Clinical Biocompatibility of Three Daily Wear Monthly Replacement Silicone Hydrogel Contact Lenses With Two Multi-purpose Disinfecting Solution Combinations
Phase: NA
Conditions: Refractive Errors
Sponsor: Alcon Research



Document ID: 
V-CLN-0004618 
Status: Approved, Version: 3.0 
Approved Date: 29 Mar 2021 
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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: 
 
 

Document ID: 
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Status: Approved, Version: 3.0 
Approved Date: 29 Mar 2021 
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1 PROTOCOL SYNOPSIS 
Trial Sponsor 
Alcon  
6201 South Freeway 
Fort Worth, Texas  76134-2099 
Name of Test Product(s) 
Test Product 1 (Test1): LID018869 pre-cycled with OPTI-
FREE® RepleniSH® multi-purpose disinfecting solution 
(RepleniSH)  
Test Product 2 (Test2): LID018869 pre-cycled with Biotrue® 
multi-purpose solution (Biotrue) 
Name of Control 
Product(s) 
Control Product 1 (Control1): Biofinity® pre-cycled with 
RepleniSH 
Control Product 2 (Control2): PureVision® (PV) pre-cycled 
with Biotrue 
Title of Trial 
Clinical Biocompatibility of Three Daily Wear Monthly 
Replacement Silicone Hydrogel Contact Lenses with Two 
Multipurpose Disinfecting Solution Combinations 
Protocol Number 
CLY935-E007 
Number of Sites 
Country 
~2 
US 
Clinical Investigation Type 
 
 Early Feasibility 
 Traditional Feasibility 
 Pivotal (pre-market monadic claims) 
 Post Market Interventional / Confirmatory 
 Post Market Non-Interventional / Observational 
Planned Duration of 
Exposure  
~ 4 hrs total (test and control, excluding washout): 
Test1: 2 hrs 
 
Test2: 2 hrs 
 
Control1: 2 hrs 
 
Control2: 2 hrs 
 
Number of Subjects  
Target to complete: 32 
 
Planned to enroll: ~36 
Study Population 
Volunteer subjects aged 18 or over who are habitual 
spherical soft contact lens wearers, have at least 3 months of 
contact lens wearing experience, and who wear their habitual 
lenses at least 5 days per week and at least 8 hours per day. 
Objective(s) 
The primary objective of this study is to evaluate corneal 

Document ID: 
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Status: Approved, Version: 3.0 
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staining observed after 2 hours of wear with LID018869 
 against both PureVision, pre-cycled with Biotrue, 
and Biofinity lenses, pre-cycled with RepleniSH. 
Endpoints 
 
Primary Effectiveness 
• Average % area of corneal staining  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Safety 
• Adverse Events (AEs) 
• Biomicroscopy findings  
• Device deficiencies 
Assessments 
 
Effectiveness 
• Corneal staining in each of the 5 corneal regions (central, 
superior, inferior, nasal and temporal) 
o Type (Grade 0-4) 
o Area (0 -100%) 
• VA (Snellen distance) with habitual correction 
• Manifest refraction 
 
 
 
 
 
 
 
 
 
 
 

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Safety 
• AEs 
• Biomicroscopy  
• Device deficiencies 
Study Design 
 
 Prospective 
 Single-masked  
(trial subject) 
 Single-masked 
(Investigator) 
 Double-masked 
 Open-label 
 Other  
 Single group 
 Parallel group 
 Crossover (MPDS) 
 Other  
 Contralateral (lenses) 
 Bilateral 
 Monocular lens wear 
 Randomized 
Lens Assignment 
Subjects will be randomized in a 1:1:1:1 manner to receive 
one of 4 regimen sequences with lens and MPDS 
combinations: 
Sequence 1: LID018869+RepleniSH (OD)/Biofinity+RepleniSH 
(OS)//PV+Biotrue (OD)/LID018869+Biotrue (OS) 
Sequence 2: Biofinity+RepleniSH (OD)/LID018869+RepleniSH 
(OS)//LID018869+Biotrue (OD)/PV+Biotrue (OS) 
Sequence 3: LID018869+Biotrue (OD)/PV+Biotrue 
(OS)//Biofinity+RepleniSH (OD)/LID018869+RepleniSH (OS) 
Sequence 4: PV+Biotrue (OD)/LID018869+Biotrue 
(OS)//LID018869+RepleniSH (OD)/Biofinity+RepleniSH (OS) 
Test Product 1 Details 
 
Primary 
component/material 
 lenses; pre-
cycled with RepleniSH 
 
 
LID Number 
LID018869 
Manufacturer 
Alcon Laboratories, Inc. 
6201 South Freeway 
Fort Worth, Texas  76134-2099 
USA 
  
 
Test Product 2 Details 
Primary 
 lenses; pre-

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Approved Date: 29 Mar 2021 
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component/material 
cycled with Biotrue 
 
 
LID Number 
LID018869 
Manufacturer 
Alcon Laboratories, Inc. 
6201 South Freeway 
Fort Worth, Texas  76134-2099 
USA 
  
 
Control Product 1 Details 
 
Primary 
component/material 
comfilcon A lenses; pre-cycled 
with RepleniSH 
Product Name 
Biofinity 
Manufacturer 
CooperVision 
  
 
Control Product 2 Details 
 
Primary 
component/material 
balafilcon A lenses; pre-cycled 
with Biotrue 
Product Name 
PureVision 
Manufacturer 
Bausch 
 
Other  
-0.50 D 
Inclusion Criteria 
 
1. Subject must be at least 18 years of age.  
2. Subject must be able to understand and must sign an ICF 
that has been approved by an IRB. 
3. Successful wear of spherical soft contact lenses in both 
eyes for a minimum of 5 days per week and 8 hours per 
day during the past 3 months. 
4. Manifest cylinder ≤ 1.50 D in each eye. 
5. BCVA (distance with manifest refraction) better than or 
equal to 20/25 Snellen in each eye. 
6. Subject must be willing to stop wearing their habitual 
contact lenses for the duration of study lens exposure and 
during the washout period. 
 
 
 
 
 
  
Exclusion Criteria 
1. Any anterior segment infection, inflammation, or 
abnormality or disease (including systemic) that 
contraindicates contact lens wear, as determined by the 
Investigator. 

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2. Any use of systemic or ocular medications for which 
contact lens wear could be contraindicated, as 
determined by the Investigator. 
3. History of refractive surgery or plan to have refractive 
surgery during the study or irregular cornea in either eye. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. Current or history of pathologically dry eye in either eye 
that, in the opinion of the Investigator, would preclude 
contact lens wear. 
 
 
 
 
 
 
 
 
 
 
 
11. Any use of topical ocular medications and artificial tear 
or rewetting drops that would require instillation during 
contact lens wear. 
 
 
 
  
 
 

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Associated Materials 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 

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Approved Date: 29 Mar 2021 
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1.1 Abbreviations 
Abbreviation 
Definition 
ADE 
Adverse device effect 
AE 
Adverse event 
ASADE 
Anticipated serious adverse device effect 
BCVA 
Best corrected visual acuity 
Biotrue 
Biotrue multi-purpose solution 
CFR 
Code of Federal Regulations 
CIP 
Clinical investigation plan 
Control1 
Biofinity® pre-cycled with RepleniSH 
Control2 
PureVision® (PV) pre-cycled with Biotrue 
 
 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
hr(s) 
Hour(s) 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
IP 
Investigational product 
IRB 
Institutional review board 
ISO 
International Organization for Standardization 
LID 
Lens identification 
 
 
 
 
 
 
MPDS 
Multi-purpose disinfecting solution 
N/A 
Not applicable 
OD 
Right eye 
OS 
Left eye 
OU 
Both eyes 
PV 
PureVision 
RepleniSH 
OPTI-FREE RepleniSH multipurpose disinfecting solution 
SAE 
Serious adverse event 
SADE 
Serious adverse device effect 
Test1 
LID018869 pre-cycled with OPTI-FREE RepleniSH multi-purpose 
disinfecting solution (RepleniSH) 
Test2 
LID018869 pre-cycled with Biotrue multi-purpose solution (Biotrue) 
US/USA 
United States 
USADE 
Unanticipated serious adverse device effect 
USV 
Unscheduled visit 
VA 
Visual acuity 
 
 

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2 TABLE OF CONTENTS 
Device Protocol for CLY935-E007 ........................................................................................... 1 
1 
PROTOCOL SYNOPSIS .................................................................................................... 3 
1.1 
Abbreviations .................................................................................................... 12 
2 
TABLE OF CONTENTS ................................................................................................... 13 
List of Tables............................................................................................................................ 15 
List of Figures .......................................................................................................................... 15 
3 
INTRODUCTION ............................................................................................................. 16 
3.1 
Study Rationale and Purpose ............................................................................. 16 
3.2 
Trial Objective ................................................................................................... 16 
3.3 
Risks and Benefits ............................................................................................. 17 
3.4 
Subject Population ............................................................................................. 17 
3.5 
Outline of Study ................................................................................................ 18 
4 
TREATMENTS ADMINISTERED .................................................................................. 18 
4.1 
Identity of Study Treatments ............................................................................. 18 
4.2 
Accountability Procedures ................................................................................. 20 
5 
STUDY PROCEDURES AND ASSESSMENTS ............................................................. 21 
5.1 
Visits and Examinations .................................................................................... 21 
 
 
5.1.2 
Visit 1 (Day 1) – Screen/Baseline/Pair 1 Exposure ........................... 21 
5.1.3 
Visit 2 (Day 1, 2 Hours 
 – Pair 1 Follow-up ....... 23 
5.1.4 
Visit 3
 – Baseline/Pair 2 Exposure .......................... 25 
5.1.5 
Visit 4 (same day as Visit 3, 2 hours 
 – Pair 2 
Follow-up/Exit ................................................................................... 27 
5.2 
Unscheduled Visits ............................................................................................ 28 
5.3 
Discontinued Subjects ....................................................................................... 28 
5.4 
Clinical Study Termination ................................................................................ 29 
6 
ANALYSIS PLAN ............................................................................................................ 29 
6.1 
Subject Evaluability........................................................................................... 29 
6.2 
Analysis Data Sets ............................................................................................. 30 
6.2.1 
Safety Analysis Set ............................................................................ 30 
6.3 
Demographic and Baseline Characteristics ....................................................... 30 

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6.4 
Effectiveness Analyses ...................................................................................... 30 
6.4.1 
Primary Effectiveness ........................................................................ 30 
6.4.1.1 
Statistical Hypotheses ........................................................ 30 
6.4.1.2 
Analysis Methods .............................................................. 30 
 
 
 
 
 
 
 
 
6.6 
Handling of Missing Data ................................................................................. 32 
 
 
6.8 
Safety Analysis .................................................................................................. 32 
 
 
 
 
7 
ADVERSE EVENTS AND DEVICE DEFICIENCIES ................................................... 33 
7.1 
General Information .......................................................................................... 36 
7.2 
Monitoring for Adverse Events ......................................................................... 39 
7.3 
Procedures for Recording and Reporting .......................................................... 39 
 
 
7.5 
Follow-Up of Subjects with Adverse Events ..................................................... 42 
 
 
8 
CONFIDENTIALITY, BIAS, AND MASKING .............................................................. 42 
8.1 
Subject Confidentiality and Methods Used to Minimize Bias .......................... 42 
8.2 
Unmasking of the Study Treatment ................................................................... 43 
9 
DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS ............................... 43 
9.1 
Completion of Source Documents and Case Report Forms .............................. 43 
 
 
 
 
10 ETHICS AND COMPLIANCE ......................................................................................... 45 
10.1 Compliance ........................................................................................................ 45 
10.2 Institutional Review Board (IRB) ..................................................................... 45 
11 PROTOCOL AMENDMENT HISTORY.......................................................................... 46 
 
 
12 REFERENCES .................................................................................................................. 47 

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12.1 References Applicable for All Clinical Trials .................................................... 47 
12.1.1 
US References Applicable for Clinical Trials ................................... 47 
 
 
13 APPENDIX ....................................................................................................................... 47 
 
List of Tables 
Table 1-1 
Schedule of Study Procedures and Assessments ............................................... 9 
 
List of Figures 
Figure 7–1 
Categorization of All AEs ................................................................................ 36 
Figure 7-2 
Categorization of All Serious Adverse Events ................................................. 37 
 
 

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3 INTRODUCTION 
3.1 Study Rationale and Purpose 
 
 
 
 
The purpose of this study is to evaluate biocompatibility of an investigational contact lens 
compared to marketed contact lenses (PureVision/Biofinity) which have been pre-
cycled in OPTI-FREE RepleniSH multi-purpose disinfecting solution (RepleniSH) and/or 
Biotrue multi-purpose solution (Biotrue). The primary endpoint (average % area of corneal 
staining) was selected to fulfill the primary objective of the study. 
 
 
 
 
  
 
 
 
 
  
RepleniSH was chosen as a representative solution containing the Polyquarterium-1 
preservative and Biotrue was chosen as a representative solution containing the 
polyaminopropyl biguanide (PHMB) preservative.  
 
 
 
 
3.2 Trial Objective 
The primary objective of this study is to evaluate corneal staining observed after 2 hours of 
wear with LID018869 
against both PureVision, pre-cycled with Biotrue, and 
Biofinity lenses, pre-cycled with RepleniSH. 

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3.3 Risks and Benefits 
 
 
 There is no intended clinical benefit to 
the subject. Material properties and design characteristics of the contact lens in development 
are features consistent with successful contact lens wear. 
Based upon non-clinical testing, the new contact lens in development is assessed to be non-
toxic and biocompatible for on-eye use.  
A summary of the known potential risks and benefits associated with the new contact lens in 
development can be found in the Investigator’s Brochure. 
 
 
 
 
 
. 
The site personnel will educate subjects on proper hygiene and lens handling, and compliance 
with the use of contact lenses according to the protocol. Subjects should be instructed not to 
wear contact lenses while sleeping or swimming. The site personnel will also advise the 
subjects to remove contact lenses and return for prompt follow-up of symptoms, such as 
ocular discomfort, foreign body sensation, excessive tearing, vision changes, or hyperemia. 
3.4 Subject Population 
The study population includes approximately 36 volunteer subjects to be enrolled at 
approximately 2 sites, with approximately 18-36 subjects enrolled per site. The study 
population will consist of subjects with normal eyes (other than the need for optical 
correction for refractive ametropia) and who are adapted, existing wearers of soft contact 
lenses in both eyes. 
Subjects must be screened according to the full list of inclusion/exclusion criteria in Section 1 
of this protocol.  
Rescreening of subjects after screen failure is not allowed in this study. 

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3.5 Outline of Study 
This will be a single-site, prospective, randomized, double-masked, contralateral crossover 
study comparing 3 contact lenses pre-cycled in two different MPDS. The expected duration 
of subject participation in the study is approximately up to 1 week, with 2 study visit days. 
The study is expected to be completed in approximately 1.5 months. 
4 TREATMENTS ADMINISTERED 
Subjects will be randomized in a 1:1:1:1 manner to receive one of 4 regimen sequences with 
lens and MPDS combinations: 
Sequence 1: LID018869+RepleniSH (OD)/Biofinity+RepleniSH (OS)//PV+Biotrue 
(OD)/LID018869+Biotrue (OS) 
Sequence 2: Biofinity+RepleniSH (OD)/LID018869+RepleniSH (OS)//LID018869+Biotrue 
(OD)/PV+Biotrue (OS) 
Sequence 3: LID018869+Biotrue (OD)/PV+Biotrue (OS)//Biofinity+RepleniSH 
(OD)/LID018869+RepleniSH (OS) 
Sequence 4: PV+Biotrue (OD)/LID018869+Biotrue (OS)//LID018869+RepleniSH 
(OD)/Biofinity+RepleniSH (OS) 
4.1 Identity of Study Treatments 
DESCRIPTION OF TEST AND CONTROL PRODUCTS 
 
Test Product 1 
Test Product 2 
Control Product 
1 
Control Product 
2 
LID Number 
LID018869 
LID018869 
N/A 
N/A 
Lens 
identified in 
randomization 
system as:  
 
LID018869+Rep
leniSH 
LID018869+Bio
true 
Biofinity + 
RepleniSH 
PV+Biotrue 
Lens 
Biofinity 
PureVision 
Material 
comfilcon A 
balafilcon A 
Water Content 
48% 
36% 
Base Curve 
(mm) 
8.6 
8.6 

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DESCRIPTION OF TEST AND CONTROL PRODUCTS 
Usage 
• Wear:  
o Daily Wear  
o Contralateral 
• Replacement period: N/A 
• Exposure: 2 hours
 exposure per crossover period 
• Lens Care: Lenses will be pre-cycled in RepleniSH or Biotrue 
  
• 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
4.2 Accountability Procedures 
Upon receipt of the study lenses, the Investigator or delegate will conduct an inventory. 
Designated study staff will provide the study lenses to the subjects in accordance with their 
randomization schedule. 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 

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5 STUDY PROCEDURES AND ASSESSMENTS 
5.1 Visits and Examinations 
Study lenses must be pre-cycled with RepleniSH or Biotrue prior to dispensing. 
 
  
 
 
  
   
 
5.1.2 
Visit 1 (Day 1) – Screen/Baseline/Pair 1 Exposure 
1.  Confirm the subject has not worn contact lenses on the visit day of and the day prior 
to the visit. If lenses have been worn, reschedule Visit 1 to allow for the washout 
period. 
2.  Explain the purpose and nature of the study, and have the subject read, sign, and date 
the IRB-approved informed consent document. Additionally, have the individual 
obtaining consent from the subject and a witness, if applicable, sign and date the 
informed consent document. Provide a photocopy of the signed document to the 
subject and place the original signed document in the subject’s chart. After signing 
the ICF, a subject will be assigned a subject number by the EDC system. A signed 
informed consent document defines the point of enrollment. 
3.  Obtain demographic information and medical history, including information on all 
medications used within the past 30 days
 
 
4.  Perform Snellen VA with habitual spectacles 
• OD, OS, OU, distance only 
Record habitual lens information (brand, power) and lens care information (brand). 
 
 
5.  Perform a manifest refraction. 

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7.  Perform slit lamp biomicroscopy (without contact lenses) to evaluate the following: 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.  Review inclusion/exclusion criteria to determine if the subject qualifies to be 
randomized into the study.  
• If subject qualifies, request randomization and continue with Step 9.  
 
 
 
 
 
 
 
 
  
• If a subject does not qualify according to any criteria other than unacceptable 
corneal staining, exit subject from study as a screen failure. 
9.  Based upon the randomized lens sequence assignment, have the subject insert Pair 1 
study lenses, being careful to maintain the correct OD and OS lens assignments and 
the correct lens pre-soaking assignment.  
 
 
 
 
  

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13.  Assess and record any AEs and device deficiencies reported or observed during the 
study visit. 
Note: AEs and device deficiencies must be recorded for all enrolled subjects from the time of 
signature of informed consent including those that screen fail. 
14.  Study lenses will be worn for approximately 2 hours of wear and instruct the subject 
refrain from using any topical ocular medications or eye drops until they remove 
lenses at Visit 2. 
15.  Schedule Visit 2 to take place 2 hours 
 after Visit 1. Instruct the 
subject to remain in the office before completing Visit 2. 
  
 
 
 
 
 
5.1.3 
Visit 2 (Day 1, 2 Hours 
 – Pair 1 Follow-up 
1.  
Obtain information on any changes in medical health and/or the use of concomitant 
medications. 
2.  
Record any device deficiencies or AEs, including those associated with changes in 
concomitant medication dosing, which are observed or reported since the previous 
visit. 
3.  
Review subject compliance with lens wear and adjunct product usage.  

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7.  
Have subject remove study lenses.  
8.  
Perform slit lamp biomicroscopy (without contact lenses) to evaluate the following: 
• Limbal hyperemia 
• Bulbar hyperemia 
• Corneal staining – 5 regions (type, area); take photos for corneal staining 
• Corneal staining  
• Conjunctival staining 
• Palpebral conjunctival observations 
• Corneal epithelial edema 
• Corneal stromal edema 
• Corneal vascularization 
• Conjunctival compression/indention 
• Chemosis 
• Corneal infiltrates 
• Other findings 
  
 
 
10.  
Schedule Visit 3 
 
 Remind subjects not 
to wear contact lenses on the day prior to and of Visit 3. 
 

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5.1.4 
Visit 3 
 – Baseline/Pair 2 Exposure 
1.  
Obtain information on any changes in medical health and/or the use of concomitant 
medications. 
2.  
Record any device deficiencies or AEs, including those associated with changes in 
concomitant medication dosing, which are observed or reported since the previous 
visit(s). 
3.  
Review subject compliance with washout period. If lenses have been worn, 
reschedule Visit 3 to allow for the washout period.  
4.  
Perform Snellen VA with habitual spectacles 
• OD, OS, distance only 
5.  
Perform slit lamp biomicroscopy (without contact lenses) to evaluate the following: 
• Limbal hyperemia 
• Bulbar hyperemia 
• Corneal staining – 5 regions (type, area); take photos for corneal staining 
• Corneal staining  
• Conjunctival staining 
• Palpebral conjunctival observations 
• Corneal epithelial edema 
• Corneal stromal edema 
• Corneal vascularization 
• Conjunctival compression/indention 
• Chemosis 
• Corneal infiltrates 
• Other findings 
  
 
  
 
 
 
 
 
 
 
 
 
 
  

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7.  
Based upon the randomized lens sequence assignment, have the subject insert Pair 2 
study lenses, being careful to maintain the correct OD and OS lens assignments and 
the correct lens pre-soaking assignment.  
 
 
 
 
 
  
  
 
 
 
  
 
   
 
 
 
 
 
 
 
  
 
  
 
 
 
 
11.  
Assess and record any AEs and device deficiencies reported or observed during the 
study visit. 
Note: AEs and device deficiencies must be recorded for all enrolled subjects from the time 
of signature of informed consent including those that screen fail. 
12.  
Study lenses will be worn for approximately 2 hours of wear and instruct the subject 
refrain from using any topical ocular medications or eye drops until they remove 
lenses at Visit 4. 
13.  
Schedule Visit 4 to take place 2 hours 
 after Visit 3. Instruct the 
subject to remain in the office before completing Visit 4. 
  
 
 
 
 

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5.1.5 
Visit 4 (same day as Visit 3, 2 hours 
 – Pair 2 
Follow-up/Exit 
1.  
Obtain information on any changes in medical health and/or the use of concomitant 
medications. 
2.  
Record any device deficiencies or AEs, including those associated with changes in 
concomitant medication dosing, which are observed or reported since the previous 
visit. 
3.  
Review subject compliance with lens wear and adjunct product usage.  
  
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
  
 
 
 
 
7.  
Have subject remove study lenses.  
8.  
Perform slit lamp biomicroscopy (without contact lenses) to evaluate the following: 
• Limbal hyperemia 
• Bulbar hyperemia 
• Corneal staining – 5 regions (type, area); take photos for corneal staining 
• Corneal staining  
• Conjunctival staining 
• Palpebral conjunctival observations 
• Corneal epithelial edema 
• Corneal stromal edema 
• Corneal vascularization 
• Conjunctival compression/indention 
• Chemosis 
• Corneal infiltrates  
• Other findings 

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9.  
Perform Snellen VA with habitual spectacles 
• OD, OS, distance only 
10.  
Exit the subject from the study. 
 
5.2 Unscheduled Visits 
Any visit that occurs between regularly scheduled visits is an Unscheduled Visit. If a subject 
requires an Unscheduled Visit, he/she must be advised to return to the office wearing the 
study lenses, if possible (unless he/she is experiencing a sign or symptom [as indicated in 
Section 3.3 Risks and Benefits]).  
The investigator may perform additional procedures for proper diagnosis and treatment of the 
subject. The investigator must document this information in the subject’s source documents. 
If during an Unscheduled Visit the subject is discontinuing from the study, the investigator 
must refer to Table 1-1. 
5.3 Discontinued Subjects 
Discontinued subjects are those who withdraw or are withdrawn from the study after signing 
the informed consent, including screen failures. 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, their continued participation poses a risk to their health. 
Discontinued subjects will not be replaced (i.e., their subject numbers will not be 
re-assigned/re-used). 
Should a subject exhibit any clinically relevant signs, symptoms, or other clinical 
observations that possibly could be associated with suspected sensitivity or intolerance to one 
of the study treatments, the Investigator must document those observations on an AE Form. 
Any subject who exits early from the study (excluding screen failures) must undergo all 
procedures outlined at Visit 4, as applicable. 
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. 

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5.4 Clinical Study Termination 
The Study Sponsor reserves the right to close the investigational site or terminate the study in 
its entirety at any time, for reasonable cause. 
If the clinical study is prematurely terminated or suspended by the Study Sponsor:  
• The Study Sponsor must: 
o Immediately notify the Investigator(s) and subsequently provide 
instructions for study termination. 
o Inform the Investigator and the regulatory authorities of the 
termination/suspension and the reason(s) for the termination/suspension, 
as applicable.  
• The Investigator must: 
o Promptly notify the IRB 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 a site’s participation in the study for reasonable cause. 
6 ANALYSIS PLAN 
Continuous variables will be summarized using the number of observations, mean, standard 
deviation, median, minimum, and maximum. Categorical variables will be summarized with 
frequencies and percentages from each category. 
Any deviations to this analysis plan will be updated during the course of the study as part of a 
protocol amendment or will be detailed in the clinical study report. 
6.1 Subject Evaluability 
The final subject evaluability will be determined prior to breaking the code for masked 
treatment (regimen) sequence assignment and locking the database, based on the Deviations 
and Evaluability Plan. 

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6.2 Analysis Data Sets 
6.2.1 
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 lens, 
whether or not presoaked in the study MPDS. For treatment-emergent safety analyses, 
subjects/eyes will be categorized under the actual study lenses/regimen exposed in the 
corresponding regimen sequence.  
6.3 Demographic and Baseline Characteristics 
Demographic information (age, sex, ethnicity, race) will be summarized on the Safety 
Analysis Set. Baseline data pertaining to habitual lens (lens brand, lens care brand) will be 
summarized on the Safety Analysis Set as well. 
6.4 Effectiveness Analyses 
This study defines one primary effectiveness endpoint 
 
The Safety Analysis Set will be used for all effectiveness analyses. 
6.4.1 
Primary Effectiveness 
The primary objective of this study is to evaluate corneal staining observed after 2 hours of 
wear with LID018869 
 against both PureVision, pre-cycled with Biotrue, and 
Biofinity lenses, pre-cycled with Replenish. The primary endpoint is the average of corneal 
staining areas observed (expressed as a percent) taken over the 5 regions: central, superior, 
nasal, inferior, and temporal, after 2 hours of lens wear. 
6.4.1.1 
Statistical Hypotheses 
No inferences are to be made on the primary effectiveness endpoint; therefore, no hypotheses 
are formulated. 
6.4.1.2 
Analysis Methods 
Descriptive statistics will be presented. 
 
 
 
 

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6.6 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 for the effectiveness analyses. 
 
 
 
 
6.8 Safety Analysis 
The safety endpoints for this study are AEs, biomicroscopy findings and device deficiencies. 
All AEs occurring from the time a subject signs informed consent to study exit will be 
accounted for in the reporting. 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, significant non-serious AEs, and 
SAEs will be identified. Individual subject listings will be provided, as necessary. 
Separate individual subject listings will be provided for AEs that occur after signing informed 
consent but prior to exposure to study lenses/MPDS, and for AEs that occur during the 
washout periods.  
 
 
 
 
 
 
 
 
  
No inferential testing will be done for safety analysis. 
 
 
 
 

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7 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
Terms and Definitions 
Adverse Event (AE) 
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. 
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.  
Anticipated Serious 
Adverse Device 
Effect (ASADE) 
An effect, which by its nature, incidence, severity or outcome has 
been identified in the risk assessment. 
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 
inadequacy in the information supplied by the manufacturer 
including labelling. This definition includes device deficiencies 
related to the investigational medical device or the comparator 

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Malfunction 
Failure of an investigational medical device to perform in 
accordance with its intended purpose when used in accordance 
with the instructions for use or clinical investigation plan (CIP), or 
investigator’s brochure (IB). 
Non-serious Adverse 
Event 
Adverse event that does not meet the criteria for a serious adverse 
event. 
Serious Adverse 
Device Effect 
(SADE) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
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, i.e., 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 
an SAE. 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).  
e) any indirect harm as a consequence of incorrect diagnostic 
test results when used within manufacturer’s instructions 
for use. 

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• Fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
Note: Planned hospitalization for a preexisting condition, or a 
procedure required by the CIP, without serious deterioration in 
health, is not considered a serious adverse event. 
 
Refer to Section 7.1 for additional SAEs. 
Serious Health 
Threat 
Signal from any adverse event or device deficiency that indicates 
an imminent risk of death or a serious deterioration in the health in 
subjects, users or other persons, and that requires prompt remedial 
action for other subjects, users or other persons 
Note: This would include events that are of significant and 
unexpected nature such that they become alarming as a potential 
serious health hazard or possibility of multiple deaths occurring at 
short intervals. 
Significant Non-
Serious Adverse 
Event 
A symptomatic, device-related, non-sight-threatening adverse 
event that warrants discontinuation of any contact lens wear for 
greater than or equal to 2 weeks. 
Refer to Section 7.1 for additional Significant Non-serious AEs. 
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 
User action or lack of user action while using the medical device 
that leads to a different result than that intended by the 
manufacturer or expected by the user.  
Note: 
a) Use error includes the inability of the user to complete a 
task. 
b) Use errors can result from a mismatch between the 
characteristics of the user, user interface, task, or use 
environment. 
c) Users might be aware or unaware that a use error has 
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d) An unexpected physiological response of the patient is not 
by itself considered a use error. 
A malfunction of a medical device that causes an unexpected result 
is not considered a use error. 
 
7.1 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 product). 
Figure 7–1 
Categorization of All AEs 
ADE
Device /
procedure-
related?
Symptomatic, 
Device-related, 
Non sight-
threatening, D/C 
Lens Wear?
Meets 
seriousness 
criteria?
SAE
All AEs
AE
Significant     
Non-Serious AE
No
No
Yes
Yes
Yes
 
 

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Figure 7-2 
Categorization of All Serious Adverse Events 
All SAEs
Device /
procedure 
related?
SAE
SADE
Anticipated?
Unanticipated 
SADE
No
Yes
No
Anticipated 
SADE
Yes
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Device Deficiencies 
A device deficiency is inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. A device deficiency may or may not be 
associated with patient harm (i.e., ADE or SADE); however, not all ADEs or SADEs are due 
to a device deficiency. The Investigator should determine the applicable category listed in the 

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Device Deficiency eCRF for the identified or suspect device deficiency and report any 
patient harm separately. 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
7.2 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?” 
Additionally, 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, as applicable. 
These clinically relevant changes will be reported regardless of causality.  
7.3 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 (i.e., before informed 
consent is signed) are not considered AEs in the study and should be recorded in the Medical 
History source. 
 
 
  

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Study Sponsor representatives may be contacted for any protocol related question. 
 
 
 
. 
 
 
 

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Intensity (Severity) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 
are upgraded from non-serious to serious or from unrelated to related. 
 
 
 
 
 
 
  

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7.5 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.  
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
8 CONFIDENTIALITY, BIAS, AND MASKING 
8.1 Subject Confidentiality and Methods Used to Minimize Bias 
The Investigator must ensure that the subject’s anonymity is maintained throughout the 
course of the study. 
 
 
  
 
 
 

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8.2 Unmasking of the Study Treatment 
Masked information on the identity of the assigned medical device should not be disclosed 
during the study. 
 
 
 
 
9 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS 
9.1 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 eCRFs exist and are accessible for verification by the site monitor, 
and all discrepancies shall be appropriately documented via the query resolution process. 
Study 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.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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10 ETHICS AND COMPLIANCE 
This trial will be conducted in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki and the referenced directives, regulations, guidelines, and/or 
standards. 
10.1 Compliance 
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, 
corrective and preventive action should be identified, implemented, and documented within 
the study records. 
10.2 Institutional Review Board (IRB) 
This trial requires IRB approval prior to initiation. This protocol, subject informed consent, 
and subsequent amendments will be reviewed and approved by an IRB. 
Before clinical study initiation, this protocol, the ICF (and assent form, if applicable), any 
other written information given to subjects, and any advertisements planned for subject 
recruitment must be approved by an IRB. The Investigator must provide documentation of 
the IRB approval to the Study Sponsor. The approval must be dated and must identify the 
applicable protocol, amendments (if any), ICF, assent form (if any), all applicable recruiting 
materials, written information for subject, and subject compensation programs. The IRB must 
be provided with a copy of the Investigator’s Brochure and Package Inserts, any periodic 
safety updates, and all other information as required by local regulation and/or the IRB. At 
the end of the study, the Investigator must notify the IRB about the study’s completion. The 
IRB also must be notified if the study is terminated prematurely. Finally, the Investigator 
must report to the IRB on the progress of the study at intervals stipulated by the IRB. 
Voluntary informed consent must be obtained from every subject (and/or legal representative, 
as applicable) prior to the initiation of any screening or other study-related procedures. 
 
 
 
 
 
 

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Amendment 2 
Itemized Changes: 
12 REFERENCES 
12.1 References Applicable for All Clinical Trials 
• ISO 11980:2012 Ophthalmic optics - Contact lenses and contact lens care products - 
Guidance for clinical investigations 
• ISO 14155:2011 Clinical investigation of medical devices for human subjects - Good 
clinical practice 
12.1.1 US References Applicable for Clinical Trials 
• 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 
 
 
 
13 APPENDIX 
N/A 

Signature Page for V-CLN-0004618 v3.0
Signature Page for V-CLN-0004618 v3.0