Pilot Study of the Contour Neurovascular SystemTM
Conditions: Intracranial Aneurysm
Sponsor: Cerus Endovascular, Inc.

  
 
  
Document Number  
DNX065-01  
Rev F  
Page 1 of 34  
Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
  
  
  
Pilot Study of the Contour Neurovascular System™ 
 
November 14, 2017 
NCT Number 02784431 
  
  
Study Sponsor  
Cerus Endovascular Limited  
John Eccles House  
Oxford Science Park  
  
Oxford, OX4 4GP, United Kingdom  
  
Tel/Fax: +44 (0) 1865 57859  
  
  
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.  
  
  
  
  
  
  
  

  
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Document Number  
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Rev F  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
 
Study Information  
Protocol Name  
Pilot Study of the Contour Neurovascular SystemTM  
Protocol Number  
DNX065 revision F  
Device Name  
Contour Neurovascular SystemTM  
Lead Principal Investigator  
  
  
  
  
Contact information:  
  
Dr. Tufail Patankar  
Consultant Interventional Neuroradiologist  
  
  
  
Leeds Teaching Hospital General Infirmary  
The Leeds Teaching Hospitals NHS Trust   
Research & Innovation Centre | St James’s University  
Hospital| Becke> Street | Leeds | LS9 7TF  
  
Tel:         0044-1133923180  
Fax:        0044-113392824  
  
  
Study Sponsor  
Cerus Endovascular Limited  
John Eccles House  
Oxford Science Park  
Oxford, OX4 4GP, United Kingdom  
Tel/Fax: +44 (0) 1865 57859  
Manufacturer  
Cerus Endovascular, Inc.   
47757 Fremont Blvd   
Fremont, CA, 94538, US  
Sponsor contact:   
  
Mary Beth Kepler  
Cerus Endovascular, Inc.   
47757 Fremont Blvd   
Fremont, CA, 94538, US   
  
marybeth.kepler@cerusendo.com  
Tel: 001-510-364-4056  
  
  
  
  

  
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Document Number  
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Rev F  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
TABLE OF CONTENTS  
1  Overview ............................................................................................................................................................. 4 
2  Pilot Study Synopsis ............................................................................................................................................ 4 
3  List of Acronyms ................................................................................................................................................. 5 
4 Introduction .......................................................................................................................................................... 5 
5 Investigational Device Description ...................................................................................................................... 7 
5.1  Implant and Delivery system ......................................................................................................................................................................................... 7 
5.2  Device Manufacturing Overview ................................................................................................................................................................................... 8 
6  Risks and Benefits ............................................................................................................................................... 8 
6.1  Risks ............................................................................................................................................................................................................................... 8 
6.2  Anticipated Benefits ....................................................................................................................................................................................................... 9 
7  Investigational Protocol ....................................................................................................................................... 9 
7.1 Design .............................................................................................................................................................................................................................. 9 
7.2 Objectives ........................................................................................................................................................................................................................ 9 
7.3 Target Patient Population ................................................................................................................................................................................................ 9 
7.4 Screening ......................................................................................................................................................................................................................... 9 
7.5 Eligibility ......................................................................................................................................................................................................................... 9 
7.6 Baseline.......................................................................................................................................................................................................................... 12 
7.7 Study Procedure ............................................................................................................................................................................................................. 12 
7.8  Hospital Discharge ....................................................................................................................................................................................................... 13 
7.9 Follow-Up ...................................................................................................................................................................................................................... 13 
7.10 Early Withdrawal ......................................................................................................................................................................................................... 14 
7.11 Variables ...................................................................................................................................................................................................................... 15 
8  Adverse Events .................................................................................................................................................. 15 
8.1 Stroke ............................................................................................................................................................................................................................. 16 
8.2 Independent Medical Monitor ....................................................................................................................................................................................... 17 
8.3  Adverse Event Reporting/Analysis .............................................................................................................................................................................. 17 
9  Statistical Analysis ............................................................................................................................................ 17 
9.1 General Principles .......................................................................................................................................................................................................... 18 
9.2 Multi-centre Trial Considerations.................................................................................................................................................................................. 18 
9.3  Interim Analysis ........................................................................................................................................................................................................... 18 
9.4  Sample Size .................................................................................................................................................................................................................. 18 
9.5  Number of Clinical Sites .............................................................................................................................................................................................. 18 
10 Additional Trial Characteristics ........................................................................................................................ 18 
10.1 Measures Taken to Avoid Bias .................................................................................................................................................................................... 19 
10.2 Special Equipment for Investigation ........................................................................................................................................................................... 19 
10.3 Procedure for Replacing Withdrawn Subjects ............................................................................................................................................................. 19 
10.4 Subject Pregnancy ....................................................................................................................................................................................................... 19 
10.5 Investigational Device(s) and Comparator(s) .............................................................................................................................................................. 19 
10.6 Justification for Comparator ........................................................................................................................................................................................ 19 
10.7 Other Devices Used During Study .............................................................................................................................................................................. 19 
10.8 Investigational Devices ................................................................................................................................................................................................ 20 
10.9 Total Expected Trial Duration ..................................................................................................................................................................................... 20 
11 Study Management ........................................................................................................................................... 20 
11.1 Investigator Responsibilities........................................................................................................................................................................................ 20 
11.2 Sponsor Responsibilities.............................................................................................................................................................................................. 25 
12 References ........................................................................................................................................................ 33 
 
APPENDIX A – Statement of Compliance and Signature Page ...................................................................... 32  
  
  
  
  
  

  
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Document Number  
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Rev F  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
  
1 Overview  
 
This document is a clinical investigation plan (CIP) for a Pilot Study of the Contour Neurovascular System™.  
The Contour Neurovascular System is an investigational device.  
  
2 Pilot Study Synopsis  
 
Study Title  
Pilot Study of the Contour Neurovascular System™   
Device Name  
Contour Neurovascular SystemTM  
Primary 
Objective  
To collect and report the safety variables data of the Contour Neurovascular System™  
Secondary 
Objective  
To collect and report the efficacy variables data of the Contour Neurovascular System™.  
Design  
Prospective, single arm, multi-centre study  
Assigned  
Intervention  
Endovascular treatment with the Contour Neurovascular System™ for an unruptured 
intracranial aneurysm (IA)  
Target Patient 
Population  
Patients with unruptured IAs suitable for treatment with the Contour Neurovascular 
System™ and who meet study eligibility criteria  
Primary 
Variables  
Safety:  Safety variables are the occurrence and frequency of adverse events (AE)s, 
adverse device effects (ADE)s, serious adverse events (SAE)s, serious adverse device 
effects (SADE)s and unanticipated serious adverse device effects (USADE)s.   
  
Specific AEs associated with this procedure that shal be evaluated include but are not 
limited to: blood vessel perforation or rupture, unintended thrombosis, adverse tissue 
reaction, infection, and hematoma formation, and major ipsilateral stroke/subarachnoid 
hemorrhage (SAH) or death due to neurologic cause within six (6) months after  treatment.  
Secondary 
Variables  
Efficacy: Efficacy variables are related to the ability of the device to emobolize the 
aneurysm and shall be analyzed relative to the baseline visit. The variables to be collected 
and reported shall include but are not limited to:  
  
Angiographic and/or magnetic resonance imaging (MRI)/MR angiogram (MRA) 
assessment of aneurysm occlusion including evaluation of occlusion grade, parent vessel 
patency, physical positioning, occlusion durability, and any device migration.  
Sample Size  
A maximum of forty-five (45) subjects  
Number of  
Sites  
A maximum of five (5) clinical study sites   
Study Visits  
Baseline, procedure, six (6) weeks, six (6) months, and one (1), two (2), three (3), four (4), 
and five (5) years  

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
Study  
Duration   
Projected to be at least 5 ½ years, including enrolment (assumes 6 months for enrolment)  
  
  
3 List of Acronyms  
 
The following list provides acronyms used in this document and their meaning:  
  
1. AE - adverse event   
2. ADE - adverse device effect  
3. CIP – clinical investigation plan  
4. CRF – case report form  
5. CRO - contract research organizations  
6. CT - computed tomography  
7. CTA - computed tomography angiography  
8. CTA – clinical trial agreement  
9. DPW - detachable pusher wire  
10. EC – ethics committee  
11. GCP - Good Clinical Practice  
12. IA - intracranial aneurysm  
13. IC – informed consent  
14. ICF – informed consent form  
15. ID - identification  
16. MC – microcatheter  
17. MR - magnetic resonance  
18. MRI – magnetic resonance imaging  
19. MRA – magnetic resonance angiogram   
20. mRS - modified Rankin Scale  
21. PI - Principal Investigator  
22. SADE – serious adverse device effect  
23. SAE - serious adverse event  
24. SAH – subarachnoid haemorrhage   
25. TOF- time-of-flight  
26. USADE - unanticipated serious adverse device effect  
27. WOS - WEB occlusion scale   
4 Introduction  
 
Intracranial aneurysms (IA)s 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.  

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
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Current treatment for IAs is provided in two settings: ruptured and unruptured IAs. When ruptured, the clinical 
goal is to stabilize the patient and reduce the risk of rebleeding from the IA. Surgical treatment involves opening 
the skull and placing clips or other devices over the offending IA. Endovascular treatment typically involves 
placement of coils into the target aneurysm through a catheter.   
Coil embolization of IAs is a well-established therapy. In ISAT, a large randomized comparison of surgical and 
endovascular treatment of IAs, endovascular treatment was shown to have a lower rate of death or dependence 
at one year compared to surgical treatment.2 Ten-year follow-up from ISAT showed that rebleeding from the 
target IA was uncommon but slightly higher in the endovascular group (p=.02). However, the rate of death or 
dependence was lower in those treated with the endovascular approach.3   
Incomplete occlusion of the target IA is associated with increased risks of aneurysmal bleeding. In CARAT, a 
large US clinical trial, in comparison to patients with complete IA occlusion, patients with 91-99% occlusion 
had a 2.9-fold increased risk of aneurysmal bleeding; relative risks of rebleeding with residual neck (70-90% 
occlusion) and partial occlusion (<70%) were 2.9 and 21.7, respectively.4 For this reason, clinicians attempt to 
occlude the target IA as completely as possible.  
Currently, the most commonly provided endovascular therapy for IAs is coil embolization. Despite the high 
prevalence of its use, coil embolization is substantially restricted due to geometric limitations and target IA 
access. Moreover, complete occlusion of the target IA is relatively uncommon; in a large randomized trial of 
coil embolization, complete occlusion of the target IA at 6-month follow-up was seen in only about 30% of 
cases.5     
It is commonly accepted that large IAs or those with a neck size >4 mm are more difficult to completely occlude 
with embolization coils. Wide-necked IAs are especially difficult to treat, as the geometry of the IA does not 
allow coils to stay in place. Adjunctive devices to improve coil embolization in wide-necked IAs are available. 
Balloon catheters may aid the clinician in packing the IA with coils and several intravascular stents are now 
commercially available. These stents are placed in the parent artery adjacent to the target IA; stent struts help to 
hold coils in place inside the target IA. Unfortunately, few studies are available to estimate the relative increase 
in complete occlusion rate provided by these adjunctive devices. Even more challenging is the treatment of 
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.  
Incomplete occlusion has additional risks, including growth of the IA and reopening related to continued 
pulsatile blood flow into the IA. Moreover, coils can become compacted and regress into the dome of the IA, 
resulting in further filling at the IA neck. In addition to exposing patients to bleeding risk, incomplete IA 
occlusion is also associated with the need for surveillance, which is stressful for patients. More importantly, 
these patients may need another embolization. Retreatment procedures can be complex and not always 
successful, thereby exposing the patient to further risk.  
Recently, a new set of devices for IA treatment have become available. These devices, called flow diverters, are 
stents placed in the parent artery. Flow diverters have a mesh component that retards the flow of blood from the 
parent artery into the IA fundus. Stasis of blood in the fundus induces IA thrombosis, which achieves the goal of 
preventing pulsatile flow into the IA. The mesh component of flow diverters has also been shown to serve as a 
scaffold for endothelial growth,8 which can promote permanent occlusion of the target IA. These two 
components (flow disruption and scaffolding for re-endothelialisation) distinguish flow diverters from standard 
coils embolization. For large (>10 mm in maximum dimension) and giant (>25 mm) IAs, flow diverters have 
been shown to have high complete occlusion rates.9  Most flow diverting devices are placed into the parent 
artery, requiring the patient to take antiplatelet agents (aspirin and clopidogrel) for prolonged periods.  This can 
be a significant limitation, which precludes their use in the acute setting of aneurysm treatment.   

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
Another group of devices used in endovascular treatment of IAs, intra-saccular flow disrupters, do not require 
antiplatelet therapy as a prerequisite. These devices are placed in the IA and their mechanism of action is to 
disrupt the intra-aneurysmal blood flow and subsequently create intra-aneurysmal (and intra-device) thrombosis. 
The Contour Neurovascular SystemTM device (Cerus Endovascular Limited, Oxford, UK) is designed to be a 
flow disruptor that is placed into the IA sac, and does not require the use of antiplatelet therapy.  The Contour 
Neurovascular SystemTM device is composed of a double layer of 72-wire platinum core Nitinol braid mesh 
heat-set into a concave shape. The device is delivered through a 0.027” microcatheter into the IA fundus and is 
placed at the IA neck. It is designed to disrupt blood flow into the IA and to act as a scaffold upon which 
endothelial cells can grow. These two mechanisms of action may increase the likelihood of complete IA 
occlusion compared to embolization coils.  
Other intra-saccular flow disruptors, such as the WEB™ Aneurysm Embolization System (Sequent Medical, 
Aliso Viejo, CA) and LUNA Aneurysm Embolization System (Medtronic, Inc., Irvine, CA), have been 
developed and have CE mark approval. Despite working in principle in the same way as the Contour 
Neurovascular SystemTM, these other devices have demonstrated certain limitations in their use 10, 11. For 
example, certain inherit properties of the WEB necessitates selected geometric “matching” of the device to the 
overall aneurysm shape. Failure to do so has led the device to migrate distally in the aneurysm or to 
compacting/foreshortening of the device with subsequent neck recanalization. It has become increasingly clear 
that accurate correlation of the shape of the WEB to the aneurysm is of critical importance and may not always 
be possible. Accordingly, there is a need to address these limitations and further improve the performance of 
intra-saccular flow disruptors.    
This CIP describes a pilot study for the  Contour Neurovascular SystemTM for the treatment of  unruptured IAs.  
5 Investigational Device Description  
 
5.1  Implant and Delivery system  
The Contour Neurovascular SystemTM is comprised of the Contour Neurovascular SystemTM implant  
(hereafter called “Contour implant”), which is pre-attached to a detachable pusher wire (DPW), and an 
Introducer. The DPW facilitates the delivery of the Contour implant through a microcatheter (MC) and 
into the aneurysm. All devices are provided sterile and non-pyrogenic, and are for single patient use 
only.  
The Contour Neurovascular SystemTM 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 1 below. 
The implant also has a platinum marker for additional visualization during the procedure.  The 
preattached DPW has a composite stainless steel and polymer construction. The Introducer is a single 
lumen polymer tube that is used to constrain the Contour implant during introduction into the MC hub. 
The Contour implant body and proximal marker can be visualized under fluoroscopy.  
Given the platinum core of the device’s mesh and the platinum marker, the Contour implant is 
radiopaque and delivered into the target IA under fluoroscopic guidance using standard endovascular 
techniques and a commercially available microcatheter. The implant is electrolytically detached from 
the DPW using a commercially available detachable coil power supply.   
The Contour Neurovascular SystemTM is provided sterile with an Introducer preloaded onto the DPW 
shaft just proximal to the implant. Refer to the Instructions for Use for additional information.  

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
    
Figure 1. Contour Neurovascular SystemTM implant  
  
5.2  Device Manufacturing Overview  
The Contour Neurovascular SystemTM is manufactured by Cerus Endovascular Inc. 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.  
6 Risks and Benefits  
 
6.1  Risks  
Risks of Contour Neurovascular SystemTM device are similar to those identified during commercially 
available endovascular IA treatment and are well known. Risks, some of which could be fatal or cause 
severe neurologic deficit, are listed below:   
• 
Aneurysm rupture causing intracranial haemorrhage  
• 
Injury to parent artery causing thrombosis or haemorrhage  
• 
Distal embolization of particles or blood clot causing stroke  
• 
Parent artery vasospasm  
• 
Parent artery dissection  
• 
Symptoms related to aneurysm occlusion  
• 
Aneurysm recanalization  
• 
Infection  
• 
Device migration causing incomplete occlusion, haemorrhage or ischemic stroke  
• 
Cerebral angiography risks such as allergic reaction to contrast media, radiation exposure, and 
groin femoral artery bleeding/infection.    
Note:  The radiation dose from 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)  
  
For a complete list of risks, see the device’s Instructions for Use. There may be unknown risks.  
   

  
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Design History Document  Title  
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6.2  Anticipated Benefits  
As previously described, recent results from the use of existing intra-saccular flow disruptor devices 
have shown a risk of compaction and neck regrowth. The Contour Neurovascular SystemTM device is 
designed to increase the likelihood of complete IA occlusion. Complete IA occlusion may reduce the 
risk of subsequent IA rupture including in difficult to treat wide-necked or bifurcation aneurysms.   
7 Investigational Protocol  
 
7.1  Design  
Single-arm multi-centre prospective clinical trial.   
7.2  Objectives  
The primary objective of this study is to collect and report the safety variables data of the Contour 
Neurovascular System™.   
The secondary objective is to collect and report the efficacy variables data of the Contour Neurovascular 
System™.  
7.3  Target Patient Population  
The target patient population is patients with unruptured IAs requiring endovascular treatment. 
Unruptured IAs are common and those that have wide necks (neck >4 mm) are difficult to treat with 
standard coil embolization.  
7.4  Screening  
Patients will 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.  
Screening involves a clinical evaluation and a review of appropriate imaging which typically includes a 
computed tomography angiography (CTA) and subsequently a cerebral angiogram, which are all 
standard of care for patients who have been diagnosed with an IA.  It is recommended that the screening 
angiogram include the acquisition of a 3D rotational angiogram of the aneurysm and parent vessel for 
proper evaluation of the anatomy.    
7.5  Eligibility  
To participate, patients must meet all inclusion criteria and no exclusion criteria listed below. The 
available sizes of the Contour implant as well as the aneurysm dimensions are provided in Table 2, and 
the Aneurysm dimension definitions are provided in Figure 2 below. All patients must sign a 
studyspecific 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 and is considered a study subject only when the patient is fully qualified and at least one 
investigational device has been placed into the patient’s body. If at the onset of the study procedure, the 
patient’s IA is not deemed appropriate by the investigator and no investigational device has been placed 

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
into the body, the patient will be excluded from the study and treated outside of the study per the 
investigator’s usual practices. The following provides examples of patient enrolment scenarios for the 
study:    
1. The patient is not considered enrolled in the study:  at the onset of the procedure, the investigator 
determined the patient’s IA was not suitable for treatment with the investigational device, thus, no 
attempt was made by the investigator to place the investigational device. The patient will be treated 
outside of the study per the investigator’s usual practices.  
2. The patient is considered enrolled in the study:  at the onset of the procedure, the investigator 
determined the subject’s IA was suitable for treatment with the investigational device. The 
investigator attempted but was unable to place the investigational 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 six-week visit.   
3. The patient is considered enrolled in the study:  at the onset of the procedure, the investigator 
determined the subject’s IA was suitable for treatment with the investigational device. The 
investigator successfully placed the investigational 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.  
4. The patient is considered enrolled in the study:  at the onset of the procedure, the investigator 
determined the subject’s IA was suitable for treatment with the investigational device. The 
investigator successfully placed the investigational 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.  
  

  
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Table 1. Study eligibility criteria Patients must meet all inclusion criteria and no exclusion criteria listed 
below  
Inclusion criteria  
1. Age 18-80 years at screening  
2. Unruptured saccular IA in the anterior or 
posterior circulation with dimensions 
consistent with Table 2  
3. IA appears suitable for Contour Neurovascular  
SystemTM device  
4. 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 Patient able to understand 
and sign a study-specific informed consent 
form  
Exclusion criteria  
1. Ruptured IA  
2. Any other IA that requires treatment in the next year  
3. IA width >8.5 or <2 mm  
4. IA neck >8 or <2 mm  
5. IA embolisation would most likely cause stroke  
6. Target IA contains other devices/implants (e.g., coils)  
7. Inability to access the target IA with the microcatheter  
8. Any congenital or iatrogenic coagulopathy  
9. Platelet count <50,000/microliter  
10. Known allergy to platinum, nickel or titanium  
11. Known allergy to contrast agents  
12. Stenosis of the target IA’s parent vessel >50%   
13. Taking daily aspirin or other platelet inhibitor (clopidogrel or 
equivalent) other than for the target aneurysm   
14. Taking any anticoagulants (e.g., warfarin)  
15. Abnormal clotting parameters  
16. Pregnant, breastfeeding or planning pregnancy in the next 2 
years  
17. Other medical conditions that could increase the risk of 
neurovascular procedures (e.g., liver failure, cancer, etc.) or 
ability to comply with study requirements   
18. Participating in another study with investigational devices or 
drugs  
  
Table 2. Contour Neurovascular SystemTM and aneurysm dimensions  
REF (Catalogue  
Number) – Diameter  
Aneurysm Neck 
(mm)*  
Aneurysm  
Width (mm)*  
CNS05 – 5 mm  
2.0 - 3.0  
2.0 - 3.5  
CNS07 – 7 mm  
3.0 - 5.0  
3.0 - 5.5  
CNS09 – 9 mm  
4.0 - 6.0  
5.0 - 7.5  
CNS11– 11 mm  
5.0 - 8.0  
7.0 - 8.5  
*See definitions in Figure 2  
 
Figure 2. Aneurysm dimension definitions  
  
  
  
Height 
Width 
Neck 

  
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7.6  Baseline  
The baseline evaluation is performed after signing the consent form and prior to the study 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. An NIH Stroke Scale1 score is to 
be recorded. NIH Stroke Scale is a commonly used assessment of clinical findings in patients with 
stroke. Since most unruptured IAs are asymptomatic, it is anticipated that most subjects will have a 
baseline NIH Stroke Scale score of 0. The investigator should have an up-to-date NIH Stroke Scale 
certification to complete the assessment. A modified Rankin Scale (mRS) will also be recorded 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. 
Premenopausal females will undergo a pregnancy test. Relevant pre-procedure imaging should be 
submitted to the independent core laboratory.  
7.6.1 Angiogram  
The angiogram should be performed prior and separate from the Contour Neurovascular SystemTM 
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.  It is not 
required to repeat the cerebral angiogram at baseline if the patient has had a cerebral angiogram that 
includes a 3D rotational angiogram within three (3) months of enrolment since the final determination 
of eligibility is based upon the cerebral angiogram at the time of the procedure.   
All images obtained at baseline, including the 3D angiogram, are to be submitted for review to the  
Sponsor’s representatives to confirm the subject’s eligibility for use of the Contour Neurovascular 
SystemTM.  The Contour Neurovascular SystemTM procedure may be scheduled following confirmation 
from the Sponsor.  Additionally, the images obtained at baseline will be submitted to the independent 
core laboratory.   
7.7  Study Procedure  
7.7.1 Preoperative Preparation  
The subject undergoes standard preoperative preparation. The procedure must be performed under 
general anaesthesia.   
7.7.2 Arterial Access  
Standard methods are used to gain access to the femoral artery. Standard methods are used (e.g., sheaths 
and guide catheters) 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.   
 
1 Described at: http://www.ninds.nih.gov/doctors/nih_stroke_scale.pdf  

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
7.7.4 Contour Neurovascular SystemTM Placement  
Contour Neurovascular SystemTM placement is described in detail in the Instructions for Use. Briefly, 
the target IA is accessed via standard methods. A 0.027” microcatheter is placed into the target IA. The 
Contour Neurovascular SystemTM device is introduced into the microcatheter and slowly delivered into 
the target IA. Once the Contour implant is in the appropriate location, the device is detached via a 
standard electrolytic mechanism.   
A final post-placement angiogram, which includes a 3D angiogram of the aneurysm and parent vessel, 
will be performed and all devices are removed from the body. All relevant radiographic images should 
be saved. Specifically, the investigator should document flow disruption compared to pre-placement 
flow. Any device deficiencies, technical complications or adverse events occurring during the procedure 
should be noted in the CRF.  
All images captured during the procedure, including the 3D angiogram, are to be submitted to the 
independent core laboratory.   
Peri-operative anti platelet use is not excluded and may be used at the discretion of the operator.  
7.8  Hospital Discharge  
The subject will be discharged from the hospital as per standard practices. Prior to discharge, the 
investigator should evaluate the subject for any adverse events and perform a neurologic examination.  
7.9  Follow-Up  
The subject will have a follow-up visit at six (6) weeks, six (6) months, and one (1), two (2), three (3), 
four (4) and five (5) years after the study procedure. At each study visit, the subject should be assessed 
for any new adverse events. 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 is recorded if a stroke has occurred.  
Cerebral angiography will be repeated at six (6) months and one (1) year.  At six (6) months, the 
cerebral angiography will include a 3D angiogram, and at one (1) year the angiogram will include the 
conventional AP, lateral and working projections. The investigator should ensure that follow-up 
angiography is done with identical views to maximize the ability to compare baseline and post-
treatment views. All angiographic images should be submitted to the independent core laboratory. The 
target IA status will be evaluated by an independent core laboratory using an appropriate aneurysm 
scoring scale(s) such as the Raymond Scale and/ or the Web Occlusion Scale (WOS).  
An MRI/MR angiogram (TOF & Contrast enhanced MRA) will be performed in all subjects at 6 months 
follow up. The purpose of the MR is to establish and compare the MR and angiographic appearances of 
the target IA.   
If the cerebral angiogram shows complete occlusion at both the 6-month and 1-year time frames, the 
investigator may choose alternative methods for the 2, 3, 4 and 5-year angiography (e.g., MRI/MRA). If 
the cerebral angiogram at either 6 months or 1 year shows incomplete target IA occlusion, the 2, 3, 4 
and 5-year exam should include a standard cerebral angiogram.  
The subject’s participation in the study is complete after the 5-year visit and angiogram/MR are 
completed.  

  
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The study’s schedule of assessments and allowed post-treatment visit windows are shown in Table 3 
below.  
  
  
  
Table 3. Schedule of assessments  
  
 
 
 
 
 
 
 
Medical history and medications  
X  
  
  
  
  
  
  
Neurologic exam  
X  
  
X  
X  
X  
X  
X  
NIH Stroke Scale  
X  
  
X*  X*  
X*  
X*  
X*  
Modified Rankin Scale (mRS)  
X  
  
X  
X  
X  
X  
X  
Pregnancy test (pre-menopausal female)  
X  
  
  
  
  
  
  
Cerebral angiogram  
X** 
w/3D  
X 
w/3D  
  
  
X  
w/3D  X  
X§  
Adverse events  
  
X  
X  
X  
X  
X  
X  
Procedure information  
  
X  
  
  
  
  
  
Aneurysm scoring scale  
  
X  
  
  
X  
X  
X#  
MRI/MRA  
  
  
  
  
X   
  
X§  
*The NIH Stroke Scale score should be obtained within 7 days after stroke in the event a subject is 
diagnosed with a stroke  
**Baseline cerebral angiogram with 3D can be completed within 3 months of enrolment  
# Aneurysm scoring scale completed when cerebral angiograms are performed  
§MRA/Cerebral Angiogram Optional: If the cerebral angiogram shows complete occlusion at both the 6month 
and 1-year time frames, the investigator may choose alternative methods for the 2, 3, 4 and 5-year 
angiography (e.g., MRI/MRA).   
   
  
7.10 Early Withdrawal  
Reasons for subject withdrawal prior to study completion will be documented on the CRF. Valid 
reasons for early study withdrawal include:  
• 
Death  
• 
Adverse event or other medical condition that prevents study participation  
• 
Withdrawal of voluntary consent  
• 
Loss to follow-up  

  
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• 
Study is terminated  
  
At least three documented attempts will be made to contact any subject who is lost to follow-up. If the 
study is terminated for any reason, the governing Ethics Committee will be notified.  
7.11 Variables  
7.11.1 Primary Variables  
 The primary varibles are safety as this is a pilot study.  
  
The safety variables to be collected and reported are the occurrence and frequency of AEs, ADEs, 
SAEs, SADEs and USADEs.   
  
Specific AEs associated with this procedure that shal be evaluated include but are not limited to: blood 
vessel perforation or rupture, unintended thrombosis, adverse tissue reaction, infection, and hematoma 
formation, and major ipsilateral stroke/ SAH or death due to neurologic cause within 6 months after  
treatment.  
7.11.2 Secondary Variables  
Secondary variables to be collected and reported in order to aid in the design of future studies are listed 
below.  
  
Efficacy: Efficacy variables are related to the ability of the device to emobolize the aneurysm and shall 
be analyzed relative to the baseline visit. The variables to be collected and reported shall include but are 
not limited to:  
  
Angiographic and/or MRI/ MRA assessment of aneurysm occlusion including evaluation of occlusion 
grade, parent vessel patency, physical positioning, occlusion durability, and any device migration.  
  
7.11.3 Independent Analysis of Imaging  
Follow-up imaging (i.e., cerebral angiograms and/or MRI/MRA) will be evaluated and angiographic 
assessments of the aneurysm will be completed by an independent core laboratory with experience in 
neurovascular imaging of IAs. Clinicians responsible for imaging analyses at the core laboratory will 
not have any financial conflict with the study sponsor and will not be affiliated with a clinical study site. 
An imaging guidance document will be prepared before analysis begins at the independent core 
laboratory.  
  
  
8 Adverse Events  
 
Definitions of adverse event subtypes are provided in Table 4 below. The occurrence of all adverse events will 
be reported by the clinical site investigator on a specific case report form (CRF).  
NOTE: As detailed in section 8.3, the reporting of AEs shall follow MEDDEV 2.7/3, 2015 and shall not make 
any difference between anticipated and unanticipated AEs.  

  
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Table 4. Adverse event definitions per ISO 14155:2011  
Adverse event  An Adverse Event (AE) is:   
“any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the 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.”    
Adverse 
device effect  
An Adverse Device Effect (ADE) is:  
 “adverse event related to the use of an investigational 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 investigational medical device.  
Serious 
adverse event  
A Serious Adverse Event (SAE) is:   
“an adverse event 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 
injury or permanent impairment to body structure or body function,  
• 
led to foetal distress, foetal 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 a serious adverse event.  
Serious 
adverse 
device effect  
A Serious Adverse Device Effect (SADE) is:  
“adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event.”   
Unanticipated 
serious 
adverse 
device effect  
An Unanticipated Serious Adverse Device Effect (USADE) is:  
“a serious adverse device effect which by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report.”  
Note:  Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report.  
8.1  Stroke  
The risk of stroke after treatment with the study device is low. However, if stroke occurs, the subject 
should be appropriately treated according to institutional standards. The investigator should obtain an 
NIH Stroke Scale within 7 days after stroke and record the value in the CRF.  

  
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8.2  Independent Medical Monitor  
An independent Medical Monitor will be appointed for the study who will be qualified by background 
and training and have expertise in neurovascular treatment of IAs.  The independent Medical Monitor 
will review all adverse events to ensure they are reported accurately and in sufficient detail, and will 
make a final determination regarding relatedness to the investigational device and/or procedure.  The 
Medical Monitor will not be an investigator on the study and will not be affiliated with a clinical site 
that is participating in the study.      
8.3  Adverse Event Reporting/Analysis  
In compliance with MEDDEV 2.7/3, 2015, for pre-market studies, the Sponsor is responsible for 
submitting reports to the Competent Authority as required by the applicable regulations and guidelines.   
Specific requirements are as follows:  
Table 5 Sponsor Adverse Event Reporting  
Event  
CA Reporting Timelines  
SAE which indicates an imminent 
risk of death, serious injury, or 
serious illness and that requires 
prompt remedial action for other 
patients/subjects, users or other 
persons or a new finding to it  
Immediately, but not later than 2 
calendar days after awareness by 
Sponsor of a new reportable event 
or of new information in relation  
with an already reported event, per  
MEDDEV 2.7/3  
Any SAE  
Immediately, but not later than 7 
calendar days following the date of 
awareness by Sponsor, per 
MEDDEV 2.7/3  
Any investigational device 
deficiency that might have led to a 
SAE if a) suitable action had not 
been taken or b) intervention had 
not been made or c) if 
circumstances had been less 
fortunate  
Same as above  
New findings/updates in relation to 
already reported events  
Same as above  
  
The Investigative Site shall report all SAEs to the study sponsor or the sponsor’s designee and 
independent Medical Monitor within 48 hours of occurrence.   
  
9 Statistical Analysis  
 

  
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9.1 General Principles  
This is a pilot study intended to collect and report data on the use of the Contour Neurovascular SystemTM.  
The primary analysis for all baseline characteristics and study variables will include all available data for 
all enrolled subjects.  Standard summary statistics will be calculated for all study variables.  For 
continuous variables, statistics will include means, standard deviations, medians and ranges.  Categorical 
variables will be summarized in frequency distributions.  
Statistical analyses will be conducted in SAS version 9.3 or above (SAS Institute, Cary, N.C.), R version 
3.2 or above (R Core Team, http://www.R-project.org) or another validated statistical software package.  
For adverse event reporting, the primary analysis will be based on subject counts, not event counts.  Both 
subject counts and event counts will be presented in tabular summaries of results.  
As this is a pilot study, formal hypothesis testing of the study variables will not be performed and multiple 
testing procedures are not incorporated in the statistical analysis.  
9.2 Multi-centre Trial Considerations  
A maximum of five (5) clinical sites will participate in the study.  The maximum enrolment at any one site 
will be 20 subjects.  
This is therefore a multi-centre clinical study with standardization of subject enrolment, data entry and 
adverse event reporting. All investigational sites will follow the requirements of a common protocol, data 
collection procedures and forms.  
Data will be presented in summary form for all subjects enrolled.  Given the intended sample size, formal 
tests of poolability are expected to have low power and will not prospectively be performed but primary 
variables will also be presented separately for each center.  
9.3 Interim Analysis  
No formal interim analyses are defined for purposes of early study termination.  
9.4 Sample Size  
As formal hypothesis testing is not a study objective, the sample size is based on precision of estimation.  
A sample size of up to 45 subjects enrolled, with at least 30 subjects providing evaluable safety data, gives 
a standard error for the primary safety variable between 4.5% and 5.4%, which is sufficient for estimation 
of the safety incidence rate.  
9.5 Number of Clinical Sites  
A maximum of five (5) clinical sites will participate in the study.  The maximum enrolment at any one site 
will be 20 subjects.  
10 Additional Trial Characteristics  
 

  
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10.1 Measures Taken to Avoid Bias  
Several measures have been included in the CIP in avoidance of bias, including the following:   
1. The study has been designed to ensure treatment and follow-up of subjects are consistent with 
current medical practice.  
2. 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.   
3. All investigators must disclose potential conflicts of interest, including financial interests, to the 
study sponsor prior to participation in the study.  
4. Data from all investigative sites will be monitored throughout the study.    
5. An independent Medical Monitor will adjudicate adverse events that may be considered serious 
and/or device related.  
6. Imaging obtained during the procedure and follow-up period will be reviewed by an independent 
Core Laboratory to verify the status of the Contour implant and the surrounding vasculature.    
10.2 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 and will be reviewed as part of 
routine monitoring visits.  
10.3 Procedure for Replacing Withdrawn Subjects  
Subjects who withdraw from the study will not be replaced.  
10.4 Subject Pregnancy  
The exclusion criterion specifies that those patients who are pregnant, breastfeeding or planning 
pregnancy in the next two years be excluded from the study.  Should a subject become pregnant after 
enrolment in the study, the subject will continue to be seen by the investigator at the time points defined 
in the CIP to ensure proper follow-up of the subject.  The subject will be assessed for any new adverse 
events, undergo a standard neurologic examination, a modified Rankin Scale (mRS) score will be 
recorded and a NIH Stroke Scale will be recorded if a stroke has occurred.  It is expected that the 
cerebral angiogram required at a specific follow-up visit will not be completed if the subject is pregnant 
or breastfeeding. Additionally, if a subject is pregnant or breastfeeding, any other imaging specified by 
the CIP for a specific follow-up visit will only be completed with the concurrence of the subject’s 
obstetrician/pertinent clinician.     
10.5 Investigational Device(s) and Comparator(s)  
The investigational device is the Contour Neurovascular SystemTM. No comparator devices will be used 
in the study.  
10.6 Justification for Comparator  
This study has no concurrent comparator.as this is a pilot study.   
10.7 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.  

  
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10.8 Investigational Devices  
A single investigational device is expected to be used for each target IA. In some situations, an 
investigational device might be inserted into the body but removed prior to deployment, in which case 
another device package could be opened and used.   
Device accountability records should be maintained at each study site. The quantity of devices received 
by the study site, those returned to the sponsor (if applicable), and those devices used at the clinical site 
will be recorded in the device accountability record. The investigator must explain in writing the 
reasons for any discrepancy noted in device accountability.  Device accountability will be verified 
during routine monitoring visits at the clinical sites.    
10.9 Total Expected Trial Duration  
Enrolment is expected to be complete in 6 months. The investigation is expected to last at least 5 ½ 
years, including enrolment.  
11 Study Management  
 
This study will be run according to ISO 14155:2011, the Declaration of Helsinki, 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.   
11.1 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-
today aspects of the study. The PI will take steps to ensure compliance with the CIP and associated 
documents and processes. The PI also protects data integrity and the rights, safety and well-being of 
clinical study subjects.  
11.1.1 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.   
11.1.2 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 11.1.1.   

  
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11.1.3 Communications with EC  
The site Principal Investigator (PI) and the site clinical study team are responsible for communication 
with site ethics committee. The Sponsor and/or designee is responsible for communication with central 
ethics committees. The PI will:  
• 
provide the sponsor with copies of any relevant EC communications regarding this CIP  
• 
comply with requirements from the EC regarding the CIP  
• 
obtain written/dated approval/favourable opinion from the site EC, before starting the study or 
recruiting subjects  
• 
obtain written/dated approval from the site EC before implementing any changes in a CIP 
amendment  
• 
ensure the timeliness of safety reporting to the site EC  
• 
promptly report deviations from the CIP to the EC that affect the rights, safety or well-being of 
the subject or the scientific integrity of the CIP  
• 
keep all EC communications in its study file  
11.1.4 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, 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, and  
• 
either he/she or an authorized designee conducts the consent process consistent with ISO 14155  
11.1.5 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.  
11.1.6 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, 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  
• 
document all deviations from the CIP2  
• 
ensure proper use and accountability of investigational devices  
• 
ensure that the site has adequate staff and capabilities  
• 
ensure that site equipment used in the study is maintained and calibrated  
 
2 The sponsor may also document deviations from the CIP.  

  
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• 
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  
11.1.7 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, MRIs) must be filed with 
the patient’s records.   
11.1.8 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.  
11.1.9 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.  
11.1.10 Medical Care  
The PI will provide standard medical care to study subjects, including:  
• 
informing the subject of the nature and possible cause of any AEs experienced  
• 
informing the subject of any new significant findings occurring during the clinical investigation, 
including the need for additional medical care that may be required  

  
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• 
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 11.1.11 
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 and/or regulatory authorities consistent with local or national requirements  
11.1.12 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.  
11.1.13 Recording Data on CRFs  
The study will use case report forms that have been standardized for the study to collect data. Site 
personnel will be trained in use of the CRFs before study initiation. The PI will ensure that data 
recorded in CRFs in a timely manner and are accurate, consistent with source documents, reliable and 
logically correct. The investigator must explain in writing the reasons for any discrepancy noted in 
device accountability.  
The PI or designee will review, sign and date all completed CRFs.   After entry into the electronic 
database and monitoring has occurred, the clinician will review, sign and date verification of data entry.  
11.1.14 Investigator Reports  
The investigator must report particular items related to the study according to Table . At the 
investigator’s discretion, the sponsor may help to prepare reports.  
  
  
  
  
  
Table 6. Reporting activities  
Report  
Submit To  
Description / Constraints  

  
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SAE &  
Unanticipated  
Adverse Device  
Effect  
Monitor & EC If an unforeseen complication is determined to be an unanticipated 
adverse device effect, then the investigator's report must be 
submitted within 48 hours after the investigator first learns of the 
effect.   
Withdrawal of EC 
Approval  
Sponsor  
The investigator must report a withdrawal of the reviewing EC 
approval within 5 working days.   
Progress Report  
EC  
The investigator must submit this report if the study lasts longer 
than one year.  
Deviation from  
Investigational Plan
Sponsor & EC If the deviation may affect the scientific soundness of the plan or 
the rights, safety and welfare of the subjects, the deviation must be 
preapproved by the Sponsor, reviewing EC, and the Competent  
Authorities if applicable. If the deviation does not affect these 
issues (study soundness, rights, safety, etc.) then only the Sponsor 
must preapprove it.  
Failure to Obtain 
Informed Consent  
Sponsor & EC The Investigator must make notification within 5 working days 
after device use. The report must include a brief description of the 
circumstances justifying the failure to obtain informed consent and 
include written concurrence by a licensed physician/clinician not 
involved in the investigation.  
Final Report  
Sponsor & EC This report must be submitted within three months after termination 
or completion of the investigation.  
  
11.1.15 Final Report  
The sponsor and coordinating investigator will prepare a final report when the study is completed or if it 
is terminated. The PI will provide the report to the EC and regulatory authorities as required.   
11.1.16 Document Retention  
The PI will maintain documents related to this investigation until 2 years after the study is complete. 
Some EU countries may require longer document retention periods. 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).  
11.1.17 Source Documents  
The PI will retain original source documents (or copies thereof) used to verify study data. The PI or site 
personnel will provide written confirmation with signature and date that copies of source documents are 
true reproductions of the original source document. The sponsor may have access to original source 
documents upon request.  

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
11.2 Sponsor Responsibilities  
11.2.1 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  
11.2.2 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.   
11.2.3 Study Preparation  
Before starting the study, the sponsor will:  
• 
define all roles and responsibilities related to this investigation  
• 
ensure that all required signatures are obtained  
• 
ensure the accuracy of translation, if required, of any aspect of the study prior to initiating the 
study at the selected site  
• 
develop a complete set of documents necessary to begin the study, including consent forms, case 
report forms (CRFs) and, if required, an investigator’s brochure   
• 
document any financial arrangements between the PI or investigation site and the sponsor  
• 
submit any required application(s) to begin the investigation to appropriate regulatory authorities 
for review, acceptance or permission, as required  
• 
ensure documented EC approval before the study is started  
• 
ensure documented ongoing EC approval of the study  
• 
ensure that the site’s ICF is consistent with requirements of ISO 14155:2011  
• 
ensure that any modifications required by the EC or regulatory authority are made and 
documented by the PI  
11.2.4 Investigational Site Qualification  
The sponsor will ensure that each investigational site:  
• 
has a qualified PI  

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
• 
has adequate staff, resources, including facilities, laboratories, equipment and a qualified 
investigation site team  
• 
is able to handle all potential adverse effects has access to an adequate number of subjects on a 
timely basis  
  
Site qualification will be documented.  
11.2.5 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  
• 
list of EC members or EC assurance number  
• 
documentation of investigational team’s designated roles and responsibilities  
• 
documentation of investigator conflict of interest  
• 
signed investigator agreement  
• 
signed clinical trial agreement (CTA). The CTA is the legal agreement between the site, PI and 
sponsor that covers all activities related to the study. The agreement will indicate that, by 
participating in a clinical investigation, the parties may share some regulatory responsibilities 
with the sponsor.  
• 
current curriculum vitae of PI and any sub-investigators  
11.2.6 Monitoring  
The sponsor is responsible for study monitoring. Monitoring is done to verify that the study has been 
performed consistent with this CIP (and its amendments), and any other local or national requirements. 
The sponsor will document a monitoring plan.  
11.2.7 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.  
11.2.8 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.   
11.2.9 On-Site Monitoring  
The monitor will perform on-site monitoring visits to verify:  

  
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Confidential & Proprietary  
• 
compliance with this CIP and its amendments  
• 
compliance with requirements, if any, of the governing /EC  
• 
compliance with local regulations pertaining to a clinical study  
• 
compliance with requirements, if any, of regulatory authorities  
continued adequacy of investigation site resources, including laboratories, equipment and the 
investigation site team  
• 
continued access to a sufficient number of potential study subjects  
• 
compliance with the informed consent process  
• 
all CIP requirements are met before the study begins at the site  
• 
adequate storage, maintenance and accountability of investigational devices  
• 
adequate storage and maintenance of source documents and other related records  
• 
source documents are accurate, complete and up-to-date  
• 
CRFs and queries are completed adequately, in a timely manner, and consistent with source 
documents  
• 
all AEs, deviations and device deficiencies are documented and reported to the sponsor  
• 
any device deficiencies/malfunctions that could have led to an SAE are reported to the sponsor 
without unjustified delay  
• 
all SAEs are reported to the EC, if required  
• 
maintenance of required reports, notifications, applications, submissions and correspondence in 
the PI’s files  
• 
maintenance and calibration (and documentation thereof) of all equipment relevant to this CIP  
• 
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.  
11.2.10 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  

  
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Design History Document  Title  
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Confidential & Proprietary  
• 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  

  
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ensure that clinical investigational report is provided to EC, investigators and regulatory 
authorities (if required)  
11.2.11 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.   
11.2.12 Safety Reporting  
The sponsor is responsible for ongoing safety evaluation in this CIP. Sponsor activities regarding safety 
include:  
• 
ensuring the independent Medical Monitor reviews all adverse events to ensure they are reported 
accurately and in sufficient detail,   
• 
classification of all AEs  
• 
review 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  
• 
informing all site PIs in writing of all SAEs at all sites in a timely fashion  
• 
ensuring that the EC and the regulatory authorities are informed of significant new information 
about the clinical investigation  
• 
updating the risk analysis and assessment of corrective or preventive actions potentially required 
as a result of new information obtained in the investigation  
  
The sponsor will evaluate all serious adverse events. The sponsor will investigate each SAE to 
determine whether the event represents an unanticipated serious adverse device effect (USADE). The 
sponsor will report any event to regulatory authorities, investigators and reviewing ECs as necessary. If 
an investigation shows that a USADE presents an unreasonable risk to subjects, the sponsor will 
terminate all investigations or parts of investigations presenting that risk as soon as possible. The 
sponsor will only resume a terminated investigation after corrective actions have taken place, site 
investigators are informed and ECs have been notified and given approval to resume the study.  
11.2.13 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.   

  
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Design History Document  Title  
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Confidential & Proprietary  
11.2.14 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 and the 
coordinating investigator. 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.   
11.2.15 Resuming a Temporarily Suspended Study  
If the sponsor temporarily suspends the study and wishes to resume it, the sponsor will inform the 
coordinating investigator and 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.  
11.2.16 Suspension of Study Centre  
The Sponsor may discontinue a study centre if the centre fails to recruit sufficient patients or if the 
centre is found to be in recurrent or continuous non-compliance with the Clinical Investigation Plan 
and/or ISO 14155:2011 or other applicable requirements.  
11.2.17 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.  
11.2.18 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  

  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
• 
will include device identification and description  
• 
summarize clinical trial methodology  
• 
include a summary of deviations  
• 
provide adequate analysis with statistical analysis, where appropriate,  
• 
critically appraise the aims of the study and whether the aims were met not provide personally 
identifying subject information  
be made available to the study Principal Investigator prior to finalization for comment and 
review  
• 
signed by the study Principal Investigator  
• 
provided to ECs and regulatory authorities, as per applicable requirements  
The sponsor is committed to publication and dissemination of the results of this study. At the conclusion 
of the study, a multi-centre publication will be prepared suitable for submission in peer-reviewed 
medical literature. The publication of results from any single centre experience within the trial is not 
allowed until the aggregate study results have been published, unless there is written consent from the 
study sponsor.   
11.2.19 Document Retention  
The sponsor will maintain documents related to this investigation as required by applicable regulatory 
standards. Required documents to retain are extensive and are listed in Annex E of ISO 14155:2011  
  
  
REVISION HISTORY  
Rev  DCO  Change Description  
Release Date  
A  
0068  Initial release.   
2016-05-17  
B  
0081  Add -01 to document number for clarity Add 
Revision History  
03 Jun 2016  
C  
0101  Add Discharge to Modified rankin Scale (mRS) in Table 3 in section 7.9 
Update sections 9.1 and 9.2  
26 Jul 2016  
D  
0108  
Changed title to Pilot Study. Updated primary and secondary Objectives. 
Changed Endpoints to Variables and updated. Changed Effectiveness to 
Efficacy. Updated safety variables. Update Table 2. Update Section 8. 
Updated Table. 6.  
05 Aug 2016  
D  
0158  
Correction Only – Correct Revision from C to D on pages 2- 32 and correct 
DCO # 109 to 108.  
Move Revision History table to end of document  
28 Nov 2016  
E  
0275  
Addition of CE Mark language (pg 4); removal of requirement for minimum 
height (pg 10, 11); Clarification of MRI/MRA and cerebral angiogram at 
years 2, 3, 4, 5 (pg. 14)  
28 Aug 2017  

  
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Document Number  
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Design History Document  Title  
Clinical Investigation Plan, Contour Neurovascular SystemTM  
Confidential & Proprietary  
F  
0323  
Change Lead Principal Investigator (page 2)  
Removal of CE Mark language (page 4);   
Update Device Manufacturing Overview (page 8)  
14 Nov 2017  
  
  

  
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Confidential & Proprietary  
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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, 
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9. Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicenter 
clinical trial. Radiology 2013;267(3):858–68.  
  
10, Cognard C, Januel AC, Remnants and recurrences after the use of the WEB intrasaccular device in 
largeneck bifurcation aneurysms. Neurosurgery. 2015 May; 76(5):522-30; discussion 530. doi:  
10.1227/NEU.0000000000000669.  
  
11. Pierot L, Costalat V, Moret J, et al. Safety and efficacy of aneurysm treatment with WEB: results of the 
WEBCAST study. J Neurosurg. 2015 Sep 18:1-7. [Epub ahead of print]