Comparison Between iLux and LipiFlow in the Treatment of Meibomian Gland Dysfunction (MGD): A 12-month, Multicenter Study
Phase: NA
Conditions: Meibomian Gland Dysfunction, Evaporative Dry Eye Disease
Sponsor: Alcon Research



Page 2 of 66
Investigator Agreement:

I have read the clinical study described herein, recognize its confidentiality, and agree 
to conduct the described trial in compliance with Good Clinical Practice (GCP), the 
ethical principles contained within the Declaration of Helsinki, this protocol, all 
applicable regulatory authority regulations, and conditions of approval imposed by the 
reviewing IRB or regulatory authority.

I will supervise all testing of the device involving human subjects and ensure that the 
requirements relating to obtaining informed consent and IRB review and approval are 
met in accordance with applicable local and governmental regulations.

I have read and understand the appropriate use of the investigational product(s) as 
described in the protocol, current Investigator’s Brochure, product information, or other 
sources provided by the Sponsor.

I understand the potential risks and side effects of the investigational product(s).

I agree to maintain adequate and accurate records in accordance with government 
regulations and to make those records available for inspection.

I agree to comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements of the Sponsor and government 
agencies.

I agree to ensure that all associates, colleagues, and employees assisting in the conduct 
of the study are informed of their obligations in meeting the above commitments.
Have you ever been disqualified as an Investigator by any Regulatory Authority?
No        Yes
Have you ever been involved in a study or other research that was terminated?
No        Yes
If yes, please explain here:
Principal Investigator:
Signature
Date
Name and professional 
position:
Address:
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9
TREATMENTS ADMINISTERED...................................................................................37
9.1
Investigational Product(s)..................................................................................37
9.2
Other Medical Device or Medication Specified for Use During the Study ......40
9.3
Treatment Assignment / Randomization ...........................................................40
9.4
Treatment masking ............................................................................................41
9.5
Accountability Procedures.................................................................................44
9.6
Changes to concomitant medications, treatments/ procedures..........................44
10 STUDY PROCEDURES AND ASSESSMENTS.............................................................45
10.1
Informed Consent and Screening ......................................................................45
10.2
Description of Study Procedures and Assessments...........................................45
10.2.1
Demographics....................................................................................45
10.2.2
Medical History.................................................................................46
10.2.3
Adverse Event Collection: Safety Assessment..................................46
10.2.4
Slit-Lamp Biomicroscopy: Safety Assessment .................................46
10.2.5
Device Deficiencies: Safety Assessment...........................................46
10.3
Unscheduled Visits ............................................................................................47
10.4
Discontinued Subjects .......................................................................................47
10.4.1
Screen Failures ..................................................................................47
10.4.2
Discontinuations................................................................................48
10.4.3
Schedule of Procedures and Assessments for Subjects Discontinued 
from Investigational Product .............................................................48
10.5
Clinical Study Termination................................................................................48
10.5.1
Follow-up of subjects after study participation has ended ................49
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES ...................................................49
11.1
General Information ..........................................................................................49
11.2
Monitoring for Adverse Events .........................................................................51
11.3
Procedures for Recording and Reporting ..........................................................51
11.4
Return product analysis .....................................................................................53
11.5
Unmasking of the Study Treatment...................................................................53
11.6
Follow-Up of Subjects with Adverse Events.....................................................54
11.7
Pregnancy in the Clinical Study........................................................................54
12 ANALYSIS PLAN ............................................................................................................54
12.1
Subject Evaluability...........................................................................................55
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12.2
Analysis Sets .....................................................................................................55
12.2.1
Safety Analysis Set............................................................................55
12.2.2
Full Analysis Set................................................................................55
12.3
Demographic and Baseline Characteristics.......................................................55
12.4
Effectiveness Analyses ......................................................................................56
12.4.1
Analysis of Primary Effectiveness Endpoint(s).................................56
12.4.1.1
Statistical Hypotheses........................................................56
12.4.1.2
Analysis Methods ..............................................................57
12.5
Handling of Missing Data .................................................................................59
12.6
Safety Analyses .................................................................................................59
12.8
Sample Size Justification...................................................................................60
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS ...............................61
13.1
Subject Confidentiality......................................................................................61
13.2
Completion of Source Documents and Case Report Forms..............................62
13.3
Data Review and Clarifications.........................................................................63
13.4
Sponsor and Monitoring Responsibilities .........................................................63
13.5
Regulatory Documentation and Records Retention ..........................................64
13.6
Quality Assurance and Quality Control.............................................................64
14 ETHICS .............................................................................................................................64
15 REFERENCES ..................................................................................................................66
15.1
References applicable for all clinical studies ....................................................66
15.1.1
US references applicable for clinical studies.....................................66
15.2
References for this clinical study ......................................................................66
List of Tables
Table 2–1
List of Acronyms and Abbreviations Used in This Protocol ...........................11
Table 3–1
Schedule of Study Procedures and Assessments .............................................17
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Table 6–1
Primary Objective(s)........................................................................................31
Table 6–4
Safety Objective(s)...........................................................................................32
Table 9–1
Test Product .....................................................................................................38
Table 9–2
Control Product................................................................................................39
List of Figures
Figure 11–1
Categorization of All Adverse Events..............................................................50
Figure 11-2
Categorization of All Serious Adverse Events.................................................50
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1
GLOSSARY OF TERMS
Names of test product(s)
Throughout this document, test product(s) will be referred to 
as iLux
Name of Control Product(s)
LipiFlow® Thermal Pulsation System (LipiFlow)
Adverse Device Effect
(ADE)
Adverse event related to the use of an investigational 
medical device (test product) or control product. Note: This 
definition includes adverse events resulting from insufficient 
or inadequate instructions for use, deployment, 
implantation, installation, or operation; any malfunction; 
and use error or intentional misuse of the test product or 
control product.
Adverse Event (AE)
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 
(test product). Note: For subjects, this definition includes 
events related to the test product, the control product, or the 
procedures involved. For users or other persons, this 
definition is restricted to events related to the test product.
Requirements for reporting Adverse Events in the study can 
be found in Section 11.
Anticipated Serious 
Adverse Device Effect
Serious adverse device effect which by its nature, incidence, 
severity, or outcome has been identified in the risk 
management file.
Device Deficiency
Inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Note: 
This definition includes malfunctions, use errors, and 
inadequate labeling.
Requirements for reporting Device Deficiencies in the study 
can be found in Section 11.
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Enrolled Subject
Any subject who signs an informed consent form for 
participation in the study.
Interventional Clinical Trial
A research trial that prospectively assigns, whether 
randomly or not, human participants or groups of humans to 
one or more health-related interventions to evaluate the 
effects on health outcomes, and/or a research trial in which 
diagnostic or monitoring procedures beyond standard of care 
are conducted and generate outcomes for use in analysis of 
data.
Malfunction
Failure of a medical device to perform in accordance with its 
intended purpose when used in accordance with the 
instructions for use or clinical investigation plan.
Non-serious Adverse Event
Adverse event that does not meet the criteria for a serious 
adverse event.
Postmarketing/Post-
authorization study
Any study conducted within the conditions laid down in 
product labelling and other conditions laid down for the 
marketing of the product or under normal conditions of use. 
A postmarketing study falls either within the definitions of 
an interventional or a non- interventional study and may also 
fall within the definition of a post-approval study.
Product Complaints
Any oral, electronic, or written communication that alleges 
deficiencies related to the identity (labeling), quality, 
durability, reliability, safety, effectiveness, or performance 
of a marketed product, including failure of the product, 
labeling or packaging to meet specifications, whether or not 
the product is related to or caused the alleged deficiency. A 
complaint may allege that an adverse event or medical 
device malfunction has occurred.
Randomized Subjects
Any subject who is assigned a randomized treatment.
Serious Adverse Device 
Effect (SADE)
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event.
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Serious Adverse Event 
(SAE)
Adverse event that led to any of the following:

Death.

A serious deterioration in the health of the subject that 
either resulted in:
a. a life-threatening illness or injury.
Note: Life-threatening means that the 
individual was at immediate risk of death from 
the event as it occurred, ie, it does not include 
an event which hypothetically might have 
caused death had it occurred in a more severe 
form.
b. any potentially sight-threatening event or 
permanent impairment to a body structure or a 
body function.
c. in-patient hospitalization or prolonged 
hospitalization.
Note: Planned hospitalization for a pre-
existing condition, without serious 
deterioration in health, is not considered a 
serious adverse event. In general, 
hospitalization signifies that the individual 
remained at the hospital or emergency ward 
for observation and/or treatment (usually 
involving an overnight stay) that would not 
have been appropriate in the physician's office 
or an out-patient setting. Complications that 
occur during hospitalization are adverse 
events. If a complication prolongs 
hospitalization or fulfills any other serious 
criteria, the event is serious. When in doubt as 
to whether “hospitalization” occurred, the 
event should be considered serious.
d. a medical or surgical intervention to prevent 
a) or b). 
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e. any indirect harm as a consequence of 
incorrect diagnostic test results when used 
within manufacturer’s instructions for use.

Fetal distress, fetal death, or a congenital abnormality or 
birth defect.
Refer to Section 11 for additional SAEs.
Serious Public Health 
Threat
Any event type which results in imminent risk of death, 
serious deterioration in state of health, or serious illness that 
requires prompt remedial action. This would include: Events 
that are of significant and unexpected nature such that they 
become alarming as a potential public health hazard, eg, 
human immunodeficiency virus (HIV) or Bird Flu.
Unanticipated Serious 
Adverse Device Effect 
(USADE)
Serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in the risk 
management file.
Use Error
Act or omission of an act that results in a different medical 
device response than intended by manufacturer or expected 
by user. Note: This definition includes slips, lapses, and 
mistakes. An unexpected physiological response of the 
subject does not in itself constitute a use error.
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2
LIST OF ACRONYMS AND ABBREVIATIONS
Table 2–1
List of Acronyms and Abbreviations Used in This Protocol
Abbreviation
Definition
ADE
Adverse device effect
AE
Adverse event
°C
Degrees Celsius
CFR
Code of Federal Regulations
CI
Confidence interval
COL
Clinical Operations Lead
CRF
Case report form
CSM
Clinical Site Manager
DEP
Deviations and evaluability plan
DFU
Directions for use
ECP
Eye Care Professionals
eCRF
Electronic case report form
EDC
Electronic data capture
EDE
Evaporative dry eye 
°F
Degrees Fahrenheit
FAS
Full analysis set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HIV
Human immunodeficiency virus
ICF
Informed consent form
ICH
International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use
IEC
Independent ethics committee
iLux
iLux System
IP
Investigational product
IRB
Institutional review board
IRT
Interactive response technology
ISO
International Organization for Standardization
LCL
Lower confidence limit
LED
Light emitting diode
LipiFlow
LipiFlow Thermal Pulsation System
MG
Meibomian gland
MGD
Meibomian Gland Dysfunction
MGE
Meibomian Gland Evaluator
MGS
Meibomian Gland Score
MOP
Manual of procedures
n
Number
N/A
Not applicable
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Endpoint(s)
Primary Effectiveness

Mean change from baseline in MGS 
 
 
 
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Safety

AEs

Biomicroscopy findings

Device deficiencies
Assessment(s) 
Effectiveness

Meibomian gland functionality assessment
 
Safety

AEs

Biomicroscopy

Device deficiencies
Study Design
This is a prospective, randomized, assessor-masked, parallel group 
study comparing the iLux to LipiFlow in subjects with EDE.
Subjects will be randomized for bilateral treatment in a 1:1 ratio to 
receive a single treatment with either iLux or LipiFlow. Subjects 
will be expected to attend a total of 8 visits (Screening/Baseline, 
Treatment, 2-Week Follow-up, 1-Month Follow-up, 3-Month 
Follow-up, 6-Month Follow-up, 9-Month Follow-up and 12 -
Month Follow-up/Exit).
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Subject population
The study population will consist of adult male and female 
subjects ≥ 18 years old at the time of informed consent. Subjects
must have signs and symptoms of EDE in both eyes.
Planned number of subjects enrolled/consented: ~278
Required number of completed subjects: 188
Key inclusion 
criteria
(See Section 8.1 for a 
complete list of 
inclusion criteria)
Adult male and female subjects ≥ 18 years of age who have signs 
and symptoms of EDE in both eyes.
Key exclusion 
criteria
(See Section 8.2 for a 
complete list of 
exclusion criteria)
Subjects with uncontrolled systemic diseases that cause dry eye or 
those who are uncontrolled on medical therapy. Subjects who are 
unwilling and/or unable to complete the study visits as outlined in 
the protocol. Subjects who have received either the iLux or the 
LipiFlow treatment in the past 12 months.
Data analysis and 
sample size 
justification
Planned Analysis
To address the primary 
 effectiveness 
objectives, planned analyses are summarized below:
Endpoint
Comparison
Statistical Method
Primary
Change from 
baseline in MGS
iLux vs LipiFlow
Noninferiority
(NI margin = 5)
Mixed effects
repeated measures
 
 
 
 
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Sample Size Justification
Sample size calculations for primary 
 
summarized below:
Endpoint
Assumptions
Type I 
error
N per 
group
Primary
Change from 
baseline in 
MGS 
Common SD = 0.068
NI margin = 7
One-sided 
0.05
94
 
 
 
 
 
 
 
 
Key words
Evaporative dry eye disease, Meibomian gland dysfunction
Associated materials

The Johnson & Johnson Vision Meibomian Gland 
Evaluator (MGE) 

iLux 
o
iLux instrument with protective cap
o
Charging Stand with Power Supply
o
Smart Tip Patient Interface 
o
Laptop computer for data download

LipiFlow
o
LipiFlow disposable patient interface
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5
INTRODUCTION
5.1
Rationale and Background
Meibomian glands are located in the tarsal plate of the upper and lower eyelids, where they 
terminate along the interior rim (or margin) of the eyelids. These glands secrete meibum, 
which is a lipid-rich essential component of a healthy tear film. When sufficient meibum is 
not present in the tear film matrix, the aqueous layer of the tear film is disrupted and readily 
evaporates resulting in irritation, redness, and inflammation of the lid margin and ocular 
surface. MGD is associated with a failure of these glands to produce adequate quality and 
quantity of meibum due to atrophy, inflammation, or obstruction, and is thought to be the 
most common cause of evaporative dry eye disease (Schaumberg 2011).
MGD is one of the most common ophthalmic conditions found in clinical practice. Yet, MGD 
is often under-diagnosed. Clearing meibomian gland (MG) obstruction may also mitigate the 
chronic pathologic progression of MGD, including atrophy of the glands. Population-based 
studies have reported a prevalence of MGD ranging from 3.5% to 69.3% with differences 
among studies by race/ethnicity and parameters used to define presence of MGD. 
Furthermore, studies have shown that 61.7% to 86% of those with dry eye symptoms have 
clinical signs of MGD (Lekhanont 2006, Lin 2003, Lemp 2012). According to the 
International Workshop on MGD Report published in 2011, “MGD may well be the leading 
cause of dry eye disease throughout the world” (Nichols 2011).
A common clinical treatment to improve meibomian gland function in patients with 
obstructive MGD involves the application of heat and pressure therapy to the eyelids to 
express the meibum and other material from the gland (Lekhanont 2006). Warming the eyelid 
tissue softens or melts the meibum, which is known to facilitate expression using pressure.
The iLux System is a commercially available medical device designed for use by the Eye 
Care Professional (ECP) to apply localized heat and pressure therapy to a patient’s eyelids.
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Warming is accomplished using light energy emitted from LED in this instrument. A 
mechanism in this device allows the operator to apply pressure to the eyelid by controlling 
the movement of the outer pad using finger pressure applied to the compression control 
button.
The LipiFlow Thermal Pulsation System is a commercially available medical device for use 
by the ECP to provide localized heat and pressure therapy to adult patients with chronic 
conditions of the eyelids, including MGD.
Additional information on both devices can be found in their respective DFUs.
5.2
Purpose of the Study
The purpose of this post-approval study is to demonstrate that iLux MGD treatment offers 
comparable treatment effectiveness to LipiFlow MGD treatment at 12 months post single 
treatment.
The primary objective of this study is to demonstrate noninferiority of iLux when compared 
to LipiFlow in change from baseline in (MGS at 12 months post single treatment in MGD 
subjects with EDE.
 
At the end of the study, a clinical study report will be prepared in accordance with applicable 
regulatory requirements and standards.
 
5.3
Risks and Benefits
The iLux and LipiFlow devices are non-significant risk devices because they do not meet 
FDA’s criteria for a significant risk device in that the product poses no significant risk to the 
subject. Potential benefit of iLux treatment is unblocking the inspissated and/or obstructed
meibomian glands and expression of the contents of the MG via heating and expression.
Known potential risks may include:

Eyelid/eye pain requiring discontinuation of the treatment procedure
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
Eyelid irritation or inflammation

Temporary reddening of the skin

Ocular surface irritation or inflammation (eg, corneal abrasion, conjunctive edema or 
conjunctival injection (hyperemia))

Ocular symptoms (eg, burning, stinging, tearing, itching, discharge, redness, foreign body 
sensation, visual disturbance, sensitivity to light)
There may also be unknown risks with the use of iLux. Any risk to subjects in this clinical 
study will be minimized by compliance with the eligibility criteria and study procedures, 
clinical oversight, and monitoring.
Risks associated with the LipiFlow can be found in the DFU.
6
STUDY OBJECTIVES
6.1
Primary Objective(s)
Table 6–1
Primary Objective(s)
Objective(s)
Endpoint(s)
The primary objective of this study is to 
demonstrate noninferiority of iLux when 
compared to LipiFlow in change from 
baseline MGS at 12 months post single 
treatment in MGD subjects with EDE.
Change from baseline in MGS at the 12-
Month Follow-up Visit
6.2
Secondary Objective(s)
Table 6–2
Secondary Objective(s)
Not applicable.
 
 
 
 
 
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6.4
Safety Objective(s)
Table 6–4
Safety Objective(s)
Objective(s)
Endpoint(s)
Describe the safety profile of the 
investigational products

AEs

Biomicroscopy findings

Device deficiencies
7
INVESTIGATIONAL PLAN
7.1
Study Design
This is a prospective, randomized, assessor-masked, parallel group study comparing the iLux 
to the LipiFlow in subjects with EDE.
Subjects will be randomized for bilateral treatment in a 1:1 ratio to receive a single treatment 
with either the iLux or LipiFlow. Subjects will be expected to attend a total of 8 visits
(Screening / Baseline, Treatment, 2-Week Follow-up, 1-Month Follow-up, 3-Month Follow-
up, 6-Month Follow-up, 9-Month Follow-up, and 12-Month Follow-up/Exit).
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. 
7.4
Rationale for Choice of Control Product
The LipiFlow is a commercially available device used in the treatment of MGD. It is cleared 
to be marketed by the United States Food and Drug Administration and will be used as the 
control device in this study.
There are several reusable warm compresses available for at home management of MGD; 
however, the LipiFlow is the only commercially available in office device that uses localized 
heat and pressure (thermal pulsation) therapy for the treatment of MGD similar to the test 
device. Hence, LipiFlow will serve as a control product in this study.
7.5
Data Monitoring Committee
Not applicable.
8
STUDY POPULATION
The study population will consist of adult male and female subjects ≥ 18 years old at the time 
of informed consent who have signs and symptoms of EDE in both eyes. The aim is to enroll
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1.
History of (laser) refractive surgery or vitreo-retinal surgery  
 
 
 
 
7.
Active ocular infection or active ocular inflammation (including allergic 
conjunctivitis, vernal or giant papillary conjunctivitis) or history of chronic, recurrent 
severe ocular inflammation within the 3 months prior to Screening
8.
Lid surface abnormalities that affect lid function in either eye
 
 
 
 
 
 
 
 
 
 
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14.
Eyelid tattoos, including permanent eyeliner makeup
15.
Individuals who were treated with LipiFlow or iLux in either eye in the last 
12 months
16.
Contact lens wear within the 1 month prior to Screening
Women of childbearing potential or women who are pregnant at the time of study entry are 
not excluded from participation. 
 
 
 
 
 
 
 
9
TREATMENTS ADMINISTERED
9.1
Investigational Product(s)
Test Product(s):
iLux Device
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Control Product(s) (If applicable):
LipiFlow Thermal Pulsation System
Table 9–1
Test Product
Test Product
iLux (Gen 1.5)
Manufacturer
TearFilm Innovations, Inc.
12625 High Bluff Drive, Suite 107
San Diego, CA 92130
Indication for use 
and intended 
purpose in the 
current study 
The iLux is indicated for the application of localized heat and 
pressure therapy in adult patients with MGD, also known as EDE.
The iLux includes the following:
o
iLux instrument with protective cap
o
Charging Stand with Power Supply
o
Smart Tip Patient Interface 
o
Laptop computer for data download
Product description 
and parameters 
available for this 
study
The iLux instrument records data during operation that is useful for 
evaluating performance and usage. The software application, 
associated computer, and data docking station provides the 
capability to download this data.
Refer to the DFU for product description and parameters.
Formulation
N/A
Usage
The iLux is a commercially available, FDA cleared medical device 
intended for use by qualified ECPs to apply localized heat and 
pressure therapy to adult patients’ lower or upper eyelids.
Packaging 
description
The Carrying Case holds the Instrument, Charging Stand, Power 
Supply, User Manual and Protective Cap. 
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The study laptop will be provided separately from the Carrying 
Case.
The Smart Tip Patient Interface is provided in separate sterile 
packaging.
Labeling description
Refer to the DFU/User Manual
Storage conditions
Test product must be stored in a safe, secure location with limited 
access separated from general stock.
Avoid exposing the iLux or Smart Tip Patient Interface to 
temperatures above 40°C (104°F) or below 10°C (50°F). Refer to 
the DFU/User Manual for additional instructions.
Supply
Alcon will provide the iLux and associated consumables.
Table 9–2
Control Product
Control Product(s)
LipiFlow Thermal Pulsation System
Manufacturer
Johnson & Johnson Vision
Indication for Use
The LipiFlow is intended for the application of localized heat and 
pressure therapy in adult patients with chronic cystic conditions of 
the eyelids, including MGD, also known as EDE or lipid deficiency 
dry eye.
Product description 
and parameters 
available for this 
study
Console, Model LFTP-1000
Activator, Model LFD – 1000, LFD -1100, (disposable) for single 
patient use and Activator II (Model LFD-2000) with the new semi-
permanent Cable (Model CBL-2000)
Refer to the DFU for product description and parameters.
Formulation
N/A
Usage
The LipiFlow is a commercially available device used in the 
treatment of MGD. It is cleared to be marketed by the US FDA and 
will be used as the control device in this study.
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Number/Amount of 
Product to be 
Provided to the 
subject
Sites will utilize their own LipiFlow and associated consumables.
Packaging 
description
Refer to the DFU
Labeling description
Refer to the DFU/User Manual
Storage conditions
Refer to the DFU/User Manual for instructions
Supply
Sites will utilize their own LipiFlow and associated consumables.
The iLux and LipiFlow must be maintained within specified environmental conditions, as 
described in their respective DFUs.
9.2
Other Medical Device or Medication Specified for Use During the 
Study
Anesthetic eye drops shall be instilled in both eyes prior to treatment.
No other medical devices or medications are required to be used in conjunction with the 
treatments during the clinical study.
9.3
Treatment Assignment / Randomization
Subjects will be randomized in a 1:1 ratio to receive bilateral treatment with either iLux or 
LipiFlow, respectively. 
Only after signing the ICF, a subject will be assigned a subject number by the electronic data 
capture system. 
A randomization list will be generated using a validated system that automates the random 
assignment of treatment arms to randomization numbers in the specified ratio. Subjects will 
be assigned treatment according to the randomization list uploaded in the IRT system. The 
randomization list will be generated and maintained by the Study Sponsor.
IRT
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At Visit 2, all eligible subjects will be randomized via the EDC/IRT integration system to one 
of the treatment arms. The Investigator or delegate will access the respective system after 
confirming that the subject meets all the eligibility criteria. A randomization number will be 
automatically assigned to the subject according to the subject randomization list but will not 
be communicated to the site user. The EDC/IRT integration system will inform the site user 
of the treatment assignment to be assigned to the subject.
9.4
Treatment masking
This study is assessor-masked with subjects randomized to receive bilateral treatment with 
either iLux or LipiFlow at Visit 2 with follow-up up at various timepoints during a 12-month
study period. Masked assessors will remain masked to the subject’s study treatment 
assignment throughout the duration of the study.  
 
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9.5
Accountability Procedures
Upon receipt, the Investigator or delegate must conduct an inventory of all IP, and IP-related
accessories by serial number and/or lot number, complete study-specific confirmation of 
receipt procedures as described in the MOP, and retain any required documentation in the 
Investigator’s clinical study records. Throughout the study, the Investigator or delegate must 
maintain records of IP use for each subject. This record must be made available to the study 
monitor for the purposes of verifying the accounting of IP supplies. Any discrepancies and/or 
deficiencies between the observed disposition and the written account must be recorded along 
with an explanation. All IPs sent to the Investigator must be accounted for by Study Sponsor 
personnel, and in no case be used in an unauthorized manner.

Return to the Study Sponsor study-related Alcon products associated with a device 
deficiency. Refer to Section 11 of this protocol for additional information on the reporting 
of device deficiencies and to the MOP for information on return of study products 
associated with these events.
The Investigator is responsible for proper reconciliation and return of the iLux and all used 
and unused accessory items at the conclusion of the study, according to the instructions 
provided in the MOP.
9.6
Changes to concomitant medications, treatments/ procedures
After the subject is enrolled into the study, the Investigator must instruct the subject to notify 
the study site about:

Any new medications 

Alterations in dose or dose schedules for current medications, 
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
Any medical procedure or hospitalization that occurred or is planned

Any non-drug therapies (including physical therapy and blood transfusions). 
The Investigator must document this information in the subject’s case history source 
documents.
The use of systemic medications known to cause dry eye is allowed, as long as the subject is 
on a stable dosage regimen for at least 1 month prior to the Screening Visit and must be on 
the same regimen for the duration of their participation in the study (see Exclusion 
Criteria 10). Subjects who are not on a stable regimen for at least 1 month prior to the
Screening Visit should not be enrolled in the study. If there is a change in a subject’s 
medication regimen while participating in the study, the subject should notify the Site 
immediately. 
10 STUDY PROCEDURES AND ASSESSMENTS
10.1 Informed Consent and Screening
The Investigator or delegate must explain the purpose and nature of the study, and have the 
subject read, sign, and date the IRB/IEC-approved informed consent document. The subject 
must sign the ICF BEFORE any study-specific procedures or assessments can be performed, 
including study-specific screening procedures. Additionally, have the individual obtaining 
consent from the subject and a witness, if applicable, sign and date the informed consent 
document.
The Investigator or delegate must provide a copy of the signed document to the subject and 
place the original signed document in the subject’s chart, or provide documentation as 
required by local regulations.
10.2 Description of Study Procedures and Assessments
Detailed descriptions of assessments and procedures are provided in the MOP. The 
Investigator is responsible for ensuring responsibilities for all procedures and assessments are 
delegated to appropriately qualified site personnel.
10.2.1 Demographics
Obtain demographic information including age, race, ethnicity, and sex.
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10.2.2 Medical History
Medical History includes both ocular and nonocular conditions, which are ongoing or 
resolved within 3 months of the Informed Consent date. 
Collect information on all medications taken within the 30 days prior to the Informed 
Consent date. Include herbal therapies, vitamins, and all over-the-counter as well as 
prescription medications. 
Throughout the subject’s participation, obtain information on any changes in medical health 
and/or the use of concomitant medications.
10.2.3 Adverse Event Collection: Safety Assessment
Assess and record any AEs that are observed or reported, including those associated with 
changes in concomitant medication dosing since the previous visit.
10.2.4 Slit-Lamp Biomicroscopy: Safety Assessment
A slit-lamp exam must be performed on both eyes at every visit.  Any significant changes to
the cornea and conjunctiva will be recorded.
10.2.5 Device Deficiencies: Safety Assessment
Assess and record any device deficiencies that are reported or observed during the study.
Requirements for reporting device deficiencies in the study can be found in Section 11.
Examples of device deficiencies include the following:

Excessive or unintended exposure

Incorrect temperature displayed

Rapid heating

Excessive pressure

Unretractable instrument

Damaged disposable tip

Error message displayed

Suspect product contamination

Unsealed device packaging
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Additional information can be found in the DFU/User manual.
10.3 Unscheduled Visits
An unscheduled visit (USV) is defined as follows:

Ocular examination that is not standard of care and is not required by the protocol,

Examination conducted by the study staff, and 

New clinically significant ocular health findings, or a change to a previous finding was 
discovered
An USV may or may not result in the capture of an AE. Likewise, an AE may be captured
without the report of an USV (eg, AE identified subsequent to study eye examination by non-
study personnel).
During all unscheduled visits, the Investigator must conduct the following procedures: 

Collect AE information

Record changes in medical condition or concomitant medication

Biomicroscopy
The Investigator may perform additional procedures for proper diagnosis and treatment of the 
subject. The Investigator must document this information in the subject’s case history source 
documents.
If during an Unscheduled Visit the subject is discontinuing from the study, the Investigator 
must conduct Early Exit procedures according to Table 3-1 Schedule of Study Procedures and 
Assessments, as possible.
10.4 Discontinued Subjects
10.4.1 Screen Failures
Subjects who discontinue from the study after signing the informed consent and prior to 
randomization will be categorized as screen failures.
The Investigator must document the reason for screen failure in the subject’s case history 
source documents and enter the subject in the EDC.
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10.4.2 Discontinuations
Discontinued subjects are individuals who have signed an ICF and who voluntarily withdraw 
or are withdrawn from the study by the Investigator post-randomization. Any subject 
receiving a subsequent treatment with the iLux or LipiFlow during the study period at any 
time will be exited from the study.
Discontinued subjects will not be replaced; subject numbers of discontinued subjects must 
not be re-used.
Subjects may discontinue from the study at any time for any reason. Subjects may also be 
discontinued from the study at any time if, in the opinion of the Investigator, continued study 
enrollment poses a risk to their health.
For subjects discontinuing from the study, the Investigator must complete all Early Exit 
procedures according to Table 3-1 Schedule of Study Procedures and Assessments, if the 
subject is willing and able, and if in the opinion of the Investigator it is safe for the subject to 
do so.
The Investigator must document the reason for study or treatment discontinuation in the 
subject’s case history source documents.
To ensure the safety of all subjects who discontinue early, Investigators must assess each 
subject and, if necessary, advise them of any therapies and/or medical procedures that may be 
needed to maintain their health.
Subjects discontinuing from the trial for any reason will continue to follow up with their eye 
care provider as applicable.
10.4.3 Schedule of Procedures and Assessments for Subjects Discontinued 
from Investigational Product 
Not Applicable
10.5 Clinical Study Termination
The Study Sponsor reserves the right to close the investigational site or terminate the study in 
its entirety at any time.
If the clinical study is prematurely terminated or suspended by the Study Sponsor: 

The Study Sponsor must:
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o
Immediately notify the Investigator(s) and subsequently provide 
instructions for study termination which may include completion of exit 
visit procedures.
o
Inform the Investigator and the regulatory authorities of the 
termination/suspension and the reason(s) for the termination/suspension. 

The Investigator must:
o
Promptly notify the IRB/IEC of the termination or suspension and of the 
reasons. 
o
Provide subjects with recommendations for post-study treatment options 
as needed.
The Investigator may terminate the site’s participation in the study for reasonable cause.
10.5.1 Follow-up of subjects after study participation has ended 
Following this study, the subject will return to their eye care professional for their routine eye 
care.
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES
11.1 General Information
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, 
whether or not related to the investigational medical device (test article). Refer to the 
Glossary of Terms for categories of AEs and SAEs.
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Device Deficiencies 
A device deficiency may or may not be associated with subject harm (ie, ADE or SADE); 
however, not all ADEs or SADEs are due to a device deficiency. The Investigator should 
determine the applicable category for the identified or suspect device deficiency and report 
any subject harm separately.
11.2 Monitoring for Adverse Events
At each visit, after the subject has had the opportunity to spontaneously mention any 
problems, the Investigator should inquire about AEs by asking the standard questions:

“Have you had any health problems since your last study visit?”

“Have there been any changes in the medicines you take since your last study visit?”
Changes in any protocol-specific parameters and/or questionnaires evaluated during the study 
are to be reviewed by the Investigator. Any untoward (unfavorable and unintended) change in 
a protocol-specific parameter or questionnaire response that is clinically relevant, in the 
opinion of the Investigator, is to be reported as an AE. These clinically relevant changes will 
be reported regardless of causality. 
11.3 Procedures for Recording and Reporting
AEs are collected from the time of informed consent. Any pre-existing medical conditions or 
signs/symptoms present in a subject prior to the start of the study (ie, before informed 
consent is signed) are not considered AEs in the study and should be recorded in the Medical 
History section of the eCRF.
For each recorded event, the ADEs and SAEs documentation must include: date of 
occurrence, severity, treatment (if applicable), outcome, and assessments of the seriousness 
and causality. In addition, the Investigator must document all device deficiencies reported or 
observed with test and control articles on the Device Deficiency eCRF. The site must submit 
all available information on ADEs, SAEs, and device deficiencies to the Study Sponsor 
immediately as follows:

All SAEs must be reported immediately (within 24 hours) of the Investigator’s or site’s 
awareness. 

ADEs that do not meet seriousness criteria and device deficiencies must be reported 
within 10 calendar days of the Investigator’s or site’s awareness. 
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
A printed copy of the completed Serious Adverse Event and Adverse Device Effect 
and/or Device Deficiency eCRF must be included with product returns. Refer to the MOP 
for additional information on product returns.

Additional relevant information after initial reporting must be entered into the eCRF as 
soon as the data become available.

Document any changes to concomitant medications on the appropriate eCRFs.

Document all relevant information from Discharge Summary, Autopsy Report, Certificate 
of Death, etc, if applicable, in narrative section of the Adverse Device Effect (for related 
AEs) and Serious Adverse Event eCRF.
Note: Should the EDC system become non-operational, the site must complete the 
appropriate paper Serious Adverse Event and Adverse Device Effect and/or Device 
Deficiency Form. The completed form is emailed to the Study Sponsor at 
msus.safety@alcon.com.according to the timelines outlined above; however, the reported 
information must be entered into the EDC system once it becomes operational.
Any AEs and device deficiencies for non-study, marketed devices/products (ie, LipiFlow, 
Johnson & Johnson Vision) will be considered and processed as spontaneous (following the 
postmarket vigilance procedures) and should be communicated to the device’s/product’s 
manufacturer as per local requirements.
Study Sponsor representatives may be contacted for any protocol related question and 
their contact information is provided in the Manual of Procedures that accompanies 
this protocol.
Further, depending upon the nature of the AE or device deficiency being reported, the Study 
Sponsor may request copies of applicable portions of the subject’s medical records. The 
Investigator must also report all AEs and device deficiencies that could have led to a SADE 
according to the requirements of regulatory authorities or IRB/IEC.
Intensity and Causality Assessments
Where appropriate, the Investigator must assess the intensity (severity) of the AE based on 
medical judgment with consideration of any subjective symptom(s), as defined below:
Intensity (Severity)
Mild 
An AE is mild if the subject is aware of but can easily tolerate the sign or 
symptom.
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Moderate 
An AE is moderate if the sign or symptom results in discomfort significant 
enough to cause interference with the subject’s usual activities.
Severe 
An AE is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities.
For every AE in the study, the Investigator must assess the causality (Related or Not Related 
to the medical device or study procedure). An assessment of causality will also be performed 
by Study Sponsor utilizing the same definitions, as shown below:
Causality
Related
An AE classified as related may be either definitely related or possibly related 
where a direct cause and effect relationship with the medical device or study 
procedure has not been demonstrated, but there is a reasonable possibility that 
the AE was caused by the medical device or study procedure.
Not Related
An AE classified as not related may either be definitely unrelated or simply 
unlikely to be related (ie, there are other more likely causes for the AE).
The Study Sponsor will assess the AEs and may upgrade the Investigator’s assessment of 
seriousness and/or causality. The Study Sponsor will notify the Investigator of any AEs that is 
upgraded from non-serious to serious or from unrelated to related.
11.4 Return product analysis
Study Sponsor representatives and their contact information are provided in the Manual of 
Procedures that accompanies this protocol. 
Alcon products associated with device deficiencies and/or product related AEs should be 
returned and must include the Complaint # which will be provided by Study Sponsor after the 
case is entered in the Study Sponsor’s Global Product Complaint Management System.
All Alcon products used or unused, regardless of AE/Device Deficiency association will be 
returned at the end of the enrollment period as instructed by the Sponsor.
11.5 Unmasking of the Study Treatment
Masked information on the identity of the assigned medical device should not be disclosed 
during the study (see Section 9.4 of the protocol). If the treatment code needs to be broken in 
the interest of subject safety, the Investigator is encouraged to contact an appropriate Study 
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Sponsor representative prior to unmasking the information if there is sufficient time. 
Dependent upon the individual circumstances (ie, medical emergency), the code may be 
broken prior to contact with the Study Sponsor. The Study Sponsor must be informed of all 
cases in which the code was broken and of the circumstances involved. Additionally, the 
Study Sponsor may be required to unmask the information in order to fulfill expedited 
regulatory reporting requirements.
11.6 Follow-Up of Subjects with Adverse Events
The Investigator is responsible for adequate and safe medical care of subjects during the 
study and for ensuring that appropriate medical care and relevant follow-up procedures are 
maintained after the study. 
The Investigator should provide the Study Sponsor with any new safety information (which 
includes new AEs and changes to previously reported AEs) that may affect the safety 
evaluation of the device. For AEs that are unresolved/ ongoing at time of subject exit from 
study, any additional information received at follow-up should be documented in the eCRFs 
up to study completion (ie, database lock). 
All complaints received after this time period will be considered and processed as 
spontaneous (following the postmarket vigilance procedures) and should be communicated to 
the medical device’s manufacturer as per local requirements.
The Investigator should also report complaints on non-Alcon products directly to the 
manufacturer as per the manufacturer’s instructions or local regulatory requirements.
11.7 Pregnancy in the Clinical Study
Women of childbearing potential or women who are pregnant at the time of study entry are 
not excluded from participation. Pregnancy is not reportable as an AE; however, 
complications may be reportable and will be decided on a case–by-case basis.
 
 
12 ANALYSIS PLAN
Continuous variables will be summarized using the number of observations, mean, standard 
deviation (SD), median, minimum, and maximum, as well as confidence intervals or 
confidence limits where applicable. Categorical variables will be summarized with counts 
and percentages from each category. Any deviations to the analysis plan will be updated 
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during the course of the study as part of a protocol amendment or will be detailed in the 
clinical study report.
12.1 Subject Evaluability
Final subject evaluability must be determined prior to breaking the code for masked 
treatment assignment and locking the database, based upon the Deviations and Evaluability 
Plan (DEP).
12.2 Analysis Sets
12.2.1 Safety Analysis Set
Safety analyses will be conducted using the safety analysis set on a treatment-emergent basis. 
As such, the safety analysis set will include all subjects/eyes exposed to any study treatment. 
For treatment-emergent safety analyses, subjects/eyes will be categorized under the actual 
study treatment exposed.
12.2.2 Full Analysis Set
The full analysis set (FAS) is the set of all randomized subjects who are exposed to any study 
treatment.
 
 
12.3 Demographic and Baseline Characteristics
Demographic and baseline characteristics will be summarized by treatment group and 
overall. Counts and percentages will be presented for categorical variables such as sex, age 
group, race, and ethnicity. Number of observations, mean, SD, median, minimum, and 
maximum will be presented for continuous variables such as age.
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12.4 Effectiveness Analyses
This study defines 1 primary, 
 
endpoints.
 will use the FAS as the primary analysis set.
 
 
 
 
12.4.1 Analysis of Primary Effectiveness Endpoint(s)
The primary objective of this study is to demonstrate noninferiority in change from baseline 
in MGS with iLux compared to LipiFlow at 12 months following a single treatment. The 
primary endpoint, change from baseline in MGS, is derived from MGS, collected separately 
for each eye, where baseline is defined as Visit 1. 
12.4.1.1 Statistical Hypotheses
The null and alternative hypotheses are formulated in terms of the predefined margin of 5 for 
noninferiority:
H0: µ(iLux) – µ(Lipiflow) ≤ -5
Ha: µ(iLux) – µ(Lipiflow) > -5
where µ(iLux) and µ(Lipiflow) denote the mean change from baseline in MGS for iLux and 
LipiFlow, respectively.
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12.4.1.2 Analysis Methods
A mixed effects repeated measures model will be utilized to test these hypotheses. The model 
will include terms for treatment, visit, treatment by visit interaction, and baseline MGS. 
Within-subject correlation due to eye will also be accounted for in the model. Treatment
difference (iLux minus LipiFlow) and the corresponding one-sided 95% lower confidence 
limit (LCL) will be computed. Noninferiority in change from baseline in MGS will be 
declared if the LCL is greater than -5.
 
 
 
 
 
 
 
 
 
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12.5 Handling of Missing Data
All data obtained in evaluable subjects/eyes will be included in the analysis. No imputation 
for missing values will be carried out f
12.6 Safety Analyses
The safety endpoints are:

AEs

Biomicroscopy findings

Device deficiencies
There are no safety hypotheses planned in this study. The focus of the safety analysis will be 
a comprehensive descriptive assessment of occurrence of AEs as well as the other listed 
parameters.
All AEs occurring from the time a subject signs informed consent to study exit will be 
accounted for in the reporting. Safety analyses will be conducted using the safety analysis set 
on a treatment-emergent basis. Descriptive summaries (counts and percentages) for ocular 
and nonocular AEs will be presented by Medical Dictionary for Regulatory Activities 
Preferred Terms. AEs leading to study discontinuation, and SAEs will be identified. 
Individual subject listings will be provided, as necessary. 
Individual subject listings will be provided for AEs that occur after signing informed consent 
but prior to exposure to IP.
Each biomicroscopy parameter will be tabulated by its grade. For select biomicroscopy 
parameters, counts and percentages of eyes that experience an increase of 1 grade from 
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baseline (last assessment prior to study treatment exposure) to any subsequent visit will be 
presented. A supportive listing will be generated which will include all biomicroscopy data 
from all visits for those eyes experiencing the increase. 
Two listings for device deficiencies, prior to exposure of study treatment and treatment-
emergent, will be provided. Additionally, each device deficiency category will be tabulated. 
No inferential testing will be done for safety analysis.
 
 
 
 
 
 
 
 
 
 
 
12.8 Sample Size Justification
 
 
 
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Primary Effectiveness
To demonstrate noninferiority (margin = 5) in change from baseline in MGS as a one-tailed 
hypothesis with α=0.05, and using a standard deviation of 11.661, 90% power can be attained 
with a sample size of 188 (94 per treatment group).
 
 
 
 
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS
13.1 Subject Confidentiality
The Investigator must ensure that the subject’s anonymity is maintained throughout the 
course of the study. In particular, the Investigator must keep an enrollment log with 
confidential identifying information that corresponds to the subject numbers and initials of 
each study participant. At the end of the clinical study, the Study Sponsor will collect a copy 
of the enrollment log without any identifying subject information. All documents submitted 
to the Study Sponsor will identify the subjects exclusively by number and demographic 
information. No other personally identifying information will be transmitted to the Study 
Sponsor.
The Study Sponsor may release anonymized study data to external researchers for purposes 
of future research directly related to the study objectives, or future research that is beyond the 
scope of the current study objectives. The Informed Consent Form explains this to study 
subjects. Anonymization means that all identifiable information will be removed from the 
dataset and all links to the subjects in the study will be removed. Anonymization of the data 
will maintain confidentiality of the subjects who participate in the study so that they cannot 
be identified by external researchers. The anonymized data set will contain records from all 
of the subjects in the current study, but the anonymization process might change the data set 
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in some ways, so external researchers will be informed that they might not be able to 
duplicate some of the results from this study.
13.2 Completion of Source Documents and Case Report Forms
The nature and location of all source documents will be identified to ensure that original data 
required to complete the CRFs exist and are accessible for verification by the site monitor, 
and all discrepancies shall be appropriately documented via the query resolution process. Site
monitors are appointed by the Study Sponsor and are independent of study site staff.
If electronic records are maintained, the method of verification must be determined in
advance of starting the study. 
At a minimum, source documents include the following information for each subject:

Subject identification (name, sex, race/ethnicity)

Documentation of subject eligibility

Date of informed consent

Dates of visits

Documentation that protocol specific procedures were performed

Results of study parameters, as required by the protocol

IP accountability records

Documentation of AEs and other safety parameters (if applicable)

Records regarding medical histories and the use of concomitant therapies prior to and 
during the study

Date of study completion and reason for early discontinuation, if applicable
It is required that the author of an entry in the source documents be identifiable. Direct access 
to source documentation (medical records) must be allowed for the purpose of verifying that 
the data recorded on the CRF are consistent with the original source data.
Only designated individuals at the site will complete the CRFs. The CRFs must be completed 
at regular intervals following the clinical study visit schedule. It is expected that all data 
reported have corresponding entries in the source documents. The Principal Investigator is 
responsible for reviewing and certifying that the CRFs are accurate and complete. The only 
subject identifiers recorded on the CRFs will be subject number, and subject demographic 
information. 
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13.3 Data Review and Clarifications
A review of CRF data to the subject’s source data will be completed by the site monitor to 
ensure completeness and accuracy. After the CRFs have been completed, additional data 
clarifications and/or additions may be needed as a result of the data cleaning process. Data 
clarifications are documented and are part of each subject’s CRF.
13.4 Sponsor and Monitoring Responsibilities
The Study Sponsor will designate a monitor to conduct the appropriate site visits at the 
appropriate intervals according to the study monitoring plan. The clinical investigation will 
be monitored to ensure that the rights and well-being of the subjects are protected, the 
reported data are accurate, complete, and verifiable from the source documents, and the study 
is conducted in compliance with the current approved protocol (and amendments[s], if 
applicable), with current GCP, and with applicable regulatory requirements.
The site may not screen subjects or perform the informed consent process on any subject
until it receives a notification from an appropriate Study Sponsor representative that the site 
may commence conducting study activities. Monitoring will be conducted periodically while 
the clinical study is ongoing. Monitoring methods may include site visits, telephone, written 
and fax correspondence. Close-out visits will take place after the last visit of the last subject
at the site.
A Coordinating Investigator may be identified by the Study Sponsor to review and endorse 
the final study report. In cases where a Coordinating Investigator is engaged, the Study 
Sponsor will select the Coordinating Investigator based upon their experience, qualifications, 
active study participation, and their willingness and availability to take on this role.
Alcon may have an expert Sponsor Representative present during subject visits to offer 
training to the Investigator on proper operation of the device to make technical observations 
during the study visit. 
The Sponsor Representative must be supervised by the Investigator or designee to ensure the 
Sponsor Representative’s presence or activities do not bias the outcome of the study, affect 
the quality of the research data, and/or compromise the rights and welfare of the subject. The 
Sponsor Representative will not intervene with the standard of care provided to study 
subjects or make safety-related decisions or assessments. The activities of Sponsor 
Representatives will be described in the Informed Consent.
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13.5 Regulatory Documentation and Records Retention
The Investigator is required to maintain up-to-date, complete regulatory documentation as 
indicated by the Study Sponsor and the Investigator’s files will be reviewed as part of the 
ongoing study monitoring. Financial information is to be kept separately. 
Additionally, the Investigator must keep study records and source documents consistent with 
the terms of the clinical study agreement with the Study Sponsor. If the Investigator retires, 
relocates, or for any other reason withdraws from responsibility of keeping the study records, 
then the Study Sponsor must be notified and suitable arrangements made for retention of 
study records and source documents needed to comply with national and international 
regulations.
13.6 Quality Assurance and Quality Control
The Study Sponsor will secure agreement from all involved parties to ensure direct access to 
all study related sites, source data and documents, and reports for the purpose of monitoring 
and auditing by the Study Sponsor, and inspection by domestic and foreign regulatory 
authorities. Quality control will be applied to each stage of data handling to ensure that all 
data are reliable and have been processed correctly. Agreements made by the Study Sponsor 
with the Investigator/Institution and any other parties involved in the clinical study will be 
provided in writing as part of the protocol or as a separate agreement.
14 ETHICS
This clinical study must be conducted in accordance with the ethical principles contained 
within: 

The Declaration of Helsinki, and in compliance with the ICH E6 GCP Consolidated 
Guideline, ISO 14155:2011, and the applicable US FDA 21 CFR Regulations. 

SOPs of the Study Sponsor and contract research organizations participating in the 
conduct of the clinical study and all other applicable regulations. 

Notifications and timelines for reporting protocol deviations should be based upon
applicable Ethics Committee requirements
The Investigator must ensure that all personnel involved in the conduct of the study are 
qualified to perform their assigned responsibilities through relevant education, training, and 
experience. The Investigator and all clinical study staff must conduct the clinical study in 
compliance with the protocol. Deviations from this protocol, regulatory requirements and/or 
GCP must be recorded and reported to the Sponsor prior to database lock. If needed, 
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corrective and preventive action should be identified, implemented, and documented within 
the study records. Use of waivers to deviate from the clinical protocol is prohibited.
Before clinical study initiation, this protocol, the informed consent form, any other written 
information given to subjects, and any advertisements planned for subject recruitment must 
be approved by an IRB/IEC. The Investigator must provide documentation of the IRB/IEC 
approval to the Study Sponsor. The approval must be dated and must identify the applicable
protocol, amendments (if any), informed consent form, assent form (if any), all applicable 
recruiting materials, written information for subject, and subject compensation programs. The 
IRB/IEC must be provided with a copy of the DFU, any periodic safety updates, and all other 
information as required by local regulation and/or the IRB/IEC. At the end of the study, the 
Investigator must notify the IRB/IEC about the study’s completion. The IRB/IEC also must 
be notified if the study is terminated prematurely. Finally, the Investigator must report to the 
IRB/IEC on the progress of the study at intervals stipulated by the IRB/IEC.
Voluntary informed consent must be obtained in writing from every subject and the process 
shall be documented before any procedure specific to the clinical investigation is applied to 
the subject. The Investigator must have a defined process for obtaining consent. Specifically, 
the Investigator, or their delegate, must explain the clinical study to each potential subject and 
the subject must indicate voluntary consent by signing and dating the approved informed 
consent form. The subject must be provided an opportunity to ask questions of the 
Investigator, and if required by local regulation, other qualified personnel. The Investigator 
must provide the subject with a copy of the consent form written in a language the subject 
understands. The consent document must meet all applicable local laws and provide subjects 
with information regarding the purpose, procedures, requirements, and restrictions of the 
study, along with any known risks and potential benefits associated with the IP and the study, 
the available compensation, and the established provisions for maintaining confidentiality of 
personal, protected health information. Subjects will be told about the voluntary nature of 
participation in the study and must be provided with contact information for the appropriate 
individuals should questions or concerns arise during the study. The subject also must be told 
that their records may be accessed by appropriate authorities and Sponsor-designated 
personnel. The Investigator must keep the original, signed copy of the consent (file in 
subject’s medical records) and must provide a duplicate copy to each subject according to 
local regulations. 
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15 REFERENCES
15.1 References applicable for all clinical studies

ISO 14155:2011 Clinical investigation of medical devices for human subjects - Good 
clinical practice
15.1.1 US references applicable for clinical studies

21 CFR Part 11 - Electronic Records; Electronic Signatures

21 CFR Part 50 - Protection of Human Subjects

21 CFR Part 56 - Institutional Review Boards

21 CFR Part 812 - Investigational Device Exemptions

21 CFR Part 54 - Financial Disclosure by Clinical Investigators

The California Bill of Rights
 
 
 
 
 
 
 
 
 
 
 
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Signature Page for V-CLN-0003078 v1.0
Signature Page for V-CLN-0003078 v1.0