Multi-Center Cross-Over Evaluation Of Avaira Vitality Silicone Hydrogel Contact Lens and Two Hydrogel Lenses in Daily Wear
Phase: NA
Conditions: Myopia
Sponsor: CooperVision, Inc.

 
 
V
IS
IONCARE RESEARCH 
 
 
 
 
 
 
 
PROTOCOL 
 
VERSION 1 
 
 
 
MULTI-CENTER CROSS-OVER EVALUATION 
OF AVAIRA VITALITY™ SILICONE HYDROGEL 
CONTACT LENS AND TWO HYDROGEL 
LENSES IN DAILY WEAR 
 
 
 
SPONSOR 
: CooperVision Inc. 
 
STUDY NUMBER 
:
 AVAR-402  (EX-MKTG-103) 
 
DATE: March 22, 2019 
 
PROPOSED START DATE: 
April2019 
 
AUTHORS 
: Graeme 
Young 
Kristine Roslin 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
 
 
 
 
 
PRO 
AVAR-402 Version 1 
22MAR2019 
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of48 

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PRO AVAR-402 Version 1 22MAR2019 
 
 
 
 
Multi-center cross-over evaluation of Avaira Vitality™ silicone hydrogel contact lens and two 
hydrogel lenses in daily wear 
 
 
AVAR-402 
(EX-MKTG-103) 
 
TABLE OF CONTENTS 
 
 
 
Page 
 
PERSONNEL AND FACILITIES 
 
6 
 
1 
 
INTRODUCTION 
 
9 
 
2 
 
STUDY 
OBJECTIVES 
 
9 
 
3 
 
STUDY DESIGN & RATIONALE 
 
9 
3.1 
Study Design 
9 
3.2 
Study Rationale 
9 
3.3 
Primary Outcome Hypothesis 
9 
3.4 
Secondary Outcome Hypotheses 
10 
3.5 
Safety 
Hypothesis 
10 
3.6 
Masking 
10 
3.7 
Randomization 
10 
 
4 
 
STUDY 
POPULATION 
 
11 
4.1 
Number of Sites 
11 
4.2 
Investigator 
Recruitment 
11 
4.3 
Number of Subjects 
11 
4.4 
Inclusion Criteria 
11 
4.5 
Exclusion 
Criteria 
12 
4.6 
Subject 
Identification 
12 
4.7 
Study 
Withdrawal Criteria 
13 
4.8 
Subject 
Replacement 
13 
4.9 
Medications/Treatments Permitted and Not Permitted During the Study 
13 
4.10 
Procedures for Monitoring Subject Adherence 
13 
 
5 
 
MATERIALS 
 
14 
5.1 
Study Lenses 
14 
5.2 
Lens Care Products and Other Study Products 
14 
5.3 
Product 
Accountability 
14 
5.4 
Lens 
Wearing Schedule 
15 
5.5 
Potential Risks and Benefits for Human Subjects 
15 
5.6 
Study Documents and eCRFs 
15 
 
6 
 
TREATMENT 
 
15 
6.1 
Study Product Formulations 
15 
6.2 
Lens 
Administration 
16 
 
7 
 
METHODS 
AND ASSESSMENTS 
 
16 
7.1 
Subject 
Recruitment 
16 
7.2 
Study Visits 
16 
7.3 
Clinical Variables 
27 
7.4 
Subject 
Discontinuation 
28 
7.5 
Unscheduled 
Visits 
29 
7.6 
Site Training and Visits 
29 
 
8 
 
ADVERSE 
EVENTS 
 
29 
8.1 
Adverse Event Categorization 
30 
8.2 
Adverse Event Reporting 
31 
8.3 
Adverse Event Documentation 
31 

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8.4 
Adverse Event Follow-up 
32 
8.5 
Study Completion 
32 
9 
DATA MANAGEMENT 
32 
9.1 
Electronic Case Report Forms/Data Collection 
32 
9.2 
Data Quality Assurance 
33 
9.3 
Data Entry and Storage 
33 
10 
SAMPLE SIZE AND STATISTICAL METHODS 
33 
10.1 
Sample Size Rationale 
33 
10.2 
End-points 
33 
10.3 
Statistical Considerations 
34 
10.4 
Analysis Population 
34 
10.5 
Descriptive Statistics 
34 
10.6 
Data Pooling 
34 
10.7 
Primary Statistical Analysis 
34 
10.8 
Secondary Statistical Analysis 
35 
10.9 
Additional Statistical Analysis 
35 
10.10 Interim Analysis 
35 
11 
GENERAL STUDY MANAGEMENT 
35 
11.1 
Relevant Standards 
35 
11.2 
Ethics Review 
35 
11.3 
Protocol Deviations 
35 
11.4 
Premature Termination of the Study 
36 
11.5 
Source Documentation 
36 
11.6 
Monitoring 
36 
11.7 
Audits 
37 
11.8 
Records Retention 
37 
11.9 
Confidentiality and Publication 
37 
12 
REFERENCES 
39 
APPENDIX A Grading Scales & Measurement Instructions 
40 

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PRO AVAR-402 Version 1 22MAR2019 
 
 
 
 
Multi-center cross-over evaluation of Avaira Vitality™ silicone hydrogel contact lens and two 
hydrogel lenses in daily wear 
 
AVAR-402 
(EX-MKTG-103) 
PERSONNEL AND FACILITIES 
 
SPONSOR: 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
    
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 

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1 
INTRODUCTION 
 
There has been a trend over the last 20 years of moving from hydrogel to silicone hydrogel 
contact lenses.
1 In 2018, three-quarters (76%) of prescribed soft lenses in the US were silicone 
hydrogel lenses and this trend is likely to continue.
2  With existing hydrogel  users, an 
impediment to refitting to silicone hydrogels is the concern that the comfort and wetting 
performance may be inferior, thus, mitigating the obvious benefits of improved oxygen 
availability. 
 
The Avaira® Vitality™ (fanfilcon A) soft contact lens is a silicone hydrogel lens indicated for the 
correction of myopia and hyperopia. This was launched recently (FDA 510k approval: 2016) 
and has, therefore, been the subject of few clinical studies. The 510k application reported a 
3-month comparative clinical study involving 90 subjects and in which the lens was found to be 
substantially equivalent to the control lens (stenfilcon A).
3 
 
This study aims to simulate the switching of hydrogel lens wearers to Avaira Vitality silicone 
hydrogel lenses. Two of the most commonly used hydrogels are Acuvue 2 (Johnson & 
Johnson) and Biomedics 55 Premier (CooperVision). Acuvue 2 is a well-established hydrogel 
lens and has been tested in a wide range of clinical studies.4-7 Biomedics 55 Premier is an 
improved version of the Biomedics 55 lens which has also been tested in a number of clinical 
studies.
8-12 
 
The purpose of the proposed study, therefore, is to evaluate the clinical performance of Avaira 
Vitality in comparison with hydrogel lenses in subjects switched from hydrogel to silicone 
hydrogel contact lenses. 
 
 
2 
STUDY 
OBJECTIVES 
 
The aim of this study will be to evaluate the comparative clinical performance of the Avaira 
Vitality™ silicone hydrogel lens used in daily wear and to compare this with competitive 
hydrogel lens products, Biomedics 55 Premier and Acuvue 2. 
 
 
3 
STUDY DESIGN & RATIONALE 
 
 
3.1 
Study 
Design 
 
An approx. 100-120 subject, 8-week, single-masked, bilateral, two-part, cross-over evaluation 
of hydrogel and silicone hydrogel lenses in daily wear. Lenses will be replaced either on a 
2-weekly or 4-weekly basis, depending on control lens group. 
 
 
3.2 
Study 
Rationale 
 
In order to compare the comfort, wetting and deposition, it is necessary to make a within-subject 
comparison. A cross-over study is therefore seen as the most appropriate comparison. 
Switching from hydrogel to silicone hydrogel lens simulates the common sequence of events in 
current clinical practice. However, this does not allow a randomized comparison and may be 
subject to sequence bias. 
 
 
3.3 
Primary 
Outcome Hypothesis 
 
Subjective comfort reported at the visit will be better with Avaira Vitality than the control contact 
lenses at the final visit. 

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3.4 
Secondary 
Outcome 
Hypotheses 
 
i. 
Average wearing time will be longer with Avaira Vitality than the control contact lenses 
at the final visit. 
 
ii. 
Comfortable wearing time will be longer with Avaira Vitality than the control contact 
lenses at the final visit. 
 
iii. 
Pre-lens 
tear 
film quality 
will be 
better 
with 
Avaira Vitality than 
the 
control 
contact 
lenses 
at the final visit. 
 
iv. 
Film deposits will be better with Avaira Vitality than the control contact lenses at the 
final visit. 
 
v. 
White spot deposits will be fewer with Avaira Vitality than the control contact lenses at 
the final visit. 
 
vi. 
Overall lens fit acceptance will be better with Avaira Vitality than the control contact 
lenses at the final visit. 
 
 
3.5 
Safety 
Hypothesis 
 
The study lenses are FDA approved, therefore, no safety end points are required. 
 
However, in order to ensure the continued safety of the subjects in the trial, slit lamp findings 
will be assessed at all visits and the spectacle refraction and VA will be collected at the start 
and end of the study. Adverse events will also be recorded and monitored following the 
procedures listed in Section 8. 
 
 
3.6 
Masking 
 
Subjects will be masked to lens type. When lenses are dispensed, the blister packs will be 
opened out of sight of the subject. Investigators will be unmasked. 
 
 
3.7 
Randomization 
 
Subjects will be randomly allocated to one of the two control groups. The order of wear of the 
test and control lenses will not be randomized. A random number generator (Microsoft Excel) 
using a blocking method and stratified by site will determine the randomization of control lenses 
to subjects, which will then be incorporated into the Randomization Log. ID numbers will be 
assigned consecutively to maintain randomization. 
 
The randomized assignment of subjects will be performed at the first assessment. The 
following must have occurred prior to randomization: 
 
• Informed consent has been obtained 
• Subject meets all the inclusion / exclusion criteria 
• Subject history and baseline information have been collected 

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4 
STUDY 
POPULATION 
 
 
4.1 
Number of Sites 
 
Approximately six sites located in the US, each recruiting approximately 22 subjects. 
Investigators will be contact lens practitioners with at least 3 years post-registration experience 
of contact lens fitting. 
 
 
4.2 
Investigator 
Recruitment 
 
Investigational 
sites will 
be identified by 
Visioncare Research. 
The investigators will be required 
to fulfil the following criteria: 
 
• Appropriately licensed eye care practitioner or contact lens optician 
• At least three years post-registration contact lens fitting experience. 
• In-office email. 
• Willingness to follow the study protocol and to co-operate with the study monitors. 
• Experienced investigators trained in Good Clinical Practice (GCP) and the study 
protocol prior to commencing the study. 
• Computers available to complete CRFs using electronic data capture (EDC). 
 
All of the investigational sites will be trained and evaluated by on-line training modules before 
enrolling 
subjects. 
 
This clinical 
study 
is designed 
to be in 
conformance 
with 
the ethical 
principles in the 
Declaration 
of Helsinki, with the ICH guidelines for GCP and all applicable local regulations. 
 
 
4.3 
Number of Subjects 
 
Approximately 100-120 habitual soft contact lens wearers will be enrolled in the study across 
all sites; approximately 50-60 subjects will use each control lens, Biomedics 55 Premier or 
Acuvue 2, before using the test lens, Avaira Vitality. 
 
Each subject will be required to attend up to five scheduled study visits over a period of 
approximately 
8-weeks. 
 
The study population has been chosen to represent the range of patients that may use these 
contact lens types. Subjects will be adapted soft contact lens wearers and will be recruited from 
the sites’ existing patient database or via IRB approved recruitment material. The enrolment 
period for the study is expected to last approximately 5 weeks. 
 
 
4.4 
Inclusion 
Criteria 
 
All subjects must satisfy the following conditions prior to inclusion in the study: 
 
i. 
Be a currently adapted soft contact lens wearer (>1 month of lens wear). 
 
ii. 
Be at least 18 years of age. 
 
iii. 
Refractive astigmatism <1.00D in both eyes. 
 
iv. 
Have clear corneas and be free of any anterior segment disorders. 
 
v. 
Be correctable through spherocylindrical refraction to 20/25 or better in each eye. 
 
vi. 
Contact lens sphere requirement between -1.00D and -6.00D (inclusive). 

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vii. Require visual correction in both eyes (monovision allowed, no monofit). 
 
viii. Have normal eyes with no evidence of abnormality or disease. For the purposes of this 
study a normal eye is defined as one having: 
a. No amblyopia 
b. No strabismus 
c. No evidence of lid abnormality or infection 
d. No conjunctival abnormality or infection that would contraindicate contact lens wear 
e. No clinically significant slit lamp findings (i.e. corneal staining, stromal edema, 
staining, scarring, vascularization, infiltrates or abnormal opacities) 
f. No other active ocular disease. 
ix. 
  
 
 
  
  
  
 
 
  
 
. 
 
x. Willing to comply with the wear and study visit schedule. 
 
 
4.5 
Exclusion 
Criteria 
 
Any of the following will render a subject ineligible for inclusion: 
 
i. 
Using CooperVision Avaira Vitality, J&J Acuvue 2 or CooperVision Biomedics 55. 
 
ii. 
Require toric or multifocal contact lenses. 
 
iii. 
Previously shown a sensitivity to any of the study solution components. 
 
iv. 
Any systemic or ocular disease or allergies affecting ocular health. 
 
v. 
Using systemic or topical medications that will in the investigator’s opinion affect ocular 
physiology or lens performance. 
 
vi. 
Clinically significant (>Grade 3) corneal staining, corneal stromal edema, corneal 
vascularization, tarsal abnormalities, bulbar hyperemia, limbal hyperemia, or any other 
abnormality of the cornea that would contraindicate contact lens wear. 
 
vii. 
Any corneal infiltrates or any corneal scarring or neovascularization within the central 
5mm of the cornea. 
 
viii. Keratoconus or other corneal irregularity. 
 
ix. 
Aphakia or amblyopia. 
 
x. 
Have undergone corneal refractive surgery or any anterior segment surgery. 
 
xi. 
Abnormal lacrimal secretions. 
 
xii. 
Has diabetes. 
 
xiii. Known/reported infectious disease (e.g., hepatitis, tuberculosis) or an 
immunosuppressive disease (e.g., HIV). 
 
xiv. History of chronic eye disease (e.g. glaucoma). 
 
xv. Pregnant or lactating or planning a pregnancy at the time of enrolment. 
 
xvi. Participation in any concurrent clinical trial or in last 30 days. 
 
 
4.6 
Subject 
Identification 
 
Subjects will be identified by a four-digit code made up of the site number and their enrolment 
number. 
 
The enrolment ID must be assigned to the subjects sequentially and in ascending order for 
each site. Therefore, the first subject at Site 1 will be allocated ID 01/01, the second subject will 
be 01/02 and so on. Subject identification is recorded in the Enrolment log and cannot be used 
more than once. 

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4.7 
Study 
Withdrawal Criteria 
 
If during the study it becomes evident to either the sponsor (CooperVision) or Visioncare 
Research that the study contact lenses pose a threat to subject well-being, the study will be 
terminated and the Institutional Review Board (IRB) will be advised of the reason for 
termination. 
 
 
4.8 
Subject 
Replacement 
 
Subjects that are discontinued from the study will not be replaced. 
 
 
4.9 
Medications/Treatments Permitted and Not Permitted During the Study 
 
Preservative free rewetting/comfort drops may be used in this study, as needed, to lubricate 
and rewet lenses, if agreed by the investigator. 
 
The use of topical ocular medications is contraindicated at all times during this study unless 
prescribed as part of a treatment for an adverse event. The use of any ocular medications to 
treat conditions that arise will require temporary suspension of lens wear, an adverse event 
report, and evaluation of the subject for discontinuation from the study. 
 
For any adverse event where lens wear is suspended, an unscheduled follow-up evaluation of 
the subject must be performed before allowing the subject to return to lens wear. Subjects may 
not return to lens wear until all topical ocular medications have been discontinued and a 
documented exam has verified the resolution of the adverse event. 
 
4.9.1 Concomitant 
Medications 
 
Changes in concomitant medications from those recorded at the initial visit should be indicated 
on the follow-up visit forms by checking ‘Yes’ on the concomitant medication question and 
recording the change on the appropriate EDC forms. 
 
 
4.10 Procedures for Monitoring Subject Adherence 
 
To track compliance, subjects will be asked at each follow-up visit about their average contact 
lens wearing times (typical insertion and removal times) and average number of days lenses 
are worn per week. 

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Study sites will not be required to retain any packaging from used lenses. 
 
Study product accountability will be checked by the study monitor (assigned by the sponsor or 
VCR) during site monitoring. All unused lenses, returned from subjects or never dispensed to 
the study subjects, must be available to the study monitor for verification of lens accountability 
at 
the completion of the study. Any discrepancies in study 
lens accountability 
must 
be explained 
by the investigator. After the study monitor has verified product accountability, any unused 
materials will be returned to VCR or to the sponsor unless the investigator is otherwise directed 
by the VCR. All product returned to VCR or sponsor will be documented on the Lens 
Accountability 
Form. 
 
 
5.4 
Lens 
Wearing Schedule 
 
The subject will be instructed to wear the lenses on daily wear basis, for a minimum of 8 hours 
a day, 6 days per week and preferably 7 days per week. 
 
 
5.5 
Potential Risks and Benefits for Human Subjects 
 
Potential Risks and benefits for human subjects wearing contact lenses are summarized in the 
Informed Consent document (separate document). 
 
 
5.6 
Study Documents and eCRFs 
 
The following forms will be completed where appropriate: 
 
eCRFs: 
• Baseline forms (including eligibility checklist) 
• Trial Fit / Dispensing form 
• Follow-up forms (including Unscheduled Visit) 
• Adverse Event forms 
• Study Exit forms 
• Protocol 
Deviation 
• Device 
Deficiency 
• Concomitant 
medication 
• Medical History 
 
Additional 
Forms 
• Statement of Informed Consent 
• Participant Information Sheet 
• Site Responsibility Log 
• Enrolment Log 
• Participant Information Guide 
• Lens Dispensing Form 
• Lens Accountability Form 
• Source Document Record Label 
 
 
6 
TREATMENT 
 
 
6.1 
Study Product Formulations 
 
The test lenses will be shipped in blister packs containing a buffered saline packaging solution. 
The labelling of lenses and packaging will be the standard packaging which will indicate lens 
power, base curve, diameter, lot number and expiration date. 

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6.2 
Lens 
Administration 
 
Lenses will be used on a 2-weekly or 4-weekly daily wear basis depending on control lens 
group, i.e. lenses worn during the day, removed at night and cleaned and stored with Opti
-Free 
PureMoist 
multipurpose solution. 
 
In the event of lens loss or damage, replacement lens(es) will be issued at an unscheduled 
visit. 
 
 
7 
METHODS AND ASSESSMENTS 
 
 
7.1 
Subject 
Recruitment 
 
Recruitment materials (adverts, letters, etc.) must be approved by the Institutional Review 
Board (IRB). If requested, VCR will provide an advertisement and letter for recruitment 
purposes. Any changes to these must be submitted back to the IRB via VCR. 
 
The procedures listed below will be conducted on all subjects. Variables must be collected in 
the order they are listed on the eCRF. 
 
To participate in this clinical study, the Investigator will explain the Statement of Informed 
Consent to the subject, ensure each subject understands the subject instructions and determine 
subject eligibility. 
 
The Investigator is required to answer any questions the subject has concerning the study or 
the information contained in the Statement of Informed Consent and Patient Information Sheet. 
 
A subject is considered enrolled when he or she signs the Statement of Informed Consent. 
Other study-related activities may not be undertaken prior to obtaining informed consent. 
 
All subjects enrolled should be accounted for, even if they are not dispensed lenses or study 
product. A signed Statement of Informed Consent constitutes enrolment. After enrolment, a 
subject is considered active and should be accounted for at every visit until the completion of 
or discontinuation from the study. 
 
Each site will be expected to enroll approximately 22 subjects. 
 
 
7.2 
Study Visits 
 
7.2.1 Visit Schedule 
 
There will be a maxi
mum of five scheduled visits depending on the lens type: 
 
Biomedics 55 Premier (Control A) 
 
Visit 1: 
Baseline / Trial Fit / Control A Dispensing 
Visit 2: 
2-week Follow Up (14 days -1/+3 days from dispensing) 
Visit 3: 
4-week Follow Up and dispense Test Lens (28 days -1/+3 days from 
Control Lens dispensing) 
Visit 4: 
6-week Follow Up (14 days -1/+3 days from Test Lens dispensing) 
Visit 5: 
8-week Follow-up 
and Exit 
(28 
days -1/+3 days from Test 
Lens 
dispensing) 
 
Acuvue 2 (Control B) 
 
Visit 1: 
Baseline / Trial Fit / Control B Dispensing 

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In the event of discontinuation, the Study Exit eCRF must be completed and the study exit date 
recorded on the Source Document Record. The Investigator will indicate the primary reason 
for discontinuation by selecting one of the boxes provided on the Exit eCRF. Comments can 
be added to the eCRF if necessary. 
 
If a subject is discontinued outside of a visit window, an Unscheduled Visit eCRF must also be 
completed 
 
 
7.5 
Unscheduled Visits 
 
An unscheduled visit is defined as any follow-up that occurs outside the visit window of the 
scheduled visit. A visit is also classified as unscheduled if the subject is seen a second time 
within the scheduled visit window. 
 
Investigators should try as far as possible to schedule follow-up visits within the window. If this 
is not possible, and the visit falls outside the window, the visit will be an unscheduled visit, 
unless it has been agreed with VCR that it can be considered a scheduled visit. 
 
Alternatively, the Investigator might judge that a follow-up visit is in the best interest of the 
subject and schedule two visits within the same window, e.g. follow-up of an adverse event. 
Unscheduled visits are also made available anytime at the subject’s request. 
 
Unscheduled visits will be recorded on the Unscheduled Visit eCRF. All variables listed on the 
forms must be completed unless the subject exhibits a condition that prohibits the completion 
of a full visit. If this is the case, a written explanation is required in the comments section (e.g. 
not wearing lenses due to discomfort). 
 
Presenting VA, slit lamp variables and symptoms including dryness must always be completed 
and the reason for the visit and any actions taken must be indicated on the forms. 
 
 
7.6 
Site Training and Visits 
 
The study initiation will take place via on-line training modules and a phone call. 
 
The sponsor or VCR may choose to initiate an on-site visit as deemed appropriate. If this 
occurs, VCR will email prior to the visit to arrange a convenient time. Interim and close-out 
monitoring visits will be documented in the Monitoring Plan which is a separate document. 
 
 
8 
ADVERSE 
EVENTS 
 
An Adverse Event (AE) is defined as any 
unfavorable or unintended sign (including an abnormal
 
finding), symptom or disease temporarily associated with the use of a study device whether or 
not related to the study device. All ocular AEs and related (to the study device and/or to the 
study procedures) non-ocular AEs, will be monitored and reported on throughout the study. 
 
Transient symptoms such as end-of-day dryness, lens awareness, itching or burning or other 
discomfort may occur with contact lens wear and may occasionally reduce wearing time. These 
are not reported as adverse events unless in the investigator’s opinion they are unexpected in 
nature, severe or have a high rate of occurrence. 
 
Possible ocular AEs are summarized in Table 3 below. 
 
The Investigator will be required to judge whether or not an AE is device-related. Re-occurring 
device-related events from the same subject are usually tabulated as separate events. In the 

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8.2 
Adverse Event Reporting 
 
On finding an AE the Investigator will complete an Adverse Event form (AE form) in EDC to 
capture the event. 
 
The Investigator must notify Visioncare Research of the AE, so that they are able to provide 
advice and support to the Investigator on how to proceed. 
 
The Investigator must do this by providing the information on the AE eCRF as soon as possible 
as and no later than: 
 
• 24 hours from discovery if event is Serious or Significant 
 
• 5 working days from discovery if event is Non-Significant 
 
Once the form is saved, an automatic email will be sent to VCR and the Sponsor to notify them 
of the event. If the AE form in EDC cannot be completed on the day of discovery of the AE, 
then the Medical Monitor must be contacted to notify them of the AE. 
 
If applicable, VCR will advise the Investigator to notify the IRB as per the IRB requirements. 
VCR may notify the IRB on behalf of the Investigator. 
 
The Investigator must notify VCR in writing that the AE has been reported to the IRB. 
 
 
8.3 
Adverse Event Documentati
on 
 
Investigators are required to document and follow-up all AEs. 
 
All AEs must documented on an AE form in EDC upon event discovery. For all ocular AEs, 
one AE form is used per eye. For AEs which are non-ocular only one AE form will need to be 
completed in EDC per AE. 
 
Procedure: 
 
The Investigator has the responsibility to: 
 
1. Complete as much information as possible on the AE form in EDC upon event discovery. 
This includes: 
 
• A detailed description of the AE and a diagnosis, including a probable cause. 
• Likelihood of the AE being device-related 
• Lens lot and power details (irrespective of whether lenses were being worn at time of 
the AE) 
 
2. Include in the patient notes detailed drawings that detail size, location and depth or 
photographs (if necessary) 
 
3. If serious, collect any contact lenses worn, solutions, and the lens case used at the time. 
 
4. Report the AE to the sponsor (via VCR) and the IRB within the specified timelines (see 
Adverse Event Reporting section 8.2). 
 
5. Follow 
study 
subject 
until 
resolution 
recording 
all 
information 
on 
an 
unscheduled 
visit 
eCRF, 
including VA, symptoms, slit lamp findings, resolution, and permanent sequelae if any. 
 
6. Complete all remaining information as required on the AE resolution eCRF. If follow-up of 
the AE is required, the resolution form can only be completed when all AE follow-up visits 
are finished. The following additional information will also be completed  on the AE 
resolution form: 
 
• Outcome, ocular sequelae if any 

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• Whether the patient is discontinued from the study as a result of the AE 
 
 
8.4 
Adverse Event Follow-up 
 
The Investigator will conduct follow-up examinations until the condition: 
 
• Has returned to pre-event status, 
• Is considered stabilized 
• Or has been satisfactorily explained. 
 
If the subject is referred for medical attention, they will be tracked by the Investigator until the 
aforementioned conditions are met. 
Follow-up data will be collected on an unscheduled visit eCRF and on the AE form in EDC. 
The 
Investigator should 
use his/her clinical 
judgement 
as to whether or 
not 
the 
subject 
reporting 
with an AE should continue in the study. 
 
8.4.1 Device 
Deficiency 
 
A device deficiency means the failure of the device to meet its performance specification or 
otherwise perform as intended. A device deficiency would be considered reportable to the 
Sponsor if considered to be likely to cause or contribute to a Serious Adverse Event. 
 
The Investigator will be required to report all reportable device deficiencies to the VCR/Sponsor 
via the applicable form in the EDC system. 
 
8.4.2 Sponsor Safety 
Responsibilities 
 
The sponsor will ensure that all participating Investigators are promptly informed of significant 
new safety information with respect to the study devices as per regulatory requirements. 
 
To comply with this, the sponsor is responsible for promptly advising (in writing, via VCR) all 
Investigators conducting clinical studies of any incidents of serious or unexpected adverse 
events/unanticipated adverse device effects reported for the devices/products involved in those 
studies. 
 
 
8.5 
Study 
Completion 
 
The study is completed when all subjects have completed the final visit (Visit 3 or 5 depending 
on control lens group) or been discontinued, and have been exited from the study. 
 
 
9 
DATA 
MANAGEMENT 
 
 
9.1 
Electronic Case Report Forms/Data Collection 
 
The 
clinical 
data 
for 
this 
study 
will 
be 
entered 
by 
designated 
study 
site 
personnel 
onto 
electronic 
report forms (eCRFs) using the electronic data collection (EDC) system Medrio. 
 
Medrio is compliant with all relevant aspects of ICH/Good Clinical Practices and 21 CFR Part 
11 (Electronic Records & Electronic Signatures) regulations. 

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v. 
Overall lens fit acceptance [0-4]. 
 
 
10.3 Statistical 
Considerations 
 
All statistical analyses will be performed using the SAS software Version 9.4 or later (SAS 
Institute, Cary, NC). 
 
The final analysis will be completed after all subjects have been exited from the study, all 
queries have been resolved, and the database has been locked. 
 
The overall type I error rate will be preserved at 5%. All tests will be two-sided. The primary 
hypothesis must be met in order to satisfy the objective of this study. 
 
From the insertion and removal times the average wearing time will be calculated. If the subject 
indicates that lens comfort deteriorates during wear, the comfortable wearing time will be 
calculated from the insertion time and the time that lenses become uncomfortable. If there is 
no deterioration in comfort then the average wearing time will be used  
    
 
 
  
 
 
Data from unscheduled visits will not be included in the analysis. 
 
Any deviations from this analysis plan will be detailed in the study report. 
 
 
10.4 Analysis 
Population 
 
Statistical analyses will be conducted on all randomized subjects who have successfully 
completed the study without a protocol deviation that is regarded as impacting the assessment 
of the primary hypothesis (as per protocol). Missing data will be excluded from the analysis 
and will not be extrapolated from the collected data. 
 
 
10.5 Descriptive 
Statistics 
 
Descriptive statistics will be reported at dispensing and each follow-up visit. Continuous 
variables will be summarized using mean, standard deviation, and range; and categorical data 
variables will be summarized using percent frequency distribution, mean, and SD. Nominal
 
variables will be summarized using percentages. 
 
Summaries will be presented by control group for each lens type. 
 
 
10.6 Data Pooling 
 
Data will be pooled from multiple study sites for this analysis, the basis for pooling comes from 
three factors: 
 
• The study sites must i
mplement one common protocol. 
• VCR must closely monitor study site protocol compliance. 
• The study sites must use common data collection procedures. 
 
 
10.7 Primary Statistical Analysis 
 
Comfort scores at the final follow-up visit will be analysed using a mixed linear model. The 
model will include the following fixed effects: lens type, control group, site, and the interaction 
of lens type by control group; and subject nested in site as a random effect. The least-square 
means and their differences will be reported with 95% confidence intervals for each lens type 

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by control group.  Conclusions will be drawn from the 95% confidence interval of the least- 
square mean differences. 
 
 
10.8 Secondary Statistical Analysis 
 
The secondary variables will be analysed using mixed linear models. The models will include 
the following fixed effects: lens type, control group, site, and the interaction of lens type by 
control group; and subject nested in site as a random effect. The least-square means and their 
differences will be reported with 95% confidence intervals for each lens type by control group. 
Conclusions will be drawn from the 95% confidence interval of the least-square mean 
differences. 
 
 
10.9 Additional Statistical Analysis 
 
Other selected variables may be analysed using appropriate statistical methods.  A P-value 
less than or equal to 0.050 will be regarded as statistically significant. 
 
 
10.10 Interim Analysis 
 
There are no planned interim analyses for this study. 
 
 
11 
GENERAL STUDY 
MANAGEMENT 
 
 
11.1 Relevant 
Standards 
 
This protocol has been developed in accordance with the following: 
 
• ISO 14155-1:2011 Clinical Investigation of Medical Devices for Human Subjects 
 
• ISO 11980:2012 Contact Lenses and Contact Lens Care Products – Guidance for Clinical 
Investigations. 
 
• ICH Harmonized Tripartite Guideline for Good Clinical Practice 
 
• Declaration of Helsinki 
 
The study will also be carried out in accordance with the VCR Quality Management System 
(ISO 9001:2015) and all the applicable local guidelines. 
 
 
11.2 Ethics Review 
 
The study protocol, Participant Information Sheet and Informed Consent Form and all other 
required documents will be submitted to Sterling IRB for each site. A favorable opinion will be 
received prior to undertaking the study. 
 
If significant protocol changes which require the preparation of an amendment are necessary, 
written IRB approval will be obtained prior to implementation. 
 
 
11.3 Protocol 
Deviations 
 
The Investigators will not deviate from the protocol without written approval from the IRB and 
VCR. 

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In medical emergencies, Investigators will use their judgement and remove the subject from 
immediate hazard.  Any significant changes or deviations in the protocol will be the subject of 
a protocol amendment and must be pre-approved by the IRB. 
 
If an unexpected deviation from the protocol occurs the Investigator must notify the VCR 
immediately and the deviation from the protocol will be reported on a Protocol Deviation form 
in EDC and appropriate action taken. 
 
 
11.4 Premature Termination of the Study 
 
The sponsor reserves the right to terminate the study at any time for any reason including 
adverse effects. If it is determined that an unanticipated adverse device effect presents an 
unreasonable risk, then the entire investigation or part of the investigation presenting the risk 
shall be terminated as soon as possible. A written statement fully documenting the reasons for 
such termination will be provided to the IRB. 
 
 
11.5 Source 
Documentation 
 
Unless otherwise documented, the eCRFs will be considered the source document. The 
sponsor or sponsor’s representatives will be authorized to gain access to the source 
documentation for the purposes of 
monitoring and auditing the study 
(See Sections 11.6, 11.7). 
 
The Source Document Record must be completed to comply with GCP guidelines. It is a 
permanent record within the patient’s chart/notes that documents the subject’s involvement in 
a clinical research study. 
 
Contents of the source document record: 
• Study number 
• Subject ID 
• Confirmation that subject met eligibility criteria 
• Confirmation that subject signed the informed consent 
• Confirmation that subject received a signed and dated copy of informed consent 
• Date enrolled 
• Details of lenses worn on study 
• General notes 
• Adverse events 
• Reportable Protocol deviations 
• Exit date 
• Whether subject completed the study or discontinued 
• Investigator’s 
signature 
 
The Source Document Record will be completed for each subject upon enrolment and then 
updated when required, e.g. when subject exits the study. 
 
 
11.6 Monitoring 
 
Investigational site monitoring will be performed by a qualified study monitor identified by the 
sponsor or VCR. On-site visits will be completed at each site.  The frequency and procedure 
of the monitoring visits will be documented in the Monitoring Plan which is in a separate 
document. The Investigator will allow the study monitor and sponsor representatives or IRB to 
observe procedures and inspect study records and subjects’ medical records throughout the 
study to verify protocol compliance, case report completeness, and investigational material
 
accountability. Should the Investigator be found to be non-compliant and unwilling or unable 
to convert noncompliant practices, VCR in consultation with the sponsor will terminate the 
Investigator’s role in the investigation and the IRB will be notified. 

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11.7 Audits 
 
The Investigator shall permit VCR, the sponsor and the IRB to inspect its facilities, equipment, 
and study-related records, data and other documents upon reasonable notice. In addition, the 
IRB may conduct such inspections as they deem necessary at any time whether or not 
advanced notice is given by them. The Investigator agrees to notify the sponsor or VCR within 
24 hours (or as soon as reasonably practicable) of the start of any unannounced inspection by 
the IRB or of the receipt from the IRB of a notice of inspection whether given in writing or orally. 
If such notice is in writing, a copy with any attachments thereto shall be provided to VCR or the 
sponsor. 
 
 
11.8 Records 
Retention 
 
According to the ICH GCP guidelines the essential documents should be retained until at least 
two years after the last approval of a marketing application in an ICH region and until there are 
no pending or contemplated marketing applications in an ICH region or at least two years have 
elapsed since the formal discontinuation of clinical development of the investigational product. 
It is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. The study lens material is already on the market 
and therefore the study documents should be kept for a minimum of two years after the end of 
the study. As the clinical research organization supervising the study, VCR will also retain the 
written records for the same period of time. Following such retention period, the Investigator 
or the Clinical Site shall deliver to the sponsor all such Research Results, unless otherwise 
instructed in writing by the sponsor. Notwithstanding the foregoing, all information provided by 
or with respect to subjects in the Study will be furnished by Investigator and Clinical Site without 
patient names. 
 
 
11.9 Confidentiality 
and Publication 
 
This study is confidential in nature. The Investigator shall make no public statement, whether 
in written, oral or electronic form, relating to the VCR, the Sponsor, the substances, materials, 
products and devices being investigated or the Study itself without obtaining the prior written 
consent of the VCR or the Sponsor. 
 
All information gathered during this study is proprietary and should be made available only to 
those directly involved in the study who have a need to know. 
 
Authorized recipients of this data include: 
 
▪ Investigator and co-investigator(s) 
▪ Other allied health care personnel necessary for the conduct of the study 
▪ IRB personnel 
▪ Sponsor 
representatives 
▪ Contract Research 
Organization 
▪ Designated study monitor 
▪ Designated medical 
monitor 
▪ FDA or other government regulatory agencies 
 
All above personnel who are provided with data concerning this study will be informed of its 
confidential and proprietary nature. Release of this data (through presentation, publication or 
other written or oral communication) to other than the above listed personnel requires the prior 
written permission from the study Sponsor. Study investigators and all office personnel are 
prohibited from acknowledging participation in the study to individuals and organizations except 
those listed above. This includes sales representatives and other departments or subsidiaries 
of the sponsor without the direct written permission of the sponsor. 

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The study will conform to the requirements of the Health Information Portability and 
Accountability Act (HIPAA). By signing the authorization to use and disclose protected health 
information the subject authorizes the sponsor and the sponsor’s representatives (VCR) to 
access their optometric clinical records. This authorization will expire 50 years from the date 
the subject signs. Subjects will have the right to reverse this authorization at any time. 
 
All patient information will have the patient name (or any information that can identify the patient 
apart from the mobile phone number) removed before leaving the Principal Investigator’s site. 
 
In accordance with the VCR Confidentiality Policy, the data, information, and reports arising 
from this project are the property of the sponsor company. By signing the Informed Consent 
Form the subject also understands that their data will be sent to VCR in the UK and the sponsor 
in the US. VCR will not release to a third party any information arising from this study unless 
required to do so by a legal or regulatory body. The electronic records will also be handled in 
accordance with Health Information Portability and Accountability Act (HIPAA). 
 
The study will be registered on the website www.clinicaltrials.gov. 

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12 
REFERENCES 
 
1. Efron N, Nichols JJ, Woods CA, Morgan PB. Trends in US Contact Lens Prescribing 2002 
to 2014. Optom Vis Sci 2015; 92:758-67. 
 
2. Morgan PB et al. International Contact Lens Prescribing in 2018 Cont Lens Spectrum, 
Volume: 34(1): 26-32. 
 
3. FDA 510k Summary: K160803 Avaira Vitality (fanfilcon A) Soft (hydrophilic) Contact 
Lenses. 
 
4. Szczotka-Flynn LB, Debanne S, Benetz BA, Wilson T, Brennan N. Daily Wear Contact 
Lenses manufactured in Etafilcon A are noninferior to two silicone hydrogel lens types with 
respect to hypoxic stress. Eye Contact Lens. 2018; 44:190-199. 
 
5. Lebow KA, Schachet JL. Evaluation of corneal staining and patient preference with use of 
three multi-purpose solutions and two brands of soft contact lenses. Eye Contact Lens. 
2003; 
29:213-20. 
 
6. Young G, Schnider C, Hunt C, Efron S. Corneal topography and soft contact lens fit. Optom 
Vis Sci. 2010; 87(5):358-66. 
 
7. Maïssa C, Guillon M, Garofalo RJ. Contact lens-induced circumlimbal staining in silicone 
hydrogel contact lenses worn on a daily wear basis. Eye Contact Lens. 2012 Jan;38(1):16- 
26. 
 
8. Berntsen DA, Merchea MM, Richdale K, Mack CJ, Barr JT. Higher-order aberrations when 
wearing sphere and toric soft contact lenses. Optom Vis Sci. 2009; 786:115-22. 
 
9. Barth B, Alves MR, Kara-José N. [Visual performance in myopic correction with spectacles 
and soft contact lenses]. Arq Bras Oftalmol. 2008;71:90-6. Portuguese. 
 
10. Efron S, Efron N, Morgan PB. Optical and visual performance of aspheric soft contact 
lenses. Optom Vis Sci. 2008;85:201-10. 
 
11. Richdale K, Berntsen DA, Mack CJ, Merchea MM, Barr JT. Visual acuity with spherical and 
toric soft contact lenses in low- to moderate-astigmatic eyes. Optom Vis Sci. 2007;84:969- 
75. 
 
12. Bucci FA Jr, Myers PJ, Evans RE, Tanner JB, Moody KJ, Lopatynsky MO. Clinical and 
overnight corneal swell comparison of the 1-Day Acuvue lens versus the Medalist, Surevue, 
Biomedics, and Acuvue lenses. CLAO J. 1997;23:103-12. 

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APPENDIX A 
 
 
 
 
 
  
 
 

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V I S I O N C A R E   R E S E A R C H 
M E A 
S 
U R E 
M E 
N 
T  I 
N 
S 
T R 
U 
C 
T I 
O N S