flow disruptor 
devices have shown a risk of compression and compaction into the dome of the aneurysm and in 
instances significant neck regrowth. The Neqstent device is designed to seat across the neck of 
the aneurysm and delivery of embolic agents such as coils into the aneurysm sac. The stable 
framework of mesh across the neck will permit the physician to confidently pack more coils into 
the sac and the flow diverting properties will contribute to more stable healing. This may reduce 
the risk of subsequent IA recurrence or rupture or necessity for re-intervention.  
In addition, potential benefits that may be associated with endovascular treatment instead of 
surgical intervention 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 Neqstent vs. standard endovascular aneurysm coiling:   
• 
Simplified sizing approach taking only the aneurysm neck diameter into consideration 
when sizing 
• 
No parent artery stabilizing component with the Neqstent device, unlike other adjunctive 
devices used in a coiling procedure. These benefits include: 
− 
eliminating the need to take the dimensions of the parent artery into consideration 
when sizing Neqstent 
− 
reduce or eliminate the need for anticoagulation therapy post procedurally. 
• 
Reduced risk of rupture since the device does not engage 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 
• 
Improved durability of embolization by creating a stable scaffold across the aneurysm 
neck to permit establishment of a stable endothelium layer 
• 
Increased scaffold coverage across the neck permitting the physician to pack more coils 
without the risk of coil herniation or migration into the parent artery 

 
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Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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• 
Ability to retreat the more challenging failed or recurrent aneurysm which have previously 
been embolized and have left little room in the neck region to accommodate other 
adjunctive devices such as pCONUS or PulseRider. Additionally, branching vessels at the 
base of the aneurysm may be too small to accommodate parent vessel stenting or flow 
diversion to retreat aneurysms in these locations 
• 
Ability for access by the coiling microcatheter either/both around or through the mesh of 
the Neqstent giving the physician the flexibility to best embolize the aneurysm with the 
coiling microcatheter  
• 
Flow diversion contribution from the Neqstent will stabilize coil mass within the 
aneurysm sac and permit the establishment of thrombus 
6.3 
Risk-to-Benefit Rationale  
Neqstent has been implanted in compassionate use patients and is designed to be used 
adjunctively with embolization coils.  The Neqstent device is an iteration of the Contour 
technology, which is the first-generation device, Contour, manufactured by the sponsor.  Contour 
has been implanted in compassionate use patients, pilot study patients and pre-market clinical 
investigation CERUS 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 Neqstent demonstrate that when used under the 
conditions intended, the benefits associated with the use of the Neqstent 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 Neqstent.   
7.3 
Target Patient Population 
The target patient population is patients with intracranial aneurysms requiring endovascular 
treatment.  

 
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Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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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.  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 as listed in Table 6. 

 
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Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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Table 6. 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 IA 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. Any patient anatomy, physiology, existing implants with failed aneurysm 
embolization that would interfere with the ability for Neqstent to seal at 
the neck of the aneurysm. (i.e., compacted coils in close proximity to the 
neck that prevent good apposition of the Neqstent to the wall of the 
aneurysm, stent and/or stent-like devices whose struts span the aneurysm 
neck to retain the coil mass that inhibit access and/or successful Neqstent 
seating at the aneurysm neck, and/or any aneurysm that has a failed 
device and confirmed thrombus-burden inside the aneurysm sac) 
4. Contraindication for arterial access 
5. Largest measured IA neck diameter >8 mm or <3 mm 
6. Target IA contains other devices/implants (e.g., coils) that will prevent 
complete expansion of Neqstent 
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 women of childbearing potential not on 
adequate birth control (only women with a highly effective method of 
contraception [oral contraception or intra-uterine device] or sterile 
women can be enrolled to the study)  
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 
18. The presence of condition that may create unacceptable risk during the 
aneurysm embolization procedure 
 
 

 
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Clinical Investigation Plan 
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Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
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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.  
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 Neqstent 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 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 
Neqstent 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 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. 
• 
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. 
• 
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 Neqstent implant along with coordinating aneurysm dimensions and 
definitions are provided in Table 7. 

 
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 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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Table 7. Neqstent Sizes 
REF (Catalog 
Number) – Diameter 
Aneurysm  
Neck (mm) 
NQS407 – 7 mm 
3.0 - 5.0 
NQS409 – 9 mm 
4.0 - 6.0 
NQS411– 11 mm 
5.0 - 8.0 
 
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 Neqstent.  The Neqstent 
procedure may be scheduled following confirmation from the patient selection 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 
Neqstent 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 and at 12 months if performed due to 
lack of complete occlusion at 6 months. All imaging must be submitted to the independent core 
lab for analysis. 
 
 

 
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Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
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 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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7.7 
Implant Procedure 
7.7.1 
Preoperative Preparation 
The subject undergoes standard preoperative preparation. The device implant procedure must be 
performed under general anesthesia.  
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. These images will be the baseline 
submitted to the independent core laboratory for future comparisons at 6 months and 12 months. 
7.7.4 
Neqstent Procedure 
Neqstent 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 
Neqstent device is introduced into the microcatheter and slowly delivered into the target IA.  The 
device is deployed at the neck of the aneurysm after the coiling microcatheter tip is inside the 
aneurysm sac, which would result in the microcatheter being jailed between the aneurysm wall 
and the Neqstent or the Neqstent is deployed prior to the introduction of the coiling microcatheter 
where the operator will navigate the coiling microcatheter through the mesh of the Neqstent to 
gain access to the aneurysm sac.  
The Neqstent remains attached to the delivery wire throughout the entire embolization procedure 
and detachment or the device is the final step in the procedure once the physician has embolized 
the aneurysm sac with coils. 
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 and 
occlusion 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. 

 
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Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
7.9 
Follow-Up 
Following discharge, the subject will have a follow-up visit at 1 month, 6 months, 12 months and 24 
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 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 and 12 months (if the 
Raymond Roy scale is Grade 2 or higher 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 following the image transfer protocol. 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 8. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 37 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
 
Table 8. Schedule of Assessments 
 
Baseline# 
Procedure 
Discharge 
1-month 
(± 1 weeks) 
6 months 
(± 1 month) 
12 months 
(± 1 month) 
24 months 
(± 1 month) 
Medical history and medications 
X 
 
 
 
 
X 
 
Neurologic Exam 
X 
 
X 
X 
X 
X 
X 
NIH Stroke Scale 
X 
X* 
X* 
X* 
X* 
X 
X* 
Modified Rankin Scale (mRS) 
X 
 
X** 
X** 
X** 
X** 
X** 
Pregnancy test (pre-menopausal 
female) 
X 
 
 
 
 
 
 
CT angiography (CTA) ^ 
X# 
 
 
 
X 
X**** 
 
Magnetic Resonance Angiogram 
(MRA) ^  
X# 
 
 
 
 
 
 
Cerebral Angiogram (DSA) ^ 
X# 
w/3D 
X 
w/3D 
 
 
X 
w/3D 
X*** 
w/3D 
 
Adverse Event assessment 
 
X 
X 
X 
X 
X 
X 
Procedure Information 
 
X 
 
 
 
 
 
Aneurysm Occlusion Status – 
Raymond Roy and general 
assessment on study form## 
 
X 
 
 
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. 
***  Cerebral angiogram is required at 6 months only; in the event of a Grade 2 or more using the Raymond 
Roy Scale at 6 months, a second cerebral angiogram assessment will be made at 12-month follow-up to 
re-assess for complete occlusion and will be reported as secondary efficacy. 
**** CTA is required at 6 months only; in the event of a Grade 2 or more using the Raymond Roy Scale at 6 
months, a second cerebral angiogram assessment will be made at 12-month follow-up to re-assess for 
complete occlusion and will be reported as secondary efficacy. 
 ##  
Aneurysm occlusion status and Raymond Roy completed when cerebral angiograms are performed. 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 38 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 39 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 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 24 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 24 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 9. All AEs and device deficiencies 
shall be reported by the clinical site investigator on a specific case report form (CRF). 
Table 9. 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 related to the procedures involved. 
Note 3:  For users or other persons, this definition is restricted to events related to 
investigational medical devices. 

 
Document Number 
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Rev.  
F 
Page 40 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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Adverse device 
effect (ADE) 
An ADE is: 
an AE related to the use of a medical device. 
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: 
an 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. 
 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 41 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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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: 
• 
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 follows.  
• 
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. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 42 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
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Table 10. AE Categorization 
AEs 
Non-Device-
Related 
Device-Related  
Device Deficiencies* 
Non-Serious 
AE 
ADE 
Without SADE potential 
Serious 
SAE 
SADE 
With SADE potential 
 
 
Anticipated 
Unanticipated 
 
 
 
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 
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 combined CEC/DSMB Committee 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. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 43 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
9.2 
Data Safety and Monitoring Board (DSMB) 
A DSMB will convene of member(s) experienced in an associated discipline.  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.  
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 is a group of physicians who are trained and experienced users of 
Neqstent/Contour who have previous experience with embolization devices used in aneurysm 
treatment.  The patient selection committee will have access to the patient images submitted by 
the investigator during the screening process.  The patient selection committee will individually 
review and cast opinion on whether the proposed aneurysm is treatable with a Neqstent device 
per product specification guidelines.  The web-based image system called CIMAR will be used to 
view and store images and patient selection committee’s opinion on aneurysm suitability for 
treatment based on the Neqstent sizing guidelines or images will be viewed as forwarded by the 
treating physician.  A minimum of two physician votes will be obtained and a third in the case of 
a tie.  
10 
Statistical Analysis 
This study intends to examine the safety and performance of the Neqstent used for the treatment 
for embolization of intracranial aneurysms.  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.  
10.1 Justification of Methodology 
This study is designed as a single arm, descriptive study to develop further understanding of the 
Neqstent. It will provide safety and performance information for subjects from the Neqstent 
implantation to 24-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.  Note: In the 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 44 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
event of a Grade 2 or more using the Raymond Roy Scale, a second assessment will be made at 
12- month follow-up to re-assess for complete occlusion and will be reported as a secondary 
efficacy. 
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 Multi-center Trial Considerations 
Up to 11 sites will participate in the study.   
This is non-randomized, single arm, multi-center clinical study to assess safety and performance 
of Neqstent device with standardization of subject enrollment, data entry and AE reporting. 
10.4 Endpoints 
10.4.1 Primary Endpoints 
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 ≥ 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.  
Note: In the event of a Grade 2 or more using the Raymond Roy Scale, a second assessment will 
be made at 12 month follow-up to re-assess for remnant stability or complete occlusion and will 
be reported as a secondary efficacy endpoint. 
10.4.2 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. 

 
Document Number 
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Rev.  
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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.   
10.5 Interim Analysis 
 
The sponsor will submit an interim analysis summary of the clinical study’s progress (on safety 
evaluation and device success) to the involved Ethics Committees and Regulatory Authorities after 
10 patients are enrolled in the study.  
Based on the results following the interim analysis summary, the sample size will be re-evaluated.  
10.6 Sample Size Rationale and Statistical Considerations 
This is a single arm study designed to provide adequate data for the purpose of a pre-market 
study.  It is expected the 51 patients with evaluable data at 6 month and 12 month follow-up 
(where necessary) will show adequate evidence of safety and performance of Neqstent device.  
For the purpose of sample size calculation, the primary outcome measurement is assumed to be 
the composite of the listed primary endpoint components.  
Extensive literature search was conducted to gather information on the non-inferiority margin. 
Due to limited results found in literature, the non-inferiority margin for this study, δ = 10%, was 
chosen to align with the study design.  
The sample size estimation was based on the following assumption: 
• 
Success rate of the investigational is expected to be 70% 
• 
Success rate of standard treatment is estimated to be 55% 
• 
Power is set at 80% and one-sided significance level is set at 5% 
• 
Expected rate of attrition is 10%  
Based on the assumptions, a total of 46 subjects are required to show that the expected success 
rate of 70% is different than the true rate of 55% with a delta of 10%. Adding in additional 
subjects for anticipated loss to follow-up, 51 subjects are needed to be enrolled for a total of 46 
subjects with 6 month data. 
Analysis Population 
The safety population consists of all patients who are implanted with the study device.  The primary 
analysis for all safety endpoints will be performed on this population. 
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. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 46 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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.   
Endpoint Analysis: 
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 follow-up.  In the 
event of a Grade 2 or more using the Raymond Roy Scale, a second assessment will be made at 
12- month follow-up to re-assess for complete occlusion and will be reported as a secondary 
efficacy. 
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.). 
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 regularly 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 Neqstent implant and the surrounding vasculature.   

 
Document Number 
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Rev.  
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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. 
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 
It is expected that the study will take 6 months to enroll a minimum of  51 patients.  Follow-ups 
for the primary endpoint are the 6-month visit and 12-month visit, depending on the Raymond 
Roy score at the 6-month visit.  Total duration of enrollment (6 months), follow-up duration for 
primary endpoint (6-12 months), 24 months follow-up and reporting (3 months) will take 
approximately 33 months. 
Any patient who is consented but has no implant attempt will be study exited. 
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 

 
Document Number 
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Rev.  
F 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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.  
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/favorable 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 

 
Document Number 
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Rev.  
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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: 
• 
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 
 
13 The sponsor may also document deviations from the CIP 
 

 
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Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 
• 
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 

 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
• 
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 
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 per EC guidelines 
• 
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.  

 
Document Number 
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Rev.  
F 
Page 52 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
The database will include built in edit checks which will facilitate data cleaning by identifying 
missing, illogical or inconsistent data at the time of entry. Monitors or other data reviewers may 
also enter manual queries to request additional data clarifications. Queries will be managed within 
the EDC as per Data Management Plan (document DNQS428-06) herewith enclosed in 
APPENDIX-E. 
The Data-Management Plan will be developed to describe: 
a) Procedures used for data review, database cleaning, and issuing and resolving data queries  
b) Procedures for verification, validation and securing of electronic clinical data systems 
c) Procedures for data retention  
d) Specified retention period  
e) Other aspects of clinical quality assurance, as appropriate 
Electronic CRF Form samples are in APPENDIX F – Case Report Form CRF . 
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 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 has fulfilled the data requirements. The 
sponsor will provide the report to the EC and regulatory authorities as required, as well as to the 
notified body.  
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 

 
Document Number 
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Rev.  
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Page 53 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 
• 
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 

 
Document Number 
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Rev.  
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
• 
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. 
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 

 
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Rev.  
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
• 
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 and/or sponsor delegate 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 study 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 
• 
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 

 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
• 
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 
• 
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. 

 
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Rev.  
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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.  
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 

 
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Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
• 
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: 
• 
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.  

 
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Rev.  
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 center 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 
• 
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 

 
Document Number 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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) 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. 
 
 

 
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Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
14 References 
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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 
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6.  Ko JK, Han IH, Cho WH, et al. Crossing Y-stent technique with dual open-cell stents for coiling of 
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7.  Akgul E, Balli T, Aksungur EH. Hybrid, Y-configured, dual stent-assisted coil embolization in the 
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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, 
flow-disrupting 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 
large-neck 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. 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 62 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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   
 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 63 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
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 
A 
0465 
Initial Release 
22 Feb 2019 
B 
0470 
• 
Revise the number of patients from 35 to 50 
• 
Revise the number of sites from 10 to 11 and remove site patient maximum 
• 
Remove secondary endpoints 
• 
Minor clarifications and corrections 
22 Mar 2019 
C 
0497 
1. The date and Rev in the header;   
2. Updated title throughout CIP;   
3. Clarified Study Purpose throughout; 
4. Updated study size FROM:  10,   TO:  11 centers, and follow up durations FROM:  12/21 
months,   TO:  24/33 months; 
5. Removed ‘and equatorial’ from Device Description ; 
6. Added Study Visit at 24 months throughout; 
7. Inclusion criteria updated to specify “unruptured” IAs.;   
8. The following inclusion criterion added:  Patients who are suitable for non-emergency 
endovascular embolization of saccular IAs;   
9. The following exclusion criterion added:  Ruptured aneurysm; 
10. The following exclusion criteria clarified:  Pregnant, breastfeeding or planning pregnancy in 
the next 2 years changed to: Pregnant, breastfeeding or women of childbearing potential not 
on adequate birth control (only women with a highly effective method of contraception [oral 
contraception or intra-uterine device] or sterile women can be enrolled to the study);   
11. The following exclusion criterion added:  The presence of condition that may create 
unacceptable risk during the aneurysm embolization procedure; 
12. Clarified 12 month follow up require mRS; 
13. Clarified Justification Methodology; 
14. Removed General Principles; 
15. Clarified Multi-center Trial Considerations; 
16. Revised Sample Size Rationale; 
17. Clarified Recording Data on Electronic CRFs; 
18. Updated Human Use for Neqstent and Contour data Tables (Sections 19.1 and 19.2); and 
19. Clarified REF nomenclature from NQS## to NQS4##-XX. 
 
16 Jul 2019 
D 
0525 
1. Updated title throughout CIP to add “in adjunctive therapy” 
2. Update number of patients to 51 where appropriate   
3. Updated risk section 6.1  
4. Added section 10.5.: Interim Analysis 
5. Update section 10.6 : Sample Size Rationale and Statistical Considerations including 
enrollment of 51 subjects to yield 46 subjects with evaluable data  
27 Sep 2019 
D 
0541 
Correction Only:  correct “four” to “three” on page 7 
31 Oct 2019 
E 
0548 
1. 
Update the Core Lab contact info 
2. 
Exclusion criteria #6 clarified to be consistent with #3 (admin error) 
14 Nov 2019 
E 
0564 
Correction Only:  In Study size and duration, remove "in Europe" 
10 Dec 2019 
F 
0573 
In §10.5, remove “Only after approval following the review of the interim analysis summary from 
Ethics Committees and Regulatory Authorities, further patient enrollment will be continued.”  
15 Jan 2020 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 64 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
 
16 APPENDIX A - Statement of Compliance and Signature Page 
Clinical Investigation Number: DNQS428-01 
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 
DNQS428-01 
 
Rev.  
F 
Page 65 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
17 APPENDIX B - Sponsor Approval Page 
 
 
Study Title: 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent in adjunctive 
therapy (CAFI Study) 
 
CIP Document Number: 
DNQS428-01 
 
CIP Revision:  
 
F 
 
CIP Date: 
 
 
15-Jan- 2020 
 
 
Signature/Date: 
 
______________________________________________ 
 
 
 
 
L. Carol Holt, MS, RN 
 
 
 
 
Vice President, Clinical Affairs 
 
 
 
 
Cerus Endovascular, Inc. 
 
 
 
 
A subsidiary of Cerus Endovascular, Ltd. 
 
 
 
 
47757 Fremont Blvd 
 
 
 
 
Fremont, CA  94538 
 
 
 
 
United States 
 
 
 
 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 66 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
18 APPENDIX C -  Report of Prior Investigations 
18.1 Human Use for Neqstent (Subject device) 
All human use to date with Neqstent is compassionate use described in Table 10. 
Table 10 Neqstent Compassionate Use 
Country 
Site 
Treating MD 
Date 
Patient Initials 
Procedure 
Implants 
Denmark 
Odense 
University 
Hospital 
Gyula Gal 
21 Aug 2017 
SP 
Successful implant 
7 
12 Oct 2017 
PT 
Successful implant 
04 Dec 2017 
DB 
Successful implant 
13 Mar 2018 
KN 
Successful implant 
24 Oct 2018 
LP 
Successful implant 
11 Dec 2018 
BB 
Successful implant 
28 Feb 2019 
BB 
Successful implant 
Greece 
Athens 
Euroclinic 
Christos Gkogkas 
01 Aug 2018 
HK 
Successful implant 
2 
01 Aug 2018 
ED 
Successful implant 
Canada 
 
Edmonton 
 
Cian O’Kelly 
 
14 Dec 2018 
Not available 
Successful implant 
5 
 
13 Feb 2019 
Not available 
Successful implant 
13 Feb 2019 
Not available 
Successful implant 
07 Jun 2019 
Not available 
Successful implant 
07 Jun 2019 
Not available 
Successful implant 
United 
States 
Stony Brook 
University, 
New York 
David Fiorella 
11 Feb 2019 
TL 
Successful implant 
1 
Total Compassionate Use as of June 2019 
15 
 
18.2 Human Use for Contour (First generation device) 
Study/ 
Assessment 
Location 
System 
Current 
Status 
Clinical Data Type 
Number of 
Patients 
Compassionate Use 
AR 
(First in Human) 
CNS 
Completed 
Compassionate Use 
4 
UK 
3 
DK 
4 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 67 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Study/ 
Assessment 
Location 
System 
Current 
Status 
Clinical Data Type 
Number of 
Patients 
INCA study 
Clinica Familia Sagrada, 
Buenos Aires 
CNS 
Enrollment 
Closed 
Feasibility 
3 
Pilot Study 
United Kingdom 
Hungary 
CNS 
Enrollment 
Closed 
Safety and 
Performance 
19 
CERUS Study 
Germany, Denmark 
CNS 
Enrolling 
Pre-Market 
29 
(as of June 
2019) 
TOTAL 
 
 
 
 
62 
 
18.3 Pre-Clinical Evaluation and Testing 
18.3.1 Table 11 lists pre-clinical evaluation/testing criteria and results for systems that 
incorporates all Implant sizes. 
Table 11 Pre-Clinical Evaluation Criteria and Results 
Evaluation Criteria 
Results 
Biocompatibility 
• 
Biological Risk Assessment  
Pass 
Sterility 
• 
Sterility Assurance Level 10-6 
Pass 
Ethylene Oxide Sterilant Residuals 
• 
Below limits in applicable standard 
Pass 
Nonpyrogenicity (Bacterial Endotoxin Testing) 
• 
2.15 Endotoxin Units/device maximum 
Pass 
Implant Magnetic Resonance Imaging (MRI) Compatibility 
• 
MR Conditional to 3 Tesla per applicable standards 
Pass 
Implant Dimensions and Size Selection 
• 
Conformance with dimensional specifications 
• 
Implant wire integrity after 3 cycles through Introducer 
• 
IFU contains Implant size selection recommendations 
Pass 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 68 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Evaluation Criteria 
Results 
Implant Preparation and Placement Into Microcatheter 
• 
Conformance with dimensional specifications 
• 
Simulated use testing 
• 
Animal studies 
Pass 
Implant Radiopacity 
• 
Materials meet specifications 
• 
Conformance with dimensional specifications 
• 
Animal studies  
Pass 
Implant/DPW Deliverability and Deployment 
• 
Conformance with dimensional specifications 
• 
Implant/DPW deployment force testing  
• 
Animal studies 
Pass 
Implant Retraction 
• 
Implant/DPW retraction force testing 
• 
Implant wire integrity after retraction force testing 
• 
Implant/DPW tensile strength testing  
• 
Animal studies 
Pass 
Implant Detachment Reliability 
• 
Conformance with dimensional specifications 
• 
Implant detachment time testing  
• 
Animal studies 
Pass 
Implant Safety and Function After Implantation 
• 
Conformance with dimensional specifications 
• 
Animal studies 
Pass 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 69 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
18.3.2 Animal Study Results 
The Neqstent implant has undergone 2 animal studies as summarized in Table 8. The first study 
was a feasibility study while the second study was a GLP study. These studies were done to 
validate the design and performance of the implant during use similar to that occurring in 
humans. The animal models used in the testing process have been either elastase model or 
surgical creation of aneurysm. The rationale for using both models has been to establish 
performance characteristics in a range of aneurysm diameters and morphologies.  
An induced experimental model is required to investigate novel treatments for IAs as these occur 
spontaneously only very rarely in animals. The rabbit model2 has evolved over recent years as the 
species of choice for endovascular ICA due to three main factors: 
1. The coagulation system of the rabbit is similar to that of humans. 
2. The dimensions of the extracranial carotid arteries are similar to those of the intra-arterial 
cerebral artery dimensions in humans. 
3. Rabbits are easier to handle and manage. 
Surgically created aneurysms were used in this study in order to create large enough aneurysm to 
accommodate the Neqstent device in wide neck aneurysms and provide a large enough aneurysm 
sac to permit the passage of a microcatheter to deliver embolic coils. Technical development of 
the model has evolved so that an experimental aneurysm model similar to those observed in 
humans with regard to arterial origin, shape, hemodynamics and patency can be reproduced. 
Measurement of performance characteristics has been undertaken at each study to inform the 
design development and evolve the design input. 
Throughout animal testing, the product deliverability was excellent without presenting any 
unforeseen issues. The results are summarized in Table 12.  
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 70 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
Table 12 Summary of Animal Studies 
Study Location 
Number of 
Animals (one 
aneurysm per 
animal) 
Survival 
Findings 
1 
Research Institute of 
Neurointervention 
Paracelsus Medical 
University 
Christian Doppler 
Medical Center 
Salzburg 
Austria 
*6 
Chronic 
30 days 
Device placement easily achieved in 6/6 aneurysm. 
Implants were delivered by 2 physician operators. 
Parent vessels remained patent in 6/6 
Immediate reduction in flow was seen in 5/6  
Intra-aneurysmal thrombus seen in 4/4 
Histopathology in 30-day specimen showed 
thrombosis in aneurysm with the establishment of a 
fine layer of neointima and all devices remained in 
position with no movement or migration observed. 
2 
Institute of 
Neurointervention 
Paracelsus Medical 
University 
Christian Doppler 
Medical Center 
Salzburg 
Austria) 
14 rabbits 
(surgically 
created 
aneurysms)* 
 
12 study rabbits 
 
2 back-up rabbits  
Chronic 
 
6 – 30 days 
6 – 60 days 
Device placement easily achieved in 12/12 
aneurysm. Implants were delivered by 2 physician 
operators. 
All Neqstent devices remained stable during the 
coiling procedure. 
Not all aneurysms were densely packed to assess 
their closure in follow-up 
Parent vessel remained patent in all subjects at the 
30 day and 60 day time points. 
At 30 days Raymond Roy <II observed in 80% of 
the subjects. 60 days showed similar results. 
All devices remained stable at the neck in follow-up 
with no device herniation into the parent vessel  
 
18.4 Conclusion 
The Neqstent device has been subjected to appropriate testing to ensure appropriate safety and 
efficacy for clinical assessment as recommended in MEDDEV guidelines. 
Preclinical use of the implant has demonstrated the ability to safely deploy and retract the implant 
into an appropriate position in the neck of the aneurysm using standard endovascular techniques 
under fluoroscopic guidance as per current standard of care. 
Histopathological results in the preclinical phase have demonstrated the development of 
organized thrombus in the aneurysm sac and the development of endothelial tissue across the 
neck of the aneurysm encapsulating the implant and coil mass into the aneurysm wall. 
The implant has undergone a range of biological and mechanical assessments as described above 
together with a thorough risk analysis to determine readiness for clinical evaluation.  
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 71 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
19 APPENDIX E – Data Management Plan  
 
 
DNQS428-06.B 
 
(9 Pages) 
 
 

 
Document Number 
DNQS428-01 
 
Rev.  
F 
Page 72 of 119 
Clinical Investigation Plan 
Title 
Coil Assisted Flow Diversion: A prospective, single arm, multi-center 
study to assess the safety and performance of Neqstent 
 in adjunctive therapy (CAFI Study) 
Confidential & Proprietary 
 
Master document is controlled electronically. Copies are not controlled. Ensure revision is valid before use. 
 
 
20 APPENDIX F – Case Report Form CRF  
 
 
DNQS425-F1.B EU EDC Study Worksheets – NQS 
 
 
(38 Pages)