Evaluation of Approved and Investigational Contact Lenses
Phase: NA
Conditions: Visual Acuity
Sponsor: Johnson & Johnson Vision Care, Inc.

 
CR-5960, v2.0 
 
JJVC CONFIDENTIAL 
 
 
Johnson & Johnson Vision Care, Inc. 
 
Clinical Study Protocol 
 
Evaluation of Approved and Investigational Contact Lenses 
 
Protocol CR-5960 
 
Version: 2.0 
                            
Date: 14 June 2017 
 
Investigational Products: Senofilcon-based contact lens containing new-UV blocker 
 
Key Words: senofilcon A, Subjective Performance, Fitting Characteristics, Dispensing, Daily 
Wear 
 
Statement of Compliance to protocol, GCP and applicable regulatory guidelines: 
This trial will be conducted in compliance with the protocol, the International Conference on 
Harmonization Good Clinical Practice E6 (ICH-GCP), ISO 14155, the Declaration of 
Helsinki, 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 .................................................................................................................................. 9 
Figure 1: Study Flowchart ..................................................................................................... 14 
COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS ...................... 15 
1. INTRODUCTION AND BACKGROUND ....................................................................... 17 
1.1. 
Name and Descriptions of Investigational Products ................................................... 17 
1.2. 
Intended Use of Investigational Products .................................................................... 17 
1.3. 
Summary of Findings from Nonclinical Studies ......................................................... 17 
1.4. 
Known Risks and Benefits to Human Subjects ........................................................... 17 
1.5. 
Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study .............................................................................................................. 17 
2. STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES .......................................... 18 
2.1. 
Objectives .................................................................................................................... 18 
2.2. 
Endpoints ..................................................................................................................... 18 
2.3. 
Hypotheses .................................................................................................................. 20 
3. TARGETED STUDY POPULATION ............................................................................... 22 
3.1. 
General Characteristics ................................................................................................ 22 
3.2. 
Inclusion Criteria ......................................................................................................... 23 
3.3. 
Exclusion Criteria ........................................................................................................ 23 
3.4. 
Enrollment Strategy ..................................................................................................... 24 
4. STUDY DESIGN AND RATIONALE .............................................................................. 24 
4.1. 
Description of Study Design ....................................................................................... 24 
4.2. 
Study Design Rationale ............................................................................................... 24 
4.3. 
Enrollment Target and Study Duration ....................................................................... 25 
5. TEST ARTICLE ALLOCATION AND MASKING ......................................................... 25 
5.1. 
Test Article Allocation ................................................................................................ 25 
5.2. 
Masking ....................................................................................................................... 25 
5.3. 
Procedures for Maintaining and Breaking Randomization Codes .............................. 26 
6. STUDY INTERVENTION ................................................................................................. 26 
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6.1. 
Identity of Test Articles ............................................................................................... 26 
Table 1: Test Articles ............................................................................................................. 27 
6.2. 
Ancillary Supplies/Products ........................................................................................ 27 
Table 2: Ancillary Supplies ................................................................................................... 27 
6.3. 
Administration of Test Articles ................................................................................... 27 
6.4. 
Packaging and Labeling .............................................................................................. 27 
6.5. 
Storage Conditions ...................................................................................................... 28 
6.6. 
Collection and Storage of Samples ............................................................................. 28 
6.7. 
Accountability of Test Articles ................................................................................... 28 
7. STUDY EVALUATIONS .................................................................................................. 29 
7.1. 
Time and Event Schedule ............................................................................................ 29 
Table 3: Time and Events ...................................................................................................... 29 
7.2. 
Detailed Study Procedures .......................................................................................... 30 
VISIT 1 .............................................................................................................................. 30 
VISIT 2 .............................................................................................................................. 34 
VISIT 3 .............................................................................................................................. 36 
VISIT 4 .............................................................................................................................. 40 
VISIT 5 .............................................................................................................................. 44 
FINAL EVALUATION .................................................................................................... 46 
7.3. 
Unscheduled Visits ...................................................................................................... 46 
7.4. 
Laboratory Procedures ................................................................................................ 47 
8. SUBJECTS COMPLETION/WITHDRAWAL.................................................................. 48 
8.1. 
Completion Criteria ..................................................................................................... 48 
8.2. 
Withdrawal/Discontinuation from the Study .............................................................. 48 
9. PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION ..................... 49 
10. DEVIATIONS FROM THE PROTOCOL ......................................................................... 49 
11. STUDY TERMINATION .................................................................................................. 50 
12. PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS ..................... 50 
13. ADVERSE EVENTS .......................................................................................................... 51 
13.1. Definitions and Classifications .................................................................................... 51 
13.2. Assessing Adverse Events ........................................................................................... 54 
13.2.1 Causality Assessment ............................................................................................ 54 
13.2.2 Severity Assessment .............................................................................................. 54 
13.3. Documentation and Follow-Up of Adverse Events .................................................... 55 
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13.4. Reporting Adverse Events ........................................................................................... 56 
13.4.1 Reporting Adverse Events to Sponsor ................................................................... 56 
13.4.2 Reporting Adverse Events to the Responsible IEC/IRB and Health Authorities .. 57 
13.5. Event of Special Interest .............................................................................................. 57 
13.6. Reporting of Pregnancy ............................................................................................... 57 
14. STATISTICAL METHODS ............................................................................................... 58 
14.1. General Considerations ............................................................................................... 58 
14.2. Sample Size Justification ............................................................................................. 58 
Table 4: Historical Study Included in Sample Size Calculation ............................................ 58 
Table 5: 
 Descriptive Summary of CLUE Comfort, Unacceptable Lens Fit and 
Outdoor Performance Items Pooled across Historical Studies- 2-Week Follow-up 
evaluation .................................................................................................................... 59 
Table 6: Descriptive Summary of Slit Lamp Findings Pooled Across Historical Studies .... 59 
Table 7: Sample Size Estimates and Power Calculations for Primary Endpoints ................. 60 
14.3. Analysis Populations ................................................................................................... 61 
14.4. Level of Statistical Significance .................................................................................. 61 
14.5. Primary Analysis ......................................................................................................... 61 
14.6. Secondary Analysis ..................................................................................................... 66 
14.7. Other Exploratory Analyses ........................................................................................ 66 
14.8. Interim Analysis .......................................................................................................... 69 
14.9. Procedure for Handling Missing Data and Drop-Outs ................................................ 69 
14.10. Procedure for Reporting Deviations from Statistical Plan .......................................... 70 
15. DATA HANDLING AND RECORD KEEPING/ARCHIVING ....................................... 70 
15.1. Electronic Case Report Form/Data Collection ............................................................ 70 
15.2. Subject Record ............................................................................................................ 70 
16. DATA MANAGEMENT.................................................................................................... 71 
16.1. Access to Source Data/Document ............................................................................... 71 
16.2. Confidentiality of Information .................................................................................... 71 
16.3. Data Quality Assurance ............................................................................................... 71 
17. MONITORING ................................................................................................................... 72 
18. ETHICAL AND REGULATORY ASPECTS ................................................................... 72 
18.1. Study-Specific Design Considerations ........................................................................ 72 
18.2. Investigator Responsibility .......................................................................................... 73 
18.3. Independent Ethics Committee or Institutional Review Board (IEC/IRB) ................. 73 
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18.4. Informed Consent ........................................................................................................ 74 
18.5. Privacy of Personal Data ............................................................................................. 74 
19. STUDY RECORD RETENTION....................................................................................... 75 
20. FINANCIAL CONSIDERATIONS ................................................................................... 76 
21. PUBLICATION .................................................................................................................. 76 
22. REFERENCES ................................................................................................................... 77 
APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES) ....... 78 
APPENDIX B: PATIENT INSTRUCTION GUIDE ............................................................... 97 
APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) ........................................... 98 
APPENDIX D: CLINICAL TECHNICAL PROCEDURES 
...................................... 101 
, LIMBAL AND CONJUNCTIVAL (BULBAR) REDNESS ............................... 102 
, EXPANDED SODIUM FLUORESCEIN CORNEAL STAINING .................... 110 
, LENS FITTING CHARACTERISTICS .............................................................. 115 
, SUBJECT REPORTED OCULAR SYMPTOMS/PROBLEMS ......................... 122 
, FRONT AND BACK SURFACE LENS DEPOSIT GRADING PROCEDURE 124 
, DETERMINATION OF DISTANCE SPHEROCYLINDRICAL 
REFRACTIONS ..................................................................................................................... 130 
, BIOMICROSCOPY SCALE ............................................................................... 137 
, DISTANCE AND NEAR VISUAL ACUITY EVALUATION .......................... 143 
, DISTANCE LOGMAR VISUAL ACUITY MEASUREMENT PROCEDURE 148 
APPENDIX E: IRIS Color...................................................................................................... 152 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE .......................... 154 
  
LISTING OF TABLES  
Table 1: Test Articles ................................................................................................................ 27 
Table 2: Ancillary Supplies ...................................................................................................... 27 
Table 3: Time and Events ......................................................................................................... 29 
Table 4: Historical Study Included in Sample Size Calculation ............................................... 58 
Table 5: 
 Descriptive Summary of CLUE Comfort, Unacceptable Lens Fit and 
Outdoor Performance Items Pooled across Historical Studies- 2-Week Follow-up evaluation59 
Table 6: Descriptive Summary of Slit Lamp Findings Pooled Across Historical Studies ....... 59 
Table 7: Sample Size Estimates and Power Calculations for Primary Endpoints .................... 60 
 
LISTING OF FIGURES 
Figure 1: Study Flowchart ........................................................................................................ 14 
 
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SYNOPSIS  
Protocol Title 
Evaluation of Approved and Investigational Contact Lenses 
Sponsor 
JJVC, 7500 Centurion Parkway, Jacksonville, FL  32256 
Clinical Phase 
Development Phase 2b 
Trial Registration 
This study will be registered on ClinicalTrials.gov after final 
product approval from the FDA. 
Test Article(s) 
Investigational Products:  Senofilcon-based contact lens 
containing new-UV blocker (a.k.a. Test lens) 
Control Products:  Commercial ACUVUE OASYS 
Wear and Replacement 
Schedules 
Wear Schedule: daily wear (DW) 
Replacement Schedule: approximately 2 weeks  
Objectives  
The primary objective of this study is to demonstrate non-
inferiority of the Test lens compared to the Control lens with 
respect to CLUE comfort, Slit Lamp Findings and Monocular 
logMAR Distance Visual Acuity. This study will also aim to 
show the Fit Acceptance rate is at least 90% in order to assess 
performance of the Test lens for eventual Design Validation 
and/or Claims studies. 
Study Endpoints 
Primary Endpoints:  
 Monocular logMAR distance visual acuity 
 Biomicroscopy 
 Fit acceptance rate 
 Overall CLUE comfort 
Secondary Endpoints:  
 Overall CLUE vision 
 Overall CLUE handling 
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Study Design 
This study is a randomized, 5-visit, partial subject-masked, 
2×3 bilateral crossover, dispensing trial.  The study lenses will 
be worn as daily wear (DW) for a period of 2 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 130 eligible subjects will be enrolled and 
randomized into the study.  Approximately 120 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.   
Study Duration 
Subjects will wear the Test and control lenses for 2 weeks 
each in random order with one of the study lenses being worn 
twice for a total of 6 weeks per subject.  The enrollment period 
will be 2 weeks, making the entire study approximately 8 
weeks in duration. 
Anticipated Study 
Population 
Approximately 130 subjects will be enrolled to ensure that at 
least 120 subjects will complete the study.  Enrolled subjects 
will be habitual wearers of spherical contact lenses.  All 
subjects will be the age of 18 and 49. 
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Eligibility Criteria 
(Inclusion Criteria) 
 
Potential subjects must satisfy all of the following inclusion 
criteria to be enrolled in the study: 
1. The subject must read and sign the Informed Consent 
form. 
2. The subject must appear able and willing to adhere to 
the instructions set forth in this clinical protocol. 
3. Healthy adult males or females age 18 and 49 years 
of age with signed informed consent.  Eligible 
presbyopes will be those that wear full distance contact 
lenses in both eyes, then wear reading glasses over 
them. 
4. The subject’s optimal vertexed spherical equivalent 
distance correction must be between -1.00 and  
– 6.00D. 
5. The subject’s refractive cylinder must be ≤ 1.00D in 
each eye. 
6. The subject must have visual acuity best correctable to 
20/25+3 or better for each eye. 
7. Subjects must own a wearable pair of spectacles.  
8. 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. 
9. Subjects must be able and willing to wear the study 
lenses at least 6 hours a day, a minimum of 5 days per 
week 
10. The subject must have normal eyes (i.e., no ocular 
medications or infections of any type). 
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 (subjects who become 
pregnant during the study will be discontinued). 
2. Any systemic disease, autoimmune disease, or use of 
medication, which may interfere with contact lens 
wear. This may include, but not be limited to, diabetes, 
hyperthyroidism, recurrent herpes simplex/zoster, 
Sjögren’s syndrome, xerophthalmia, acne rosacea, 
Stevens-Johnson syndrome, and immunosuppressive 
diseases or any infectious diseases (e.g. hepatitis, 
tuberculosis). 
3. Use of any of the following medications within 1 week 
prior to enrollment: oral retinoid isotretinoin (e.g. 
Accutane), oral tetracyclines, topical scopolamine, oral 
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(e.g., Chlor-Trimeton, and Benadryl) and ophthalmic 
antihistamines, oral phenothiazines (e.g., Haldol, 
Mellaril, Thorazine, Elavil, Pamelor, Compazine), oral 
and 
ophthalmic 
Beta-adrenergic 
blockers 
(e.g., 
Propranolol, Timolol, and Practolol), systemic steroids, 
and any prescribed or over the counter (OTC) ocular 
medication. 
4. Entropion, ectropion, extrusions, chalazia, recurrent 
styes, glaucoma, history of recurrent corneal erosions, 
aphakia, or moderate or above corneal distortion. 
5. Any previous, or planned, ocular or intraocular surgery 
(e.g., radial keratotomy, PRK, LASIK, etc.). 
6. Any Grade 3 or greater slit lamp findings (e.g.., edema, 
corneal neovascularization, corneal staining, tarsal 
abnormalities, conjunctival injection) on the FDA 
classification scale, 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 may contraindicate 
contact lens wear. 
7. Any known hypersensitivity or allergic reaction to 
Optifree®PureMoist® multi-purpose care solution or 
Eye-Cept® rewetting drop solution  
8. Any ocular infection, allergy or clinically significant 
ocular disease (e.g. corneal edema, uveitis, severe 
keratoconjunctivitis sicca, ocular hypertension), or 
ocular conditions (e.g. strabismus), which might 
interfere with the study. 
9. Any corneal distortion resulting from previous hard or 
rigid gas permeable contact lens wear. 
10. Toric, extended wear, monovision or multi-focal 
contact lens correction. 
11. Participation in any contact lens or lens care product 
clinical trial within 30 days prior to study enrollment. 
12. Participation in clinical trials involving the Test lens 
within 3 months prior to study enrollment. 
13. History of binocular vision abnormality or strabismus. 
14. Employee, relative or friends of employees of any 
ophthalmic company, or investigational clinic (e.g., 
Investigator, Coordinator, Technician). 
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Disallowed 
Medications/Interventions  
Use of any of the following medications within 1 week prior to 
enrollment: oral retinoid isotretinoin (e.g. Accutane), oral 
tetracyclines, topical scopolamine, oral (e.g. Seldane, Chlor-
Trimeton, and Benadryl) and ophthalmic antihistamines, oral 
phenothiazines (e.g., Haldol, Mellaril, Thorazine, Elavil, 
Pamelor, Compazine), oral and ophthalmic Beta-adrenergic 
blockers (e.g., Propranolol, Timolol, and Practolol), systemic 
steroids, and any prescribed or over the counter (OTC) ocular 
medication 
Measurements and 
Procedures 
Monocular distance visual acuity on logMAR scale using 
ETDRS charts,  physiological responses, fitting characteristics, 
individual performance metrics, CLUE comfort, vision and 
handling. 
Microbiology or Other 
Laboratory Testing 
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. 
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.  In the event of a UADE or SAE, the 
Sponsor Medical Monitor may unmask the control lens 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 
UV 
 
 
Ultraviolet 
HEV  
 
High energy visible 
PG 
 
 
Propylene glycol 
IPA 
 
 
Isopropyl alcohol 
 
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4. Leguire, L. E., & Suh, S. (1993). Effect of light filters on contrast sensitivity function 
in normal and retinal degeneration subjects. Ophthalmic and Physiological Optics, 
13(2), 124-128. 
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 
The primary objective of this study is to demonstrate non-inferiority of the Test lens 
compared to the Control lens with respect to CLUE comfort, Slit Lamp Findings and 
Distance Monocular logMAR Visual Acuity. This study will also aim to show that the Fit 
Acceptance rate is at least 90% for subjects wearing the Test lens. 
 
Secondary Objective 
The secondary objective of this study is to demonstrate non-inferiority of the Test lens 
compare to the Control lens with respect to CLUE Overall quality of Vision and Handling. 
 
Exploratory Objective 
This study also aims to explore the performance of Indoor, Outdoor and Driving performance 
using individual questionnaire items.  
2.2. 
Endpoints  
Primary Endpoints 
 
The primary endpoints are as follows: 
 
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the Test and Control contact lenses approximately 2 weeks each bilaterally on a daily wear 
(DW) basis, then wear either the Test or Control lens again for 2 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:  
  
1. The subject must read and sign the Informed Consent form. 
2. The subject must appear able and willing to adhere to the instructions set forth in this 
clinical protocol. 
3. Healthy adult males or females age 18 and 49 years of age with signed informed 
consent.  Eligible presbyopes will be those that wear full distance contact lenses in 
both eyes, then wear reading glasses over them. 
4. The subject’s optimal vertexed spherical equivalent distance correction must be 
between -1.00 and -6.00D. 
5. The subject’s refractive cylinder must be ≤1.00D in each eye. 
6. The subject must have visual acuity best correctable to 20/25+3 or better for each eye. 
7. Subjects must own a wearable pair of spectacles.  
8. 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. 
9. Subjects must be able and willing to wear the study lenses at least 6 hours a day, a 
minimum of 5 days per week 
10. The subject must have normal eyes (i.e., no ocular medications or infections of any 
type). 
3.3. 
Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from participating 
in the study:  
 
1. Currently pregnant or lactating (subjects who become pregnant during the study will 
be discontinued). 
2. Any systemic disease, autoimmune disease, or use of medication, which may interfere 
with contact lens wear. This may include, but not be limited to, diabetes, 
hyperthyroidism, 
recurrent 
herpes 
simplex/zoster, 
Sjögren’s 
syndrome, 
xerophthalmia, acne rosacea, Stevens-Johnson syndrome, and immunosuppressive 
diseases or any infectious diseases (e.g. hepatitis, tuberculosis). 
3. Use of any of the following medications within 1 week prior to enrollment: oral 
retinoid isotretinoin (e.g. Accutane), oral tetracyclines, topical scopolamine, oral (e.g. 
Seldane, Chlor-Trimeton, and Benadryl) and ophthalmic antihistamines, oral 
phenothiazines (e.g., Haldol, Mellaril, Thorazine, Elavil, Pamelor, Compazine), oral 
and ophthalmic Beta-adrenergic blockers (e.g., Propranolol, Timolol, and Practolol), 
systemic steroids, and any prescribed or over the counter (OTC) ocular medication. 
4. Entropion, ectropion, extrusions, chalazia, recurrent styes, glaucoma, history of 
recurrent corneal erosions, aphakia, or moderate or above corneal distortion. 
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5. Any previous, or planned, ocular or interocular surgery (e.g., radial keratotomy, PRK, 
LASIK, etc.). 
6. Any Grade 3 or greater slit lamp findings (e.g.., edema, corneal neovascularization, 
corneal staining, tarsal abnormalities, conjunctival injection) on the FDA 
classification scale, 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 may contraindicate contact lens wear. 
7. Any known hypersensitivity or allergic reaction to Optifree®PureMoist® multi-
purpose care solution or Eye-Cept® rewetting drop solution 
8. Any ocular infection, allergy or clinically significant ocular disease (e.g. corneal 
edema, uveitis, severe keratoconjunctivitis sicca, ocular hypertension), or ocular 
conditions (e.g. strabismus), which might interfere with the study. 
9. Any corneal distortion resulting from previous hard or rigid gas permeable contact 
lens wear. 
10. Toric, extended wear, monovision or multi-focal contact lens correction. 
11. Participation in any contact lens or lens care product clinical trial within 30 days prior 
to study enrollment. 
12. Participation in clinical trials involving the Test lens within 3 months prior to study 
enrollment. 
13. History of binocular vision abnormality or strabismus. 
14. Employee, relative or friends of employees of any ophthalmic company, or 
investigational clinic (e.g., Investigator, Coordinator, Technician). 
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, 5-visit, partial subject-masked, 2×3 bilateral crossover, 
dispensing trial.  Both study lenses will be worn as daily wear (DW) for a period of 2 weeks 
each, and 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. 
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. 
 
 significant carryover effects were 
observed when assessing clinically relevant differences between the Test lens and a 
comparator while using a 2×2 crossover study design. Therefore this study utilizes a 3-period 
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by 2-treatment in order 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 130 subjects will be enrolled to ensure that at least 120 subjects will complete 
the study.  Enrolled subjects will be habitual wearers of spherical contact lenses.  All subjects 
will be the age of 18 and <49 years old.  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 bilaterally approximately 2 weeks each on a daily wear 
(DW) basis, then wear either the Test or Control lens again for 2 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  
This is a multi-site, partially-subject masked (control lens only) and randomized study.  The 
study lenses will be worn in a bilateral and random fashion using a 2 treatment by 3 period 
(2×3) crossover design.  
 
Permuted block randomization will be used to minimize the potential for treatment 
imbalance.  A block size of two (2) sequences will be utilized.  A computer-generated 
randomization scheme will be used to randomly assign subjects to one of the two possible 
lens wear sequences (TEST/CONTROL/CONTROL or CONTROL/TEST/TEST). The 
random scheme will be generated 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 
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 
Complete masking is impossible due to the functioning nature of the Test lens.  The control 
lens will be over-labeled to mask the identity since the control lens may be the subject’s 
habitual lens by chance.  Therefore the study is partially-subject masked (control lens only). 
 
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 notified before the 
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mask is broken. The date, time, and reason for the unmasking must be documented in the 
source document. The investigator is also advised not to reveal the study treatment 
assignment to the study 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 may be replaced. 
 
Use of the test articles will be randomized using a randomization scheme supplied by the 
study biostatistician. 
 
If the test article is randomized, the order will be based on the randomization scheme 
assigned to the study site.   The study site will follow the randomization scheme provided 
and will complete enrollment according to the randomization list and will not pre-select or 
assign subjects. 
5.3. 
Procedures for Maintaining and Breaking Randomization Codes 
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: 
 
1. Investigator or designee (documented on the Delegation Log) will consult the lens 
fitting schedule/randomization scheme to obtain the test article assignment for that 
subject prior to dispensing 
2. Investigator or designee will record the subject’s number on the appropriate line of 
the randomization scheme  
3. Investigator or designee will pull the appropriate test articles from the study supply.  
All test articles that are opened, whether dispensed (placed/fit on eye or dispensed 
outside the clinical site) or not, must be recorded on the Test Article Accountability 
Log in the “Dispensed” section 
6. STUDY INTERVENTION 
6.1. 
Identity of Test Articles  
The following contact lenses will be used in this study: 
 
 
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investigational cartons sealed with a tamper evident seal, commercial cartons, or in plastic 
bags as the secondary packaging form. The sample study label is shown below: 
 
US label A (for control lens over-label) 
 
6.5. 
Storage Conditions 
Test articles will be maintained at ambient temperatures at the clinical site. Test articles must 
be kept under secure conditions and out of direct sunlight. 
6.6. 
Collection and Storage of Samples 
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. 
6.7. 
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 
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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 package and return all unused test articles to JJVC. 
 
If there is a discrepancy between the shipment documents and the contents, contact the study 
monitor immediately. 
 
 
:  Site Instructions for Test Article Receipt and Test Article 
Accountability for additional information. 
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, 3, 4 
2, 3, 4, 5 
PRN 
5 
Visit Window 
- 
- 
6-8 Days 
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 
- 
 
 
* 
- 
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8. SUBJECTS COMPLETION/WITHDRAWAL  
8.1. 
Completion Criteria 
The disposition (accountability) of all enrolled subjects will be presented by study lens and 
overall to show the number and percentage of subjects in each of the following status 
subgroups:  
 
1. Completed: Subjects are considered to have completed the study if they have 
completed all scheduled visits.  
 
2. Discontinued: Subjects are considered to have discontinued from the study if they are 
(i) randomized (ii) Successfully Dispensed and (iii) discontinued because of one of 
the following reasons: a) Withdrew Consent (b) Lost to Follow Up (c) Subject no 
longer meets eligibility criteria (e.g. pregnancy) (d) Subject withdrawn by PI due to 
non-compliance to protocol (e) Discontinuation of study treatment as a result of the 
investigator’s belief that for safety (f) Reasons it is in the best interest of the subject 
to stop treatment (g) Study lens no longer available (h) A scheduled visit was missed. 
 
3. Total dispensed:  Completed + Discontinued 
 
4. Enrolled not Successfully Dispensed: Subjects are considered to be Enrolled Not 
Successfully Dispensed Subjects if they were (i) enrolled to the study (provided 
informed consent) but failed to satisfy the eligibility criteria (inclusion/exclusion 
criteria), (ii) were not randomized to study lens for any reason or (iii) if they are 
randomized but did not satisfactorily complete the dispensing process. This includes 
subjects who were dispensed a different type of study lens for each eye or who were 
dispensed same study lens for both eyes but did not return for any follow-up visits. 
 
5. Total enrolled: Completed +  Discontinued  +  Enrolled not Successfully Dispensed 
 
6. The percentage will be calculated using total enrolled as denominator. 
 
7. Safety and efficacy analysis sets will be defined as subsets of dispensed subjects 
(Completed + Discontinued). 
 
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) 
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 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 0 
 Collect all unused test article(s) from the subject 
 
Investigator will discuss with sponsor before enrolling any additional subjects 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 
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 
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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. 
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. 
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 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 or not 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 (
 
 
 for test article return instructions) 
 
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 
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 (unwanted) medical occurrence in a patient 
or clinical investigation subject administered a test article, study treatment or study procedure 
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whether or not caused by the test article, study treatment or procedure.  An AE can therefore 
be any unfavorable or unintended sign (including an abnormal finding), symptom, or disease 
temporally associated with the use of the test article, study treatment, or study procedure 
whether or not related to the test article, study treatment, or study procedure. 
 
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. 
 
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 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 
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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 
 Any corneal event not explicitly defined as serious or significant adverse event, 
which necessitates temporary lens discontinuation < 2 weeks 
 
Adverse Device Effect (ADE) – A sub-set of AEs, and include only those adverse events 
that are cause by or related to the investigational device. 
 
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. 
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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; doubtful; possible; 
probable; very likely - 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 13.2.2).   
 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 
action taken 
13.2.1 
Causality Assessment 
Causality Assessment – A determination of the relationship between an adverse event and 
the test article, study treatment, or study procedure. The test article, study treatment or study 
procedure relationship for each adverse event shall 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. 
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 
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 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 
 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.  
 
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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 or not 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. 
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 or not the 
adverse event was considered to be related to the test article, study treatment or study 
procedures. 
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 
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 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.  
13.5. Event of Special Interest 
None 
13.6. Reporting of Pregnancy 
Subjects reporting pregnancy (by self-report) during the course of 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. 
 
 
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14. STATISTICAL METHODS 
14.1. General Considerations 
All data summaries and statistical analyses will be performed using the SAS software 
Version 9.4 or higher (SAS Institute, Cary, NC).  
 
Description of Summary Tables: 
Summary tables (Descriptive statistics and/or frequency tables) will be provided for all 
baseline variables, efficacy variables and safety variables for each subject/eye by study lens 
type (as appropriate). All variables will be summarized on the safety population.  Analysis 
variables will be summarized on both the analysis and safety populations.  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. Unscheduled visits will be 
summarized separately if applicable.  
 
14.2. Sample Size Justification 
This study was designed and powered to show non-inferiority of the Test lens compared to 
the Control lens with respect to CLUE Comfort, logMAR Visual Acuity and Slit Lamp 
Findings (Grade 3 or higher). It was assumed there was no difference between the Test and 
Control lens with respect to CLUE comfort, visual performance and slit lamp findings.   
 
In addition to the endpoints mentioned above this study was also powered to demonstrate the 
proportion of eyes with acceptable fitting on the Test lens is significantly superior to 90% as 
wells as the cumulative odds ratio of (individual reduction items) the Test lens compared to 
the control lens is significantly superior to 1.00.  
 
Unless otherwise specified, the sample size was calculated to achieve a minimum statistical 
power of 80% and a type I error of 5%.  
 
The sample size calculation was based on historical data from a four similar randomized 
bilateral multi-site studies 
 
 
 
 where the same 
Test and Control lenses were used. Both lenses were worn as daily wear for at least 5 days 
per week for at least 6 hours per day.  Follow-up visits occurred at 1 and 2-weeks after the 
initial visit.  Subject accountability for each study is listed in Table 4 below.  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Model details: 
CLUE comfort was analyzed using a linear mixed model. Lens type, period and the 
interaction between lens type and period were included in the model as fixed effects.  A 
compound symmetric (CS) covariance was used to model the correlation between 
measurements on the same subject across study periods.  Below is the variance-covariance 
matrix used in the CLUE Comfort model.  
 
∑
(
202
105
105
105
202
105
105
105
202
)
𝑐𝑜𝑚𝑓𝑜𝑟𝑡
 
 
Visual Performance 
The sample size calculation for distance monocular visual performance was performed 
assuming that there was no difference between the Test and Control lenses to achieve a 
minimum statistical power of 80%. Assuming a mean of 0 LogMAR, a standard deviation of 
0.10 (based on historical ACUVUE® OASYS®) and a correlation between eye of 0.80, 2000 
replicating trials were simulated for the repeated measurements from the multivariate normal 
distribution.  
 
Acceptable Lens Fit  
Acceptable lens fit is a binary response as y=1 if a subject eye has an acceptable fit and 0 
otherwise. The common reference rate of 95% was selected for the sample size calculation, 
since this is considered to be a more conservative reference proportion. Assuming a 
correlation 0.80 between measurements within the same subject and period; and assuming a 
correlation of 0.50 between measurements within the same subject across periods. A total of 
2000 replicating trials were simulated to estimate a sample size with a minimum statistical 
power of 80%. 
 
Slit Lamp Findings 
There was no Grade 3 or higher SLFs in any of the four historical studies. Therefore an 
incidence rate of 0.5% was chosen based on previous research literature3, 4. Assuming a 
correlation 0.50 between measurements within the same subject and period; and assuming a 
correlation of 0.30 between measurements within the same subject across periods. A total of 
2000 replicating trials were simulated to estimate a sample size with a minimum statistical 
power of 80%.   
Table 7: Sample Size Estimates and Power Calculations for Primary Endpoints  
Endpoint 
Number per Subjects to 
Complete 
Power 
Distance Monocular Visual 
Acuity 
40 
>99% 
SLFs Grade 3 or Higher 
120 
86% 
Acceptable lens Fit 
70 
83% 
CLUE Comfort 
60 
80% 
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14.3. Analysis Populations 
A separate Statistical Analysis Plan (SAP) will be provided for this study. If there are any 
discrepancies between the protocol and the SAP, the SAP will supersede the statistical 
sections in the protocol. 
 
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 
The primary and secondary hypotheses will be tested with a type I error of 5% individually.   
14.5. Primary Analysis  
Primary efficacy analysis: 
 
Visual Acuity 
Distance monocular visual acuity (logMAR) will be analyzed using a Bayesian multivariate 
normal random-effects model to compare the Test and control lenses. The regression model 
will include sequence of lens wear, lens type and first-order carryover effect as fixed effects. 
Clinical site and subject nested within clinical site will be included as random effects. Other 
subject characteristics such as gender and age will be included as fixed effects when 
appropriate.  
 
The Model: 
Let 𝑦𝑖𝑗𝑘𝑙𝑚= (𝑦1𝑖𝑗𝑘𝑙𝑚, 𝑦2𝑖𝑗𝑘𝑙𝑚 , 𝑦3𝑖𝑗𝑘𝑙𝑚) denote the visual acuity (logMAR) for the 𝑚𝑡ℎ 
subject at the 𝑙𝑡ℎ site, assigned to the 𝑖𝑡ℎ lens for the 𝑗𝑡ℎ eye using the 𝑘𝑡ℎ sequence at 
periods 1, 2, 3, respectively.  The likelihood for 𝑦𝑖𝑗𝑘𝑙  is constructed as follows:  
𝑦𝑖𝑗𝑘𝑙𝑚 ~ N(𝜇𝑖𝑗𝑘𝑙𝑚, Σ)  
 
Where 𝜇𝑖𝑗𝑘𝑙𝑚 = (µ1𝑖𝑗𝑘𝑙𝑚 , µ2𝑖𝑗𝑘𝑙𝑚 , µ3𝑖𝑗𝑘𝑙𝑚)𝑇 and Σ is a 3X3 variance-covariance matrix. 
Here,  
 
µ1𝑖𝑗𝑘𝑙𝑚 = µ0 +  𝜋1 + 𝛽1𝐿𝑒𝑛𝑠𝑖[𝑗,𝑘] + 𝛽4𝑆𝑒𝑞𝑢𝑒𝑛𝑐𝑒𝑘+                              𝛾𝑙  + 𝛿𝑙(𝑚)+ 𝛼𝑗(𝑚(𝑙)) 
µ2𝑖𝑗𝑘𝑙𝑚 = µ0 +  𝜋2 + 𝛽2𝐿𝑒𝑛𝑠𝑖[𝑗,𝑘] -  𝛽4𝑆𝑒𝑞𝑢𝑒𝑛𝑐𝑒𝑘 + 𝛽5𝐶𝑎𝑟𝑟𝑦1𝑖[𝑗,𝑘]+ 𝛾𝑙 + 𝛿𝑙(𝑚) + 𝛼𝑗(𝑚(𝑙)) 
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µ3𝑖𝑗𝑘𝑙𝑚 = µ0 +  𝜋3 + 𝛽3𝐿𝑒𝑛𝑠𝑖[𝑗,𝑘]+  𝛽4𝑆𝑒𝑞𝑢𝑒𝑛𝑐𝑒𝑘 - 𝛽5𝐶𝑎𝑟𝑟𝑦1𝑖[𝑗,𝑘]+  𝛾𝑙 + 𝛿𝑙(𝑚) + 𝛼𝑗(𝑚(𝑙)) 
 
In this model 𝜋1, 𝜋2, 𝜋3 represent the effect of period with the constraint 𝜋1 + 𝜋2 + 𝜋3= 0. In 
Lens I will be determined by the subject eye j and sequence k, therefore i is denoted as a 
function of j and k. We define 𝐿𝑒𝑛𝑠𝑖=0 for the control lens and 𝐿𝑒𝑛𝑠𝑖=1 for the Test lens, 
sequence is defined as: Sequence=0 for the order Control/Test/Test and Sequence=1 for 
order Test/Control/Control. The first-order carryover effect will be defined as carry=0 for the 
Control lens and carry=1 for the Test lens. So 𝛽1 stands for the difference between the Test 
and control lens with respect to visual performance at period 1. A negative 𝛽2 indicates the 
Test performed better than the control lens.  
 
We assume random subject eye effects are independent and identically distributed (i.i.d) as 
𝛼𝑗(𝑚(𝑙))~ N(0, 𝜎𝑒𝑦𝑒/𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
 ) as random eye nested within subject within clinical site, the 
random subject effect are i.i.d as 𝛿𝑙(𝑚)~(0, 𝜎𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
) as random subject nested within 
clinical site and the random site effect is i.i.d as  𝛾𝑙 ~ N(0, 𝜎𝑠𝑖𝑡𝑒
2
) for i=1,2 (lens),  j=1, 2  
(eye), k=1, 2 (sequence), carry1=1, 2 (first-order carryover effect)  and  l=1…| 
𝑚𝑙(subject/site)  and l=1,2, 3, 4 and 5 (site). 
 
For the β coefficients, independent non-informative priors N(0, 1000) will be used. For the 
variance of random effects 𝜎𝑒𝑦𝑒/𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
 , 𝜎𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
and 𝜎𝑠𝑖𝑡𝑒
2
 independent non-
informative conjugate priors inverse-gamma(0.001, 0.001) will be used. For Σ, non-
informative conjugate priors inverse-wishart(3,S) will be used where S is a 3X3 variance-
covariance matrix of  𝑦𝑖𝑗𝑘𝑙𝑚. The metropolis sampler algorithm as implemented in the 
SAS/STAT MCMC procedure will be used to estimate the posterior distribution of the 
unknown parameters. Inferences will be made based on the 95% posterior credible intervals 
for relevant parameters.  
 
Hypothesis Testing  
The null and alternative hypothesis for visual acuity (logMAR) to test for non-inferiority of 
the Test lens relative to the control lens is as follows:  
𝐻𝑜: 
𝛽1+ 𝛽2+ 𝛽3
3
 ≥ 0.05 
𝐻𝐴: 
𝛽1+ 𝛽2+ 𝛽3
3
 < 0.05 
 
Non-inferiority will be declared if the upper limit of the 95% credible interval of the 
difference between the Test and Control is below 0.05, i.e. P(
𝛽1+ 𝛽2+ 𝛽3
3
 < 0.05) ≥ 0.975.  
Superiority will be established if the upper limit of the 95% credible interval of the difference 
between the Test and Control lens is below 0.0, i.e.  P(
𝛽1+ 𝛽2+ 𝛽3
3
 < 0.0) ≥ 0.975.  Superiority 
will be tested only if non-inferiority is met. 
 
CLUE Overall Comfort  
CLUE Comfort scores will be analyzed using a Bayesian multivariate normal random-effects 
model to compare the Test and control lenses. The regression model will include baseline 
CLUE comfort scores, sequence of lens wear, lens type and first-order carryover as fixed 
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effects. Clinical site will be included as random effects. Other subject characteristics such as 
age, gender, race and iris category will be included when appropriate.  
 
The Model:  
Let 𝑦𝑖𝑗𝑘𝑙= (𝑦1𝑖𝑗𝑘𝑙 , 𝑦2𝑖𝑗𝑘𝑙 , 𝑦3𝑖𝑗𝑘𝑙) denote the CLUE Comfort score for the 𝑙𝑡ℎ subject at the 
𝑘𝑡ℎ site, assigned to the  𝑖𝑡ℎ lens using the 𝑗𝑡ℎ sequence at periods 1, 2 and 3.  The likelihood 
for 𝑦𝑖𝑗𝑘𝑙  is constructed as follows:  
𝑦𝑖𝑗𝑘𝑙 ~ N(𝜇𝑖𝑗𝑘, Σ)  
 
Where 𝜇𝑖𝑗𝑘𝑙 = (µ1𝑖𝑗𝑘𝑙 , µ2𝑖𝑗𝑘𝑙 , µ3𝑖𝑗𝑘𝑙)𝑇 and Σ is a 3X3 variance-covariance matrix. Here,  
µ1𝑖𝑗𝑘𝑙 = µ0 +  𝜋1 + 𝛽1𝐿𝑒𝑛𝑠[𝑖,𝑗] + 𝛽4baseline +  𝛽5𝑆𝑒𝑞𝑢𝑒𝑛𝑐𝑒𝑗                            +  𝛾𝑘  
µ2𝑖𝑗𝑘𝑙 = µ0 +  𝜋2 + 𝛽2𝐿𝑒𝑛𝑠[𝑖,𝑗] + 𝛽4baseline -   𝛽5𝑆𝑒𝑞𝑢𝑒𝑛𝑐𝑒𝑗+ 𝛽6𝐶𝑎𝑟𝑟𝑦1[𝑖,𝑗]+ 𝛾𝑘  
µ3𝑖𝑗𝑘𝑙 = µ0 +  𝜋3 + 𝛽3𝐿𝑒𝑛𝑠[𝑖,𝑗] + 𝛽4baseline +   𝛽5𝑆𝑒𝑞𝑢𝑒𝑛𝑐𝑒𝑗- 𝛽6𝐶𝑎𝑟𝑟𝑦1[𝑖,𝑗]+  𝛾𝑘  
 
In this model 𝜋1, 𝜋2, 𝜋3 represent the effect of period with the constraint 𝜋1 + 𝜋2 + 𝜋3= 0. 
Lens I will be determined by sequence j, therefore i is denoted as a function of j. We define 
Lens=0 for the control lens and Lens = 1  for the Test lens, sequence is defined as: 
Sequence=0 for the order Control/Test/Test and Sequence=1 for order Test/Control/Control. 
The first-order carryover effect will be defined as carry=0 for the Control lens and carry=1 
for the Test lens. So 𝛽1 stands for the difference between the Test and Control lens with 
respect to CLUE comfort; A positive 𝛽1 indicates the Test performed better than the control.  
 
We assume random site effect is independent and identically distributed (i.i.d) as  𝛾𝑘 ~ N(0, 
𝜎𝑠𝑖𝑡𝑒
2
)  for site for i=1, 2 (lens), j=1, 2, (sequence), k=1,2, 3, 4 and 5 (site) . 
 
For the β coefficients, independent non-informative priors N(0, 1000) will be used. For the 
variance of random effect of 𝜎𝑠𝑖𝑡𝑒
2
 an independent non-informative conjugate prior, inverse-
gamma(0.001, 0.001) will be used. For Σ, non-informative conjugate priors inverse-
wishart(3,S) will be used where S is a 3X3 variance-covariance matrix of  𝑦𝑖𝑗𝑘𝑙. Starting 
values for the mean and variance of CLUE scores will be 60 and 400 (since standard 
deviation of CLUE is normalized to be 20), respectively. The Metropolis sampler algorithm 
as implemented in the SAS/STAT MCMC procedure will be used to estimate the posterior 
distribution of the unknown parameters. Inferences will be made based on the 95% posterior 
credible intervals for relevant parameters.  
 
Hypothesis Testing 
The null and alternative hypotheses for CLUE comfort non-inferiority of the Test lens 
relative to the control lens are as follows:  
𝐻𝑜:  
𝛽1+ 𝛽2+ 𝛽3
3
≤ -5 
 
𝐻𝐴: 
𝛽1+ 𝛽2+ 𝛽3
3
 > -5 
 
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Non-inferiority will be declared if the lower bound of the 2-sided 95% credible interval of 
the difference between the Test lens and the control lens is greater than -5, i.e., P(
𝛽1+ 𝛽2+ 𝛽3
3
 > 
-5) ≥ 0.975. Superiority will be declared if the lower bound of the 2-sided 95% credible 
interval of the difference between the Test and Control lens is greater than 0, i.e., P(
𝛽1+ 𝛽2+ 𝛽3
3
 
> 0) ≥ 0.975. Superiority will only be tested if non-inferiority is established.  
 
Lens Fit Acceptance 
Lens fit acceptance will be analyzed using a Bayesian Logistic regression random-effects 
model to estimate the proportion of subjects eyes wearing the Test lens having acceptable 
lens fitting. The regression model will include period, sequence of lens wear and first order 
carryover effect. Site, subject nested within site and eye within subject within site will be 
included in the model as random effects.  
Let 𝑦𝑖𝑗𝑘𝑙𝑚=1 if an acceptable lens fit is observed for eyes wearing the Test lens only and 
𝑦𝑖𝑗𝑘𝑙𝑚=0 otherwise for the 𝑚𝑡ℎ subject, from the 𝑙𝑡ℎ site, for the 𝑖𝑡ℎ eye in the 𝑗𝑡ℎ period 
using the 𝑘𝑡ℎ sequence. 
yijklm ~ Binary (pijklm) 
 
pijklm = 
exp (𝑁𝑢𝑚𝑒𝑟𝑎𝑡𝑜𝑟)
1 + exp (𝑁𝑢𝑚𝑒𝑟𝑎𝑡𝑜𝑟) 
 
𝑁𝑢𝑚𝑒𝑟𝑎𝑡𝑜𝑟=  β0 + 𝛽1𝐿𝑒𝑛𝑠𝑖[𝑗,𝑘] + β3𝑝𝑒𝑟𝑖𝑜𝑑𝑗1 + β4𝑝𝑒𝑟𝑖𝑜𝑑𝑗2 + β5sequencek + β6𝐶𝑎𝑟𝑟𝑦1𝑖[𝑗,𝑘] +
γl + 𝛿𝑚(𝑙)+ 𝛼𝑗(𝑚(𝑙)) 
 
We assume the random subject eye effects are i.i.d as 𝛼𝑗(𝑚(𝑙))~N(0, 𝜎𝑒𝑦𝑒/𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
) for eye 
nested within subject within clinical site, the random effect for subject are i.i.d as  
𝛿𝑚(𝑙)~N(0,𝜎𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
) for subject nested within clinical site and the random clinical site 
effects are i.i.d as γm~N(0, 𝜎𝑠𝑖𝑡𝑒
2
) for i=1, 2 (eye) , j=1, 2, 3 (period) k=1, 2(Sequence) l=1, …5 
(Site) m=1, …𝑛𝑙(subject/site). 
 
For the β coefficients, independent non-informative priors N(0, 10000) will be used. For the 
variance of random effects of  𝜎𝑒𝑦𝑒/𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
, σsubject/site
2
 and σsite
2
, independent non-
informative conjugate priors inverse-gamma (0.001, 0.001) will be used. The Metropolis-
Hastings algorithm as implemented in the SAS/STAT 14.1 PROC MCMC procedure will be 
used to estimate posterior distributions of the unknown parameters. Inferences will be made 
based on the posterior credible interval for the relevant parameters.  
 
Hypothesis Testing 
With respect to Acceptable lens fit the null and alternative hypothesis for superiority is as 
follows: 
H0 = p ≤ 0.90  
H1 = p >  0.90 
 
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Where, p represents the proportion of subject eyes that achieve acceptable fit for the Test 
lens.  
Success for acceptable fit will be declared if the lower bound of the 2-sided 95% credible 
interval of the proportion is greater than 0.90; i.e. P(P > 0.90) ≥.975.  
 
Primary safety analysis: 
 
Slit Lamp Findings 
Grade 3 or higher slit lamp findings will be analyzed using a Bayesian Logistic regression 
random-effects model to compare the Test and Control lenses.  The regression model will 
include baseline slit lamp findings, lens type, period, sequence of lens wear and first order 
carryover effect. Site, subject nested within site and eye within subject within site will be 
included in the model as random effects.  
Let 𝑦𝑖𝑗𝑘𝑙𝑚𝑛=1 if a Grade 3 or higher SLF is observed and 𝑦𝑖𝑗𝑘𝑙𝑚=0 otherwise for the 𝑛𝑡ℎ 
subject, from the 𝑚𝑡ℎ site, assigned to the 𝑖𝑡ℎ study lens for the 𝑗𝑡ℎ eye in the 𝑘𝑡ℎ period 
using the 𝑙𝑡ℎ sequence. 
yijklmn ~ Binary (pijklmn) 
 
pijklmn = 
exp (𝑁𝑢𝑚𝑒𝑟𝑎𝑡𝑜𝑟)
1 + exp (𝑁𝑢𝑚𝑒𝑟𝑎𝑡𝑜𝑟) 
 
𝑁𝑢𝑚𝑒𝑟𝑎𝑡𝑜𝑟= β0 + 𝛽1𝐿𝑒𝑛𝑠𝑖𝑗[𝑘,𝑙] + β2Baseline SLFl + β3𝑝𝑒𝑟𝑖𝑜𝑑𝑘1 + β4𝑝𝑒𝑟𝑖𝑜𝑑𝑘2 +
 β5sequencek + β6𝐶𝑎𝑟𝑟𝑦1𝑖[𝑘,𝑙] + γm + 𝛿𝑛(𝑚) + 𝛼𝑗(𝑛(𝑚)) 
 
We assume the random subject eye effects are i.i.d as 𝛼𝑗(𝑛(𝑚))~N(0, 𝜎𝑒𝑦𝑒/𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
) for eye 
nested within subject within clinical site, the random effect for subject are i.i.d as  
𝛿𝑛(𝑚)~N(0, 𝜎𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
) for subject nested within clinical site and the random clinical site 
effects are i.i.d as γm~N(0, 𝜎𝑠𝑖𝑡𝑒
2
) for i=1,2 (lens), j=1, 2 (eye) , k=1, 2, 3 (period) l=1, 
2(Sequence) m=1, …5 (Site) m=1, …𝑛𝑚(subject/site). 
 
In this model, the lens I will be determined by the period k and sequence l, therefore i is 
denoted as a function of j and k. We define 𝐿𝑒𝑛𝑠𝑖=0 for the Control lens and 𝐿𝑒𝑛𝑠𝑖=1 for the 
Test lens. 
 
For the β coefficients, independent non-informative priors N(0, 10000) will be used. For the 
variance of random effects of  𝜎𝑒𝑦𝑒/𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
, σsubject/site
2
 and σsite
2
, independent non-
informative conjugate priors inverse-gamma (0.001, 0.001) will be used. The Metropolis-
Hastings algorithm as implemented in the SAS/STAT 14.1 PROC MCMC procedure will be 
used to estimate posterior distributions of the unknown parameters. Inferences will be made 
based on the posterior credible interval for the relevant parameters.  
 
Hypothesis Testing 
The null and alternative hypothesis for Non-inferiority is as follows:  
𝐻𝑜: p = ( 𝑝𝑇𝑒𝑠𝑡−𝑝𝐶𝑜𝑛𝑡𝑟𝑜𝑙) ≥ 0.05 
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𝑦𝑖𝑗𝑘𝑙𝑚~ Multinomial (𝑃𝑖𝑗𝑘𝑙𝑚1,  𝑃𝑖𝑗𝑘𝑙𝑚2 , 𝑃𝑖𝑗𝑘𝑙𝑚3, 𝑃𝑖𝑗𝑘𝑙𝑚4, 𝑃𝑖𝑗𝑘𝑙𝑚5) 
𝑃𝑖𝑗𝑘𝑙𝑚1 = 𝛾𝑖𝑗𝑘𝑙𝑚1 
𝑃𝑖𝑗𝑘𝑙𝑚𝑋= 𝛾𝑖𝑗𝑘𝑙𝑚𝑋-𝛾𝑖𝑗𝑘𝑙𝑚(𝑋−1) 2 ≤ n ≤4 
𝑃𝑖𝑗𝑘𝑙𝑚5 = 1 −∑𝑃𝑖𝑗𝑘𝑙𝑚𝑋
𝑥=1,..4
 
 
Logit( 𝛾𝑖𝑗𝑘𝑙𝑚𝑋)= 𝜃𝑛 + 𝛽1𝐿𝑒𝑛𝑠𝑖[𝑗,𝑘]  + 𝛽2𝑃𝑒𝑟𝑖𝑜𝑑𝑗1  +  𝛽3𝑃𝑒𝑟𝑖𝑜𝑑𝑗2  + 𝛽4𝑆𝑒𝑞𝑢𝑒𝑛𝑐𝑒𝑘 + 
𝛽5𝐶𝑎𝑟𝑟𝑦𝑖[𝑗,𝑘] +   𝛾𝑙 + 𝛿𝑚(𝑙) 
Where 𝜃𝑛is the intercept for levels n=1,2,3,4, 𝑃𝑖𝑗𝑘𝑙𝑚1 = Pr (𝛾𝑖𝑗𝑘𝑙𝑚1 = 1) with respect to 
outdoor glare preference. We assume the random subject effects are independent identically 
distributed (i.i.d) as 𝛿𝑚(𝑙)~N(0, 𝜎𝑠𝑢𝑏𝑗𝑒𝑐𝑡/𝑠𝑖𝑡𝑒
2
 )for subject m nested within clinical site l and the 
random clinical site effects are i.i.d as  𝛾𝑙~N(0, 𝜎𝑠𝑖𝑡𝑒
2
) for i=1,2 (lens), j=1, 2, 3 (Period) k=1, 
2(Sequence) l=1, …5 (Site) m=1, …𝑛𝑙(subject/site). 
In this model, the lens I will be determined by the period j and sequence k, therefore i is 
denoted as a function of j and k. We define 𝐿𝑒𝑛𝑠𝑖=0 for the Control lens and 𝐿𝑒𝑛𝑠𝑖=1 for the 
Test lens. The odds ratio for having higher rating can be written as OR=𝑒−𝛽1.  
 
Independent vague N(0, 1000) priors for the regression coefficients 𝛽𝑖 i=1,…5. For 𝜃𝑛, we 
are considering the following priors  
 
π0(θ1) ~ N(0,100) 
π0(θ2| θ1) ~ N(0,100)I(θ>θ1) 
π0(θ3| θ2) ~ N(0,100)I(θ>θ2) 
π0(θ4| θ3) ~ N(0,100)I(θ>θ3) 
For the variance of random effects independent vague normal priors will also be used; 
𝜎𝑃
2 ~inverse-gamma(0.001, 0.001) and 𝜎𝑠
2 ~inverse-gamma(0.001, 0.001). The Metropolis 
sample algorithim as implemented in the SAS/Stat MCMC Procedure will be used to 
estimate the posterior distributions of the unknown parameters. Inferences will be made 
based on the posterior credible interval for the relevant parameters.  
 
Hypothesis Testing 
The null and alternative hypotheses for superiority are as follows:  
𝐻𝑜  𝑂𝑅≤ 1 
𝐻𝐴 𝑂𝑅 > 1 
 
Where OR represent the odds ratio of having higher rating of the Test lens compared to the 
Control lens. Superiority will be declared if the lower bound of the 2-sided 95% credible 
confidence interval is above 1, i.e. P(OR=𝑒−𝛽1>1|y)=0.975. 
 
Indoor Glare Reduction 
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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.  
 
External Date Sources for this study include: If external Data is collected outside of EDC, 
enter vendor contact information in this section of the protocol and type of external data 
collected. Enter information for each external data source. 
 Vendor Name:  
 Vendor Address:  
 Vendor Contact:  
 Phone:  
 Email:  
 Type of Data collected: 
 
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.  
 
The content and structure of the eCRFs are compliant with ISO14155:2011. 
15.2. Subject Record 
At a minimum, subject record should be available for the following:  
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 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. 
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-
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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 risks, benefits, and potential adverse events of the study, and provide their 
consent voluntarily will be enrolled. 
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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), 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 2013 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), 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) 
 Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB) 
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 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, current ICH and GCP 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 
compliance with the Data Protection Act of 1998 and other applicable personal data 
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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 
19. STUDY RECORD RETENTION 
In compliance with the ICH/GCP guidelines, 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/GCP Section 8, Essential Documents for the Conduct of 
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a Clinical Trial, 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 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 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 Investigator’s 
Research Agreement.  The Research Agreement will be signed by the Principal Investigator 
and a JJVC management representative prior to study initiation. 
 
Case Report Forms will be completed in real time according to the study procedures 
specified in the study protocol.  Case Report Forms should be completed and reviewed and 
signed as applicable by the Investigator within 3 days of visit completion.  Data queries must 
be addressed with complete responses within 3 days of generation.  JJVC reserves the right to 
withhold remuneration until these activities are addressed. 
 
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 
21. PUBLICATION 
This study will be registered on ClinicalTrials.gov. 
 
 
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APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES) 
 
 
 
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APPENDIX B: PATIENT INSTRUCTION GUIDE  
 
Patient Instruction Guide will be provided separately.  
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APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) 
 
 
 
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 LIMBAL AND CONJUNCTIVAL (BULBAR) REDNESS 
 
 
 
 
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EXPANDED SODIUM FLUORESCEIN CORNEAL STAINING  
 
 
 
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LENS FITTING CHARACTERISTICS  
 
 
 
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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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DETERMINATION OF DISTANCE SPHEROCYLINDRICAL 
REFRACTIONS 
 
 
 
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BIOMICROSCOPY SCALE 
 
 
 
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 DISTANCE AND NEAR VISUAL ACUITY EVALUATION 
 
 
 
 
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DISTANCE LOGMAR VISUAL ACUITY MEASUREMENT 
PROCEDURE 
 
 
 
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APPENDIX E: IRIS COLOR   
 
 
 
 
 
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PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE 
Protocol Number and Title: CR-5960, Evaluation of Approved and Investigational Contact 
Lenses 
Version and Date: v2.0, 14 June 2017 
 
I have read and understand the protocol specified above and agree on its content.   
 
I agree to conduct this study according to GCP and ICH guidelines, the Declaration of 
Helsinki, ISO 14155, United States (US) Code of Federal Regulations (CFR), 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 ICH 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 ICH 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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