Safety and Feasibility of the EyeControl Device (Eye-based Communication Device) for ALS Patients
Phase: NA
Conditions: ALS (Amyotrophic Lateral Sclerosis)
Sponsor: Eyefree Assisting Communication Ltd

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 1 of 36 
 
 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
SAFETY AND FEASIBILITY OF THE EYECONTROL DEVICE (EYE-BASED 
COMMUNICATION DEVICE) FOR ALS PATIENTS 
Sponsor: 
Eyefree assistive communication Ltd.  
Or Retzkin, CEO 
31 Ma'ale ha-Tsofim St, Ramat Gan, Israel 
Tel: +972-526490093  
Email: orretzkin@gmail.com  
Investigators:  
Israel 
Prof. David Yarnitsky 
Rambam Medical Center 
 
 
Clinical Research 
Organization:  
Israel 
Duet Medical 
Consulting Ltd. 
 
 
 
Protocol Number: 
CLN-001  
Protocol Date: 
May 16th,  2016 
Protocol Version 
01 
 
Confidentiality Statement 
This protocol and related documents are the confidential property of Eyefree Ltd.  
No unpublished information contained herein may be disclosed without the prior written approval of 
Eyefree Ltd.  

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 2 of 36 
 
 
CONFIDENTIAL 
SPONSOR STATEMENT OF COMPLIANCE 
 
The sponsor of this study, Eyefree assistive communication Ltd., manufacturer of the 
investigational device, legally represented by Or Retzkin, Chief Executive Officer, 
states the following: 
 to assume responsibility related to the clinical investigation; 
 that the treatments used to perform the clinical study are adequate for the 
device under investigation; 
 that the clinical study, as for the responsibility of the manufacturer, will be 
conducted in conformity with: 
Annex X of the Council Directive 93/42/EEC concerning medical devices, the 
Declaration of Helsinki, and the applicable parts of the ICH/GCP guidelines, the UNI 
EN ISO 14155:2011 standards, MEDDEV 2.7/3 and following revisions or other 
analogous internationally recognized standards, to be specified, and only after the 
approval, by the competent Ethics Committee, of the investigational protocol, the 
informed consent and the documentation required by the above mentioned 
standards; 
 
 
 
 
 
Signature: ___________________________ 
Date: __________________ 
 
 
 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 3 of 36 
 
 
CONFIDENTIAL 
REVISION HISTORY 
 
Title: 
Eyefree Clinical Study Protocol 
Device name: 
EyeControl  
 
 
Version number:  01, dated 16May2016 
 
Previous version number:  N/A 
 
 
 
Summary of Changes 
 
 
Rev. 
Page/Section 
Description of change 
Reason for change 
1 
--- 
First issue 
--- 
 
 
 
 
 
 
 
 
 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 4 of 36 
 
 
CONFIDENTIAL 
INVESTIGATOR AGREEMENT 
 
Prior to participation in this study, a written approval must be obtained from the 
Ethics Committee, and copy should be provided to the Sponsor, Eyefree Ltd., or their 
authorized representatives, along with the Ethics Committee approved Informed 
Consent Form.    
 
The Principal Investigator must also: 
Conduct the study in accordance with the study protocol, the Investigator 
Agreement, Declaration of Helsinki, Good Clinical Practices, international 
harmonized standards for clinical investigation of medical devices (ISO 14155, 
Clinical investigation of medical devices for human subjects), the laws and 
regulations of the countries where the study will take place, indemnity/insurance 
requirements and any other applicable regulations.   
Agree to participate in an appropriate training program as part of the study 
initiation. 
Assure that informed consent is obtained from each subject prior to enrollment, 
using the Ethics Committee approved form.   
Assure that the study is not commenced until Ethics Committee approval has been 
obtained. 
Provide all required data and agree to source document verification of study data 
with subject’s medical records.   
Allow staff of the Sponsor and its authorized representatives, as well as 
representatives from regulatory agencies, to review, inspect and copy any 
documents pertaining to this clinical investigation.  
Understand that this investigation, protocol, and trial results are confidential and 
agree not to disclose any such information to any person other than a representative 
of Study Sponsor or regulatory agency without the prior written consent of Study 
Sponsor. 
The Principal Investigator (PI) may delegate one or more of the above functions to 
an associate or sub-investigator. However, the PI retains overall responsibility for 
proper conduct of the study, including obtaining and documenting subject informed 
consent, compliance with the study protocol, and the collection of all required data. 
 
Principal Investigator Statement: 
I the undersigned, have reviewed this protocol and agree to conduct this study in 
adherence to the study protocol, GCP compliance, Ethical principles set forth in the 
declaration of Helsinki and authority regulations for the protection of human 
subjects participating in clinical trials. 
 
Print Name 
Signature 
Date 
 
 
 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 5 of 36 
 
 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Sponsor: 
Eyefree assistive communication Ltd,  
31 Ma'ale ha-Tsofim St, Ramat Gan, Israel 
Tel: +972-526490093 
Protocol title: 
Safety and Feasibility of the EyeControl device (eye-based 
communication device) for ALS patients.  
Protocol number: 
CLN-001 
Study 
Purpose/objective: 
To demonstrate the safety and feasibility of the EyeControl device in 
healthy volunteers, and ALS patients in early stages.  
Study phase: 
 
First in Human – Proof of concept 
The Device: 
The EyeControl device is an eye movement-based communication 
device in the form of wearable glasses with connected infrared cam-
era that tracks the pupil and translates blinks and movements into 
commands.  
The camera communicates with a small computer called "Odroid" 
via USB. 
The "Odroid" translates the user’s eyes movements into commands 
and can transmit the commands to three outputs: an earphone, a 
speaker and a smartphone via Bluetooth.  
The smartphone runs an application which enables the patient to 
communicate. 
An algorithm is used to allow for a quick auto- calibration of the de-
vice, so that the patient does not need assistance in order to do so.  
The device is currently based on a 3-steps solution: 
1. Alert sound - calling for assistance. 
2. Predefined sentences - such as “I’m hot", "my hand hurts” 
etc. 
3. Composing sentences - (similar to SMS). 
 
Study Design: 
The study will be conducted in 2 enrollment stages. Initially, up to 10 
healthy volunteers will be recruited and go through a short training 
for the use of the device followed by actual controlled use of several 
hours. In the second stage, up to 5 early stage ALS patients will be 
recruited and go through the same steps of training and device use. 
Any feedback or safety concerns raised during the first stage of 
recruitment of healthy volunteers will be considered before moving 
forward to the second group of ALS patients.  

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 6 of 36 
 
 
CONFIDENTIAL 
The overall duration of participation for each subject will be up to 3 
weeks.  
The place: Rambam health care campus. 
Each subject will go through a series of 4 meetings (2 meetings per 
week), and up to 3 hours per meeting. Meetings will be 
accompanied by company representatives and/or trained study 
team. 
Procedure will consist of an introduction and demonstration of the 
device features followed by actual use of the device by each subject 
(including   control of gestures, use of menus, activation of pre- 
defined modes and writing full sentences). User feedback/ 
questionnaire will be completed after the 2nd and 4th session. 
The user’s ability to perform each of the pre-defined tasks, will be 
measured in each session. In addition, success rate and measured 
time for completion of pre-defined tasks, collected after the 4th 
session, will be compared to the success rate and times collected in 
previous sessions. 
Patient Population: 
The subject population is divided into two groups: 
1. Healthy volunteers- up to 10 subjects 
2. Early stage ALS patients – up to 5 early stage ALS patients that can 
still communicate orally. 
No. of Subjects/Sites: 
1 site - Rambam Health Care Campus 
Study duration: 
Screening: one day. 
Procedure: 4 sessions of about 2.5-3 hours for each participant, 
performed over 2 weeks’ time.  
Follow up: none. 
Endpoints 
Primary endpoint:   
Assessment of the feasibility of the use of EyeControl device, 
measured by: 
 
Ability to perform device features: 
o Controlling the EyeControl’s Joystick [measured by 
successful correct performance of over 70% of the 
gestures].  
o Controlling the Rest mode and Siren mode [measured by 
successful correct performance of over 70% of the 
gestures]. 
o Testing 
the 
logic 
of 
the 
pre-defined 
sentences;  
a. ability to say 10 pre-defined sentences [over 80% 
success rate]; 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 7 of 36 
 
 
CONFIDENTIAL 
b. Time - perform each sentence in less than 2 minutes – 
[over 80% success rate for all sentences]. 
o Controlling the application and Free text features –words 
per minute, using the application Alphabet   
 
Required Training time/ learning curve of; 
o pre-defined device features [selected results after the 
4the meeting compared with results results of previous 
meetings] 
o free speech  [selected results after the 4th meeting 
compared with results after the 3rd meeting] 
 
Usability feedback (user experience) questionnaire completed by 
each user. 
Secondary endpoints: 
Clinical Safety assessment, measured by number of device related 
adverse events. 
Inclusion criteria 
1. 
Subjects 18 to 65 years old 
2. 
Subject with understandable speaking communication 
3. 
Subject fluent in Hebrew (speech and writing skills) 
Additional inclusion criteria for Stage 2 of the study: 
4. 
Subjects with early stage ALS diagnosis – whose speech 
capability is unaffected 
Exclusion criteria 
1. 
Subjects with glasses or contact lenses  
2. 
Subjects with eye conditions such as Ptosis, Strabismus And 
Crossed Eyes 
3. 
Medical history of epilepsy 
4. 
Subjects who according to investigator’s judgement,  are 
unable to comply with the  requirements of this protocol   
5. 
Pregnant or lactating women 
 
 
 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 8 of 36 
 
 
CONFIDENTIAL 
Table of Content 
SPONSOR STATEMENT OF COMPLIANCE .................................................................................2 
REVISION HISTORY .................................................................................................................3 
INVESTIGATOR AGREEMENT ..................................................................................................4 
PROTOCOL SYNOPSIS .............................................................................................................5 
1 
INTRODUCTION .......................................................................................................... 11 
1.1 
BACKGROUND-ALS ........................................................................................................ 11 
1.2 
OTHER “LOCKED IN” ...................................................................................................... 11 
1.3 
THE SOLUTION ............................................................................................................... 12 
1.4 
STUDY RATIONALE ......................................................................................................... 13 
1.5 
STUDY JUSTIFICATION ..................................................................................................... 13 
1.6 
STUDY OBJECTIVES ........................................................................................................ 14 
1.7 
STUDY ENDPOINTS ......................................................................................................... 14 
2 
STUDY DESIGN............................................................................................................ 14 
3 
STUDY POPULATION ................................................................................................... 15 
3.1 
INCLUSION CRITERIA ...................................................................................................... 15 
3.2 
EXCLUSION CRITERIA ...................................................................................................... 15 
3.3 
SUBJECT IDENTIFICATION ................................................................................................ 16 
3.4 
ENROLLMENT POINT ...................................................................................................... 16 
3.5 
REMOVAL, REPLACEMENT, OR EARLY WITHDRAWAL OF SUBJECTS FROM TREATMENT OR 
ASSESSMENTS ............................................................................................................... 16 
3.6 
HANDLING OF WITHDRAWALS ......................................................................................... 16 
3.7 
STUDY TERMINATION ..................................................................................................... 16 
4 
STUDY PROCEDURES ................................................................................................... 17 
4.1 
SCREENING VISIT (VISIT 0) .............................................................................................. 17 
4.2 
VISIT 1 (PROCEDURE DAY/ MEETING #1) .......................................................................... 17 
4.3 
VISIT 2 (PROCEDURE DAY/ MEETING #2) .......................................................................... 18 
4.4 
VISIT 3 (PROCEDURE DAY / MEETING #3).......................................................................... 18 
4.5 
VISIT 4 (PROCEDURE DAY / MEETING #4).......................................................................... 19 
4.6 
DEVIATIONS FROM STUDY PROTOCOL ................................................................................ 19 
5 
MEDICAL DEVICE DESCRIPTION ................................................................................... 19 
5.1 
DEVICE INTENDED USE ................................................................................................... 19 
5.2 
DEVICE DESCRIPTION ..................................................................................................... 20 
5.3 
DEVICE OPERATIONS ...................................................................................................... 20 
5.3.1 
General ...................................................................................................... 20 
5.3.2 
Installation & Calibration ........................................................................... 20 
5.3.3 
Top Menu .................................................................................................. 21 
5.3.4 
WORDS MENU ........................................................................................... 22 
5.3.5 
SWITCHING FROM THE WORDS TO OTHER MENUS ................................. 22 
5.3.6 
SOLVING INITIAL PROBLEMS ..................................................................... 22 
5.4 
MANUFACTURING, SUPPLY AND SUPPORT OF DEVICE .......................................................... 23 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 9 of 36 
 
 
CONFIDENTIAL 
5.5 
DISTRIBUTION AND SHIPMENT ......................................................................................... 23 
5.6 
TRAINING ..................................................................................................................... 23 
5.7 
ACCOUNTABILITY AND COMPLIANCE OF INVESTIGATIONAL PRODUCT ..................................... 23 
5.8 
DEVICE FAILURES, MALFUNCTIONS AND MISUSE ................................................................. 23 
5.9 
CONTRA-INDICATION ..................................................................................................... 23 
6 
RISK BENEFIT ANALYSIS .............................................................................................. 24 
6.1 
RISK MITIGATION MEASURES ........................................................................................... 24 
6.1.1 
Mechanical Tests ....................................................................................... 24 
6.1.2 
Software validation tests ........................................................................... 24 
6.2 
RISKS ........................................................................................................................... 24 
6.3 
BENEFITS...................................................................................................................... 25 
6.4 
MINIMIZATION OF RISKS WITHIN THE STUDY ...................................................................... 25 
7 
SAFETY AND MEDICAL DEVICE VIGILANCE ................................................................... 25 
7.1 
DEFINITIONS ................................................................................................................. 25 
7.1.1 
Adverse Event (AE) .................................................................................... 25 
7.1.2 
Adverse Device Effect (ADE) ...................................................................... 26 
7.1.3 
Serious Adverse Events (SAE) .................................................................... 26 
7.1.4 
Serious Adverse Device Effect (SADE) ....................................................... 26 
7.1.5 
Unanticipated Serious Adverse Device Effect (USADE) ............................. 26 
7.2 
ADVERSE EVENTS CLASSIFICATION .................................................................................... 27 
7.2.1 
Intensity/Severity Definition ..................................................................... 27 
7.2.2 
Relationship ............................................................................................... 27 
7.2.3 
Outcome .................................................................................................... 28 
7.2.4 
Treatment or Action taken ........................................................................ 28 
7.3 
REPORTING REQUIREMENTS ............................................................................................ 29 
7.3.1 
Initial notification ...................................................................................... 29 
7.3.2 
Follow- Up of SADE/USADEs ...................................................................... 29 
7.3.3 
Notification to Authorities (CA/IECs) ......................................................... 30 
8 
DEVICE DEFICIENCY ..................................................................................................... 30 
9 
STATISTICAL ANALYSIS PLAN ....................................................................................... 30 
10 
ETHICS AND REGULATORY .......................................................................................... 30 
10.1 INDEPENDENT ETHICS COMMITTEE (IEC) AND COMPETENT AUTHORITY (CA) .......................... 30 
10.2 ETHICAL CONDUCT OF THE STUDY .................................................................................... 31 
10.3 SUBJECT INFORMATION AND CONSENT ............................................................................. 31 
10.4 SUBJECT INSURANCE ...................................................................................................... 31 
10.5 PERSONAL DATA PROTECTION ......................................................................................... 31 
10.6 INFORMING THE GENERAL PRACTITIONER .......................................................................... 32 
11 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................................ 32 
11.1 DATA MONITORING ....................................................................................................... 32 
11.2 STUDY DOCUMENTATION ............................................................................................... 32 
12 
STUDY ADMINISTRATION ........................................................................................... 33 
12.1 PARTICIPATING CENTERS ................................................................................................. 33 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 10 of 36 
 
 
CONFIDENTIAL 
12.2 SELECTION OF CENTERS & INVESTIGATORS ......................................................................... 33 
12.3 CLINICAL STUDY SUPPLIES ............................................................................................... 33 
12.4 STUDY COMPLETION ...................................................................................................... 33 
12.5 FINAL REPORT ............................................................................................................... 34 
12.6 RETENTION OF STUDY RECORDS ....................................................................................... 34 
12.7 PUBLICATION POLICY ..................................................................................................... 34 
13 
APPENDICES ............................................................................................................... 35 
 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 11 of 36 
 
 
CONFIDENTIAL 
1 
INTRODUCTION 
1.1 
BACKGROUND-ALS 
Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig’s disease) is an adult-
onset, fatal neurodegenerative disease.  The disease is characterized by degeneration of 
motor neurons in the primary motor cortex, brainstem and spinal cord, leading to 
progressive weakness and atrophy of voluntary skeletal muscles. It is recognized as a 
multi-system disorder. In about a quarter of ALS patients, the disease is associated with 
subtle cognitive deficits. 
The majority of patients die within 3-5 years from disease onset, usually from 
respiratory failure. Only about 10% of the patients survive for more than a decade. 
ALS exhibits phenotypic heterogeneity. Most ALS cases are sporadic, with unknown 
etiology, whereas 10-15% are familial with clear genetic background – both types are 
clinically indistinguishable and share several pathogenetic pathways. The incidence of 
sporadic ALS is 1-2 per 100,000 person-years with an estimated lifetime risk of 1 in 400. 
The mean age at onset for sporadic ALS is 58-63. 
There is no cure for ALS. Riluzole is the only FDA approved drug – which appears to 
prolong ALS survival by 3 months on average. 
Almost all people with amyotrophic lateral sclerosis (ALS) experience a motor speech 
disorder, such as dysarthria, as the disease progresses. At some point, 80 to 95% of 
people with ALS are unable to meet their daily communication needs using natural 
speech1. 
1.2 
OTHER “LOCKED IN” 
Neurodegenerative and cerebrovascular diseases often lead to deterioration of motor 
function in patients. These diseases impair traffic capacity, but in some cases they do 
not harm the mind and cognitive function  
These diseases lead to involuntary loss of ability to exercise the muscles of the limbs 
and the ability to speak, preserving eye movement function. Since in most cases the 
patient’s cognitive function is not impaired, but given their lack of ability to exercise the 
muscles, they lose their ability to interact with their environment. These patients are 
defined as “Locked In” as they are imprisoned in their own bodies. 
Among these diseases and injuries are stroke of the posterior circulation, MJD 
(Machado-Joseph disease) and other degenerative diseases such as MG, MS, some of 
the muscular dystrophies and Parkinson's disease in some cases. Events such as traffic 
accidents and other accidents also bring patients to such situation, making them arget 
population for our proposed solution. Each segment of the target population, as a 
standalone, is relatively small, and therefore there are no available appropriate 
                                                 
1 Communication Support for People with ALS- David Beukelman, Susan Fager, and Amy Nordness 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 12 of 36 
 
 
CONFIDENTIAL 
solutions. However, looking at all patients within the different categories above as a 
whole, there is a large common denominator and significant demand which our generic 
systems can address. 
1.3 
THE SOLUTION  
Today, the major leading company that controls the communication devices market is 
the Swedish company "Tobii"."Tobii" offers a "high-end" technology to the clients, with 
a variety of products for the fields of gaming and assistive technology. 
 
Tobii's Assistive technology - Tobii products are designed to allow control over the 
computer via Eye tracker. 
 
The company offers several products: The EyeMobile and the PCEye GO, allowing con-
trolling the computer using the eyes, but they restrict movement - every movement 
requires re-calibration by another (healthy) person (an assistant) and the device must 
be connected to the computer and to the power supply. This is an expensive technology 
that requires learning, training and maintenance, as well as third-party assistance per 
session.  
Two other devices that Tobii offers are the I12 and I5. These devices enable communica-
tion via tablets, with a 24-hour battery. These two products enable mobility on the one 
hand but on the other hand all other faults such as the need for re-calibration, high 
price and the limitation of "environmental restrictions"(Inside the shower, at bed, 
etc.).These devices costs even more and can sum up to 14,000$ per unit. The "low cost" 
mobile solution that Tobii offers is a tablet based on Microsoft hardware with the Tobii 
software installed on it. This product costs about $4,000 and still has the same problems 
such as the need of calibration by third party and the dependent in the screen. 
Today, Tobii as a huge company in the field of Eye Tracking offers low cost devices for 
Eye Tracking in the field of gaming although when coming to the field of assistive 
communication devices field they use "high end" hardware and a screen as hardware 
and hours of developing to reach Tobii specific software which is estimated around 
$2,000-3,000 per unit (including Tobii's eyetracking camera). This situation takes out 
automatically many clients who can't afford buying those products (most of the clients) 
and also doesn’t solve the necessary to communicate anywhere, anytime 
The EyeControl solution is a set of glasses which are connected to an infrared camera 
detecting the movement of the pupil and blinks. 
The camera connects to a small computer, "Odroid", which is connected to a speaker. 
The computer translates the pupil's movements and gives an audible sound 
environment. In addition, by broadcasting through Bluetooth, the patient can use 
various applications on their smart phone to communicate with others. An outstanding 
benefit is the fact that the calibration of the pupils is automatic process based on an 
algorithm without the need for outside aid. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 13 of 36 
 
 
CONFIDENTIAL 
The Product is based on an innovative technology that enables the eye to function as a 
joystick. The product is innovative (being portable), significantly cheaper than other 
products on the market, comfortable (automatic calibration and independence), Mobile 
(glasses and a tiny small computer), and allows the patient to communicate with the 
environment anywhere and anytime. This is a revolution for patients and their 
surroundings – the possibility to return to social activity regaining independence and 
the ability to communicate with the environment.  
The solution developed consists of 3 levels: a call for help, choosing from pre-defined 
phrases (English and Hebrew) and composing sentences using a virtual board with the 
alphabet encoding. All these can be played over the loudspeaker while the user is able 
to hear with headset every letter/word/sentence before he chooses\ it, so that the user 
doesn't need the screen in front of him. 
 
 
 
 
 
 
 
 
 
Chart 1: The product 
 
 
1.4 
STUDY RATIONALE 
As discussed above, validity of this concept of eye tracking devices used for “locked-in” 
patients, such as ALS patients, have been proved and is vastly used on the market today. 
The EyeControl device is indicated for the same group of patients, but due to its size and 
ease of mobility will allow patients the possibility to return to social activity regaining 
independence and the ability to communicate with the environment. 
1.5 
STUDY JUSTIFICATION 
The justification for the experiment is based on the fact that the group of people tested 
are cognitive in the same status of the ALS patients that will be the final user of the 
product. Moreover, the product is being tested on an early stage ALS patients.  
In order to minimize possible risks prior to clinical application, Eyefree Ltd. designed and 
performed verification and validation tests for the EyeControl device. The testing 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 14 of 36 
 
 
CONFIDENTIAL 
included aspects of the device’s clinical safety, production and software and quality 
assurance. 
1.6 
STUDY OBJECTIVES 
To demonstrate the safety and feasibility of the EyeControl device in healthy volunteers, 
and ALS patients in early stages. 
1.7 
STUDY ENDPOINTS 
Primary endpoint: 
Assessment of the feasibility of the use of EyeControl device, measured by: 
 Ability to perform device features: 
o Controlling the EyeControl’s Joystick [measured by successful correct 
performance of over 70% of the gestures].  
o Controlling the Rest mode and Siren mode [measured by successful 
correct performance of over 70% of the gestures]. 
o Testing the logic of the pre-defined sentences; 
a. ability to say 10 pre-defined sentences [over 80% success rate]; 
b. Time - perform each sentence in less than 2 minutes – [over 80% 
success rate for all sentences]. 
o Controlling the application and Free text features –words per minute, 
using the application Alphabet   
 Required Training time/ learning curve of; 
o pre-defined device features [selected results after the 4the meeting 
compared with results results of previous meetings] 
o free speech  [selected results after the 4th meeting compared with results 
after the 3rd meeting] 
 Usability feedback (user experience) questionnaire completed by each user. 
Secondary endpoints: 
Clinical Safety assessment, measured by number of device related adverse events. 
 
2 
STUDY DESIGN 
This will be a single center, single arm, open label, prospective study.  
The study will be conducted in 2 enrollment stages. Initially, up to 10 healthy volunteers 
will be recruited and go through a short training for the use of the device followed by 
actual controlled use of several hours. In the second stage, up to 5 early stage ALS 
patients will be recruited and go through the same steps of training and device use. 
Any feedback or safety concerns raised during the first stage of recruitment of healthy 
volunteers will be considered before moving forward to the second group of ALS 
patients.  

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 15 of 36 
 
 
CONFIDENTIAL 
The overall duration of participation for each subject will be up to 3 weeks.  
The place: Rambam health care campus. 
Each subject will go through a series of 4 meetings (2 meetings per week), and up to 3 
hours per meeting. Meeting will be accompanied by  company representatives and/or 
trained study team for support and guidance in each session.. 
Procedure will consist of an introduction and demonstration of the device features 
followed by actual use of the device by each subject (including   control of gestures, use 
of menus, activation of pre- defined modes and writing full sentences). User feedback/ 
questionnaire will be completed after the 2nd and 4th session. 
The user’s ability to perform each of the pre-defined tasks will be measured in each 
session. In addition, success rate and measured time for completion of pre-defined 
tasks, collected after the 4th session, will be compared to the success rate and times 
collected in previous sessions. 
For detailed study procedures refer to section 4, as well as appendix A. 
3 
STUDY POPULATION  
The patient population is divided into two groups: 
1. Healthy volunteers- up to 10 subjects.   
2. Early stage ALS patients – up to 5 early stage ALS patients that can still 
communicate orally.  
3.1 
INCLUSION CRITERIA 
1. Subjects 18 to 65 years old 
2. Subject with understandable speaking communication 
3. Subject fluent in Hebrew (speech and writing skills) 
Additional inclusion criteria for Stage 2 of the study: 
4. Subjects with early stage ALS diagnosis – whose speech capability is unaffected. 
3.2 
EXCLUSION CRITERIA 
1. Subjects with glasses or contact lenses  
2. Subjects with eye conditions such as Ptosis, Strabismus And Crossed Eyes 
3. Medical history of epilepsy 
4. Subjects who according to investigator’s judgement,  are unable to comply with 
the  requirements of this protocol   
5. Pregnant or lactating women. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 16 of 36 
 
 
CONFIDENTIAL 
3.3 
SUBJECT IDENTIFICATION 
A unique identification number will be assigned when an individual subject is qualified 
for study enrollment (based on inclusion/exclusion criteria). All enrolled subjects will be 
identified by the 2 digit identification number as well as their initials.  
3.4 
ENROLLMENT POINT 
A subject will be considered enrolled once the use of the EyeControl is initiated 
according to the Instructions for Use.  
Subjects withdrawn prior to this point of enrollment will be considered screen failure, 
and the reason will be documented in the study logs.  
3.5 
REMOVAL, REPLACEMENT, OR EARLY WITHDRAWAL OF SUBJECTS FROM TREATMENT OR 
ASSESSMENTS 
Subjects are free to discontinue their participation in the study at any time and without 
prejudice to further treatment.  The investigator must withdraw any subject from the 
study if that subject requests to be withdrawn.   
The subject’s participation in this study may be discontinued due to the following 
reasons: 
 Request of regulatory agency, or sponsor or primary care physician or 
investigator 
 Subject withdrew consent 
 AE 
 Investigator decides that withdrawal from the study is in the best interest of the 
subject.   
3.6 
HANDLING OF WITHDRAWALS 
If a subject is withdrawn from the study either at his or her request or at the 
investigator’s discretion, every effort should be made to determine the reason.   
The reason for study exit (including screen failure) will be documented on the applicable 
CRF from.  
3.7 
STUDY TERMINATION 
Eyefree assistive communication Ltd., reserves the right to discontinue the study for 
administrative reasons at any time, such as, but not limited to a decision to discontinue 
further clinical investigation with the device, improper conduct of the study by the 
investigator, inability to obtain the number of subjects required by the protocol, etc.  
Reimbursements for reasonable expenses will be made if such an action is necessary. 
A principal investigator, EC, or regulatory authority may suspend or prematurely 
terminate participation in a clinical investigation at the investigation sites for which they 
are responsible. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 17 of 36 
 
 
CONFIDENTIAL 
If suspicion of an unacceptable risk to subjects arises during the clinical investigation, or 
when so instructed by the EC or regulatory authorities, the sponsor shall suspend the 
clinical investigation while the risk is assessed. The sponsor shall terminate the clinical 
investigation if an unacceptable risk is confirmed. 
Subjects that were already included to the study must be followed according to the 
clinical procedures, and all information obtained for these subjects shall be reported to 
sponsor on the appropriate CRF. 
4 
STUDY PROCEDURES 
Schedule of events for this study are shown in Appendix A.  No protocol related 
procedures should be performed before written informed consent is signed as required 
by local regulations (i.e. subject, legal guardian, independent physician, etc). Study 
related events and activities including specific instructions, procedures, concomitant 
medications, dispensing of study device, and descriptions of AEs should be recorded in 
the appropriate source documents and CRF.  
The study duration for each subject participating in the study will be identical.  
The study duration for each subject will be approximately 2 weeks, as follows: 
Screening period:  
one day (could be same day as procedure) 
Surgery/Prodecure day:   4 meetings (up to 3 hours each) which will take place over 2 
weeks time. 
4.1 
SCREENING VISIT (VISIT 0) 
The purpose as well as the risks and benefits of the procedures of the study will be fully 
explained to participating subjects.  Those wishing to enroll in the study will sign a 
written informed consent prior to initiating any study related evaluations or procedures.  
The following procedures should be done at the screening visit: 
 Review inclusion and exclusion criteria 
 Obtain medical history and demographic data 
 Record prior and concomitant medications  
4.2 
VISIT 1 (PROCEDURE DAY/ MEETING #1)  
First meeting  
Subjects will be asked to arrive to the clinic. Meeting duration is expected to be up to 3 
hours. Activities for the meeting are detailed hereafter: 
1. Intro to EyeControl - explanation about the device, the components, the logic of the 
device etc.- ~30 min 
2. Demonstration of the EyeControl - demonstration of the device - ~30 min 
3. Controlling the EyeControl’s Joystick - ~ 1 hour. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 18 of 36 
 
 
CONFIDENTIAL 
The user will be asked to use the logic of the joystick- the user will be asked to perform 
the eye gestures of: left, right, up, down and blink -10 times for each gesture (total:50 
gestures). A computer with a visual software feedback will be attached to the user in 
order to assess and present the user results. The eye movement will be recorded in this 
stage. Subject’s face will not be recorded. 
4. The Logic of the pre-defined sentences - ~ 1 hour.  
The user will go through the menus with the guiding team to explore the options of the 
device and to get a feel of the device capabilities. In addition the user will be guided 
about the Siren mode and rest mode, and will be asked to independently turn on these 
modes. 
5. Any adverse events will be recorded. 
4.3 
VISIT 2 (PROCEDURE DAY/ MEETING #2)  
Second meeting – will be performed at the clinic on the same week as the 1st meeting 
occurred (2-3 days post 1st meeting). (Each meeting will take about 2.5 hours): 
1. Refreshing about controlling the EyeControl’s Joystick- ~ 1 hour.  
The user will be asked to use the logic of the joystick - the user will be asked to perform 
the eye gestures of: left, right, up, down and blink -10 times for each gesture (total: 50 
gestures). A computer with a visual software feedback will be attached to the user in 
order to assess and present the user results. The eye movement will be recorded in this 
stage, without recording the subject’s face. The user will also be asked to turn on the 
Siren and rest modes. 
2. Testing the logic of the pre-defined sentences - ~ 1 hour. 
The first 20 min of the meeting will be dedicated for a short re-training on the logic of 
the device and the pre- defined sentences. Once completed, the user will be asked to 
perform specific gestures to complete 10 pre-defined sentences. 
The participant will also be asked to complete a usability and feedback questionnaire at 
the end of meeting #2. 
3. Any adverse events will be recorded. 
 
4.4 
VISIT 3 (PROCEDURE DAY / MEETING #3)  
Third meeting - to be performed 1 week after the 1st meeting. 
Activities for the meeting are detailed hereafter: 
1. Learning about the application: Reviewing the manuals of the application, the different 
options, the logic etc. - ~30 min. 
2.  Using the application (with guidance of instructor): Writing free sentences, using the 
features of the application, calling for help, going to rest mode etc. - ~1 hour. 
3. Using the full logic of the EyeControl: ~30 min  
The user will be asked to go through the menus and turn on the application, and 
compose full sentences using the system. (The tests in this session will focus on the 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 19 of 36 
 
 
CONFIDENTIAL 
application features. The test will include also the pre-defined sentences and the idea is 
to show the learning curve when compared to the Second meeting of the pre- defined 
sentences). The test will include: 5 pre-defined sentences, Opening the application and 
writing 2-3 Words. 
Using the Alpha Bet feature / free text: writing the alphabet without the screen. 
Writing 2-3 Words-same words as in the application ~1 hour. 
4. Any adverse events will be recorded. 
 
4.5 
VISIT 4 (PROCEDURE DAY / MEETING #4)  
Fourth meeting – to be performed on the same week as meeting #3 (2-3 days later).   
1. Using the full logic of the EyeControl -~1.5 hours 
The user will be asked to go through the menus and turn on the application, and 
compose full sentences using the device. The user will also be asked to use the 
application in order to write free text.  Finally the user will be asked to write words in 
the application comparing to the Alpha Bet mode. (The tests will focus on the 
application features and different than the first test. Now the test will include writing 
free text in the application. The test will also consist the pre-defined sentences and the 
idea is showing the learning curve from the last test)- The test will include: 5 pre-
defined sentences, Opening the application and writing 5 Words in the application, 
writing 5 words in the Alpha Bet mode. 
2. Final Questionnaire – The users will be asked to complete a usability and feedback 
questionnaire at the end of meeting #4 - ~1 hour. 
3. Any adverse events will be recorded. 
4. Complete study exit form. 
 
4.6 
DEVIATIONS FROM STUDY PROTOCOL 
Any deviations from the study protocol should be notified to the sponsor and 
documented on study deviation forms. 
5 
MEDICAL DEVICE DESCRIPTION 
5.1 
DEVICE INTENDED USE 
Paralyzed people cannot interact with their environment, despite the cognitive compe-
tence, due to motor limitations. Existing communication devices on the market are ex-
pensive and cumbersome, and unfortunately most of these devices are not portable. 
Even if a patient can afford to purchase one of these products financially, he cannot use 
the device without the screen of a portable computer, so that these patients are left 
without many appropriate means of communication when they are in bed, on the move 
in a wheelchair, car, at a hospital, etc. This fact is truly limiting and isolating for the pa-
tients and they might even find themselves in a life-threatening situation without the 
ability to express this to those surrounding them. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 20 of 36 
 
 
CONFIDENTIAL 
The EyeControl device  is a speech generating device based on eye-movement detec-
tion, used by patients with ALS (Lou Gehrig’s Disease), and other “locked in” conditions 
for communicating with their loved ones and caregivers. 
 
5.2 
DEVICE DESCRIPTION 
The EyeControl device is an eye-based communication device in the form of wearable 
glasses with connected infrared camera that tracks the pupil and translates blinks and 
movements into commands.  The camera communicates with a small computer that 
transmits the eye movement into speaking/writing.  For further details please refer to 
device investigator’s brochure. 
 
5.3 
DEVICE OPERATIONS 
5.3.1 General 
The EyeControl device enables the following list of actions:  
1. Calling for help. 
2. Choosing from a variety of predefined sentences.  
3. Free text speech - using the Android app.  
 The user will navigate through the options and execute them using blinking and 4 
pupil movements: up, down, right, left.  
 Fully supported in English and Hebrew. 
5.3.2 Installation & Calibration 
The device arrives ready for activation. The user/caregiver should plug it in to a battery 
or an electrical outlet and wait until the "All set" sound is spoken through the speaker. 
The calibration process begins several seconds afterwards.  
The user will hear “Calibration” in earphone. 
Then he will hear “1”, “2”, “3” which are corresponding to three stages of calibration. 
We recommend the following: 
- 
After the “Calibration” – the user should blink few times to allow the camera 
spot the area of interest – when he will hear “1” he can stop blink. 
- 
After “1” he can look straight at the camera – to allow the camera to spot the 
pupil – when he will hear “2” he ca stop look at the camera. 
- 
After “2” he user can move his eye randomly to all sides – to allow the camera to 
understand the range of movement of the pupil. When the user hear the word 
“3” he can stop do that, and the calibration is actually over. 
The whole calibration stage should take 5-10 seconds. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 21 of 36 
 
 
CONFIDENTIAL 
After calibration stage the user immediately gets to the main menu which is described 
in the next section. 
There is no visual display for the device, but it can be described schematically in the 
following way:  
Chart 2: Navigation schema 
To navigate between the words options, a user needs to look left or right. 
To make a selection of a specific word, for example “father” the user need to look few 
times left or right (the menu is cyclic) until he hear “family” in the earphone, then he 
need to look down in order to hear “Father”. If he wants to say “Father” in the speaker 
he needs to blink to confirm. 
Next to the words menu (look left or right) there are more menus which allow the user 
to connect to the application or to be in rest mode or to change settings. 
 
 
  
Chart 3: The menus schema 
 
 
To choose any option that you hear- A blink.  
 
An "I need your help!" siren – 3 blinks (each blink should be about 0.25 seconds long). 
All three blinks should be executed in 4 seconds (default x = 4, can be configured in con-
figuration file). If for example the user is making: 
o Blink1, Right, Blink2, Blink3 – that will count as two blinks (blink2 and blink3) If 
he will make another blink 4 seconds after blink2, a siren will be played. 
 
Going out of Rest Mode:  
o Looking Down- Center- Down- Center- Down- Center in 4 seconds. 
 
Getting in to Rest Mode: via menu or by making a sequence of  
o Blink-Up-Blink-Up in 4 seconds 
5.3.3 Top Menu 
 
The Settings menu includes the following options   
o Toggle earphone language – select the language you will hear on earphone 
 
English or Hebrew (other languages will be available in the future) 
o Toggle speaker language – select the language you and others will hear on 
speaker 
 
English or Hebrew (other languages will be available in the future) 
o Toggle gender – select the gender of the voice heard on earphone and speaker 
 
Male or Female 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 22 of 36 
 
 
CONFIDENTIAL 
 
Rest mode- A mode in which the application does not respond to the eyes' movements 
of the user. This mode allows the user to rest or look in different directions without ac-
tivating the system, for example, in the middle of a treatment. In order to switch back 
from Rest Mode to regular Activation Mode, the user must look down quickly 3 times 
(Down- Center- Down- Center- Down) in a 4 seconds time frame. Outside of this se-
quence of gestures, there is another sequence that allows the user to express distress (3 
quick blinks). These are the only two gestures sequences that are activated during Rest 
Mode. A partial execution of these commands will not be effective after 4 seconds since 
the beginning of the sequence. 
 
Application - Choosing the Application option results in trying to connect the device via 
Bluetooth, to a smartphone that went through Pairing in advance.  In the case that the 
connection attempt is successful, the device goes from playing pre-recorded 
words/siren or settings menu mode to a mode in which eye gestures are sent to the app 
and there they're converted to letters and free speech. To return to the regular mode in 
which the user hears the pre-recorded words through a headphone/speaker, the com-
panion will close the app on the smartphone. 
5.3.4 WORDS MENU 
The words menu includes more than 100 pre-recorded words in English or Hebrew 
(Based on the settings menu choice). The user can browse through the words in a group 
by looking left or right. The user can get out of a group by looking up or to get in the 
group by looking down. 
The user first hears the words through the headphone only, and in order to play this 
word through the speaker the user has to blink.  
5.3.5 SWITCHING FROM THE WORDS TO OTHER MENUS  
To switch from words menu to the other options, the user must look up few times until 
he hears “words”, only then he will be able to navigate to other options such as “appli-
cation” or “rest mode” by looking left or right. 
CALLING FOR HELP 
Blinking 4 times at any stage of the execution will issue a call for help.  
5.3.6 SOLVING INITIAL PROBLEMS 
 
In case the user cannot hear words through the headphone, check the connection to the 
device.  
 
In case the user blinks and no sound is produced through the speaker, check the con-
nection to the device. Also check that the speaker's battery is not empty (a light in the 
speaker is on). 
 
In case that one of the above issues was not resolve solved, check that the device is on 
(a blue light and a red light are on in the device's box). 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 23 of 36 
 
 
CONFIDENTIAL 
 
Check that the battery isn't empty. Recharge it if needed. If the battery is intact and the 
device still does not function properly, turn the device off and then turn it on.  
In case turning the device off and on does not resolve the issue, make sure that the blue 
light is on inside the camera itself. If the issue is not resolved, please refer to the tech-
nical support section.  
5.4 
MANUFACTURING, SUPPLY AND SUPPORT OF DEVICE 
The EyeControl device is manufactured by Eyefree assistive communication Ltd. (Ramat 
Gan, Israel).  
The device is supplied packed in a box that will be brought by the company. 
5.5 
DISTRIBUTION AND SHIPMENT 
The EyeControl device will be distributed to the investigational site following 
completion of regulatory clearance, including approval by the site’s EC and training of 
the interventional staff.  
Shipment of the study devices will be performed by Eyefree or their agents.  
5.6 
TRAINING 
Each Investigator participating in the clinical trial and the associated clinical study staff 
will receive training on the clinical protocol, as well as the investigational device. 
Investigators will be trained on device characteristics; storage requirements; device 
application; device use; and warnings, precautions, and contraindications. 
5.7 
ACCOUNTABILITY AND COMPLIANCE OF INVESTIGATIONAL PRODUCT 
Complete traceability records will be kept of all devices during the study. The device will 
be provided by Eyefree Ltd., bearing required labeling. Device number will be 
documented in subject medical records, CRF and in center log. 
Each clinical investigator will be responsible for the safe storage with restricted access 
of the investigational materials in their possession, thereby preventing use of any 
materials by any persons not participating in the study. 
After completion of the study, all unused devices must be returned in their original 
package to Eyefree Ltd. 
All investigators will be responsible for using the products according to the instruction 
for use and protocol and maintaining product inventory and records. 
5.8 
DEVICE FAILURES, MALFUNCTIONS AND MISUSE 
Investigators are instructed to report all possible device failures, malfunctions or misuse 
observed during the course of the trial (refer also to section ‎8, Device Deficiency). These 
incidents will be documented in the case report form provided and sent by fax or e-mail 
to the monitor within two working days. 
5.9 
CONTRA-INDICATION 
Only per exclusion criteria. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 24 of 36 
 
 
CONFIDENTIAL 
6 
RISK BENEFIT ANALYSIS 
The EyeControl device is designed according to international standards for medical 
devices. Compliance with these standards ensures that the device can be used safely in 
human beings. This study is intended to provide further data on the device safety and 
performance. 
6.1 
RISK MITIGATION MEASURES 
Several mitigation measures were taken to minimize the possible risks; 
6.1.1 
Mechanical Tests 
The device was tested in the SII in a radiation test in order the check that the Infra Red 
radiation of the device doesn’t cause damage to the eye of the pupil. 
The conclusions were that the device is safe in the “Infra Red” aspect. The Led light is 
classified as Exempt Group (For: Actinic UV, Near UV, Blue light, Blue light small source, 
Retinal thermal, Retinal thermal, weak visual stimulus, IR radiation, eye) 
For detailed results refer to the device Investigator Brochure. 
6.1.2 
Software validation tests 
A software validation was made by Med-Dev Design Ltd. The validation test included: 
ATP and ATR tests.  The tests were successfully completed without any bugs or other 
unexpected results.  
For detailed results refer to the device Investigator Brochure. 
 
6.2 
RISKS 
1.Infra-Red Radiation:  the cameras has 4 LEDs with 850 nm wave length- and the risk is 
that the waves transmitted will heat the eye and by that will cause damages to the user- 
This risk was tested by the SII . 
2. Electricity damages:  the hardware of the device is composed from a battery, Odroid 
U3 and a speaker which can all go through an electricity damage. All the products are 
off the shelf products, bearing CE mark.  
3. Parts falling apart: The device is not a one product device yet- so pieces of the device 
can be split- this risk may cause damages in a very specific conditions. – We are creating 
a custom made boxes (3D printer) for the battery and the additional hardware which 
shouldn’t be exposed. 
4. True Emergency situations – In cases the user truly needs to call for help and the de-
vice doesn’t work. Our pilot involves only users who can communicate without any 
communication device. 
5. Allergy to the device - In case the user is has allergy to the device material (plastic, 
wires etc’) in this case the patient will be switched. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 25 of 36 
 
 
CONFIDENTIAL 
Anticipated clinical risks to the participants, based on the above hazards may be (but 
not limited to); headache, nausea or dizziness caused by the multiple required eye-
movements, local irritation due to allergy to device materials (glasses), burning sensa-
tion in the eyes. 
 
6.3 
BENEFITS 
Based on compliance with standard requirements, the risk of occurrence of adverse 
events is not expected to be greater than the risk reported for other devices available in 
the market today. However, as the device is investigational, this study is intended to 
validate this. All adverse events reported will be recorded.  
No direct benefit to the subject is expected in this study. Information gathered in this 
study will contribute to the development of the EyeControl solution which in the future 
may be more beneficial for the subjects with the same indication for treatment, when 
compared to the available solution on the market.  
6.4 
MINIMIZATION OF RISKS WITHIN THE STUDY 
This study will be monitored to ensure (1) the identification, documentation and 
analysis of all AEs, and (2) compliance with the protocol, the terms of the participating 
IEC to protect the safety and rights of all subjects, and federal and local regulations. In 
addition, risks have been minimized through selection of investigators who are 
experienced in the surgical procedures included in this protocol. 
7 
SAFETY AND MEDICAL DEVICE VIGILANCE 
All adverse events occurring during the study will be recorded on the appropriate case 
report form page by the investigator.  The nature, severity and relation of the adverse 
event to the study device will be documented. 
7.1 
DEFINITIONS 
7.1.1 Adverse Event (AE) 
AE is defined as any untoward medical occurrence in a subject. This definition does not 
imply that there is a relationship between the adverse event and the device under 
investigation.  An AE can therefore be any unintended sign, symptom, disease or injury 
or any untoward clinical signs (including an abnormal laboratory findings) in subjects, 
users or other persons whether or not related to the investigational medical device. The 
following should be reported as AE: 
 Untoward medical conditions or signs or symptoms that were absent before 
starting study treatment. 
 Untoward medical conditions or signs or symptoms present before starting study 
treatment and worsen (increase severity or frequency) after starting study 
treatment. 
 Abnormal laboratory findings. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 26 of 36 
 
 
CONFIDENTIAL 
 Clinical signs or symptoms that require therapy. 
7.1.2 
Adverse Device Effect (ADE) 
ADE is adverse event, related to the use of an investigational medical device. This 
includes any adverse event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device, the operation, or any malfunction 
of the investigational medical device, device failure or misuse, and any event that is a 
result of a user error. 
7.1.3 
Serious Adverse Events (SAE) 
A SAE is an adverse event that: 
 
Led to a death, 
 
Led to a serious deterioration in the health of the subject that: 
o Resulted in a life-threatening illness or injury 
o Resulted in a permanent impairment of a body structure or a body function 
o Required in-patient hospitalization or prolongation of existing hospitalization  
o Resulted in medical or surgical intervention to prevent permanent impairment 
to body structure or a body function. 
 
  Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be serious when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed above. 
Inpatient hospitalization or prolongation of existing hospitalization means that hospital 
inpatient admission and/or prolongation of hospital stay were required for treatment of 
AE, or that they occurred as a consequence of the event. Hospitalization for elective 
treatment of a pre-study condition that did not worsen while on study and 
hospitalizations for treatment of non-adverse events (e.g. cosmetic surgery or 
diagnostic procedure) are not considered serious adverse events. 
Any new SAE that occurs after the study period and is considered to be related 
(possibly/probably) to the investigational product or study participation should be 
recorded and reported immediately. 
7.1.4 
Serious Adverse Device Effect (SADE) 
A Serious Adverse Device Effect is an adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event. 
7.1.5 
Unanticipated Serious Adverse Device Effect (USADE) 
USADE is defined as 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 or other study related documents. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 27 of 36 
 
 
CONFIDENTIAL 
Note: Anticipated adverse events expected (with relation to the device and/or 
procedure) are detailed in section ‎6.2. 
7.2 
ADVERSE EVENTS CLASSIFICATION 
AEs reported by the subject or observed by the investigator will be individually listed on 
an adverse event form in the CRF as follows: the specific event or condition, whether 
the event was present pre-study, the dates and times of occurrence, duration, severity, 
relationship to study device, specific countermeasures, and outcome.  
Note: Event which was present pre-study is not considered as an adverse event unless it 
has worsened since the enrollment to the study. 
All AEs will be characterized by the following criteria: 
 
Intensity or Severity 
 
Relatedness 
 
Outcome 
 
Treatment or Action Taken 
7.2.1 
Intensity/Severity Definition 
The intensity or severity of the AE will be characterized as follows: 
Mild:  
Transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required. 
Moderate:  Mild to moderate limitation in activity; some assistance may be needed; no 
or minimal medical intervention/therapy required. 
Severe:   
Marked limitation in activity, some assistance usually required; medical 
intervention/therapy required, hospitalization possible. 
7.2.2 Relationship 
The investigator will document in his opinion the relationship of the AE to the 
investigational medical device using the criteria outlined in Table 1. 
Table 1 
Adverse Event Relationship Criteria 
Relationship 
Criteria 
Unrelated  
The subject was not treated by the investigational device. 
OR 
The temporal sequence of the AE onset relative to treatment by the investiga-
tional device is not reasonable. 
OR 
There is another obvious cause of the AE 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 28 of 36 
 
 
CONFIDENTIAL 
Unlikely 
The relationship with the use of the device seems not relevant and/or the 
event can be reasonably explained by another cause, but additional infor-
mation may be obtained. 
Possible 
The relationship with the use of the investigational device is weak but cannot 
be ruled out completely. Alternative causes are also possible (e.g. an underly-
ing or concurrent illness/ clinical condition or/and an effect of another device, 
drug or treatment). Cases were relatedness cannot be assessed or no infor-
mation has been obtained should also be classified as possible. 
Probable 
The relationship with the use of the investigational device seems relevant 
and/or the event cannot reasonably explained by another cause, but additional 
information may be obtained. 
Related 
There is evidence of exposure to the investigational device. 
 The temporal sequence of the AE onset relative to use with the investi-
gational device is reasonable. 
 The AE is more likely explained by the investigational device than by 
another cause. 
 The AE shows a pattern consistent with previous knowledge of the in-
vestigational device. 
7.2.3 Outcome 
The clinical outcome of the AE or SAE will be characterized as follows: 
Death - The SAE CRF must be completed for this outcome 
Recovered - The patient returned to baseline status 
Ongoing - Patient did not recover and symptoms continue; 
Recovered with sequelae - The patient has recovered but with clinical sequelae from 
the event 
Unknown - The patient outcome is unknown 
7.2.4 Treatment or Action taken 
The treatment or action taken after the occurrence of an AE or SAE will be reported as: 
Interventional Treatment - Surgical, percutaneous or other procedure 
Medical Treatment - Medication dose reduction/interruption or discontinuation, or 
medication initiated for event 
None - No action is taken 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 29 of 36 
 
 
CONFIDENTIAL 
7.3 
REPORTING REQUIREMENTS 
7.3.1 Initial notification  
If the investigator identifies a SAE, a SAE report form must be completed and sent by fax 
or email to Eyefree within 24 hours of the investigator’s knowledge of the event. Also 
fax copies of hospital case reports (i.e., hospital progress notes, results of applicable 
diagnostic tests, lab results and biopsy results) should be sent as soon as they become 
available. Autopsy reports and other documents, as applicable, should be sent upon 
request. 
Reports should be made to the following safety contact person: 
Or Retzkin, CEO 
Tel: +972-526490093 
Email: orretzkin@gmail.com  
 
The reporting should then be followed up by written notification within 5 days, using 
the Serious Adverse Event form in the study file.  
Any fatal or life-threatening event should be reported immediately. These preliminary 
reports will be followed as soon as reasonably possible by detailed descriptions that will 
include a completed SAE form, copies of hospital case reports, autopsy reports, and 
other documents, when requested and applicable. 
In accordance with European regulations, all investigators will be notified of the 
occurrence of serious unexpected AEs, if such AEs are associated with the use of the 
study device (i.e., if there is a reasonable possibility that the AE may have been caused 
by the device and are thus deemed significant new adverse effects or risks with respect 
to the investigational device). 
If applicable, the investigator should also inform the representative of the appropriate 
local Ethics Committee, within 24 hours of investigator's awareness of the event. A copy 
of the report cover letter should be filed within the study file. 
7.3.2 Follow- Up of SADE/USADEs 
Follow-up of SADEs/ USADE that occur during the study will continue until their 
satisfactory resolution or stabilization. 
If/ when supplementary information is available, a follow-up SAE Report Form must be 
completed by the site and faxed within 24 hours to Eyefree Ltd. 
The contact information for follow up SAE reporting is the same as for initial SAE reports 
(see above section).  
Once faxed, the SAE form and accompanying documentation should be placed in the 
SAE section of the investigator’s file. If supplementary information on a SAE has to be 
sent, the SAE form has to be used marked as ‘follow-up report‘. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 30 of 36 
 
 
CONFIDENTIAL 
All other SAE/AEs will be followed for new information/resolution as possible, or may be 
defined as ‘ongoing without further follow-up‘ by the Investigator and Sponsor’s 
decision. 
7.3.3 Notification to Authorities (CA/IECs) 
Events will be reviewed to determine any reporting obligations to Competent 
Authorities as well as IECs. Reporting to Competent Authorities will occur within the 
timelines described as per local regulations. 
In the event of a USADE, sponsor or designee will conduct and report the results of an 
evaluation to the Competent Authorities (as appropriate), reviewing IEC, and all 
participating investigators within 7 working days after sponsor first receives notice of 
the effect, unless the USADE indicates an imminent risk of death, serious injury, or 
serious illness and requires prompt remedial action, in which case reporting will occur 
within 2 days. 
8 
DEVICE DEFICIENCY 
A Device deficiency is an inadequacy of a medical device related to its identity, quality, 
durability, reliability, safety or performance, such as malfunction, misuse or use error 
and inadequate labeling.  
All investigational device deficiencies will be documented on the appropriate Device 
malfunction CRF and the device should be returned to the study sponsor for analysis, if 
possible. Instructions for returning the investigational device will be provided. Device 
deficiencies should also be documented in the subject’s medical record. 
Device deficiencies are not to be reported as AEs. However, if there is an AE that results 
from a device deficiency, that specific event would be recorded on the appropriate CRF. 
9 
STATISTICAL ANALYSIS PLAN 
The planned sample size is considered adequate for this study. No formal sample size 
calculation was performed for this study, as the study was not expected to show 
statistical significance or statistical power. 
10 ETHICS AND REGULATORY 
10.1 INDEPENDENT ETHICS COMMITTEE (IEC) AND COMPETENT AUTHORITY (CA) 
Prior to initiation of the study, the PI will submit the study protocol and amendments, 
sample Informed Consent Form (ICF), and any other documents that may be requested 
to the IEC for review and approval.  The PI/Sponsor will request that the IEC and CA (if 
applicable) provide written approval of the study and will keep on file records of 
approval of all documents pertaining to this study. The PI will not begin the study until 
the protocol and ICF have been approved by the IEC and CA (if applicable). The PI must 
agree to make any required progress reports to the IEC and CA, as well as reports of 
SAEs, life-threatening conditions, or death. 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 31 of 36 
 
 
CONFIDENTIAL 
10.2 ETHICAL CONDUCT OF THE STUDY 
This study will be performed in accordance with the Declaration of Helsinki, the 
European Union’s Medical Device Directive (93/42/EEC art.15) and local Member States 
transpositions. The study will be conducted in agreement with the guidelines for 
conducting a Clinical Investigation as outlined in the European Harmonized Standard, EN 
ISO 14155:2011(E), and in accordance with the principles of ICH GCP, and additional 
local guidelines. 
The clinical investigation will not begin until all necessary approvals/favorable opinions 
are obtained from the appropriate IEC or regulatory authority, as appropriate. Should 
an IEC or regulatory authority impose any additional requirements, they will be 
followed. 
Information regarding the study and study data will be made available via publication 
on clinicaltrials.gov. 
10.3 SUBJECT INFORMATION AND CONSENT 
Prior to screening for the study each subject will be informed in detail about the study 
device, and the nature of the clinical investigation with its risks and discomforts to be 
expected. The basic elements of informed consent as specified by ISO 14155:2011 and 
ICH-GCP will be followed.  Written consent will be obtained from each subject to be 
involved in the clinical trial by using the IEC-approved Informed Consent Form (ICF) prior 
to the conduct of any study-related activity.  Each subject will be given a copy of the 
written ICF.  The subjects will also be instructed that they are free to withdraw their 
consent and discontinue their participation in the study at any time without prejudice. 
Each subject’s chart will include the signed ICF for study participation.  If new 
information becomes available that may affect a subject’s decision to continue to take 
part in the study, this information will be discussed with the subject by the investigator 
and a new ICF version will be signed as needed. When the study treatment is completed 
and the CRF has been monitored, the ICF will be kept in the investigator’s central study 
file for the required period of time.  Regulatory authorities may check the existence of 
the signed ICF in this central study folder if not having done so during the study.   
10.4 SUBJECT INSURANCE 
The Sponsor has an insurance policy for the total duration of the study covering the 
subjects and investigators in respect of the risks involved in conducting this study 
according to this protocol.  The insurance policy will be filed in the investigator’s file or 
can be made available to the Investigator and to the IEC upon request. 
10.5 PERSONAL DATA PROTECTION 
The Sponsor complies with the principle of subject’s right to protection against invasion 
of privacy.  Throughout this trial, all data will be identified only by an identification 
number and subject initials.  The data will be blinded in all data analyses.  The subject 
must be informed and consent is required that authorized personnel of the Sponsor 
and/or designee (Study Monitor, Auditor, etc.) and relevant Health regulatory agency 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 32 of 36 
 
 
CONFIDENTIAL 
will have direct access to personal medical data to assure a high quality standard of the 
study 
10.6 INFORMING THE GENERAL PRACTITIONER 
The Investigator will inform the subject's primary care physician of the subject’s 
participation in the study, by sending a letter to the physician as required by the local 
regulations for the conduct of clinical trials. 
11 QUALITY CONTROL AND QUALITY ASSURANCE 
The study will be conducted according to GCP as outlined by ICH Topic E6 step 5 
guidelines, and ISO 14155, Clinical investigation of medical devices for human subjects.  
11.1 DATA MONITORING  
Monitoring of the study is the responsibility of the Sponsor and may be delegated to a 
CRO or a contract monitor. The study monitor will advise the Investigator regarding the 
practical conduct of the study and maintaining compliance with the protocol, GCP and 
all applicable regulatory requirements. Throughout the course of the study, the study 
monitor will oversee the conduct and the progress of the study by frequent contacts 
with the investigator, performed as defined within the study monitoring plan.  This will 
include telephone calls and on-site visits.  During the on-site visits, the CRF will be 
reviewed for completeness with corresponding source documents.  As part of the data 
audit, source documents will be made available for review by the study monitor.  The 
study monitor will also perform device accountability checks and may periodically 
request review of the investigator study file to ensure completeness of documentation 
in all respects of clinical study conduct.  
Upon completion of the study, the study monitor will arrange for a final review of the 
study files after which the files should be secured for the appropriate time period.  The 
investigator or appointed delegate will receive the study monitor during these on-site 
visits, cooperate in providing the documents for inspection, and respond to inquiries. 
To ensure the rights, safety, and welfare of study subjects are being maintained, the 
monitor will maintain assurance that all study staff are trained on the study protocol 
and use of the study devices. If the monitor discovers that an investigator is not 
complying with the signed Investigator Agreement, the investigational plan, applicable 
laws, or any conditions of approval imposed by the reviewing IEC or Competent 
Authority, the monitor will report to the Sponsor and take such steps necessary to 
promptly secure compliance. If compliance cannot be secured, device shipments to the 
investigator may be discontinued and the investigator’s participation in the 
investigation terminated. The monitor shall also require such an investigator to dispose 
of or return the device, unless this action would jeopardize the rights, safety, or welfare 
of a subject. 
11.2 STUDY DOCUMENTATION 
Study documents will include the following: 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 33 of 36 
 
 
CONFIDENTIAL 
 Signed ICFs 
 Source documents (e.g., subject files, medical notes, study worksheets) 
 Investigator copies of the CRFs and SAE reports 
 Investigator site file + contents 
 Investigator training materials, if applicable 
Upon completion of the study, the study monitor will arrange for a final review of the 
study files after which the files should be secured for the appropriate time period.   
12 STUDY ADMINISTRATION 
12.1 PARTICIPATING CENTERS 
Single site in Israel will participate in this study. 
12.2 SELECTION OF CENTERS & INVESTIGATORS 
The investigative site will meet the following selection criteria prior to inclusion in this 
study: 
 Clinical research study experience and resources that demonstrate good 
compliance with study requirements and timely, complete documentation of 
subject follow-up.   
 Sufficient subject volume to meet enrolment timeframe. 
 Investigators who are certified surgeons experienced in the surgical procedures 
included in this protocol. 
12.3 CLINICAL STUDY SUPPLIES 
The Sponsor will be responsible for the supplying, administrating, inventory, and 
accountability of all clinical trial supplies, exercising accepted medical and 
pharmaceutical practices.  An accurate and timely record of the disposition of all clinical 
supplies must be maintained.  The supplies and inventory record must be made 
available for inspection upon request.  Upon completion or termination of the study, 
the Investigator will keep the remaining clinical supplies along with a copy of the 
inventory record and a record of the clinical supplies returned.  Under no circumstances 
will the Investigator allow the study devices to be used other than as directed by this 
protocol. 
Clinical trial supplies include, however, not limited to: CRF, study worksheets, lab 
supplies and study device. 
12.4 STUDY COMPLETION 
This study is expected to end when all required subjects have been enrolled and the last 
subject has completed the study and the query resolution has been completed. 
 Data and materials that are required before the study can be considered 
complete and/or terminated are: 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 34 of 36 
 
 
CONFIDENTIAL 
 Laboratory findings, clinical data, and all special test results from screening 
through the end of the follow-up period 
 CRF (including correction forms) properly completed by appropriate study 
personnel and electronically signed by the Investigator 
 Completed Device Accountability Records 
 Statement of outcome for each SAE reported 
 Copies of protocol amendments and IRB/IEC as well as relevant health authority 
approval/notification (if applicable) 
12.5 FINAL REPORT 
A clinical study report will be developed by the Sponsor at completion of data analysis. 
This report will be a clinical and statistical integrated report, according to ISO 14155 
guidelines. 
12.6 RETENTION OF STUDY RECORDS  
It is required that a copy of all records (e.g., informed consent documents, source 
documents, safety reports, study device dispensing record, etc.) which support case 
report forms for this study, be retained in the files of the responsible investigator for a 
period of time as defined per local regulations following notification by the sponsor that 
all investigations (not merely the investigator's portion) are completed, terminated 
and/or discontinued.  If the principal investigator retires, relocates, or for other reasons 
withdraws from the responsibility of keeping the study records, custody must be 
transferred to a person who will accept the responsibility. Eyefree Ltd. must be notified 
in writing of the name and address of the new custodian. 
12.7 PUBLICATION POLICY 
All information concerning this study that was not previously published is considered 
confidential information. This confidential information shall remain the sole property of 
Eyefree Ltd.; it shall not be disclosed to others without written consent of Eyefree Ltd. 
and shall not be used except in the performance of this study. 
Any investigator involved with this study is obligated to provide the Sponsor with 
complete test results and all data derived from the study. 
 
 
 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 35 of 36 
 
 
CONFIDENTIAL 
13 APPENDICES 
 
Appendix A 
Study Activity Flow Chart ................................................................ 36 
 
 
 

 
EYECONTROL CLINICAL STUDY  
PROTOCOL 
Doc No.: CLN-001 
Rev: 01 Date: 16May16 
Pg. 36 of 36 
 
 
CONFIDENTIAL 
Appendix A 
Study Activity Flow Chart 
                     Visit  
Procedures 
Screening 
(Visit 0) 
Procedure day 
#1 
Procedure day 
#2 
Procedure 
day #3 
Procedure 
day #4 
Informed Consent 
+ 
 
 
 
 
Eligibility Criteria 
+ 
 
 
 
 
Medical History 
+ 
 
 
 
 
General physical 
assessment 
+ 
 
 
 
 
Device use 
 
+ 
+ 
+ 
+ 
User Questionnaire  
 
 
+ 
 
+ 
Adverse Events 
 
+ 
+ 
+ 
+ 
Each meeting will be conducted 3 days (±1 day) from the previous meeting.