Contact Lenses With New UV-blocker Manufactured With Different Techniques
Phase: PHASE2
Conditions: Correction of Refraction Error, Attenuation of Bright Light
Sponsor: Johnson & Johnson Vision Care, Inc.

Johnson & Johnson Vision Care, Inc. 
 
Clinical Study Protocol 
 
 
Contact Lenses with New UV-blocker Manufactured with Different Techniques 
 
Protocol CR-6140 
 
Version: 2.0, amendment 1 
                            
Date: 07 February 2018 
 
 
Investigational Products: senofilcon A with new UV-blocker 
 
Key Words: senofilcon A, daily wear, dispensing, subjective responses. 
 
Statement of Compliance to protocol, GCP and applicable regulatory guidelines: 
This trial will be conducted in compliance with the protocol, ISO 141551, the International 
Conference on Harmonization Good Clinical Practice E6 (ICH-GCP)2, the Declaration of 
Helsinki3, and all applicable regulatory requirements. 
 
Confidentiality Statement: 
This document contains confidential information, which should not be copied, referred to, 
released or published without written approval from Johnson & Johnson Vision Care, Inc.  
The information may not be disclosed to others except to the extent necessary to obtain 
Institutional Review Board/Independent Ethics Committee approval and informed consent, or 
as required by International, Federal and State Laws, as applicable. Persons to whom this 
information is disclosed must be informed that this information is privileged and confidential 
and that it should not be further disclosed without the written permission of Johnson & 
Johnson Vision Care, Inc.  Any supplemental information that may be added to this document 
is also confidential and proprietary to Johnson & Johnson Vision Care, Inc. and must be kept 
in confidence in the same manner as the contents of this document. 
 
 
 
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TABLE OF CONTENTS  
PROTOCOL TITLE, NUMBER, VERSION .......................................................................... 6 
SPONSOR NAME AND ADDRESS ...................................................................................... 6 
MEDICAL MONITOR ............................................................................................................ 6 
AUTHORIZED SIGNATURES .............................................................................................. 7 
CHANGE HISTORY............................................................................................................... 8 
SYNOPSIS ............................................................................................................................... 8 
COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS ................... 14 
1. 
INTRODUCTION AND BACKGROUND .................................................................. 15 
1.1. 
Name and Descriptions of Investigational Products ............................................... 15 
1.2. 
Intended Use of Investigational Products................................................................ 15 
1.3. 
Summary of Findings from Nonclinical Studies ..................................................... 15 
1.4. 
Summary of Known Risks and Benefits to Human Subjects .................................. 16 
1.5. 
Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study..................................................................................................................... 16 
2. 
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES ..................................... 17 
2.1. 
Objectives ................................................................................................................ 17 
2.2. 
Endpoints ................................................................................................................. 17 
2.3. 
Hypotheses .............................................................................................................. 19 
3. 
TARGETED STUDY POPULATION .......................................................................... 20 
3.1. 
General Characteristics ........................................................................................... 20 
3.2. 
Inclusion Criteria ..................................................................................................... 20 
3.3. 
Exclusion Criteria .................................................................................................... 20 
3.4. 
Enrollment Strategy................................................................................................. 21 
4. 
STUDY DESIGN AND RATIONALE ......................................................................... 21 
4.1. 
Description of Study Design ................................................................................... 21 
4.2. 
Study Design Rationale ........................................................................................... 22 
4.3. 
Enrollment Target and Study Duration ................................................................... 22 
5. 
TEST ARTICLE ALLOCATION AND MASKING .................................................... 22 
5.1. 
Test Article Allocation ............................................................................................ 22 
5.2. 
Masking ................................................................................................................... 23 
5.3. 
Procedures for Maintaining and Breaking the Masking.......................................... 23 
6. 
STUDY INTERVENTION ............................................................................................ 24 
6.1. 
Identity of Test Articles........................................................................................... 24 
6.2. 
Ancillary Supplies/Products .................................................................................... 25 
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6.3. 
Administration of Test Articles ............................................................................... 25 
6.4. 
Packaging and Labeling .......................................................................................... 25 
6.5. 
Storage Conditions .................................................................................................. 26 
6.6. 
Collection and Storage of Samples ......................................................................... 26 
6.7. 
Accountability of Test Articles ............................................................................... 26 
7. 
STUDY EVALUATIONS ............................................................................................. 27 
7.1. 
Time and Event Schedule ........................................................................................ 27 
7.2. 
Detailed Study Procedures ...................................................................................... 28 
VISIT 1 .......................................................................................................................... 28 
VISIT 2 .......................................................................................................................... 32 
VISIT 3 .......................................................................................................................... 36 
VISIT 4 .......................................................................................................................... 40 
FINAL EVALUATION ................................................................................................. 42 
7.3. 
Unscheduled Visits .................................................................................................. 42 
7.4. 
Laboratory Procedures ............................................................................................ 44 
8. 
SUBJECTS COMPLETION/WITHDRAWAL............................................................. 44 
8.1. 
Completion Criteria ................................................................................................. 44 
8.2. 
Withdrawal/Discontinuation from the Study .......................................................... 44 
9. 
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION ................ 45 
10. 
DEVIATIONS FROM THE PROTOCOL ................................................................. 45 
11. 
STUDY TERMINATION .......................................................................................... 45 
12. 
PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS ............. 46 
13. 
ADVERSE EVENTS .................................................................................................. 47 
13.1. 
Definitions and Classifications ............................................................................ 47 
13.2. 
Assessing Adverse Events ................................................................................... 49 
13.2.1. 
Causality Assessment ................................................................................... 49 
13.2.2. 
Severity Assessment ..................................................................................... 50 
13.3. 
Documentation and Follow-Up of Adverse Events ............................................. 50 
13.4. 
Reporting Adverse Events ................................................................................... 51 
13.4.1. 
Reporting Adverse Events to Sponsor ......................................................... 52 
13.4.2. 
Reporting Adverse Events to the Responsible IEC/IRB and Health 
Authorities...................................................................................................................... 52 
13.4.3. 
Event of Special Interest .............................................................................. 53 
13.5. 
Reporting of Pregnancy ....................................................................................... 53 
14. 
STATISTICAL METHODS ....................................................................................... 53 
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14.1. 
General Considerations ........................................................................................ 53 
14.2. 
Sample Size Justification ..................................................................................... 53 
14.3. 
Analysis Populations ........................................................................................... 55 
14.4. 
Level of Statistical Significance .......................................................................... 55 
14.5. 
Primary Analysis ................................................................................................. 55 
14.6. 
Secondary Analysis ............................................................................................. 56 
14.7. 
Other Exploratory Analyses ................................................................................ 56 
14.8. 
Interim Analysis .................................................................................................. 56 
14.9. 
Procedure for Handling Missing Data and Drop-Outs ........................................ 57 
14.10. 
Procedure for Reporting Deviations from Statistical Plan .................................. 57 
15. 
DATA HANDLING AND RECORD KEEPING/ARCHIVING ............................... 57 
15.1. 
Electronic Case Report Form/Data Collection .................................................... 57 
15.2. 
Subject Record ..................................................................................................... 58 
16. 
DATA MANAGEMENT............................................................................................ 58 
16.1. 
Access to Source Data/Document ....................................................................... 58 
16.2. 
Confidentiality of Information............................................................................. 58 
16.3. 
Data Quality Assurance ....................................................................................... 59 
17. 
MONITORING ........................................................................................................... 59 
18. 
ETHICAL AND REGULATORY ASPECTS ........................................................... 59 
18.1. 
Study-Specific Design Considerations ................................................................ 59 
18.2. 
Investigator Responsibility .................................................................................. 60 
18.3. 
Independent Ethics Committee or Institutional Review Board (IEC/IRB) ......... 60 
18.4. 
Informed Consent ................................................................................................ 61 
18.5. 
Privacy of Personal Data ..................................................................................... 61 
19. 
STUDY RECORD RETENTION............................................................................... 63 
20. 
FINANCIAL CONSIDERATIONS ........................................................................... 63 
21. 
PUBLICATION .......................................................................................................... 64 
22. 
REFERENCES ........................................................................................................... 64 
APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES) .... 65 
APPENDIX B: PATIENT INSTRUCTION GUIDE ............................................................ 76 
APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) ........................................ 77 
APPENDIX D: 
 ..................................... 78 
 LIMBAL AND CONJUNCTIVAL (BULBAR) REDNESS .............................. 79 
EXPANDED SODIUM FLUORESCEIN CORNEAL STAINING ................... 87 
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, LENS FITTING CHARACTERISTICS ............................................................. 92 
 SUBJECT REPORTED OCULAR SYMPTOMS PROBLEMS ........................ 99 
 FRONT AND BACK SURFACE LENS DEPOSIT GRADING PROCEDURE
.............................................................................................................................................. 101 
 
DETERMINATION 
OF 
DISTANCE 
SPHEROCYLINDRICAL 
REFRACTIONS .................................................................................................................. 107 
, BIOMICROSCOPY SCALE ............................................................................ 114 
 DISTANCE AND NEAR VISUAL ACUITY EVALUATION ....................... 120 
 PATIENT REPORTED OUTCOMES ............................................................. 125 
WHITE LIGHT LENS SURFACE WETTABILITY ....................................... 127 
APPENDIX E: JJVC IRIS COLOR SCALE ....................................................................... 129 
APPENDIX F: STARTING CONTACT LENS POWER GUIDELINE ............................ 130 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE ....................... 131 
 
TABLE OF CONTENTS  
Figure 1: Study Flowchart ..................................................................................................... 13 
 
TABLE OF CONTENTS  
Table 1: Test Articles ............................................................................................................. 24 
Table 2: Ancillary Supplies ................................................................................................... 25 
Table 3: Time and Events ...................................................................................................... 27 
 
 
 
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PROTOCOL TITLE, NUMBER, VERSION 
Title: Contact Lenses with New UV-blocker Manufactured with Different Techniques 
Protocol Number:  CR-6140 
Version: 2.0, amendment 1 
Date: 07 February 2018 
SPONSOR NAME AND ADDRESS 
Johnson & Johnson Vision Care (JJVC) 
7500 Centurion Parkway  
Jacksonville, FL 32256 
MEDICAL MONITOR 
Name:  John R. Buch, O.D., M.S. 
Title:  Principal Research Optometrist 
Address:  7500 Centurion Parkway, Suite 100, Jacksonville, FL 32256 
 
Email:  jbuch@its.jnj.com 
 
 
The Medical Monitor must be notified by the clinical institution/site by e-mail, fax, or 
telephone within 24 hours of learning of a Serious Adverse Event. The Medical Monitor may 
be contacted during business hours for adverse event questions. General study related 
questions should be directed towards your assigned clinical research associate. 
 
The Medical Monitoring Plan is maintained as a separate document and included in the Trial 
Master File. 
 
 
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AUTHORIZED SIGNATURES 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all stipulations 
of the protocol, including all statements regarding confidentiality, and according to local legal 
and regulatory requirements and applicable U.S. federal regulations4, ICH guidelines2, ISO 
141551,  and the Declaration of Helsinki3.  
 
 
 
Author 
See Electronic Signature Report  
 
 
 
John R. Buch, O.D., M.S., F.A.A.O. 
Principal Research Optometrist 
 
DATE 
 
Clinical Operations 
Manager 
 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
Biostatistician 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
Data Management  
See Electronic Signature Report 
 
 
 
 
 
 
 
 
 
 
 
DATE 
 
Biostatistician 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
 
Reviewer 
 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
Approver 
See Electronic Signature Report 
 
 
 
 
 
 
DATE 
 
 
 
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Study Endpoints 
Primary Endpoint(s):  
The primary endpoints are overall quality of vision and 
overall comfort scores using 
 
 
 
Other observation(s):  
Other endpoints are being evaluated chiefly to design future 
studies. 
1. Outdoor Performance 
• 
Ability to see comfortably in bright sunlight 
• 
Reduction in glare in bright sunlight 
• 
Reduction in squinting in bright sunlight 
• 
Reduction in eye strain in bright sunlight 
• 
Reduction in glare while driving during the day 
• 
Reduction in glare while driving during the night 
2. Indoor Performance 
• 
Reduction in Squinting while working on the 
computer 
• 
Reduction in glare from the computer screen 
• 
Reduction in glare caused by bright indoor lights 
• 
Reduction in glare caused by bright light coming 
through the window 
3. CLUE handling 
4. Rate of Grade 3 or higher slit lamp findings. 
Study Design 
This study is a randomized, 4-visit, double-masked, 2x3 
bilateral crossover, dispensing trial.  The study lenses will be 
worn as daily wear (DW) for a period of two weeks each 
with one of the study lenses being worn twice.  Each study 
lens is expected to be worn at least five (5) days per week 
for at least six (6) hours per day worn.  There will be no 
washout period between study lenses. 
See the flow chart at the end of the synopsis table for the 
schematic of the study visits and procedures of main 
observations 
Sample Size 
Approximately 90 eligible subjects will be enrolled and 
randomized into the study.  Approximately 80 subjects are 
targeted to complete the study.  A replacement subject may 
be enrolled if a subject discontinues from the study 
prematurely; the decision whether to enroll replacement 
subjects will be made by the joint agreement of the 
Investigator and Sponsor 
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Study Duration 
Subjects will wear the Test and Control lenses for two weeks 
each in random order with one of the study lenses being 
worn twice for a total of 6 weeks per subject.  The 
enrollment will be 2 weeks, making the entire study 
approximately 8 weeks in duration. 
Anticipated Study 
Population 
The subject is a current spherical soft contact lens wearer 
(defined as a minimum of 6 hours of DW per day, at least 5 
days per week, for a minimum of 1 month prior to the study) 
and willing to wear the study lenses on a similar basis.  
Subjects must be age 18 and older. 
Eligibility Criteria 
(Inclusion Criteria) 
Eligibility Criteria:  
Potential subjects must satisfy all of the following inclusion 
criteria to be enrolled in the study: 
1. The subject must read, understand, and sign the 
STATEMENT OF INFORMED CONSENT and 
receive a fully executed copy of the form. 
2. Appear able and willing to adhere to the instructions 
set forth in this clinical protocol. 
3. Healthy adult males or females age 18 years of age 
with signed informed consent. 
4. Eligible presbyopes will be those that wear full 
distance contact lenses in both eyes, then wear reading 
glasses over them. 
5. The subject is a current spherical soft contact lens 
wearer (defined as a minimum of 6 hours of DW per 
day, at least 5 days per week, for a minimum of 1 
month prior to the study) and willing to wear the study 
lenses on a similar basis. 
6. Subjects must be able and willing to wear the study 
lenses at least 6 hours a day, a minimum of 5 days per 
week. 
7. The subject’s vertex-corrected spherical equivalent 
distance refraction must be in the range of -1.00 to -
6.00 (inclusive) in each eye. 
8. The subject’s refractive cylinder must be  -1.00 D in 
each eye. 
9. Have spherocylindrical best corrected visual acuity of 
20/25+3 or better in each eye. 
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Eligibility Criteria 
(Exclusion Criteria) 
 
Potential subjects who meet any of the following criteria will 
be excluded from participating in the study:  
1. Currently pregnant or lactating. 
2. Any active or ongoing systemic disease (e.g., 
Sjögren’s Syndrome), allergies, infectious disease 
(e.g., 
hepatitis, 
tuberculosis), 
contagious 
immunosuppressive diseases (e.g., HIV), autoimmune 
disease (e.g. rheumatoid arthritis), or other bodily 
diseases or infections, by self-report, which are known 
to interfere with contact lens wear and/or participation 
in the study. 
3. Use of systemic medications (e.g., chronic steroid use) 
that are known to interfere with contact lens wear.  
Habitual medications taken by successful contact lens 
wearers are generally considered acceptable. 
4. Habitual toric, extended wear, or multifocal contact 
lens wear. 
5. Any current use of ocular medication. 
6. Any known hypersensitivity or allergic reaction to 
Optifree PureMoist. 
7. Any previous, or planned (during the course of the 
study) ocular surgery (e.g., radial keratotomy, PRK, 
LASIK, etc.). 
8. Participation in any contact lens or lens care product 
clinical trial within 14 days prior to study enrollment. 
9. Employee or immediate family member of an 
employee 
of 
clinical 
site 
(e.g., 
Investigator, 
Coordinator, Technician). 
10. Any active or ongoing ocular allergies, infections or 
other ocular abnormalities that are known to interfere 
with contact lens wear and/or participation in the 
study. This may include, but not be limited to 
entropion, ectropion, extrusions, chalazia, recurrent 
styes, glaucoma, history of recurrent corneal erosions, 
aphakia, or corneal distortion. 
11. Any Grade 3 or greater slit lamp findings (e.g., edema, 
corneal neovascularization, corneal staining, tarsal 
abnormalities, conjunctival injection) on the FDA slit-
lamp scale.  
12. Binocular vision abnormality or strabismus.  
13. Any previous history or signs of a contact lens-related 
corneal inflammatory event (e.g., past peripheral ulcer 
or round peripheral scar), or any other ocular 
abnormality that would contraindicate contact lens 
wear. 
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Disallowed 
Medications/Interventions  
Use of any prescription or over-the-counter (OTC) 
medications that may affect contact lens wear from 24 hours 
prior to receiving the study product through the study period 
of  6 weeks.  Habitual medications taken by successful soft 
contact lens wearers are considered acceptable.  Note that 
habitual medications should be taken throughout the study 
period. 
Measurements and 
Procedures 
Subjective assessments, physiological responses, fitting 
characteristics. 
Microbiology or Other 
Laboratory Testing 
None  
Study Termination 
The occurrence of one or more Unanticipated Adverse 
Device Effect (UADE), or any SAE where relationship to 
study agent cannot be ruled out, will result in stopping 
further dispensing investigational product for further 
investigation.  In the event of a UADE or SAE, the Sponsor 
Medical Monitor may unmask the treatment regimen of 
subject(s) and may discuss this with the Principal 
Investigator before any further subjects are enrolled. 
Ancillary Supplies/ Study-
Specific Materials 
Opti-Free PureMoist,  Preservative-free rewetting 
drops/artificial tears 
Principal Investigator(s) 
and Study 
Institution(s)/Site(s) 
A full list of Principal Investigators, clinical sites, and 
institutions is kept separately from the Study Protocol and is 
included in the study Trial Master File.   
 
 
 
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COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADD  
 
Plus Power Required for Near Use 
ADE  
 
Adverse Device Effect 
AE 
 
 
Adverse Event/Adverse Experience 
BCVA  
 
Best Corrected Visual Acuity 
BSCVA 
 
Best Spectacle Corrected Visual Acuity 
CFR 
 
 
Code of Federal Regulations 
CLUE  
 
Contact Lens User Experience 
COAS  
 
Complete Ophthalmic Analysis System 
COM  
 
Clinical Operations Manager 
CRA  
 
Clinical Research Associate 
CRF 
 
 
Case Report Form 
CRO  
 
Contract Research Organization 
CT 
 
 
Center Thickness 
CTP 
 
 
Clinical Technical Procedure 
D 
 
 
Diopter 
DMC  
 
Data Monitoring Committee 
eCRF  
 
Electronic Case Report Form 
EDC  
 
Electronic Data Capture 
ETDRS 
 
Early Treatment Diabetic Retinopathy Study 
FDA  
 
Food and Drug Administration 
GCP  
 
Good Clinical Practice 
HIPAA 
 
Health Insurance Portability and Accountability Act 
IB 
 
 
Investigator’s Brochure 
ICF 
 
 
Informed Consent Form 
ICH 
 
 
International Conference on Harmonization 
IDE 
 
 
Investigational Device Exemption 
IEC 
 
 
Independent Ethics Committee 
IRB 
 
 
Institutional Review Board 
ISO 
 
 
International Organization for Standardization 
ITT 
 
 
Intent-to-Treat 
JJVC  
 
Johnson & Johnson Vision Care, Inc. 
LC 
 
 
Limbus Center 
LogMAR 
 
Logarithm of Minimal Angle of Resolution 
MedDRA© 
 
Medical Dictionary for Regulatory Activities 
MOP  
 
Manual of Procedures 
NIH 
 
 
National Institutes of Health 
OD 
 
 
Right Eye 
OHRP  
 
Office for Human Research Protections 
OHSR  
 
Office for Human Subjects Research 
OS 
 
 
Left Eye 
OU 
 
 
Both Eyes 
PD 
 
 
Protocol Deviation 
PHI 
 
 
Protected Health Information 
PI 
 
 
Principal Investigator 
PIG 
 
 
Patient Instruction Guide 
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PQC  
 
Product Quality Complaint 
PRO  
 
Patient Reported Outcome 
QA 
 
 
Quality Assurance 
QC 
 
 
Quality Control 
SAE 
 
 
Serious Adverse Event/Serious Adverse Experience 
SAP 
 
 
Statistical Analysis Plan 
SAS 
 
 
Statistical Analysis System 
SD 
 
 
Standard Deviation 
SOP 
 
 
Standard Operating Procedure 
UADE  
 
Unanticipated Adverse Device Effect 
USADE 
 
Unanticipated Serious Adverse Device Effect 
VA 
 
 
Visual Acuity 
1. INTRODUCTION AND BACKGROUND 
Curing is the process used in manufacturing of contact lenses that solidifies the monomer into 
a lens shape.  Curing is achieved at JJVC by the use of special lights assembled in a light 
tunnel within the manufacturing line.  Historically, the lights have varied in intensity 
throughout the tunnel.  It is unknown what happens if the manufacturing line stalls and the 
lens is exposed to a static curing process.  A static curing process is also a more robust process 
and is therefore desirable provided similar clinical performance to a variable intensity process. 
 
The present study is designed to demonstrate non-inferiority of the Test lens (static-curing 
process) compared to the Control lens (step-curing process) with respect to 
 comfort 
and quality of vision. 
1.1. Name and Descriptions of Investigational Products  
This study will evaluate two senofilcon-based contact lenses containing a new UV-blocker.  
Both lenses are investigational.  
 
 they will serve as the Control lens while the lenses 
manufactured with static-curing will serve as the Test lens. 
1.2. Intended Use of Investigational Products 
The intended use of the investigative product in this study is for correcting myopia and 
providing visual benefits in bright lighting situations. During the study, each test article will 
be worn bilaterally in a daily wear modality for at least 6 hours per day and 5 days per week 
for approximately two weeks each. The subject will wear either the test or control article twice 
and the other study article once. 
1.3. Summary of Findings from Nonclinical Studies 
All previous pre-clinical findings were deemed satisfactory prior to proceeding with clinical 
trials on humans.  For the most comprehensive nonclinical information regarding senofilcon 
A with new UV-blocker, refer to the latest version of the Investigator’s Brochure. 
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5 Morse, R. S. (1985, October). Glare filter preference: influence of subjective and 
objective indices of glare, sharpness, brightness, contrast and color. In Proceedings of 
the Human Factors and Ergonomics Society Annual Meeting (Vol. 29, No. 8, pp. 782-
786). SAGE Publications. 
6 Pérez-Carrasco, M. J., Puell, M. C., Sánchez-Ramos, C., López-Castro, A., & Langa, 
A. (2005). Effect of a yellow filter on contrast sensitivity and disability glare after 
laser in situ keratomileusis under mesopic and photopic conditions. Journal of 
Refractive Surgery, 21(2), 158-165. 
7 Sheedy, J. E., Hayes, J., & ENGLE, J. (2003). Is all asthenopia the same? Optometry 
& Vision Science, 80(11), 732-739. 
8 Steen, R., Whitaker, D., Elliott, D. B., & Wild, J. M. (1994). Age-related effects of 
glare on luminance and color contrast sensitivity. Optometry & Vision Science, 
71(12), 792-796. 
9 Vincent, A. J., Spierings, E. L., & Messinger, H. B. (1989). A controlled study of 
visual symptoms and eye strain factors in chronic headache. Headache: The Journal 
of Head and Face Pain, 29(8), 523-527. 
10 Wilkins, A. J., & Evans, B. J. (2010). Visual stress, its treatment with spectral filters, 
and its relationship to visually induced motion sickness. Applied Ergonomics, 41(4), 
509-515. 
2. STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES 
2.1. Objectives  
Primary Objective(s) 
The primary objective of this study is to compare the clinical performance of two study 
contact lenses using different curing techniques with respect to CLUE comfort and vision. 
 
Other Objectives(s) 
Other objectives of this study are to compare the clinical performance of two study contact 
lenses using different curing techniques with respect to driving, indoor and outdoor 
performance items, CLUE handling and the rate of Grade 3 or higher slit lamp findings. 
2.2. Endpoints  
Primary Endpoint(s) 
CLUE Comfort and Vision 
The primary endpoints are overall quality of vision and overall comfort scores using Contact 
Lens User Experience (CLUE)™ questionnaire at the two-week follow-up.  CLUE is a 
validated patient-reported outcomes questionnaire to assess patient-experience attributes of 
soft, disposable contact lenses (comfort, vision, handling, and packaging) in a contact-lens 
wearing population in the US, ages 18-65. Scores follow a normal distribution with a 
population average score of 60 (SD 20), where higher scores indicate a more 
favorable/positive response.  
 
 
 
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Other Observation(s)  
Other endpoints are being evaluated chiefly to design future studies. 
1. Driving Performance   
Driving performance will be assessed by two individual patient reported outcome (PRO) 
questions at the 2-week follow-up evaluation. The individual items are as follows: 
 
A. Reduction in glare while driving during the day (Item ID:  MIS00617)  
B. Reduction in glare while driving during the night (Item ID: MIS00618)  
 
2. Indoor Performance  
Indoor performance will be assessed by three individual patient reported outcome (PRO) 
questions at the 2-week follow-up evaluation. The individual items are as follows: 
 
A. Reduction in glare from the computer screen (Item ID: MIS00628) 
B. Reduction in glare caused by bright indoor lights (Item ID: MIS00625) 
C. Reduction in glare caused by bright light coming through the window (Item ID: 
MIS00626) 
 
3. Outdoor Performance  
Outdoor performance will be assessed by four individual patient reported outcome (PRO) 
questions at the 2-week follow-up evaluation. The individual items are as follows: 
 
A. Ability to see comfortably in bright sunlight (Item ID: MIS00613) 
B. Reduction in glare in bright sunlight (Item ID: MIS00614) 
C. Reduction in squinting in bright sunlight (Item ID: MIS00615) 
D. Reduction in eye strain in bright sunlight (Item ID: MIS00616) 
 
All driving, indoor and outdoor (PRO) items above will be assessed using the same excellence 
scale of; 0: Not Applicable, 1: Excellent, 2: Very Good, 3: Good, 4: Fair and 5: Poor.  
 
4. CLUE Handling 
Handling scores will be assessed by using Contact Lens User Experience (CLUE)™ 
questionnaire at the two-week follow-up.   
 
5. Physiological Response assessed at each visit. 
 
 
 
 
 
 
 
 
 
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2.3. Hypotheses 
Primary Hypotheses 
Primary Hypotheses 
Endpoint 
Hypothesis 
Overall CLUE Vision 
The test lens will be non-inferior to the control lens at the 
2-week follow-up with respect to CLUE overall quality of 
vision.  A non-inferiority margin of -5 points will be used. 
Overall CLUE Comfort 
The test lens will be non-inferior to the control lens at the 
2-week follow-up with respect to CLUE overall comfort.  A 
non-inferiority margin of -5 points will be used. 
 
Both Primary hypotheses must be met for this study to be considered successful. 
 
Other Hypotheses 
Other Hypotheses 
Endpoint 
Hypothesis 
Outdoor Performance 
Measures 
The test lens will be superior to the control lens in at least 2 of 
the following 4 outdoor performance measure(s) at the 2-week 
follow-up. An odds ratio margin of 1 will be used.  
1. Ability to see comfortably in bright sunlight 
2. Reduction in glare in bright sunlight 
3. Reduction in squinting in bright sunlight 
4. Reduction in eye strain in bright sunlight 
Driving Performance 
Metrics 
The test lens will be non-inferior to the control lens in both of 
the following driving performance metrics at the 2-week 
follow-up.  An odds ratio margin of 0.67 will be used. 
1. Reduction in glare while driving during the day 
2. Reduction in glare while driving during the night 
Indoor Performance 
Measures 
The test lens will be superior to the control lens in at least 2 of 
the following 4 outdoor performance measure(s) at the 2-week 
follow-up.  An odds ratio margin of 1 will be used.  
1. Reduction in squinting while working on the computer 
2. Reduction in glare from the computer screen 
3. Reduction in glare caused by bright indoor lights 
4. Reduction in glare caused by bright light coming 
through the window 
CLUE Handling 
CLUE handling of the step-cure and static cure lenses will be 
no different from each other. 
Physiological Response Physiological responses of the step-cure and static cure lenses 
will be no different from each other. 
 
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3. TARGETED STUDY POPULATION 
3.1. General Characteristics  
Approximately 90 subjects will be enrolled to ensure that at least 80 subjects will complete 
the study.  Enrolled subjects will be habitual wearers of spherical contact lenses.  All subjects 
will be the age of 18 or older.  Eligible presbyopes will be those that wear full distance contact 
lenses in both eyes, then wear reading glasses over them.  Subjects will wear the test and 
control contact lenses approximately two weeks each on a daily wear (DW) basis, then wear 
either the test or control lens again for two weeks, for a total study duration of approximately 
42 days (6 weeks) per subject.   
3.2. Inclusion Criteria 
Potential subjects must satisfy all of the following criteria to be enrolled in the study: 
  
Inclusion Criteria after Screening 
  
1. The subject must read, understand, and sign the STATEMENT OF INFORMED 
CONSENT and receive a fully executed copy of the form. 
2. Appear able and willing to adhere to the instructions set forth in this clinical protocol. 
3. Healthy adult males or females age 18 years of age with signed informed consent. 
4. Eligible presbyopes will be those that wear full distance contact lenses in both eyes, 
then wear reading glasses over them. 
5. The subject is a current spherical soft contact lens wearer (defined as a minimum of 
6 hours of DW per day, at least 5 days per week, for a minimum of 1 month prior to 
the study) and willing to wear the study lenses on a similar basis. 
6. Subjects must be able and willing to wear the study lenses at least 6 hours a day, a 
minimum of 5 days per week. 
 
Inclusion Criteria after Baseline 
 
7. The subject’s vertex-corrected spherical equivalent distance refraction must be in the 
range of -1.00 to -6.00 (inclusive) in each eye. 
8. The subject’s refractive cylinder must be  -1.00 D in each eye. 
9. Have spherocylindrical best corrected visual acuity of 20/25+3 or better in each eye. 
3.3. Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from participating 
in the study:  
 
Exclusion Criteria after Screening: 
 
1. Currently pregnant or lactating. 
2. Any active or ongoing systemic disease (e.g., Sjögren’s Syndrome), allergies, 
infectious disease (e.g., hepatitis, tuberculosis), contagious immunosuppressive 
diseases (e.g., HIV), autoimmune disease (e.g. rheumatoid arthritis), or other bodily 
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diseases or infections, by self-report, which are known to interfere with contact lens 
wear and/or participation in the study. 
3. Use of systemic medications (e.g., chronic steroid use) that are known to interfere with 
contact lens wear.  Habitual medications taken by successful contact lens wearers are 
generally considered acceptable. 
4. Habitual toric, extended wear, or multifocal contact lens wear. 
5. Any current use of ocular medication. 
6. Any known hypersensitivity or allergic reaction to Optifree PureMoist. 
7. Any previous, or planned (during the course of the study) ocular surgery (e.g., radial 
keratotomy, PRK, LASIK, etc.). 
8. Participation in any contact lens or lens care product clinical trial within 14 days prior 
to study enrollment. 
9. Employee or immediate family member of an employee of clinical site (e.g., 
Investigator, Coordinator, Technician). 
 
Exclusion Criteria after Baseline 
 
10. Any active or ongoing ocular allergies, infections or other ocular abnormalities that 
are known to interfere with contact lens wear and/or participation in the study. This 
may include, but not be limited to entropion, ectropion, extrusions, chalazia, recurrent 
styes, glaucoma, history of recurrent corneal erosions, aphakia, or corneal distortion. 
11. Any Grade 3 or greater slit lamp findings (e.g., edema, corneal neovascularization, 
corneal staining, tarsal abnormalities, conjunctival injection) on the FDA slit-lamp 
scale.  
12. Binocular vision abnormality or strabismus.  
13. Any previous history or signs of a contact lens-related corneal inflammatory event 
(e.g., past peripheral ulcer or round peripheral scar), or any other ocular abnormality 
that would contraindicate contact lens wear. 
3.4. Enrollment Strategy 
Study subjects will be recruited from the Institution/clinical site’s subject database and/or 
utilizing Independent Ethics Committee (IEC) or Institutional Review Board (IRB) approved 
materials. 
4. STUDY DESIGN AND RATIONALE 
4.1. Description of Study Design 
This study is a randomized, 4-visit, double-masked, 2x3 bilateral crossover, dispensing trial.  
Approximately 90 subjects will be screened and enrolled to ensure that at least 80 subjects to 
complete. 
 
The study begins with an initial visit (Visit 1). If a subject is found to meet all eligibility 
criteria, they will be random to one of two lens wear sequences (Test/Control/Control or 
Control/Test/Test).  
 
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If the subject is dispensed study lenses at the initial visit, 3 follow-up visits will be conducted. 
The follow-up visits occur approximately 2, 4 and 6 weeks after the initial visit. Unscheduled 
follow-up visits may occur during the study. Subjects will be advised to wear the study lenses 
at least five (5) days per week for at least six (6) hours per day for a period of two weeks each. 
Lens replacement is scheduled at 2 and 4-week follow-up visits.  
4.2. Study Design Rationale 
Crossover designs are a well-established study design in which subjects are exposed to 
multiple treatments during different time periods. This design was considered since the study 
period is relatively short the design can be cost effective and more efficient comparisons 
between treatments can be made than compared a parallel study since fewer subjects are 
required to achieve the same pre-specified statistical power. 
 
 
 
 
 
 
 Therefore, this study utilizes a high order 3-period by 
2-treatment crossover design to estimate the true effect of the Test lens without any potential 
bias from the carry-over effect. 
4.3. Enrollment Target and Study Duration 
Approximately 90 subjects will be enrolled to ensure that at least 80 subjects will complete 
the study.  Enrolled subjects will be habitual wearers of spherical contact lenses.  All subjects 
will be the age of 18 or older.  Eligible presbyopes will be those that wear full distance contact 
lenses in both eyes, then wear reading glasses over them.  Subjects will wear the Test and 
Control contact lenses approximately two weeks each on a daily wear (DW) basis, then wear 
either the Test or Control lens again for two weeks, for a total study duration of approximately 
42 days (6 weeks) per subject. 
5. TEST ARTICLE ALLOCATION AND MASKING 
5.1. Test Article Allocation  
Use of the test articles will be randomized using a randomization scheme supplied by the 
study biostatistician. 
 
This is a multi-site, double-masked, dispensing and randomized study.  The study lenses will 
be worn in a bilateral and random fashion using a 2 treatment by 3 period (2x3) crossover 
design.  
 
A block size of two (2) sequences will be utilized. A computer-generated randomization 
scheme will be used to randomly assign subjects, in blocks of 2, to one of the two possible 
lens wear sequences (TEST/CONTROL/CONTROL or CONTROL/TEST/TEST). The 
random scheme will be generated by site using the PROC PLAN procedure from SAS 
Software Version 9.4 or higher (SAS Institute, Cary, NC).  
 
The study site must follow the randomization scheme provided and complete enrollment 
according to the randomization list and not pre-select or assign subjects. The randomized 
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assignment of subjects will be performed at the first visit prior to the first fitting. 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 has been collected. 
5.2. Masking 
Both test lenses will contain the same new UV-blocker.  Therefore, double-masking is 
possible and will be used to keep both the subject and investigators masked to the identity of 
the study lenses throughout the duration of the study period. Every attempt will be made to 
keep the other clinical trial personnel involved in the study (e.g. Data management and 
Biostatistician) unaware of the identity of the study lenses. 
 
The identity of the study lenses will be masked by over labeling the blister packs with a label 
containing the study number, lot number, sphere power, expiration date and the randomization 
codes P or W. Only the personnel involved in the over labeling and the unmasked statistician 
will have access to the lens decode information translating the randomization codes into test 
and control groups. The medical monitor will also have access to the decode information in 
case breaking the mask is necessary for the urgent medical treatment of a subject.  
 
Masking will be used to reduce potential bias. Subjects will be unaware of the identity of the 
investigational product.  Investigators and clinical site personnel involved in the data 
collection will be masked as to the identity of the investigational product. 
 
Under normal circumstances, the mask should not be broken until all subjects have completed 
the study and the database is finalized. Otherwise, the mask should be broken only if specific 
emergency treatment/course of action would be dictated by knowing the treatment status of 
the subject. In such cases, the Investigator may, in an emergency, contact the medical monitor.  
In the event the mask is broken, the Sponsor must be informed as soon as possible. The date, 
time, and reason for the unmasking must be documented in the subject record. The 
Investigator is also advised not to reveal the study treatment assignment to the clinical site or 
Sponsor personnel.  
 
Subjects who have had their treatment assignment unmasked are expected to return for all 
remaining scheduled evaluations.  Subjects who are discontinued will be replaced. 
5.3. Procedures for Maintaining and Breaking the Masking 
The test articles mask shall not be broken unless information concerning the lens type is 
necessary for the urgent medical treatment of a subject.  The Sponsor must be notified before 
the mask is broken. 
 
When dispensing test articles, the following steps should be followed to maintain 
randomization codes: 
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6.5. Storage Conditions 
All worn study lenses will be collected from the subject, placed in labeled glass vials with 
Opti-Free® Puremoist®, and stored refrigerated or frozen until they are shipped back to the 
Sponsor.  The lenses will be shipped in special containers to keep the lenses refrigerated. 
 
When possible, any lens or test article associated with an Adverse Events and/or a Product 
Quality Complaint must be retained and stored in a glass vial with moderate solution pending 
directions from the sponsor for potential return back to JJVC. 
All worn study lenses will be collected from the subject, placed in labeled glass vials with 
Opti-Free® Puremoist®, and stored refrigerated or frozen until they are shipped back to the 
Sponsor.  The lenses will be shipped in special containers to keep the lenses refrigerated. 
 
When possible, any lens or test article associated with an Adverse Events and/or a Product 
Quality Complaint must be retained and stored in a glass vial with moderate solution pending 
directions from the sponsor for potential return back to JJVC. 
6.6. Collection and Storage of Samples 
All worn lenses will be collected and stored in a labeled vial.  The lenses will be stored cold 
at the investigational site and shipped back to JJVC cold for lab testing. 
 
When possible, any lens or test article associated with an Adverse Events and/or a Product 
Quality Complaint must be retained and stored in a glass vial with moderate solution pending 
directions from the sponsor for potential return back to JJVC. 
6.7. Accountability of Test Articles 
JJVC will provide the Investigator with sufficient quantities of study articles and supplies to 
complete the investigation.  The Investigator is asked to retain all lens shipment 
documentation for the test article accountability records.  
 
Test article must be kept in a locked storage cabinet, accessible only to those assigned by the 
Investigator for dispensing. The Investigator may delegate this activity to authorized study 
site personnel listed on the Site Delegation Log.  All test articles must be accounted.  This 
includes: 
 
1. What was dispensed for the subject for trial fitting, to wear out of the office, or issued 
for the subject to replace appropriately between visits  
2. What was returned to the Investigator unused 
3. The number and reason for unplanned replacements   
 
The Investigator will collect all unused test articles from the subjects at the end of the subject’s 
participation. Subject returned unused test articles must be separated from the clinical study 
inventory of un-dispensed test articles, and must be labeled with the subject number and date 
of return.  Following final reconciliation of test articles by the monitor, the Investigator or 
monitor will return all unused test articles to JJVC. 
 
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If there is a discrepancy between the shipment documents and the contents, contact the study 
monitor immediately. 
 
 
  
 
 
7. STUDY EVALUATIONS  
7.1. Time and Event Schedule 
Table 3: Time and Events 
Procedure 
Baseline 
Trial Fit & 
Dispense 
Follow-up 
Unsched Exit 
Visit 
1 
1, 2, 3 
2, 3, 4 
PRN 
4 
Visit Window 
- 
- 
13-15 
Days 
- 
- 
Informed consent 
 
- 
- 
- 
- 
Eligibility screening 
 
- 
- 
- 
- 
CLUE Baseline Questionnaire 
 
- 
- 
- 
- 
GSI Background Questionnaire 
 
 
 
 
 
Other Questionnaires 
 
- 
- 
- 
- 
Subject demographics 
 
- 
- 
- 
- 
General health and medication 
history 
 
- 
- 
- 
- 
Subject’s own contact lens 
information 
 
- 
- 
- 
- 
Habitual lens care 
 
- 
- 
- 
- 
Entrance visual acuity  
 
- 
- 
- 
- 
Spherocylindrical refraction 
and BVA 
 
- 
- 
 
 
Slit lamp biomicroscopy 
 
- 
 
 
- 
Expanded Conjunctival 
Redness 
 
- 
 
 
- 
Expanded Corneal Staining 
 
- 
 
 
- 
Trial fitting lens information 
- 
 
- 
- 
- 
Lens Damage 
- 
 
- 
- 
- 
Distance spherical over-
refraction 
- 
 
 
- 
- 
Lens modification 
- 
 
- 
- 
- 
Visual acuity 
- 
 
 
 
- 
Lens fitting assessment 
- 
 
 
* 
- 
Lens wettability 
- 
 
 
* 
- 
Lens dispensing information 
and criteria 
- 
 
- 
- 
- 
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7.4. Laboratory Procedures  
The optical bench will be used to measure the light transmission characteristics for all worn 
Test lenses.  The findings are for internal information only and will not be part of the final 
report.  
8. SUBJECTS COMPLETION/WITHDRAWAL  
8.1. Completion Criteria 
Subjects are considered to have completed the study if they:  
• provided informed consent 
• completed all scheduled visits 
8.2. Withdrawal/Discontinuation from the Study 
A subject will be withdrawn from the study for any of the following reasons: 
• Subject death during the study period 
• Subject withdrawal of consent 
• Subject not compliant to protocol (e.g. Subject more than 2 days out of visit window). 
• Subject lost to follow-up  
• Subject no longer meets eligibility criteria (e.g. the subject becomes pregnant) 
• Subject develops significant or serious adverse events causing discontinuation of 
study lens wear (subjects missing more than 2 days of missed lens wear within a period 
1 of week should be discontinued)  
• Subjects who have experienced a Corneal Infiltrative Event (CIE) 
• Investigator’s clinical judgment regarding the subject safety reasons (that it is in the 
best interest of the subject to stop treatment) 
• Subject missed any scheduled study visits  
• Subject not compliant with study lens wear schedule  
• Subject not successfully dispensed due to lack of efficacy and safety including poor 
vision, poor comfort or unacceptable fit 
 
For discontinued subjects, the Investigator will: 
• Complete the current visit (scheduled or unscheduled) 
• Complete the Final Evaluation, indicating the reason that the subject was discontinued 
from the study 
• Record the spherocylindrical refraction with best corrected distance visual acuity  
• Collect used test article(s) (worn or brought to the visit) from the subject and discard 
them, unless otherwise stated in Section 7.2 
• Collect all unused test article(s) from the subject 
 
An additional subject will be enrolled if a subject discontinues from the study prematurely.  
 
In cases where a subject is lost to follow-up, every possible effort must be made to contact 
the subject and determine the reason for discontinuation/withdrawal.  The measures taken to 
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follow up must be documented including two written attempts and a certified letter (or 
equivalent) as the final attempt.  
9. PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION 
Concomitant medications will be documented during screening and updated during the study.  
Disallowed medications for this study include:  see Section 3.3.   
Concomitant therapies that are disallowed include:  see Section 3.3. 
10. DEVIATIONS FROM THE PROTOCOL 
Investigator will notify study sponsor upon identification of a protocol deviation. Major 
protocol deviations must be reported to the sponsor within 24 hours after discovery of the 
protocol deviation.  The Investigator will report deviations per IRB/IEC requirements.  All 
deviations will be tracked and corrective actions implemented as appropriate.  
 
If it becomes necessary for the Investigator to implement a deviation in order to eliminate an 
immediate hazard to the trial subject, the Investigator may implement the deviation 
immediately without notification to the sponsor. Within 24 hours after the implemented 
deviation, the Investigator must notify and provide the rationale to the Sponsor and, as 
required, the IEC/IRB.  
11. STUDY TERMINATION 
The occurrence of one or more Unanticipated Serious Adverse Device Effect (USADE), or 
any SAE where the relationship to study agent cannot be ruled out, may result in stopping 
further dispensing of test article.  In the event of a USADE or SAE, the Sponsor may unmask 
the treatment regimen for the subject(s) and will discuss this with the Investigator before any 
further subjects are enrolled. 
 
The Sponsor will determine when a study will be stopped.  The Principal Investigator always 
has the discretion to initiate stopping the study based on patient safety or if information 
indicates the study’s results are compromised. 
 
JJVC reserves the right to terminate the study at any time for any reason.  Additionally, the 
IEC/IRB reserves the right to terminate the study if an unreasonable risk is determined.  The 
study can be terminated by the Principal Investigator at the individual clinical site due to 
specific clinical observations, if in their opinion, after a discussion with JJVC, it is determined 
that it would be unwise to continue at the clinical site.    
 
JJVC (and the IEC/IRB and DMC, if applicable) will evaluate all adverse events.  If it is 
determined that an adverse event presents an unreasonable risk, the investigation, or that part 
of the investigation presenting the risk, will be terminated, as soon as possible. 
 
Should the study be terminated (either prematurely or as scheduled), the Investigator will 
notify the IEC/IRB and Regulatory Authority as required by local regulatory requirements. 
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12. PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS 
A Product Quality Complaint (PQC) refers to any written, electronic, or oral communication 
that alleges deficiencies related to the identity, quality, durability, reliability, safety, 
effectiveness or performance of test articles after they have been released for clinical trial use.   
 
Potential complaints may come from a variety of sources including but not limited to subjects, 
clinical research associates (CRA), clinical operations managers (COM), medical monitors, 
and site personnel, etc. The following are not considered product quality complaints: 
• Subject satisfaction inquiries reported via “Subjective Questionnaires” and “Patient 
Reported Outcomes (PRO)” 
• Clinical test articles that are stored improperly or damaged after receipt at the 
investigational site 
• Lens replacements that occur due to drops/fall-outs 
• Damage deemed by clinicians or clinical staff to be caused by handling by the user, 
and not indicative of a quality deficiency (i.e. tears, rips, etc.), only in situations where 
there is no deficiency alleged by the subject 
 
Within 24 hours of site personnel becoming aware that a PQC has occurred, the PQC must be 
recorded in the EDC system, which will trigger an automatic email notification to the 
appropriate COM/CRA and Clinical QA representative. In cases where the EDC system in 
use is not configured to send automatic notifications or when an EDC system is not used, the 
COM/CRA is responsible for notifying Clinical QA upon discovery that a PQC has occurred.   
 
Upon receipt of the EDC notification, the COM/CRA will contact the study site to collect 
additional information which will include:  
• Date the complaint was received/recorded in the EDC System (Date of Sponsor 
Awareness) 
• Who received the complaint 
• Study number 
• Clinical site information (contact name, site ID, telephone number) 
• Lot number(s) 
• Unique Subject Identifier(s) 
• Indication of who first observed complaint (site personnel or subject) 
• OD/OS indication, along with whether the lens was inserted 
• Any related AE number if applicable 
• Detailed complaint description (scheduled/unscheduled visit, wear time, symptoms, 
resolution of symptoms, etc.) 
• Eye Care Provider objective (slit lamp) findings if applicable 
• Confirmation of product availability for return (and tracking information, if available), 
or rationale if product is not available for return 
 
 
Once a complaint is received, it will be assessed by the COM, CRA, or trained site personnel 
to determine if it is an Adverse Event/Serious Adverse Event (AE/SAE).  If the complaint 
results in an AE/SAE, the COM/CRA, or trained site personnel will follow Section 13 of this 
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protocol. If the AE/SAE was potentially the result of a product quality related deficiency, 
these procedures also applies and will be executed in parallel.   
 
In some cases, a PQC form may be generated in EDC by the site in error.  In this event, the 
PQC forms will be marked “Intentionally Left Blank” or “ILB”.  Justification for ILB must 
be documented. 
13. ADVERSE EVENTS 
13.1. Definitions and Classifications 
Adverse Event (AE) – 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.  
Note 1 to entry: This definition includes events related to the investigational medical device 
or the comparator. 
Note 2 to entry: This definition includes events related to the procedures involved. 
Note 3 to entry: For users or other persons, this definition is restricted to events related to 
investigational medical devices.”0 
 
An AE includes any condition (including a pre-existing condition) that: 
1. Was not present prior to the study, but appeared or reappeared following initiation of 
the study  
2. Was present prior to the study, but worsened during the study. This would include any 
condition resulting from concomitant illnesses, reactions to concomitant medications, 
or progression of disease states  
3. Pregnancy must be documented as an adverse event and must be reported to the 
clinical monitor and to the Sponsor immediately upon learning of the event 
 
Serious Adverse Event (SAE) – An SAE is any untoward medical occurrence that: 
• Results in death 
• Is life threatening 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity (e.g., a sight threatening event, 
a significant persistent or permanent change, impairment, damage, or disruption to the 
subject’s body) 
• Is a congenital anomaly/birth defect, or 
• Requires intervention to prevent permanent damage (the use of the test article resulting 
in a condition which requires medical or surgical intervention to preclude permanent 
impairment of the body structure or a body function).  Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be 
considered an SAE when, based upon appropriate medical judgment, they may 
jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in the above definition 
 
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Diagnoses and conditions that are considered Ocular Serious Adverse Events include, but not 
limited to: 
• Microbial Keratitis (MK) 
• Iritis (including cells in the anterior chamber) 
• Permanent decrease in best spectacle corrected visual acuity (BSCVA) equivalent to 
2 acuity lines or greater 
• Central Corneal Opacity 
• Central Corneal Neovascularization 
• Uveitis 
• Endophthalmitis 
• Hypopyon 
• Hyphemia 
• Penetration of Bowman’s Membrane 
• Persistent Epithelial Defect 
• Limbal cell Damage leading to Conjunctivalization 
 
Significant Adverse Events – Those events that are usually symptomatic and warrant 
discontinuation (temporary or permanent) of the test article (excluding Serious Adverse 
Events).   
 
Diagnoses and conditions that are considered Ocular Significant Adverse Events include, but 
not limited to the following: 
• Contact Lens Induced Peripheral Ulcer (CLPU) 
• Significant Infiltrative Events (SIE) 
• Superior Epithelial Arcuate Lesions (SEALs) 
• Any Temporary Loss of >2 Lines of BSCVA 
• Other grade 3 or higher corneal findings, such as abrasions or edema 
• Non-contact lens related corneal events - e.g. Epidemic Keratoconjunctivitis (EKC) 
• Asymptomatic Corneal Scar 
• Any corneal event which necessitates temporary lens discontinuation >2 weeks 
 
Non-Significant Adverse Events – Those conditions that are usually asymptomatic and 
usually do not warrant discontinuation (temporary or permanent) of the test article.  However, 
the Investigator may choose to treat as a precautionary measure.   
 
Diagnoses and conditions that are considered Ocular Non-Significant Adverse Events include, 
but not limited to the following: 
• Non-significant Infiltrative Event (NSIE) 
• Contact Lens Papillary Conjunctivitis (CLPC) 
• Superficial Punctate Keratitis (SPK) 
• Conjunctivitis: Bacterial, Viral, Allergic 
• Blepharitis 
• Meibomianitis 
• Contact Dermatitis 
• Localized Allergic Reactions 
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• Any corneal event not explicitly defined as serious or significant adverse event, which 
necessitates temporary lens discontinuation <2 weeks 
 
Adverse Device Effect (ADE) – An ADE is an “adverse event related to the use of an 
investigational medical device. 
Note 1 to entry: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device. 
Note 2 to entry: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device.”0 
 
Unanticipated Adverse Device Effect (UADE) – Any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, the test article, 
if that effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan, Investigator’s Brochure or protocol, or any other 
unanticipated serious problem associated with the test article that relates to the rights, safety 
and welfare of subjects. 
13.2. Assessing Adverse Events 
In conjunction with the medical monitor, the Investigator will evaluate adverse events to 
ensure the events are categorized correctly.  Elements of categorization will include: 
• Seriousness/Classifications (see definition in Section 13.1) 
• Causality or Relatedness – i.e. the relationship between the test article, study treatment 
or study procedures and the adverse event (not related; unlikely related; possibly 
related; related - see definition in Section 13.2.1) 
• Adverse Event Severity – Adverse event severity is used to assess the degree of 
intensity of the adverse event (mild; moderate; severe for all events - see definition in 
Section 0)   
• Outcome – not recovered or not resolved; recovering or resolving; recovered or 
resolved with sequelae; recovered or resolved; death related to adverse event; 
unknown 
• Actions Taken – none; temporarily discontinued; permanently discontinued; other 
13.2.1. Causality Assessment 
Causality Assessment – A determination of the relationship between an adverse event and 
the test article. The test article relationship for each adverse event should be determined by 
the investigator using these explanations: 
• Not Related- An adverse event that is not related to the use of the test article, study 
treatment or study procedures 
• Unlikely Related – An adverse event for which an alternative explanation is more 
likely, e.g. concomitant treatment, concomitant disease(s), or the relationship of time 
suggests that a causal relationship is not likely 
• Possibly Related – An adverse event that might be due to the use of the test article, or 
to the study treatment or study procedures. An alternative explanation, e.g. 
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concomitant treatment, concomitant disease(s), is inconclusive.  The relationship in 
time is reasonable.  Therefore, the causal relationship cannot be excluded 
• Related – An adverse event that is listed as a possible adverse effect (device) or 
adverse reaction (drug) and cannot be reasonably explained by an alternative 
explanation, e.g. concomitant treatment of concomitant disease(s).  The relationship 
in time is very suggestive, e.g. it is confirmed by de-challenge and re-challenge 
13.2.2. Severity Assessment 
Severity Assessment – A qualitative assessment of the degree of intensity of an adverse event 
as determined by the Investigator or reported to him/her by the subject.  The assessment of 
severity is made irrespective of test article, study treatment or study procedure relationship or 
seriousness of the event and should be evaluated according to the following scale: 
• Mild – Event is noticeable to the subject, but is easily tolerated and does not interfere 
with the subject’s daily activities 
• Moderate – Event is bothersome, possible requiring additional therapy, and may 
interfere with the subject’s daily activities 
• Severe – Event is intolerable, necessitates additional therapy or alteration of therapy 
and interferes with the subject’s daily activities 
13.3. Documentation and Follow-Up of Adverse Events 
The recording and documenting of adverse events (ocular and non-ocular) begins when the 
subjects are exposed to the test article, study treatment or study procedure.  Adverse events 
reported before the use of test article, start of study treatment, or study procedures will be 
recorded as medical history. However, if the condition deteriorates at any time during the 
study it will be recorded and reported as an AE. Untoward medical events reported after the 
subject’s exit from the study will be recorded as adverse events at the discretion of the 
Investigator. 
 
Upon finding an adverse event, the Principal Investigator will document the condition in the 
subject record and in the eCRFs. He/she will complete the Adverse Event /eCRF.   
 
Complete descriptions of all adverse events must be available in the subject record. All 
Adverse Events including local and systemic reactions not meeting the criteria for “serious 
adverse events” shall be captured on the appropriate case report form or electronic data 
system. All adverse events occurring while the subject is enrolled in the study must be 
documented appropriately regardless of relationship.   
 
It is the Investigator’s responsibility to maintain documentation of each reported adverse 
event. All adverse events will be followed in accordance with applicable licensing 
requirements.  Such documentation will include the following: 
• Adverse event (diagnosis not symptom) 
• Drawings or photographs (where appropriate) that detail the finding (e.g., size, 
location, and depth, etc.)  
• Date the clinical site was notified  
• Date and time of onset 
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• Date and time of resolution 
• Adverse event classification, severity, and relationship to test articles, as applicable 
• Treatment regimen instituted, including concomitant medications prescribed, in 
accordance with applicable licensing requirements 
• Any referral to another health care provider if needed 
• Outcome, ocular damage (if any) 
• Likely etiology 
• Best corrected visual acuity at the discovery of the event and upon conclusion of the 
event 
 
In addition, if an infiltrate(s) is present, he/she will complete the Corneal Infiltrate Assessment 
eCRF.  Where necessary, a culture of the corneal lesion will be collected to determine if the 
infection is microbial in nature.  If cultures are collected, the date of culture collection and 
laboratory utilized will be recorded.  
 
Changes in the severity of an AE shall be documented to allow an assessment of the duration 
of the event at each level of intensity to be performed.  Adverse events characterized as 
intermittent require documentation of the onset and duration of each episode. Changes in the 
assessment of relationship to the Test Article shall also be clearly documented. 
 
Subjects who present with an adverse event shall be followed by the Investigator, within 
licensure, until all signs and symptoms have returned to pre-treatment status, stabilized, or 
been satisfactorily resolved.  If further treatment beyond licensure is required, the patient will 
be referred to the appropriate health care provider.  The Investigator will use his/her clinical 
judgment as to whether a subject reporting with an adverse event will continue in the study.  
If a subject is discontinued from the study, it will be the responsibility of the Investigator to 
record the reason for discontinuation.  The Investigator will also document the adverse event 
appropriately and complete the Adverse Event eCRF. Any subjects with ongoing adverse 
events related to the test article, study treatment or study procedures, as of the final study visit 
date, should be followed to resolution of the adverse event or until referral to an appropriate 
health care provider, as recommended by the Investigator. Non-ocular adverse events that are 
not related to the test article, study treatment, or study procedures may be recorded as 
“ongoing” without further follow-up. 
13.4. Reporting Adverse Events  
The Investigator will notify the Sponsor of an adverse event by e-mail, facsimile, or telephone 
as soon as possible and no later than 24 hours from discovery for any serious /significant 
adverse events, and 2 days from discovery for any non-significant adverse event.  In addition, 
a written report will be submitted by the Principal Investigator to the IEC/IRB according to 
their requirements (Section 13.4.2).  The report will comment whether the adverse event was 
considered to be related to the test article, study treatment or study procedures. 
 
 
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13.4.1. Reporting Adverse Events to Sponsor 
Serious/Significant Adverse Events 
The Investigator will inform the sponsor of all serious/significant adverse events occurring 
during the study period as soon as possible by e-mail, fax, or telephone, but no later than 24 
hours following discovery of the event.  The Investigator is obligated to pursue and obtain 
information requested by the Sponsor in addition to that information reported on the eCRF. 
All subjects experiencing a serious/significant adverse event must be followed up and all 
outcomes must be reported. 
 
When medically necessary, the Investigator may break the randomization code to determine 
the identity of the treatment that the subject received.  The Sponsor and study monitor should 
be notified prior to unmasking the test articles. 
 
In the event of a serious/significant adverse event, the Investigator must: 
• Notify the Sponsor immediately 
• Obtain and maintain in the subject’s records all pertinent medical information and 
medical judgment for colleagues who assisted in the treatment and follow-up of the 
subject 
• Provide the Sponsor with a complete case history which includes a statement as to 
whether the event was or was not related to the use of the test article 
• Notify the IEC/IRB as required by the IEC/IRB reporting procedure according to 
national regulations 
 
Unanticipated (Serious) Adverse Device Effect (UADE) 
In the event of an Unanticipated (Serious) Adverse Device Effect (UADE), the Investigator 
will submit a report of the UADE to the Sponsor and IEC/IRB as soon as possible, but no 
later than 24 hours after the Investigator first learns of the effect.  This report is in addition to 
the immediate notification mentioned above. 
 
The Sponsor must conduct an evaluation of the UADE and must report the results of the 
evaluation to FDA, the IEC/IRB and participating Investigators within 10 working days after 
the Sponsor first receives notification of the effect. 
 
Non-Serious Adverse Events 
All non-serious adverse events, including non-serious adverse device effects, will be reported 
to the sponsor by the Investigator no later than 2 days from discovery. 
13.4.2. Reporting Adverse Events to the Responsible IEC/IRB and Health Authorities 
Adverse events that meet the IEC/IRB requirements for reporting must be reported within the 
IEC/IRB’s written guidelines. Each clinical site will refer to and follow any guidelines set 
forth by their Approving IEC/IRB. Each clinical site will refer to and follow any guidelines 
set forth by their local governing Health Authorities. 
 
The Sponsor will report applicable Adverse Events to the local health authorities according 
the written guidelines, including reporting timelines.  
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13.4.3. Event of Special Interest 
Adverse events that meet the IEC/IRB requirements for reporting must be reported within the 
IEC/IRB’s written guidelines. Each clinical site will refer to and follow any guidelines set 
forth by their Approving IEC/IRB. Each clinical site will refer to and follow any guidelines 
set forth by their local governing Health Authorities. 
 
The Sponsor will report applicable Adverse Events to the local health authorities according 
the written guidelines, including reporting timelines.  
13.5. Reporting of Pregnancy 
Subjects reporting pregnancy (by self-report) during the study will be discontinued after the 
event is recorded as an Adverse Event.  Once discontinued, pregnant participants and their 
fetuses will not be monitored for study related purposes.  At the Investigator’s discretion, the 
study participant may be followed by the Investigator through delivery. However, this data 
will not be collected as part of the clinical study database.  Pregnant participants are not 
discontinued from contact lens or solution related studies for safety concerns, but due to 
general concerns relating to pregnancy and contact lens use.  Specifically, pregnant women 
are discontinued due to fluctuations in refractive error and/or visual acuity that occur 
secondary to systemic hormonal changes, and not due to unforeseen health risks to the mother 
or fetus. 
14. STATISTICAL METHODS 
14.1. General Considerations 
Statistical Analysis will be undertaken by the sponsor or under the authority of the sponsor. 
A general description of the statistical methods to be implemented in this clinical trial is 
outlined below.  
 
All data summaries and statistical analyses will be performed using the SAS software Version 
9.4, add/modify software if necessary (SAS Institute, Cary, NC). Throughout the analysis of 
data, the results for each subject/eye will be used when available for summarization and 
statistical analysis.  Unscheduled visits will summarized separately and will be excluded from 
the statistical analysis. 
Summary tables (descriptive statistics and/or frequency tables) will be provided for all 
baseline variables, efficacy variables and safety variables as appropriate.  Continuous 
variables will be summarized with descriptive statistics (n, mean, standard deviation (SD), 
median, minimum and maximum). Frequency count and percentage of subjects or eyes within 
each category will be provided for categorical data. 
14.2. Sample Size Justification 
This study was designed and powered to show non-inferiority between the Test lens compared 
to the Control lens with respect to CLUE comfort and vision. It was assumed there was no 
difference between the Test and Control lenses. The sample size was calculated to achieve a 
minimum statistical power of 90% and a type I error of 5%.  
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The sample size calculation was based on historical data from a similar study, CR-5960 The 
Test lens from CR-5960 is the Control for this study.  CR-5960 enrolled 133 subjects, of 
which 130 (97.7%) were dispensed study lenses. Of the dispensed subjects, 127 (95.5%) 
completed the study and 3 (2.3%) subjects were discontinued. The per-protocol population 
included 121 (91.0%) subjects out of the total 127 that completed. Table 4 summarizes CLUE 
scores from CR-5960 at the 2-week follow-up.13 
 
Table 4: Descriptive CLUE scores from CR-5960 (Historical Data) 
 
CLUE Domain 
Study Lenses 
Acuvue Oasys 
Solace – 25% differential 
Comfort [mean (SD1)] 
61.185 (24.2024)  
64.339 (24.2132) 
Vision [mean (SD1)] 
66.792 (20.0073) 
69.445 (20.1752) 
1SD: Standard Deviation 
 
Sample size calculation for CLUE comfort and vision were carried out using an 
approximation of the power of an F-test derived from the non-centrality parameter calculated 
form the observed F-statistic of a linear model. 14 
 
Model details: 
CLUE comfort and vision were analyzed separately using a linear mixed model. Lens type, 
was included as the only fixed effect.  A compound symmetric (CS) covariance was used to 
model the correlation between measurements within the same subject across study periods.  
Below is the variance-covariance matrix used in the CLUE each model. 
 
∑
(
349.3
110.9
110.9
110.9
349.3
110.9
110.9
110.9
349.3
)
𝑐𝑜𝑚𝑓𝑜𝑟𝑡
 
 
∑
(
257.4
82.1
82.1
82.1
257.4
82.1
82.1
82.1
257.4
)
𝑣𝑖𝑠𝑖𝑜𝑛
 
 
Table 5: Sample Size Calculations for CLUE Comfort and Vision 
 
CLUE Domain 
Number to Complete 
Power (%) 
Comfort 
50 
77% 
60 
85% 
80 
93% 
Vision 
50 
88% 
60 
93% 
80 
98% 
 
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Assuming no difference between the Test lens and Control lens, the sample size required to 
achieve non-inferiority with a minimum power of 90% and a type I error controlled at 5% 
was estimated to be 80 subjects.  
14.3. Analysis Populations 
Safety Population: 
All subjects who were administered any test article excluding subjects who drop out prior to 
administering any test article. At least one observation should be recorded. 
 
Per-Protocol Population:  
All subjects who have successfully completed all visits and did not substantially deviate from 
the protocol as determined by the trial cohort review committee prior to database hard lock 
(Per-Protocol Population). Justification of excluding subjects with protocol deviations in the 
per-protocol population set will be documented in a memo to file. 
 
Intent-to-Treat (ITT) Population: 
All randomized subjects regardless of actual treatment and subsequent withdrawal from study 
or deviation from protocol. At least one observation should be recorded. 
14.4. Level of Statistical Significance 
All planned analysis for this study will be conducted with an overall type I error rate of 5%.  
14.5. Primary Analysis  
CLUE Comfort and Vision 
 
Overall comfort and vision CLUE scores will be analyzed separately using a linear mixed 
model adjusting for baseline values as a covariate. Sequence of lens wear, period, lens type, 
first order carryover effect will be included in each model as fixed effects. An appropriate 
covariance structure will be used to model the residual errors between measurements within 
same subject across study periods (R-side). The covariance structure will be selected based 
on the finite-sample corrected Akaike’s Information Criterion. Covariance structures 
considered include: 
 
• Unstructured Covariance Structure (UN) 
• Homogenous Compound symmetry (CS) 
• Heterogeneous Compound Symmetry (CSH) 
• Autoregressive first order (AR (1)) 
 
For autoregressive first order (AR (1)), Site and Subject nest within site will be included as 
random effects (G-side). For the remaining covariance structures only site will be included as 
a random effect (G-side). The Kenward and Roger method (Kenward and Roger, 1997) will 
be used for the denominator degree of freedom.  
 
Comparisons between the test and control lens at the 2-weeks follow-up will be carried out 
using two-sided 95% confidence intervals constructed for least-square mean differences (test 
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minus control). The lower limit of the 95% confidence interval will be compared to -5 and 0 
to test for non-inferiority and superiority, respectively. Non-inferiority of the test lens relative 
to the control will be concluded if a lower limit is above -5.  If non-inferiority is established 
the superiority will be tested. Superiority will be declared if the lower limit of the 95% 
confidence interval is above 0. 
14.6. Secondary Analysis 
Not Applicable. 
14.7. Other Exploratory Analyses  
Driving, Indoor and Outdoor Performance 
 
Each driving, indoor and outdoor performance item will be analyzed separately using a 
generalized linear mixed model for ordinal data with a multinomial distribution and 
cumulative logit as a link function. The experimental design factors: sequence of lens wear, 
period, lens type, first order carryover effect will be included in each model as fixed effects.  
Site will be included as a random effect. An appropriate covariance structure will be used to 
model the residual errors between measurements within same subject across study periods.  
 
The assumption of proportionality of odds across response categories will be assessed 
graphically. If this assumption is violated then the distribution of responses will be 
investigated.  If sparse data is observed then the sparse response categories may be collapsed 
to ensure there is sufficient data for analysis.  If the assumption of proportionality of odds is 
still violated in the collapsed categories then a partial proportional odds model may be 
considered. If any of the above models fail to converge, then reduced versions may be 
considered.  A Generalized Estimating Equation (GEE) may also be considered as necessary. 
 
Comparison between the test lens and the control lens at the 2-week follow-up will be carried 
out using two-sided 95% confidence intervals of the odds ratios (Test over Control); where 
the odds ratio represents the odds of having a higher positive rating/experience for the Test 
lens compared to the Control lens.  
 
For driving items, non-inferiority of the test lens relative to the control will be concluded if 
the lower limit of the 95% confidence interval of the odds ratio is above 0.67. If non-inferiority 
is met, then superiority will be tested. Superiority of the test lens relative to the control lens 
will be concluded if the lower limit of the confidence interval of the odds ratio is above 1. 
 
 
CLUE Handling 
CLUE handling will be analyzed and tested in the same exact manner as CLUE comfort and 
vision as describe above in Section 14.5.  
 
Physiological Responses will be descriptively summarized for each lens type.  
14.8. Interim Analysis 
There will not be an interim analysis performed on this study.  
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14.9. Procedure for Handling Missing Data and Drop-Outs 
Missing or spurious values will not be imputed. The count of missing values will be included 
in the summary tables and listings.  
 
Subject dropout is expected to be one of the main reasons of missing data in this clinical trial. 
Past clinical trials don’t provide the evidence that subject dropout is systematic or not-at-
random. To evaluate the impact of missing data, sensitivity analysis will be conducted using 
multiple imputation methods if the proportion of subject dropout is greater than the 15%. The 
SAS/STAT procedures PROC MI and PROC MIANALYZE will be utilized with a parametric 
regression method used to make at least 10 imputations. 
14.10. Procedure for Reporting Deviations from Statistical Plan 
The analysis will be conducted according to that specified in above sections.  There are no 
known reasons for which it is planned to deviate from these analysis methods.  If for any 
reason a change is made, the change will be documented in the study report along with a 
justification for the change. 
15. DATA HANDLING AND RECORD KEEPING/ARCHIVING 
15.1. Electronic Case Report Form/Data Collection 
The data for this study will be captured on electronic case report forms (eCRFs) using an EDC 
system (Bioclinica).  An authorized data originator will enter study data into the eCRFs using 
the EDC system. Data collected on equipment that is not captured in EDC will be formatted 
to the specification of the JJVC database manager and sent to JJVC for analysis.  
 
No external data will be collected of the study.  
 
The clinical data will be recorded on dedicated eCRFs specifically designed to match the 
study procedures for each visit.  Once completed, the eCRFs will be reviewed for accuracy 
and completeness and signed by the Investigator.  The sponsor or sponsor’s representatives 
will be authorized to gain access to the subject recordation for the purposes of monitoring and 
auditing the study.  
 
Edit checks, electronic queries, and audit trails are built into the system to ensure accurate and 
complete data collection. Data will be transmitted from the clinical site to a secure central 
database as forms are completed or updated, ensuring information accuracy, security, and 
confidentiality. After the final database lock, the Investigator will be provided with Individual 
Patient Profiles (IPP) including the full audit trail on electronic media in PDF format for all 
of the study data. The IPP must be retained in the study files as a certified copy of the source 
data for the study.  
 
 
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15.2. Subject Record 
At a minimum, subject record should be available for the following:  
 
• subject identification 
• eligibility 
• study identification 
• study discussion 
• provision of and date of informed consent 
• visit dates 
• results of safety and efficacy parameters as required by the protocol 
• a record of all adverse events 
• follow-up of adverse events 
• medical history and concomitant medication 
• test article receipt/dispensing/return records 
• date of study completion 
• reason for early discontinuation of test article or withdrawal from the study, if 
applicable 
 
The subject record is the eCRF or an external record.  The author of an entry in the subject 
record must be identifiable.  The first point of entry is considered to be the source record. 
 
Adverse event notes must be reviewed and initialed by the Investigator. 
16. DATA MANAGEMENT 
16.1. Access to Source Data/Document 
The Investigator/Institution will permit trial-related monitoring, audits, IEC/IRB review and 
regulatory inspection(s) by providing direct access to source data/documents.  Should the 
clinical site be contacted for an audit by an IEC/IRB or regulatory authority, JJVC must be 
contacted and notified in writing within 24 hours. 
16.2. Confidentiality of Information 
Information concerning the investigational product and patent application processes, 
scientific data or other pertinent information is confidential and remains the property of JJVC.  
The Investigator may use this information for the purposes of the study only. It is understood 
by the Investigator that JJVC will use information developed in this clinical study in 
connection with the development of the investigational product and therefore may disclose it 
as required to other clinical investigators and to regulatory agencies. In order to allow the use 
of the information derived from this clinical study, the Investigator understands that he/she 
has an obligation to provide complete test results and all data developed during this study to 
the Sponsor. 
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16.3. Data Quality Assurance 
Steps will be taken to ensure the accuracy and reliability of data, include the selection of 
qualified investigators and appropriate clinical sites and review of protocol procedures with 
the Principal Investigator.  The Principal Investigator, in turn, must ensure that all Sub-
Investigators and clinical site personnel are familiar with the protocol and all study-specific 
procedures and have appropriate knowledge of the study article. 
 
Training on case report form completion will be provided to clinical site personnel before the 
start of the study.  The Sponsor will review case report forms for accuracy and completeness 
remotely during the conduct of the study, during monitoring visits, and after transmission to 
data management.  Any data discrepancies will be resolved with the Investigator or designee, 
as appropriate. 
 
Quality Assurance representatives from JJVC may visit clinical sites to review data produced 
during the study and to access compliance with applicable regulations pertaining to the 
conduct of clinical trials.  The clinical sites will provide direct access to study-related source 
data/documents and reports for the purpose of monitoring and auditing by JJVC and for 
inspection by local and regulatory authorities. 
17. MONITORING 
The study monitors will maintain close contact with the Principal Investigator and the 
Investigator’s designated clinical site personnel.  The monitor’s responsibilities will include: 
• Ensuring that the investigation is being conducted according to the protocol, any 
subsequent amendments, and regulatory requirements are maintained 
• Ensuring the rights and wellbeing of subjects are protected 
• Ensuring adequate resources, including facilities, laboratories, equipment, and 
qualified clinical site personnel 
• Ensuring that protocol deviations are documented with corrective action plans, as 
applicable 
• Ensuring that the clinical site has sufficient test article and supplies 
• Clarifying questions regarding the study 
• Resolving study issues or problems that may arise 
• Reviewing of study records and source documentation verification in accordance with 
the monitoring plan 
18. ETHICAL AND REGULATORY ASPECTS 
18.1. Study-Specific Design Considerations 
Potential subjects will be fully informed of the risks and requirements of the study and, during 
the study, subjects will be given any new information that may affect their decision to continue 
participation.  Subjects will be told that their consent to participate in the study is voluntary 
and may be withdrawn at any time with no reason given and without penalty or loss of benefits 
to which they would otherwise be entitled.  Only subjects who are fully able to understand the 
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risks, benefits, and potential adverse events of the study, and provide their consent voluntarily 
will be enrolled. 
18.2. Investigator Responsibility 
The Principal Investigator is responsible for ensuring that the clinical study is performed in 
accordance with the signed agreement, the investigational plan, Section 4 of the ICH E6 
guidelines on Good Clinical Practice (GCP),2 and applicable regulatory requirements.  GCP 
is an international ethical and scientific quality standard for designing, conducting, recording, 
and reporting studies that involve the participation of human subjects. Compliance with this 
standard provides public assurance that the rights, safety, and well-being of study subjects are 
protected, consistent with the principles of the Declaration of Helsinki 64th WMA General 
Assembly 20133 and that the clinical study data are credible.  The Investigator must maintain 
clinical study files in accordance with Section 8 of the ICH E6 guidelines on Good Clinical 
Practice (GCP),2 and applicable regulatory requirements. 
18.3. Independent Ethics Committee or Institutional Review Board (IEC/IRB) 
Before the start of the study, the Investigator (or Sponsor when applicable) will provide the 
IEC/IRB with current and complete copies of the following documents (where applicable): 
• Final protocol and, if applicable, amendments 
• Sponsor-approved informed consent form (and any other written materials to be 
provided to the subjects) 
• Investigator’s Brochure (or equivalent information) and amendments 
• Sponsor-approved subject recruitment materials 
• Information on compensation for study-related injuries or payment to subjects for 
participation in the study 
• Investigator’s curriculum vitae, clinical licenses, or equivalent information (unless not 
required, as documented by IEC/IRB) 
• Information regarding funding, name of the Sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for subjects 
• Any other documents that the IEC/IRB requests to fulfill its obligation 
 
This study will be undertaken only after IEC/IRB has given full approval of the final protocol, 
amendments (if any), the informed consent form, applicable recruiting materials, and subject 
compensation programs, and the Sponsor has received a copy of this approval. This approval 
letter must be dated and must clearly identify the documents being approved. 
 
During the study, the Investigator (or Sponsor when applicable) will send the following 
documents to the IEC/IRB for their review and approval, where appropriate: 
• Protocol amendments 
• Revision(s) to informed consent form and any other written materials to be provided 
to subjects 
• If applicable, new or revised subject recruitment materials approved by the Sponsor 
• Revisions to compensation for study-related injuries or payment to subjects for 
participation in the study 
• Investigator’s Brochure amendments or new edition(s) 
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• Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB) 
• Reports of adverse events that are serious, unanticipated, and associated with the test 
articles, according to the IRB’s requirements 
• New information that may adversely affect the safety of the subjects or the conduct of 
the study 
• Major protocol deviations as required by the IEC/IRB 
• Report of deaths of subjects under the Investigator's care 
• Notification if a new Investigator is responsible for the study at the clinical site 
• Any other requirements of the IEC/IRB 
 
For protocol amendments that increase subject risk, the amendment and applicable informed 
consent form revisions must be submitted promptly to the IEC/IRB for review and approval 
before implementation of the change(s). 
 
At least once a year, the IEC/IRB will review and reapprove this clinical study. This request 
should be documented in writing. 
 
At the end of the study, the Investigator (or Sponsor where required) will notify the IEC/IRB 
about the study completion.  Documentation of this notification must be retained at the clinical 
site and a copy provided to the CRO or Sponsor as applicable. 
18.4. Informed Consent 
Each subject must give written consent according to local requirements after the nature of the 
study has been fully explained. The consent form must be signed before performance of any 
study-related activity. The consent form that is used must be approved by both the Sponsor 
and by the reviewing IEC/IRB. The informed consent is in accordance with principles that 
originated in the Declaration of Helsinki,3 current ICH2 and ISO 141551 guidelines, applicable 
regulatory requirements, and Sponsor Policy. 
 
Before entry into the study, the Investigator or an authorized member of the clinical site 
personnel must explain to potential subject the aims, methods, reasonably anticipated benefits, 
and potential hazards of the study, and any discomfort it may entail. Subjects will be informed 
that their participation is voluntary and that they may withdraw consent to participate at any 
time.  
 
The subject will be given sufficient time to read the informed consent form and the 
opportunity to ask questions. After this explanation and before entry into the study, consent 
should be appropriately recorded by means of the subject's dated signature. After having 
obtained the consent, a copy of the informed consent form must be given to the subject. 
18.5. Privacy of Personal Data 
The collection, processing and disclosure of personal data and medical information related to 
the Study Subject, and personal data related to Principal Investigator and any clinical site 
personnel (e.g., name, clinic address and phone number, curriculum vitae) is subject to 
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compliance with the Health Information Portability and Accountability Act (HIPAA) in the 
United States15/Data Protection Act in the United Kingdom16 /insert applicable country 
specific regulations and add the appropriate reference in Section 22 and other applicable 
personal data protection and security laws and regulations.  Appropriate measures will be 
employed to safeguard these data, to maintain the confidentiality of the person’s related health 
and medical information, to properly inform the concerned persons about the collection and 
processing of their personal data, to grant them reasonable access to their personal data and 
to prevent access by unauthorized persons. 
 
All information obtained during the course of the investigation will be regarded as 
confidential. All personal data gathered in this trial will be treated in strictest confidence by 
Investigators, monitors, Sponsor’s personnel and IEC/IRB.  No data will be disclosed to any 
third party without the express permission of the subject concerned, with the exception of 
Sponsor personnel (monitor, auditor), IEC/IRB and regulatory organizations in the context of 
their investigation related activities that, as part of the investigation will have access to the 
CRFs and subject records. 
 
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to investigate the efficacy, safety, quality, and utility 
of the investigational product(s) used in this study. 
 
These data must be collected and processed with adequate precautions to ensure 
confidentiality and compliance with applicable data privacy protection laws and regulations. 
The Sponsor ensures that the personal data will be: 
• processed fairly and lawfully 
• collected for specified, explicit, and legitimate purposes and not further processed in 
a way incompatible with these purposes 
• adequate, relevant, and not excessive in relation to said purposes 
• accurate and, where necessary, kept current 
 
Explicit consent for the processing of personal data will be obtained from the participating 
subject before collection of data. Such consent should also address the transfer of the data to 
other entities and to other countries. 
 
The subject has the right to request through the Investigator access to his personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps 
should be taken to respond to such a request, taking into consideration the nature of the 
request, the conditions of the study, and the applicable laws and regulations. 
 
Appropriate technical and organizational measures to protect the personal data against 
unauthorized disclosures or access, accidental or unlawful destruction, or accidental loss or 
alteration must be put in place. Sponsor personnel whose responsibilities require access to 
personal data agree to keep the identity of study subjects confidential. 
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19. STUDY RECORD RETENTION 
In compliance with the ICH/GCP guidelines,2 the Investigator/Institution will maintain all 
CRFs and all subject records that support the data collected from each subject, as well as all 
study documents as specified in ICH/GCP2 and all study documents as specified by the 
applicable regulatory requirement(s). The Investigator/Institution will take measures to 
prevent accidental or premature destruction of these documents. 
 
Essential documents must be retained until at least two (2) 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 until at least two (2) years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents will be retained for a longer period if required by the applicable regulatory 
requirements or instructed by the Sponsor. It is the responsibility of the Sponsor to inform the 
Investigator/Institution as to when these documents no longer need to be retained. 
 
If the responsible Investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The Sponsor must be notified in writing of the name and address of 
the new custodian. Under no circumstance shall the Investigator relocate or dispose of any 
study documents before having obtained written approval from the Sponsor. 
 
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the Investigator must permit access to such reports. 
If the Investigator has a question regarding retention of study records, he/she should contact 
JJVC. 
20. FINANCIAL CONSIDERATIONS 
Remuneration for study services and expenses will be set forth in detail in the Clinical 
Research Agreement.  The Research Agreement will be signed by the Principal Investigator 
and a JJVC management representative prior to study initiation. 
 
JJVC reserves the right to withhold remuneration for costs associated with protocol violations 
such as: 
• Continuing an ineligible subject in the study 
• Scheduling a study visit outside the subject’s acceptable visit range 
 
JJVC reserves the right to withhold final remuneration until all study related activities have 
been completed, such as: 
• Query resolution 
• Case Report Form signature 
• Completion of any follow-up action items.  
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APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES) 
 
 
 
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PRO SPECIFICATION Version 2 Final  2018-01-16
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1
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APPENDIX B: PATIENT INSTRUCTION GUIDE  
 
A Patient Instruction Guide (PIG) will be provided separately. 
 
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APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) 
Not Applicable for Investigational Products.   
 
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APPENDIX D: 
 
 
Limbal and Conjunctival (BULBAR) Redness  
 Expanded Sodium Fluorescein Corneal Staining  
Lens Fitting Characteristics 
 Subject Reported Ocular Symptoms Problems  
 Front and Back Surface Lens Deposit Grading Procedure  
 Determination of Distance Spherocylindrical Refractions  
 Biomicroscopy Scale  
 Distance and Near Visual Acuity Evaluation 
 Patient Reported Outcomes 
 White Light Lens Surface Wettability 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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LIMBAL AND CONJUNCTIVAL (BULBAR) REDNESS 
 
 
 
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Page 3 of 7 
 
  
 
 
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Page 4 of 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Page 5 of 7 
 
  
 
 
 
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Page 7 of 7 
 
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 EXPANDED SODIUM FLUORESCEIN CORNEAL STAINING 
  
 
 
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Page 4 of 4 
 
 
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 LENS FITTING CHARACTERISTICS 
 
 
 
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Page 5 of 6 
 
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Page 6 of 6 
 
 
 
 
 
 
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SUBJECT REPORTED OCULAR SYMPTOMS PROBLEMS 
 
 
 
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FRONT 
AND 
BACK 
SURFACE 
LENS 
DEPOSIT 
GRADING 
PROCEDURE 
 
 
 
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Page 2 of 5 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
 
 
 
 
 
  
 
 
 
 
 
 
 
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Page 4 of 5 
 
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Page 5 of 5 
 
 
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DETERMINATION 
OF 
DISTANCE 
SPHEROCYLINDRICAL 
REFRACTIONS 
 
 
 
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 BIOMICROSCOPY SCALE 
 
 
 
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Page 5 of 5 
 
 
 
 
 
 
 
 
 
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 DISTANCE AND NEAR VISUAL ACUITY EVALUATION 
 
 
 
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 PATIENT REPORTED OUTCOMES 
 
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Page 1 of 1 
 
 Patient Reported Outcomes  
 
 
 
 
 
   
 
 
 
 
   
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
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 WHITE LIGHT LENS SURFACE WETTABILITY 
 
 
 
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PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE 
Protocol Number and Title: CR-6140 / Contact Lenses with New UV-blocker Manufactured 
with Different Techniques  
 
Version: 2.0, amendment 1   Date: 07 February 2018 
 
I have read and understand the protocol specified above and agree on its content.   
 
I agree to conduct this study according to ISO 14155,1 GCP and ICH guidelines,2 the 
Declaration of Helsinki,3 United States (US) Code of Federal Regulations (CFR),4 and the 
pertinent individual country laws/regulations and to comply with its obligations, subject to 
ethical and safety considerations. The Principal Investigator is responsible for ensuring that all 
clinical site personnel, including Sub-Investigators adhere to all ICH2 regulations and GCP 
guidelines regarding clinical trials during and after study completion. 
 
I will assure that no deviation from, or changes to the protocol will take place without prior 
agreement from the Sponsor and documented approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants. 
 
I am responsible for ensuring that all clinical site personnel including Sub-Investigators adhere 
to all ICH2 regulations and GCP guidelines regarding clinical trials during and after study 
completion. 
 
All clinical site personnel involved in the conduct of this study have completed Human 
Subjects Protection Training.  
 
I agree to ensure that all clinical site personnel involved in the conduct of this study are 
informed about their obligations in meeting the above commitments. 
 
I shall not disclose the information contained in this protocol or any results obtained from this 
study without written authorization. 
 
Principal 
Investigator: 
 
 
  
 
Signature 
 
 
 Date 
 
Name and Professional Position (Printed) 
  
 
Institution/Site: 
 
  
 
Institution/Site Name 
 
 
  
 
Institution/Site Address 
  
 
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