Evaluation of the Clinical Performance of Daily Disposable Silicone Hydrogel Multifocal Toric Contact Lenses
Phase: NA
Conditions: Visual Acuity
Sponsor: Johnson & Johnson Vision Care, Inc.

Clinical Study Protocol 
Johnson & Johnson Vision Care, Inc. 
Protocol Title: Evaluation of the clinical performance of Daily Disposable Silicone Hydrogel 
Multifocal Toric Contact Lenses 
Protocol Number: CR-6542 
Version: 4.0  
Date: 25 March 2024 
Investigational products: JJVC Investigational Multifocal Toric Contact Lenses manufactured 
in Senofilcon A (C3) material with UV blocker and HEV filter 
Key Words: Presbyopia, Multifocal, Astigmatism, Daily Wear, Daily Disposable, Dispensing, 
senofilcon A, logMAR visual acuity, CLUE questionnaire, Single arm 
Statement of Compliance to protocol, GCP and applicable regulatory guidelines: 
This trial will be conducted in compliance with ISO 14155:2020 Clinical investigation of 
medical devices for human subjects – Good clinical practice1, the Declaration of Helsinki2, and 
all applicable regulatory requirements3. 
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 AND DATE...................................................... 7 
SPONSOR NAME AND ADDRESS ....................................................................................... 7 
MEDICAL MONITOR ............................................................................................................. 7 
AUTHORIZED SIGNATURES ............................................................................................... 8 
CHANGE HISTORY.............................................................................................................. 10 
SYNOPSIS .............................................................................................................................. 11 
COMMONLY USED ABBREVIATIONS, ACRONYMS AND DEFINITIONS OF TERMS
................................................................................................................................................. 17 
1. 
INTRODUCTION AND BACKGROUND ................................................................... 19 
1.1. 
Name and Descriptions of Investigational Products ................................................ 19 
1.2. 
Intended Use of Investigational Products................................................................. 19 
1.3. 
Summary of Findings from Nonclinical Studies ...................................................... 19 
1.4. 
Summary of Known Risks and Benefits to Human Subjects ................................... 19 
1.5. 
Relevant Literature References and Prior Clinical Data Relevant to Proposed Clinical 
Study…. .............................................................................................................................. 19 
2. 
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES ...................................... 21 
2.1. 
Objectives ................................................................................................................. 21 
2.2. 
Endpoints .................................................................................................................. 21 
2.2.1. 
Co-Primary Efficacy Endpoints .................................................................... 21 
2.2.2. 
Co-Primary Safety Endpoints........................................................................ 22 
2.2.3. 
Secondary Efficacy Endpoints ...................................................................... 23 
2.3. 
Hypotheses ............................................................................................................... 23 
2.3.1. 
Co-Primary Efficacy Hypotheses .................................................................. 23 
2.3.2. 
Co-Primary Safety Hypotheses ..................................................................... 24 
2.3.3. 
Secondary Efficacy Hypotheses .................................................................... 24 
3. 
TARGETED STUDY POPULATION ........................................................................... 25 
3.1. 
General Characteristics ............................................................................................ 25 
3.2. 
Inclusion Criteria ...................................................................................................... 25 
3.3. 
Exclusion Criteria ..................................................................................................... 25 
3.4. 
Enrollment Strategy.................................................................................................. 26 
4. 
STUDY DESIGN AND RATIONALE .......................................................................... 27 
4.1. 
Description of Study Design .................................................................................... 27 
4.2. 
Study Design Rationale ............................................................................................ 27 
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4.3. 
Enrollment Target and Study Duration .................................................................... 27 
5. 
TEST ARTICLE ALLOCATION AND MASKING ..................................................... 27 
5.1. 
Test Article Allocation ............................................................................................. 27 
5.2. 
Masking .................................................................................................................... 28 
5.3. 
Procedures for Maintaining and Breaking the Masking........................................... 28 
6. 
STUDY INTERVENTION ............................................................................................. 28 
6.1. 
Identity of Test Articles............................................................................................ 28 
6.2. 
Ancillary Supplies/Products ..................................................................................... 29 
6.3. 
Administration of Test Articles ................................................................................ 29 
6.4. 
Packaging and Labeling ........................................................................................... 30 
6.5. 
Storage Conditions ................................................................................................... 30 
6.6. 
Collection and Storage of Samples .......................................................................... 30 
6.7. 
Accountability of Test Articles ................................................................................ 30 
7. 
STUDY EVALUATIONS .............................................................................................. 31 
7.1. 
Time and Event Schedule ......................................................................................... 31 
7.2. 
Detailed Study Procedures ....................................................................................... 33 
VISIT 1…. ...................................................................................................................... 33 
VISIT 2…. ...................................................................................................................... 41 
VISIT 3…. ...................................................................................................................... 47 
FINAL EVALUATION .................................................................................................. 49 
7.3. 
Unscheduled Visits ................................................................................................... 50 
7.4. 
Laboratory Procedures ............................................................................................. 52 
8. 
SUBJECTS COMPLETION/WITHDRAWAL.............................................................. 53 
8.1. 
Completion Criteria .................................................................................................. 53 
8.2. 
Withdrawal/Discontinuation from the Study ........................................................... 53 
9. 
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION ................. 54 
9.1. 
Systemic Medications .............................................................................................. 54 
10. 
DEVIATIONS FROM THE PROTOCOL .................................................................. 54 
11. 
STUDY TERMINATION ........................................................................................... 56 
12. 
PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS .............. 56 
13. 
ADVERSE EVENTS ................................................................................................... 57 
13.1. Definitions and Classifications................................................................................. 57 
13.2. Assessing Adverse Events ........................................................................................ 60 
13.2.1. 
Causality Assessment .................................................................................... 60 
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13.2.2. 
Severity Assessment ...................................................................................... 61 
13.3. Documentation and Follow-Up of Adverse Events ................................................. 61 
13.4. Reporting Adverse Events ........................................................................................ 62 
13.4.1. 
Reporting Adverse Events to Sponsor .......................................................... 62 
13.4.2. 
Reporting Adverse Events to the Responsible IEC/IRB and Health 
Authorities…................................................................................................................... 63 
13.5. Event of Special Interest .......................................................................................... 63 
13.6. Reporting of Pregnancy ............................................................................................ 63 
14. 
STATISTICAL METHODS ........................................................................................ 64 
14.1. General Considerations ............................................................................................ 64 
14.2. Sample Size Justification ......................................................................................... 64 
14.3. Analysis Populations ................................................................................................ 69 
14.4. Level of Statistical Significance ............................................................................... 69 
14.5. Primary Analysis ...................................................................................................... 69 
14.5.1. 
Co-Primary Efficacy Analyses ...................................................................... 69 
14.5.2. 
Co-Primary Safety Analyses ......................................................................... 73 
14.6. Secondary Analyses ................................................................................................. 74 
14.7. Exploratory Analyses ............................................................................................... 77 
14.8. Interim Analysis ....................................................................................................... 77 
14.9. Procedure for Handling Missing Data and Drop-Outs ............................................. 77 
14.10. Procedure for Reporting Deviations from Statistical Plan ....................................... 77 
15. 
DATA HANDLING AND RECORD KEEPING/ARCHIVING ................................ 77 
15.1. Electronic Case Report Form/Data Collection ......................................................... 77 
15.2. Subject Record ......................................................................................................... 78 
15.3. Trial Registration on ClinicalTrials.gov................................................................... 78 
16. 
DATA MANAGEMENT............................................................................................. 78 
16.1. Access to Source Data/Document ............................................................................ 78 
16.2. Confidentiality of Information ................................................................................. 79 
16.3. Data Quality Assurance ............................................................................................ 79 
16.4. Data Monitoring Committee .................................................................................... 79 
17. 
CLINICAL MONITORING ........................................................................................ 79 
18. 
ETHICAL AND REGULATORY ASPECTS ............................................................ 80 
18.1. Study-Specific Design Considerations ..................................................................... 80 
18.2. Investigator Responsibility ....................................................................................... 80 
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18.3. Independent Ethics Committee or Institutional Review Board (IEC/IRB) .............. 80 
18.4. Informed Consent ..................................................................................................... 81 
18.5. Privacy of Personal Data .......................................................................................... 82 
19. 
STUDY RECORD RETENTION................................................................................ 83 
20. 
FINANCIAL CONSIDERATIONS ............................................................................ 84 
21. 
PUBLICATION ........................................................................................................... 84 
22. 
REFERENCES ............................................................................................................ 84 
APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES) ..... 86 
APPENDIX B: PATIENT INSTRUCTION GUIDE ........................................................... 107 
APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) ....................................... 108 
APPENDIX D: LENS FITTING GUIDE ............................................................................. 109 
APPENDIX E: PRESBYOPIC SYMPTOMS QUESTIONNAIRE ..................................... 113 
APPENDIX F: OCULAR DOMINANCE............................................................................ 114 
APPENDIX G: BINOCULAR OVER REFRACTION ....................................................... 115 
APPENDIX H: 
 .................................... 116 
, DETERMINATION OF NEAR ADDITION .................................................... 117 
, NEAR logMAR VISUAL ACUITY MEASUREMENT PROCEDURE .......... 123 
, LENS FITTING CHARACTERISTICS ............................................................ 126 
, SUBJECT REPORTED OCULAR SYMPTOMS ............................................. 132 
, DETERMINATION OF DISTANCE SPHEROCYLINDRICAL REFRACTIONS
............................................................................................................................................... 134 
, BIOMICROSCOPY SCALE ............................................................................. 140 
, KERATOMETRY .............................................................................................. 146 
, DISTANCE AND NEAR VISUAL ACUITY EVALUATION ........................ 148 
, TORIC FIT EVALUATION .............................................................................. 153 
, DISTANCE LogMAR VISUAL ACUITY MESAUREMENT PROCEDURE 158 
, VISUAL ACUITY CHART LUMINANCE AND ROOM ILLUMINATION     
TESTING .............................................................................................................................. 162 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE ........................ 171 
 
LIST OF FIGURES 
Figure 1: Study Flowchart ...................................................................................................... 16 
 
 
 
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LIST OF TABLES 
Table 1: Test Article ............................................................................................................... 28 
Table 2: Ancillary Supplies .................................................................................................... 29 
Table 3: Time and Events ....................................................................................................... 31 
Table 4: Disallowed systemic medications ............................................................................. 54 
Table 5: Examples of major and minor protocol deviations ................................................... 55 
Table 6: Sample Size Estimates by Study Endpoint ............................................................... 65 
Table 7:  Historical Data by Endpoint .................................................................................... 66 
 
 
 
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SYNOPSIS  
Protocol Title 
Evaluation of the clinical performance of Daily Disposable 
Silicone Hydrogel Multifocal Toric Contact Lenses 
Sponsor 
JJVC, 7500 Centurion Parkway, Jacksonville, FL 32256 
Clinical Phase 
Clinical trial phase: Confirmatory (Design Validation Study) 
Design control phase: 3 
Trial Registration 
This study will be registered on ClinicalTrials.gov based on 
the following: The purpose of the study is for confirmation of 
lens performance, not feasibility. 
Test Article 
Investigational Product: JJVC Investigational Multifocal 
Toric Contact Lens manufactured in Senofilcon A (C3) 
material with UV blocker / HEV filter 
Wear and Replacement 
Schedules 
Wear Schedule: The study lenses will be used on a daily 
disposable basis. 
Replacement Schedule: The study lenses will be replaced each 
day of wear or if lost or damaged. 
Objectives  
Primary Objectives 
The primary objectives of this study are to demonstrate that 
the investigational multifocal toric contact lens in its final lens 
design made on the 3GT platform, meets the validation 
requirements with respect to visual acuity (logMAR), 
subjective CLUE vision scores, lens fit acceptance, toric fit 
acceptance, and ocular health.  
 
Secondary Objectives 
The secondary objectives of this study are to demonstrate that 
the investigational lens meet the users’ needs in subjective 
CLUE comfort and handling scores and lens fit success. 
Although CLUE vision scores are a part of the primary 
objectives, an additional secondary objective is to 
demonstrate the value proposition of the investigational lens 
with respect to subject CLUE vision scores. The value 
proposition for this product requires a more stringent 
threshold, compared to the primary objective, to meet the 
user’s needs in terms of CLUE vision scores.  
 
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Study Endpoints 
Primary Endpoints 
1. Visual Acuity (logMAR)- Distance (4m),  
2. Visual Acuity (logMAR)- Intermediate (64cm)  
3. Visual Acuity (logMAR)- Near (40cm) 
4. CLUE Vision scores 
5. Percentage of eyes with an unacceptable lens fit  
6. Percentage of lens fits with rotation stability within 5 
degrees at 15 minutes after insertion  
7. Percentage of lens fits with absolute rotation error 
within 10 degrees at 15 minutes after insertion  
8. Percentage of eyes with Grade 3 or 4 slit lamp findings 
related to the Test lens   
 
Secondary Endpoints 
1. CLUE Vision scores (with modified criteria) 
2. CLUE Comfort scores 
3. CLUE Handling scores 
4. Lens Fit Success [Number of lenses needed to fit 
(optimize) the subject’s vision] 
 
Study Design 
This is an open-label, 3-visit, single-arm, dispensing clinical 
trial. 
Approximately 155 subjects will be enrolled with the aim that 
approximately 140 subjects will complete. At Visit 1, eligible 
subjects will be fit in the study lenses and dispensed for 7±1 
days.  Subjects will return for Visit 2 for lens optimization and 
will be dispensed the optimized pair for 7±1 days. At the 
follow-up visit (Visit 3), study endpoints will be measured, 
and the exit evaluation will be performed.  
 
See the flowchart (Figure 1) at the end of the synopsis table 
for the schematic of the study visits and procedures of main 
observations. 
Sample Size 
Approximately 155 subjects will be enrolled (targeting 93 
myopic and 62 hyperopic subjects with astigmatism) with the 
aim of completing 140 subjects (approximately 84 myopes 
and 56 hyperopes).   
Study Duration 
Each individual subject is expected to attend for 3 study visits 
over a period of approximately 2 weeks. The total study 
duration from first subject’s first visit (FSFV) to last subject’s 
last visit (LSLV) is expected to be approximately 8 to 12 
weeks. 
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Anticipated Study 
Population 
Healthy male and female volunteers with presbyopia, 
ametropia (hyperopia or myopia) and astigmatism will be 
screened as per criteria outlined below.  All volunteers will 
have baseline measurements taken to ensure eligibility.  The 
baseline procedures will occur after informed consent has 
been obtained.   
For a detailed list of procedures see the time and events 
schedule listed below.     
Eligibility Criteria - 
Inclusion 
Potential subjects must satisfy all of the following criteria to 
be enrolled in the study: 
 
Inclusion Criteria following Screening 
The subject must: 
  
1. Read, understand, and sign the STATEMENT OF 
INFORMED CONSENT and receive a fully executed 
copy of the form. 
2. Appear able and willing to adhere to the instructions 
set forth in this clinical protocol. 
3. Be at least 40 and not more than 70 years of age at 
the time of screening. 
4. Own a wearable pair of spectacles if required for 
their distance vision. 
5. Be an adapted soft contact lens wearer in both eyes 
(i.e. worn lenses for at least 8 hours per day at least 
two days per week for the past 4 weeks). 
6. Be already wearing a presbyopic contact lens 
correction (e.g., reading spectacles over contact 
lenses, multifocal or monovision contact lenses, etc.) 
or if not respond positively to at least one symptom 
on the “Presbyopic Symptoms Questionnaire”.  
 
Inclusion Criteria at Baseline Evaluation: 
 
7. The subject’s distance spherical component of their 
refraction must be in the range of either -1.25 D to -
3.75 D, or +1.25 D to +4.25 D. 
8. The subject’s refractive cylinder must be in the range 
of -1.00 D to -1.75 D in each eye, with the cylinder 
axes in the range of either 90° ± 15° or 180° ± 15°. 
9. The subject’s ADD power must be in the range of 
+0.75 D to +2.50 D in each eye. 
10. The subject must have best corrected distance visual 
acuity of 20/20-3 or better in each eye. 
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Eligibility Criteria - 
Exclusion 
Potential subjects who meet any of the following criteria will 
be excluded from participating in the study:  
 
Exclusion Criteria following Screening 
The subject must not: 
 
1. Be currently pregnant or lactating. 
2. By self-report, have any systemic disease (e.g. Sjögren’s 
Syndrome), allergies, infectious disease (e.g., hepatitis, 
tuberculosis), contagious immunosuppressive diseases 
(e.g., HIV), autoimmune disease (e.g. rheumatoid 
arthritis), or other diseases, which are known to interfere 
with contact lens wear and/or participation in the study. 
3. Use systemic medications that may interfere with contact 
lens wear or cause blurred vision. See Section 9.1 for 
additional 
details 
regarding 
excluded 
systemic 
medications.  
4. Currently use ocular medication (with the exception of 
rewetting drops). 
5. Have any known hypersensitivity or allergic reaction to 
single use preservative free rewetting drops or sodium 
fluorescein. 
6. Have had any previous, or have any planned, ocular or 
intraocular surgery (e.g. radial keratotomy, PRK, LASIK, 
cataract surgery, retinal surgery, etc.). 
7. Have had previous eyelid injuries, surgeries or procedures 
which are known to have caused abnormal eyelid position 
or movement, by self-report. 
8. Have participated in any contact lens or lens care product 
clinical trial within 7 days prior to study enrollment. 
9. Be an employee or immediate family member of an 
employee of clinical site (e.g., Investigator, Coordinator, 
Technician). 
10. Have a history of amblyopia or strabismus, by self-report. 
11. Have a history of herpetic keratitis, by self-report. 
 
Exclusion Criteria at Baseline Evaluation 
The subject must not: 
 
12. Have ocular allergies, infections or other ocular 
abnormalities that are known to interfere with contact lens 
wear and/or participation in the study. This may include, 
but not be limited to entropion, ectropion, chalazia, 
recurrent styes, glaucoma, history of recurrent corneal 
erosions, aphakia, or corneal distortion.  
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13. Have any Grade 3 or greater slit lamp findings (e.g., 
edema, corneal neovascularization, corneal staining, tarsal 
abnormalities, conjunctival injection) on the FDA scale. 
Disallowed 
Medications/Interventions  
Use of any prescription or over-the-counter (OTC) 
medications that may affect contact lens wear.   
See Section 9.1 for details regarding disallowed systemic 
medications. 
Measurements and 
Procedures 
logMAR visual acuity charts for distance and near vision.  
Subjective responses for vision, comfort and lens handling 
using the CLUE questionnaire, as well as MRD questions.  
Lens rotation assessment will be made using a slit lamp 
biomicroscope with an adjustable beam orientation and axis 
dial, or an eyepiece reticle with axis protractor.  
Microbiology or Other 
Laboratory Testing 
None 
Study Termination 
The occurrence of one or more Unanticipated Adverse Device 
Effect (UADE), or any SAE where relationship to study agent 
cannot be ruled out, may result in stopping the further 
dispensing of investigational product.  In the event of a UADE 
or SAE, the Sponsor Medical Monitor will discuss this with 
the Principal Investigator before any further subjects are 
enrolled. 
Ancillary Supplies/ Study-
Specific Materials 
Non-preserved saline and RevitaLens MPDS.  Lens cases for 
storage of subject’s habitual lenses.  Lens vials and caps and 
materials for returning worn contact lenses will be supplied to 
sites. 
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, ACRONYMS 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 
CI 
 
 
Confidence Interval or Credible Interval (Bayesian) 
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 
 
 
 
 
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 
MPDS  
 
Multi-Purpose Disinfecting Solution 
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 
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PD 
 
 
Protocol Deviation 
PHI 
 
 
Protected Health Information 
PI 
 
 
Principal Investigator 
PIG 
 
 
Patient Instruction Guide 
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 
SLF 
 
 
Slit Lamp Findings 
SOP 
 
 
Standard Operating Procedure 
UADE  
 
Unanticipated Adverse Device Effect 
USADE 
 
Unanticipated Serious Adverse Device Effect 
VA 
 
 
Visual Acuity 
 
 
 
 
 
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1. INTRODUCTION AND BACKGROUND 
Johnson & Johnson Vision launched their most recent multifocal contact lens called 
ACUVUE® OASYS 1-DAY MAX MULTIFOCAL in 2022.  The lens is recommended for 
presbyopes who have up to -0.75 D of refractive cylinder.  There is a considerable population 
of presbyopic patients who have greater than -0.75 D of cylinder, in one or both eyes.  Currently 
there are a limited number of soft toric multifocal lenses available.  This study will evaluate 
the performance of prototype daily disposable multifocal toric lenses with a similar multifocal 
optics design to ACUVUE® OASYS 1-DAY MAX MULTIFOCAL and manufactured in the 
same senofilcon A (C3) material with an added high energy visible (HEV) light filter. The 
performance of the lens will be compared to historical control values. 
1.1. Name and Descriptions of Investigational Products 
Test Article:  JJVC Investigational Multifocal Toric Contact Lenses manufactured in 
Senofilcon A (C3) material with UV blocker / HEV filter  
Refer to Table 1 in Section 6.1 the protocol.    
1.2. Intended Use of Investigational Products 
The intended use of the Investigational Test lens is for the optical correction of distance and 
near vision in presbyopic persons with non-diseased eyes who have 0.75D to 1.75D of 
astigmatism. In this study, the lenses will be used in a population of presbyopes who require 
+1.25 D to +4.25 D or -1.25 D to -3.75 D of spherical correction, -1.00 D to -1.75 D of cylinder 
at axes 90°±15° or 180°±15° and ADD powers of +0.75 D to +2.50 D (see Section 3.2). 
1.3. Summary of Findings from Nonclinical Studies 
All previous pre-clinical findings were deemed satisfactory prior to proceeding with clinical 
trials on humans. For the most comprehensive nonclinical information regarding JJVC 
Multifocal Toric Contact Lenses manufactured in senofilcon A material refer to the latest 
version of the CR-6542 Investigator's Brochure4. 
1.4. Summary of Known Risks and Benefits to Human Subjects 
For the most comprehensive risk and benefit information regarding JJVC Multifocal Toric 
Contact Lenses manufactured in senofilcon A material refer to the latest version of the CR- 
6542 Investigator’s Brochure4. 
1.5. Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study 
Investigational multifocal toric lenses with similar designs and materials have been evaluated 
in three prior dispensing clinical studies and one non-dispensing clinical study. A summary of 
these studies is shown below, and relevant safety information for these studies is included in 
the CR-6542 Investigator’s Brochure4. 
 
 was a single-arm dispensing evaluation of multifocal toric investigational lenses in 
a myopic population with against-the-rule astigmatism.  Lenses used in this study had a slightly 
different material formulation than the lenses used in subsequent studies (
, 
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 and the current CR-6542 study).  The study lenses were worn for 
approximately 2 weeks (with a first follow-up visit after 6-8 days, and second follow-up visit 
after a further 6-8 days).  Forty subjects were enrolled in the study and thirty-seven completed 
it.  No adverse events were reported. 
 
 was a single-arm dispensing evaluation of multifocal toric investigational lenses in 
a hyperopic population with against-the-rule astigmatism.  This study tested lenses with an 
older formulation (same as the one used in 
) in comparison with a newer formulation 
(same as the one used in later studies).  In the 2×3 crossover study design involving 6 visits, 
subjects wore one of the study lens types for approximately 2 weeks, and the other study lens 
type for approximately 3 weeks.   Thirty-five subjects were enrolled, with 3 screen failures and 
3 discontinuations.  Of the 29 subjects who completed the study, one was excluded from the 
Per Protocol Population. One non-significant ocular adverse event which led to the subject 
being discontinued from the study was determined to be not related to the study lens.  Another 
non-significant ocular adverse event for a subject who completed the study was considered as 
unlikely related to the test article. 
 
 was a single-arm, single-masked dispensing evaluation of multifocal toric 
investigational lenses with 4 study visits (fitting visit, optimization visit, then follow-up visits 
after 1 and 2 further weeks of wear).   The subjects were required to have distance spherical 
component of their refraction in the range of either -1.25 D to -3.75 D, or +1.25 D to +3.75 D; 
and refractive cylinder in the range of -1.00 D to -1.50 D with axes in the range of 90°±30°.   
Ninety-five subjects were enrolled, of whom 9 were screen failures that were not administered 
the test article.  Of the 86 subjects (48 myopes and 38 hyperopes) who wore the study lens, 2 
discontinued the study and 1 was excluded from cohort.  As a result, the Per Protocol 
population was 83 subjects (48 myopes and 35 hyperopes).  There were no adverse events 
reported for the study. 
 
 was a bilateral, single-masked, single-visit, non-dispensing crossover study of 
investigational multifocal toric lenses with cylinder corrections of -1.00 and -1.75 diopters.  
Lens performance in terms of rotation, initial comfort and lens handling was assessed for 
participants representing four segments of the population (myopic with with-the-rule 
astigmatism, myopic with against-the-rule astigmatism, hyperopic with with-the-rule 
astigmatism, and hyperopic with against-the-rule astigmatism).   A total of 102 subjects were 
enrolled, and all completed the study.  No adverse events were reported. 
 
In addition to these multifocal toric studies, a series of studies have been performed on the 
non-toric multifocal version of the study lens during the development of Acuvue® Oasys 1-
Day Max Multifocal.  Further details of the safety profile of these related lens types are 
included in the CR-6542 Investigator’s Brochure4. 
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2. STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES 
2.1. Objectives  
Primary Objectives 
The primary objectives of this study are to demonstrate that the investigational multifocal toric 
contact lens in its final lens design made on the 3GT platform, meets the validation 
requirements with respect to visual acuity (logMAR), subjective CLUE vision scores, lens fit 
acceptance, toric fit acceptance, and ocular health.  
 
Secondary Objectives 
The secondary objectives of this study are to demonstrate that the investigational lens meet the 
users’ needs in subjective CLUE comfort and handling scores and lens fit success. Although 
CLUE vision scores are a part of the primary objectives, an additional secondary objective is 
to demonstrate the value proposition of the investigational lens with respect to subjective 
CLUE vision scores. The value proposition for this product requires a more stringent threshold, 
compared to the primary objective, to meet the user’s needs in terms of CLUE vision scores.  
2.2. Endpoints  
2.2.1. Co-Primary Efficacy Endpoints 
2.2.1.1. High Luminance High Contrast (HLHC) Binocular logMAR Visual Acuities  
  
Multiple additional assessments of binocular and monocular visual acuity will be made at all 
three distances (4m, 64cm and, 40cm) during the study, but the binocular measurements taken 
at the 2-Week follow-up in the optimized lens pair using high contrast letters in bright 
illuminance conditions will be the primary endpoint. The logMAR visual acuity scores at each 
position are continuous co-primary endpoints.  
 
• VA will be evaluated for 3 different distances. At distance (4 meters), VA will be 
assessed using ETDRS Charts; while near (40 cm) and intermediate (64 cm) 
assessments will be made using reduced Guillon-Poling charts.  Additional visual 
acuity will be measured using high and low contrast charts in bright illuminance 
conditions.   
• Visual acuity will also be measured using high contrast charts in dim illuminance 
conditions (created by the use of goggles) . 
 
in Appendix H for details regarding the collection of visual acuity (logMAR).   
 
2.2.1.2. Subjective Vision CLUE Scores  
Subjective vision scores assessed using the Contact Lens User Experience (CLUE™) 
questionnaire at the 2-Week follow-up in the optimized lens pair will be the co-primary 
endpoint. The overall vision score is a continuous endpoint.    
 
CLUE is a validated patient-reported outcomes questionnaire to assess patient-experience 
attributes of soft, disposable contact lenses (comfort, vision, handling, and packaging) in a 
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contact-lens wearing population in the US, ages 18-659.  Derived CLUE™ scores using Item 
Response Theory (IRT) follow a normal distribution with a population average score of 60 
(SD 20), where higher scores indicate a more favorable/positive response with a range of 0-
120.  A 5-point increase in an average CLUE™ score translates into 10% shift in the 
distribution of scores for population of soft contact lens wearers.  
 
2.2.1.3. Rotational Stability 
Rotational stability assessed at least 15 minutes after lens insertion at the dispensing visit (Visit 
1) is the co-primary endpoint.  
 
Rotation stability will be assessed for each eye at least 15 minutes after lens insertion at the 
fitting visit, and also at each follow-up visit. Rotational stability is amount of observed 
rotational movement of the lens’ scribe markings in degrees that occurs while blinking in 
primary gaze. Rotational stability will be converted into a binary endpoint for the purpose of 
statistical analyses, where Y=1 if the lens stability with blinks is ≤ 5° and Y=0, otherwise. 
 
2.2.1.4. Absolute Rotation Error 
Absolute rotation error assessed at least 15 minutes after lens insertion at the dispensing visit 
(Visit 1) is the co-primary endpoint.  
 
Absolute rotation error is quantified by the absolute value of mis-location of the lens’ scribe 
markings in degrees relative to a vertical reference line.  It is measured for each eye at 1, 3 and 
at least 15 minutes after lens insertion at the fitting visit, and also at each follow-up visit. 
Absolute rotation error will be converted into a binary endpoint for the purpose of statistical 
analyses where Y=1 if the absolute toric lens rotation is ≤ 10° and Y=0, otherwise. 
2.2.2. Co-Primary Safety Endpoints 
2.2.2.1. Incidence of Unacceptable Lens Fit 
The co-primary safety endpoint is the incidence (percentage) of eyes with unacceptable fitting 
at any time during the study.  
 
Unacceptable lens fit will be assessed at all study visits (scheduled and unscheduled) for each 
eye. Eyes with multiple unacceptable fitting events and or with multiple criteria met at a given 
visit will be counted only once. Unacceptable lens fit is a binary response where Y=1 if lens 
fit is unacceptable and Y=0 otherwise. Lens fit is defined as “unacceptable” if any one of the 
following criteria is met: 
• limbal exposure at primary gaze or with extreme eye movement; 
• edge lift; 
• excessive movement in primary gaze; 
• insufficient movement in all three of the following conditions: primary gaze, up gaze, 
and push up test. 
 
 in Appendix H for additional details regarding lens fit assessments.  
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2.2.2.2. Slit Lamp Findings 
The co-primary safety endpoint is the incidence (percentage) of eyes with Grade 3 or higher 
SLF (including any corneal infiltrates) related to the Test lens. 
 
Slit Lamp Findings (Grade 3 or higher) will be assessed for each subject eye at all study visits 
(scheduled and unscheduled). SLFs will be evaluated and classified using the FDA Grading 
scale rating from 0 to 4, where Grade 0 represents the absence of findings and 1 to 4 
representing successively worse findings (i.e., Grade 1=trace, Grade 2=mild, Grade 
3=moderate and Grade 4=severe). Eyes with multiple SL findings of Grade≥3 at different 
timepoint during the visit, or with different grade level over time, will be counted only once. 
 
2.2.3. Secondary Efficacy Endpoints 
• Subjective Handling Scores at the 2-Week follow-up visit will be assessed using the 
CLUE™ questionnaire. The overall mean handling score is a continuous endpoint.  
 
• Subjective Comfort Scores at the 2-Week follow-up visit will be assessed using the 
CLUE™ questionnaire. The overall mean comfort score is a continuous endpoint.  
 
• Subjective Vision Scores at the 2-Week follow-up visit will be assessed using the 
CLUE™ questionnaire. The overall vision score is a continuous endpoint.  
 
• Lens Fit Success is the number of lenses needed to fit (optimize) the subject’s vision. 
Lens fit success is a binary endpoint where, Y=1 if a subject’s vision was optimized in 
four lenses or less, and Y=0, otherwise.   The number of lenses needed is determined 
using lens selection data from both Visit 1 and Visit 2. 
2.3. Hypotheses 
All Co-Primary Efficacy and Safety hypotheses listed below must be statistically significantly 
demonstrated to satisfy the study objectives.  
2.3.1. Co-Primary Efficacy Hypotheses  
1. After approximately 2-weeks of wear, the mean HLHC distance (4 m) visual acuity 
score of the Test lens will be statistically significantly lower than 0.00 logMAR 
(equivalent to 20/20 on Snellen Visual Acuity scale). 
2. After approximately 2-Weeks of wear, the mean HLHC intermediate (64 cm) visual 
acuity score of the Test lens will be statistically significantly lower than 0.17 logMAR 
(equivalent to 20/30 on Snellen Visual Acuity scale). 
3. After approximately 2-Weeks of wear, the mean HLHC near (40 cm) visual acuity 
score of the Test lens will be statistically significantly lower than 0.17 logMAR 
(equivalent to 20/30 on Snellen Visual Acuity scale). 
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4. After approximately 2-weeks of wear, the mean CLUE overall quality of vision score 
of the Test lens will be statistically significantly better (greater) than 41 for the myope 
population. 
5. After approximately 2-weeks of wear, the mean CLUE overall quality of vision score 
of the Test lens will be statistically significantly better (greater) than 36 for the 
hyperope population. 
6. Following lens settling (at least 15 minutes) at the dispensing visit, the percentage of 
eyes with Test lens rotational stability with blink ≤ 5° will be statistically 
significantly ≥ 80%.   
7. Following lens settling (at least 15 minutes) at the dispensing visit, the percentage of 
eyes with Test lens absolute rotation ≤ 10° will be statistically significantly ≥ 80%.  
2.3.2. Co-Primary Safety Hypotheses  
1. The percentage of eyes with at least one clinically significant slit-lamp finding (Grade 
3 or 4) related to the Test lens will be statistically significantly less than 5%.  
2. The percentage of eyes with an unacceptable Test lens fit will be statistically 
significantly less than 20%.  
 
2.3.3. Secondary Efficacy Hypotheses  
A fixed sequence approach will be used to control the type I error. The order of testing 
secondary hypotheses are as follows:  
 
1. After approximately 2-Weeks of wear, the mean CLUE handling score of the Test lens 
will be statistically significantly better (greater) than 46 for the hyperope population. 
2. After approximately 2-Weeks of wear, the mean CLUE comfort score of the Test lens 
will be statistically significantly better (greater) than 38 for the hyperope population. 
3. After approximately 2-Weeks of wear, the mean CLUE handling score of the Test lens 
will be statistically significantly better (greater) than 55 for the myope population. 
4. After approximately 2-Weeks of wear, the mean CLUE overall quality of vision score 
of the Test lens will be statistically significantly better (greater) than 41 for the 
hyperope population. 
5. After approximately 2-Weeks of wear, the mean CLUE comfort score of the Test lens 
will be statistically significantly better (greater) than 51 for the myope population. 
6. After approximately 2-Weeks of wear, the mean CLUE overall quality of vision score 
of the Test lens will be statistically significantly better (greater) than 46 for the myope 
population. 
7. The percentage of subjects who are fit with the optimized lens pair in 4 lenses or less 
will be statistically significantly better (greater) than 90%. 
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3. TARGETED STUDY POPULATION 
3.1. General Characteristics  
The population to be studied will consist of adapted contact lens wearers with presbyopia, 
ametropia (hyperopia or myopia) and astigmatism.  
3.2. Inclusion Criteria 
Potential subjects must satisfy all of the following criteria to be enrolled in the study: 
 
Inclusion Criteria following Screening 
The subject must: 
  
1. Read, understand, and sign the STATEMENT OF INFORMED CONSENT and receive a 
fully executed copy of the form. 
2. Appear able and willing to adhere to the instructions set forth in this clinical protocol. 
3. Be at least 40 and not more than 70 years of age at the time of screening. 
4. Own a wearable pair of spectacles if required for their distance vision. 
5. Be an adapted soft contact lens wearer in both eyes (i.e. worn lenses for at least 8 hours 
per day at least two days per week for the past 4 weeks). 
6. Be already wearing a presbyopic contact lens correction (e.g., reading spectacles over 
contact lenses, multifocal or monovision contact lenses, etc.) or if not respond positively 
to at least one symptom on the “Presbyopic Symptoms Questionnaire”.  
 
Inclusion Criteria at Baseline Evaluation 
 
7. The subject’s distance spherical component of their refraction must be in the range of 
either -1.25 D to -3.75 D, or +1.25 D to +4.25 D. 
8. The subject’s refractive cylinder must be in the range of -1.00 D to -1.75 D in each eye, 
with the cylinder axes in the range of either 90°±15° or 180°±15°. 
9. The subject’s ADD power must be in the range of +0.75 D to +2.50 D in each eye. 
10. The subject must have best corrected distance visual acuity of 20/20-3 or better in each 
eye. 
3.3. Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from participating 
in the study:  
 
Exclusion Criteria following Screening 
The subject must not: 
 
1. Be currently pregnant or lactating. 
2. By self-report, have any systemic disease (e.g. Sjögren’s Syndrome), allergies, infectious 
disease (e.g., hepatitis, tuberculosis), contagious immunosuppressive diseases (e.g., HIV), 
autoimmune disease (e.g. rheumatoid arthritis), or other diseases, which are known to 
interfere with contact lens wear and/or participation in the study. 
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3. Use systemic medications that may interfere with contact lens wear or cause blurred vision. 
See Section 9.1 for additional details regarding excluded systemic medications.  
4. Currently use ocular medication (with the exception of rewetting drops). 
5. Have any known hypersensitivity or allergic reaction to single use preservative free 
rewetting drops or sodium fluorescein. 
6. Have had any previous, or have any planned, ocular or intraocular surgery (e.g. radial 
keratotomy, PRK, LASIK, cataract surgery, retinal surgery, etc.). 
7. Have had previous eyelid injuries, surgeries or procedures which are known to have caused 
abnormal eyelid position or movement, by self-report. 
8. Have participated in any contact lens or lens care product clinical trial within 7 days prior 
to study enrollment. 
9. Be an employee or immediate family member of an employee of clinical site (e.g., 
Investigator, Coordinator, Technician). 
10. Have a history of amblyopia or strabismus, by self-report. 
11. Have a history of herpetic keratitis, by self-report. 
 
Exclusion Criteria at Baseline Evaluation 
The subject must not: 
 
12. Have ocular allergies, infections or other ocular abnormalities that are known to interfere 
with contact lens wear and/or participation in the study. This may include, but not be 
limited to entropion, ectropion, chalazia, recurrent styes, glaucoma, history of recurrent 
corneal erosions, aphakia, or corneal distortion.  
13. Have any Grade 3 or greater slit lamp findings (e.g., edema, corneal neovascularization, 
corneal staining, tarsal abnormalities, conjunctival injection) on the FDA scale. 
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.  
 
In order to enroll a study population which is reasonably representative of the presbyopic 
contact lens market, the enrolment targets have been designed based on a 60:40 ratio between 
myopes and hyperopes for the total study population.  Individual sites will also be asked to try 
to enroll myopes and hyperopes according to this ratio, when possible. 
 
In order to ensure that the performance of study lenses with Low, Mid and High near addition 
power are tested in this study, study sites will be asked to try, when possible, to enroll  at least 
one myopic and one hyperopic subject that have a near ADD requirement in each of these 
ranges (+0.75 to +1.25 D, +1.50 to +1.75 D, and +2.00 to +2.50 D). 
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4. STUDY DESIGN AND RATIONALE 
4.1. Description of Study Design 
This is an open-label, single-arm, 3-visit, dispensing clinical trial. Approximately 155 subjects 
(93 myopes and 62 hyperopes) will be enrolled into the study with the aim of completing 
approximately 140 subjects (84 myopes and 56 hyperopes). 
 
The study begins with an initial visit, Visit 1 (Day 0), then if a subject is found to meet all 
eligibility criteria, they will be fit with the study lens in both eyes. Otherwise, the subject will 
be deemed ineligible and classified as a screen failure and exited from the study. 
 
If a subject is dispensed lenses at the initial visit, then two additional visits will be conducted. 
Visit 2 will be conducted 7±1 days after Visit 1, where subjects will undergo lens optimization, 
if needed. Subjects will be dispensed the optimized pair for 7±1 days and return for Visit 3. 
Study endpoints will be measured, and the subject will be exited from the study.  
 
Subjects will be instructed to wear lenses for a minimum of 6 hours a day, every day between 
visits. Lost or damaged lenses may be replaced when necessary. Unscheduled visits may be 
conducted, if necessary.  
4.2. Study Design Rationale 
The objective of this study is to demonstrate that the investigational lens, in its final design, 
meets criteria for visual acuity (logMAR), CLUE scores, lens fit attributes, and ocular health 
compared to predefined thresholds specified in the Customer Requirements Document (
. Therefore, a single-arm study was chosen as the appropriate design to test 
co-primary efficacy and safety hypotheses.  
    
4.3. Enrollment Target and Study Duration 
Approximately 155 subjects will be enrolled with the aim that approximately 140 subjects will 
complete.  The study will be conducted at up to 16 clinical sites.  Approximately 93 myopic 
subjects with astigmatism will be enrolled, with the aim that at least 84 will complete the study.  
Approximately 62 hyperopic subjects with astigmatism will be enrolled, with the aim that at 
least 56 will complete the study.    Each individual subject is expected to attend for 3 study 
visits over a period of approximately 2Weeks.   The total study duration from first subject’s 
first visit (FSFV) to last subject’s last visit (LSLV) is expected to be approximately 8 to 12 
weeks. 
5. TEST ARTICLE ALLOCATION AND MASKING 
5.1. Test Article Allocation 
This is a single-arm study. All eligible subjects will be dispensed the study lens in a bilateral 
fashion.  
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8. SUBJECTS COMPLETION/WITHDRAWAL  
8.1. Completion Criteria 
Subjects are considered to have completed the study if they:  
• provided informed consent. 
• are eligible. 
• completed all visits 
8.2. Withdrawal/Discontinuation from the Study 
A subject will be withdrawn from the study for any of the following reasons: 
• Subject death during the study period. 
• Subject withdrawal of consent. 
• Subject not compliant to protocol  
• Subject lost to follow-up. 
• Subject no longer meets eligibility criteria (e.g., the subject becomes pregnant). 
• Subject develops significant or serious adverse events causing discontinuation of study 
lens wear. 
• Subjects 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 not compliant with study lens wear schedule. 
• Subject not successfully dispensed due to lack of efficacy and safety including poor 
vision, poor comfort or unacceptable fit. 
 
For discontinued subjects, the Investigator will: 
• Complete the current visit (scheduled or unscheduled). 
• Complete the Final Evaluation, indicating the reason that the subject was discontinued 
from the study. 
• Record the spherocylindrical refraction with best corrected distance visual acuity. 
• Collect used test article(s) (worn or brought to the visit) from the subject and discard 
them, unless otherwise stated in Section 7.2. 
• Collect all unused test article(s) from the subject. 
• Make arrangements for subject care, if needed, due to their study participation 
 
An additional subject may be enrolled if a subject discontinues from the study prematurely.  
 
In cases where a subject is lost to follow-up, every possible effort must be made to contact the 
subject and determine the reason for discontinuation/withdrawal. The measures taken to follow 
up must be documented including two written attempts and a certified letter (or equivalent) as 
the final attempt.  
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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 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, 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. 
• 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 
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is not configured to send automatic notifications or when an EDC system is not used, the 
COM/CRA is responsible for notifying Clinical QA upon discovery that a PQC has occurred.   
 
Upon receipt of the EDC notification, the COM/CRA will contact the study site to collect 
additional information which will include:  
• Date the complaint was received/recorded in the EDC System (Date of Sponsor 
Awareness). 
• Who received the complaint. 
• Study number. 
• Clinical site information (contact name, site ID, telephone number). 
• Lot number(s). 
• Unique Subject Identifier(s). 
• Indication of who first observed complaint (site personnel or subject). 
• OD/OS indication, along with whether the lens was inserted. 
• Any related AE number if applicable. 
• Detailed complaint description (scheduled/unscheduled visit, wear time, symptoms, 
resolution of symptoms, etc.). 
• Eye Care Provider objective (slit lamp) findings if applicable. 
• Confirmation of product availability for return (and tracking information, if available), 
or rationale if product is not available for return 
 
 
 
Once a complaint is received, it will be assessed by the COM, CRA, or trained site personnel 
to determine if it is an Adverse Event/Serious Adverse Event (AE/SAE). If the complaint 
results in an AE/SAE, the COM/CRA, or trained site personnel will follow Section 13 of this 
protocol. If the AE/SAE was potentially the result of a product quality related deficiency, these 
procedures also apply and will be executed in parallel.   
 
In some cases, a PQC form may be generated in EDC by the site in error. In this event, the 
PQC forms will be marked “Intentionally Left Blank” or “ILB”.  Justification for ILB must be 
documented. 
13. ADVERSE EVENTS 
13.1. Definitions and Classifications 
Adverse Event (AE) – An AE is “any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users 
or other persons, whether or not related to the investigational medical device.”  
Note: This definition includes events related to the investigational medical device or the 
comparator, and to the procedures involved. For users or other persons, this definition is 
restricted to events related to investigational medical devices.  
 
An AE includes any condition (including a pre-existing condition) that: 
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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. 
Note: 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 adverse event that led to any of the following: 
• Death 
• Serious deterioration in the health of the subject that resulted in any of the following: 
o Life-threatening illness or injury 
o Permanent or persistent impairment of a body structure or a body function 
o Hospitalization or prolongation of patient hospitalization 
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
o Chronic disease 
• Foetal distress, foetal death or a congenital physical or mental impairment of birth 
defect. 
 
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 
 
Significant Adverse Events – are defined as events that are symptomatic and warrant 
discontinuation (temporary or permanent) of the contact lens wear 
 
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) 
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• 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 – are defined as those events that are usually asymptomatic 
and usually do not warrant discontinuation of contact lens wear but may cause a reduction in 
wear time.  However, the Investigator may choose to prescribe treatment 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 
• Hordeolum 
• Any corneal event not explicitly defined as serious or significant adverse event, which 
necessitates temporary lens discontinuation < 2 weeks 
 
Adverse Device Effect (ADE) – An ADE is an “adverse event related to the use of an 
investigational medical device.” 
Note 1: This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any malfunction 
of the investigational medical device. 
Note 2: This definition includes any event resulting from use error or from intentional misuse 
of the investigational medical device.  
Note 3: This includes ‘comparator’ if the comparator is a medical device. 1 
 
Serious Adverse Device Effect (SADE) - Any adverse device effect that has resulted in any 
of the consequences characteristic of a serious adverse event.   
 
Unanticipated Serious Adverse Device Effect (USADE): serious adverse device effect 
(SADE) which by its nature, incidence, severity or outcome has not been identified in the 
current risk assessment.  
Note 1: USADE is synonymous with UADE below from the United States (US) Code of 
Federal Regulations (CFR). 
Note 2: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk assessment. 
 
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Unanticipated Adverse Device Effect (UADE) – A UADE is 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.   
Note 1: UADE is synonymous with USADE above from ISO 14155. 
13.2. Assessing Adverse Events 
In conjunction with the medical monitor, the Investigator will evaluate adverse events to ensure 
the events are categorized correctly. Elements of categorization will include: 
• Seriousness/Classifications (see definition in section 13.1). 
• Causality or Relatedness – i.e. the relationship between the test article, study treatment 
or study procedures and the adverse event (not related, unlikely related, possibly 
related, or related - see definition in Section 13.2.1). 
• Adverse Event Severity – Adverse event severity is used to assess the degree of 
intensity of the adverse event (mild, moderate, or severe - 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, or 
unknown. 
• Actions Taken – none, temporarily discontinued, permanently discontinued, or other. 
13.2.1. Causality Assessment 
Causality Assessment – A determination of the relationship between an adverse event and the 
test article, study treatment, or the study procedures. The test article, study treatment, or study 
procedures relationship for each adverse event should be determined by the investigator using 
these explanations: 
• Not Related- An adverse event that is not related to the use of the test article, study 
treatment or study procedures. 
• Unlikely Related – An adverse event for which an alternative explanation is more 
likely, e.g. concomitant treatment, concomitant disease(s), or the relationship of time 
suggests that a causal relationship is not likely. 
• Possibly Related – An adverse event that might be due to the use of the test article, or 
to the study treatment or study procedures. An alternative explanation, e.g. 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. 
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13.2.2. Severity Assessment 
Severity Assessment – A qualitative assessment of the degree of intensity of an adverse event 
as determined by the Investigator or reported to him/her by the subject. The assessment of 
severity is made irrespective of test article, study treatment or study procedure relationship or 
seriousness of the event and should be evaluated according to the following scale: 
• Mild – Event is noticeable to the subject but is easily tolerated and does not interfere 
with the subject’s daily activities. 
• Moderate – Event is bothersome, possible requiring additional therapy, and may 
interfere with the subject’s daily activities. 
• Severe – Event is intolerable, necessitates additional therapy or alteration of therapy 
and interferes with the subject’s daily activities. 
13.3. Documentation and Follow-Up of Adverse Events 
The recording and documenting of adverse events (ocular and non-ocular) begin 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 and 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 (where appropriate), 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. 
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• Best corrected visual acuity at the discovery of the event and upon conclusion of the 
event, if the AE is related to the visual system. 
 
Upon discovery of an AE that is deemed ‘possibly related’ or ‘related’ to the test article or 
study procedures (whether related to the visual system or not), an AE review form 
 
must be completed. Additional dated and initialed entries should be made at follow-up 
evaluations. Separate forms must be completed for each eye if the AE is bilateral.  
 
In addition, if an infiltrate(s) is present, he/she will complete the Corneal Infiltrate Assessment 
eCRF. Where necessary, a culture of the corneal lesion will be collected to determine if the 
infection is microbial in nature. If cultures are collected, the date of culture collection and 
laboratory utilized will be recorded.  
 
Changes in the severity of an AE shall be documented to allow an assessment of the duration 
of the event at each level of intensity to be performed. Adverse events characterized as 
intermittent require documentation of the onset and duration of each episode. Changes in the 
assessment of relationship to the Test Article shall also be clearly documented. 
 
Subjects who present with an adverse event shall be followed by the Investigator, within 
licensure, until all signs and symptoms have returned to pre-treatment status, stabilized, or 
been satisfactorily resolved. If further treatment beyond licensure is required, the subject will 
be referred to the appropriate health care provider. The Investigator will use his/her clinical 
judgment as to whether a subject reporting with an adverse event will continue in the study. If 
a subject is discontinued from the study, it will be the responsibility of the Investigator to 
record the reason for discontinuation. The Investigator will also document the adverse event 
appropriately and complete the Adverse Event eCRF. Any subjects with ongoing adverse 
events related to the test article, study treatment or study procedures, as of the final study visit 
date, should be followed to resolution of the adverse event or until referral to an appropriate 
health care provider, as recommended by the Investigator. Non-ocular adverse events that are 
not related to the test article, study treatment, or study procedures may be recorded as 
“ongoing” without further follow-up. 
13.4. Reporting Adverse Events  
The Investigator will notify the Sponsor of an adverse event by EDC System, e-mail, or 
telephone as soon as possible and no later than 24 hours from discovery for any serious 
/significant adverse events, and 2 days from discovery for any non-significant adverse event. 
In addition, a written report will be submitted by the Principal Investigator to the IEC/IRB 
according to their requirements (Section 13.4.2). The report will comment whether the adverse 
event was considered to be related to the test article, study treatment or study procedures. 
 
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 EDC system, e-mail or telephone, but no later 
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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. 
 
In the event of a serious/significant adverse event, the Investigator must: 
• Notify the Sponsor immediately. 
• Obtain and maintain in the subject’s records all pertinent medical information and 
medical judgment for colleagues who assisted in the treatment and follow-up of the 
subject. 
• Provide the Sponsor with a complete case history which includes a statement as to 
whether the event was or was not related to the use of the test article. 
• Notify the IEC/IRB as required by the IEC/IRB reporting procedure according to 
national regulations. 
 
Unanticipated (Serious) Adverse Device Effect (UADE) 
In the event of an Unanticipated (Serious) Adverse Device Effect (UADE), the Investigator 
will submit a report of the UADE to the Sponsor and IEC/IRB as soon as possible, but no later 
than 24 hours after the Investigator first learns of the effect. This report is in addition to the 
immediate notification mentioned above. 
 
The Sponsor must conduct an evaluation of the UADE and must report the results of the 
evaluation to FDA, the IEC/IRB and participating Investigators within 10 working days after 
the Sponsor first receives notification of the effect. 
 
Non-Serious Adverse Events 
All non-serious adverse events, including non-serious adverse device effects, will be reported 
to the sponsor by the Investigator no later than 2 days from discovery. 
13.4.2. Reporting Adverse Events to the Responsible IEC/IRB and Health Authorities 
Adverse events that meet the IEC/IRB requirements for reporting must be reported within the 
IEC/IRB’s written guidelines. Each clinical site will refer to and follow any guidelines set forth 
by their Approving IEC/IRB. Each clinical site will refer to and follow any guidelines set forth 
by their local governing Health Authorities. 
 
The Sponsor will report applicable Adverse Events to the local health authorities according to 
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 study will be discontinued after the 
event is recorded as an Adverse Event. Once discontinued, pregnant subjects and their fetuses 
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will not be monitored for study related purposes. Pregnant subjects are not discontinued from 
contact lens or solution related studies for safety concerns, but due to general concerns relating 
to pregnancy and contact lens use. Specifically, pregnant women are discontinued due to 
fluctuations in refractive error and/or visual acuity that occur secondary to systemic hormonal 
changes, and not due to unforeseen health risks to the mother or fetus. 
14. STATISTICAL METHODS 
14.1. General Considerations 
Statistical Analysis will be undertaken by the sponsor or under the authority of the sponsor. A 
general description of the statistical methods to be implemented in this clinical trial is outlined 
below. More details will be included in the stand-alone Statistical Analysis Plan (SAP). The 
SAP will be developed and finalized prior to database lock. 
 
Data manipulation, statistical summaries and statistical analyses will be performed using the 
Statistical Analysis System (SAS) software Version 9.4 or higher (SAS Institute, Cary, NC)11.   
 
Descriptive statistics will be reported for all key variables as appropriate. Continuous data will 
be summarized descriptively by sample size (n), mean, standard deviation (SD), median, 
minimum (Min) and maximum (Max). Categorical data will be summarized descriptively by 
frequency count (n) and percentage (%) of subjects or eyes within each category level. 
Summary tables will be presented by event (Baseline, Fitting, 1-Week follow-up, 2-Week 
follow-up, Unscheduled and Final Evaluations) and study lens type as applicable, for the 
analysis set of interest. The denominator for all percentages will be the number of subjects (or 
eyes, as applicable) with available data in the lens group under consideration. Unscheduled 
visits and tele-visits will be summarized separately and will be excluded from the co-primary 
and secondary efficacy analyses.  
14.2. Sample Size Justification 
The total sample size of 140 subjects who complete the study (Visit 3) was calculated to 
provide adequate power in detecting statistical superiority of the Test lens relative to pre-
specified thresholds for binocular distance, intermediate and near logMAR VA, CLUE vision 
Scores, Absolute toric rotation, rotational stability, rate of unacceptable lens fitting and rate of 
grade 3 or higher SLFs. All co-primary effectiveness and safety hypotheses are required to 
achieve statistical significance for the study objective to be satisfied, therefore no adjustment 
for multiple primary hypotheses is necessary. Each co-primary hypothesis will be tested using 
a 1-sided Type I error rate of 0.025.  
 
Thresholds for hypotheses associated with CLUE vision, comfort and, handling scores are 
from a meta-analysis of 14 JJVCI clinical trials of toric and multifocal toric contact lenses used 
by habitual contact lens wearers aged 40 to 70 years12. In this analysis, baseline CLUE scores 
(for subjects’ habitual contact lenses) from 14 clinical studies were analyzed to establish 
thresholds reflecting the “real-world” performance of contact lenses wearers in this population 
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with respect to CLUE vision, comfort, and handling scores. Thresholds for all other endpoints 
were based on clinically relevant margins.    
 
Additionally, this study was also powered to test superiority for secondary endpoints with 
respect to CLUE vision, comfort and, handling scores and lens fit success using a 1-sided Type 
I error rate of 0.025. Secondary endpoints will be tested using a fixed sequence approach. 
Further details on the preservation of the study overall Type I error rate are in Section 14.4.  
 
The sample size of 140 to complete yields at least 81% overall power to detect statistical 
superiority for all co-primary endpoints. This sample size provides a statistical power of at 
least 99% for each co-primary and secondary endpoint. To account for subject drop-out 
approximately 155 subjects will be enrolled to ensure at least 140 subjects complete the study. 
 
Table 6: Sample Size Estimates by Study Endpoint  
 
Endpoint 
Domain 
Endpoint 
Statistical Test Type 
(Statistically 
Significantly) 
Sample 
Size 
Power 
(%) 
Primary 
Efficacy  
Distance (4m) Binocular Visual 
Acuity (logMAR) 
Superiority:  mean VA< 0.00 
9 
99.1 
Intermediate (64cm) Binocular 
Visual Acuity (logMAR) 
Superiority:  mean VA< 0.17 
6 
99.5 
Near (40cm) Binocular Visual 
Acuity (logMAR) 
Superiority:  mean VA< 0.17 
29 
99.1 
CLUE Vision Scores - Myopes 
Superiority: mean score> 41 
29 
99.2 
CLUE Vision Scores - Hyperopes 
Superiority: mean score> 36 
23 
99.0 
Absolute Toric Rotation ≤ 10° 
Superiority: percentage>80%  
140 
>99 
Lens Stability with Blinks ≤ 5° 
Superiority: percentage>80%  
140 
96.8 
Primary 
Safety  
Grade 3 or Higher SLFs (%) 
 
Superiority: percentage< 5% 
140 
89.3 
Unacceptable Lens Fitting (%) 
Superiority: percentage<20%   
140 
>99 
Secondary 
Efficacy  
CLUE Handling Scores: Hyperopes 
Superiority: mean score> 46 
15 
99.2 
CLUE Comfort Scores - Hyperopes 
Superiority: mean score> 38 
23 
99.2 
CLUE Vision Scores - Hyperopes 
Superiority: mean score> 41 
42 
99.1 
CLUE Handling Scores - Myopes 
Superiority: mean score> 55 
26 
99.1 
CLUE Comfort Scores - Myopes 
Superiority: mean score> 51 
46 
99.1 
CLUE Vision Scores - Myopes 
Superiority: mean score> 46 
55 
99.0 
Lens Fit Success Rate (%) 
Superiority: percentage>90%  
140 
99.8 
 
 
This will be the first dispensing study since the lens design was changed hence, historical 
clinical data on the previous lens design has been used for the sample size calculations for any 
of the study endpoints except for toric rotation and lens stability with blinks. The changes made 
to the lens design improved the rotational performance of the contact lens and were not 
considered to impact the visual acuity or the subjective performance of the lens. Sample size 
estimates for toric rotation and lens stability with blinks were calculated using the results from 
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Toric Rotation and Lens Stability  
The reference rate for absolute toric lens rotation ≤10° was based on the historical results of 
90.2%. The reference rate for lens stability ≤ 5° was based on the worst-case scenario of 99%, 
given the historical results show 100%. Toric lens orientation and rotational stability, 
respectively, are defined as a binary response: 
𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿 𝑂𝑂𝑂𝑂𝑂𝑂𝑂𝑂𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛∶𝑌𝑌
= ቄ1
if a subject eye has absolute toric lens rotation ≤ 10°
0
Otherwise
, 
𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠: 𝑍𝑍= ቄ1
if a subject eye has lens stability with blinks ≤ 5°,
0
Otherwise
  
Historical data of the Test lens indicates there is a high rate (≥90%) for both toric lens rotation 
≤10° and rotational lens stability. Assuming a correlation of 0.70 between left and right eyes, 
a total of 5000 replicating trials were simulated with reference rate of 90.2% for the percentage 
of eyes with small (≤10° ) absolute toric lens rotation (or 99% of eyes with rotational stability). 
Given the high event rate of the binary outcome, Y=1, each replicated sample was analyzed 
using a Bayesian beta-binomial model with correlated binary data (Diniz et al; 2010)14. A non-
informative prior distribution, beta (0.5, 0.5) was used to model 𝑃𝑃𝑇𝑇 (proportion of eyes with 
absolute toric lens rotation ≤10° [or lens stability ≤5°] for the Test lens). For each simulated 
trial, the 95% central posterior credible interval (CrI) constructed for the percentage of eyes 
with absolute toric lens rotation ≤10°  [or lens stability ≤5°] for the Test lens was calculated. 
The null and alternative hypothesis for determining statistical significance in both endpoints 
were 𝑃𝑃𝑇𝑇 ≤ 80% and 𝑃𝑃𝑇𝑇 > 80%, respectively. With the proposed sample size, each endpoint 
(percentage of eyes with absolute toric lens rotation ≤10° and lens stability ≤5°) has at least 
96% power, i.e., 96% of the estimated 95% CrIs had the lower bound above 80%. 
Co-Primary Safety Endpoint Sample Size Calculations: 
 
Grade 3 or Higher Slit Lamp Findings (SLF) and Unacceptable Lens Fitting  
 
Grade 3 or Higher SLFs related to study lens wear was converted to a binary response as 𝑌𝑌=1, 
if a subject eye has a clinically significant SLF, and 𝑌𝑌=0 otherwise, for analysis purposes. 
Historical data show none or an extremely low rate (<1%) for clinically significant SLFs 
(Grade 3 or higher) for the test lens. Assuming a correlation of 0.70 between left and right 
eyes, a total of 5000 replicating trials were simulated with a reference rate of 1% (worse-case 
scenario). Given the rare event binary outcome of slit lamp findings, each replicated sample 
was analyzed using a Bayesian beta-binomial model with correlated binary data (Diniz et al; 
2010)14. A non-informative prior distribution, beta (0.5, 0.5) was used to model 𝑃𝑃𝑇𝑇 (proportion 
of eyes with Grade 3 or higher SLF for the Test lens). For each simulated trial, the 95% central 
posterior credible interval constructed for the percentage of eyes with grade 3 or higher SLFs 
for the Test lens was calculated. The null and alternative hypothesis for statistical significance 
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were 𝑃𝑃𝑇𝑇 ≥ 5% and 𝑃𝑃𝑇𝑇 < 5%, respectively. With the proposed sample size, at least 99% of the 
estimated 95% credible intervals had the upper bound below 5%. 
 
As indicated in  Table 6, co-primary safety endpoints were powered to at least ~89% 
individually, yielding a combined power of ~88%. With respect to co-primary efficacy, each 
hypothesis, was powered to ~99%, which provided a combined power of ~92%. Therefore, the 
overall combined study power for co-primary safety and co-primary efficacy hypotheses is 
~81%.  
Secondary Efficacy Endpoint Sample Size Calculations: 
 
CLUE Vision, Comfort and, Handling (Hyperopes and Myopes)  
Sample size calculations for the secondary endpoints of CLUE vision, comfort, and handling 
scores were carried out separately for each sphere stratum (hyperopes and Myopes) for all three 
CLUE domains using one-sided, one-sample mean t-test, with a one-sided Type I error rate of 
0.025 for each hypothesis using the One-Sample T-Tests for Superiority by a Margin procedure in 
Power Analysis & Sample Size (PASS2021) software Version 21.0.6 (NCSS LLC, Kaysville 
UT)13.  The assumptions for averages and standard deviations were made based on historical 
values from previous studies (Table 7). 
 
 
Lens Fit Success 
The reference rate for lens fit success was based on the worst-case scenario of 99%, given the 
historical results show 100% (Table 6). Lens fit is a binary response and is defined as follows: 
𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿 𝐹𝐹𝐹𝐹𝐹𝐹 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆∶𝑌𝑌= ቄ1
if a subjects′𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑖𝑖𝑖𝑖 𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜 𝑖𝑖𝑖𝑖 2 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑜𝑜𝑜𝑜 𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙
0
Otherwise
, 
Historical data of the Test lens indicates there is an extremely high rate (100%) for lens fit 
success. Assuming a correlation of 0.70 between left and right eyes, a total of 5000 replicating 
trials were simulated with reference rate of 99% for the percentage of eyes optimized in 4 
lenses (2 pairs) or less. Given the high event rate of the binary outcome, Y=1, each replicated 
sample was analyzed using a Bayesian beta-binomial model with correlated binary data (Diniz 
et al; 2010)14. A non-informative prior distribution, beta(1, 1) was used to model 𝑃𝑃𝑇𝑇 (proportion 
of eyes with optimized in 4 lenses or less). For each simulated trial, the 95% central posterior 
credible interval (CrI) constructed for the percentage of eyes optimized in 4 lenses or less was 
calculated. The null and alternative hypothesis for determining statistical significance were 𝑃𝑃𝑇𝑇 
≤ 90% and 𝑃𝑃𝑇𝑇 > 90%, respectively. With the proposed sample size, the percentage of eyes 
optimized in 4 lenses or less has at least 99% power, i.e., 99% of the estimated 95% CrIs had 
the lower bound above 90%. 
 
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14.3. Analysis Populations 
 
Safety Population: 
All subjects who were administered any test article.  
 
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 will be 
documented in a memo to file. 
 
Intention-to-Treat (ITT) Population: 
Intention-to-treat population will include all assigned subjects.  
14.4. Level of Statistical Significance 
The Type I error rate of the trial will be controlled at 1-sided 0.025 level. Each co-primary 
safety and efficacy hypothesis will be tested using a 1-sided Type I error of 0.025. All 
co-primary hypotheses must be met to satisfy the study objectives and to test any secondary 
hypotheses. 
 
Based on a gate keeping approach between the primary and secondary families of hypotheses, 
all primary endpoints must show statistical significance at one-sided 0.025 level in order to 
pass the full alpha level to test the secondary endpoints hypotheses.  
 
A fixed sequence testing procedure will be utilized to test the secondary hypotheses to control 
the Type I error rate also in the secondary family of hypotheses. Each secondary hypotheses 
will be tested using a 1-sided 0.025 level following the order prespecified in section 2.3.3.   
Based on the fixed sequence principle, each secondary endpoint must be found statistically 
significant at a one-sided 0.025 level in order to proceed to the next step. If not, the testing 
procedure of the secondary endpoints will stop.  
14.5. Primary Analysis  
The co-primary efficacy analyses will be conducted on the ITT population, while co-primary 
safety analyses will be conducted on the safety population. All efficacy and safety analyses 
will be based on observed case data with no imputation of missing values. 
 
14.5.1. Co-Primary Efficacy Analyses 
Binocular HLHC Distance, Intermediate and, Near LogMAR Visual Acuity 
Binocular, high luminance, high contrast visual acuity on logMAR scale after approximately 
2-Weeks in the optimized lenses will be analyzed using a linear mixed model. Distance 
(distance/intermediate/near), sphere strata (hyperope and myope) and the interaction between 
distance by sphere strata will be included as fixed effects. Other baseline characteristics, such 
as age, gender and add power may be included as covariates when appropriate. Site will be 
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included as random effect (G-side). The covariance between residual errors from the same 
subject across distance will be modeled using an unstructured (UN) covariance structure. Mean 
estimates will be conducted using two-sided confidence intervals (CI) constructed for the least 
square mean. One-sided p-values will also be calculated.      
 
The null and alternative hypothesis for binocular distance HLHC visual performance to test 
for superiority of the investigational lens relative to the pre-defined threshold of 0.00 logMAR 
is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇≥ 0.00 logMAR 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇< 0.00 logMAR 
 
 
Where 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 represents the population mean for the investigational lens after 2-weeks lens 
wear with respect to distance binocular HLHC VA. The investigational lens will be declared 
statistically significantly lower than 0.00 logMAR if the one-sided p-values is below 0.025.  
 
The null and alternative hypothesis for binocular intermediate HLHC visual performance to 
test for superiority of the investigational lens relative to the pre-defined threshold of 0.17 
logMAR is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇≥ 0.17 logMAR 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇< 0.17 logMAR 
 
 
Where 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 represents the population mean for the investigational lens after 2-Weeks lens 
wear with respect to intermediate binocular HLHC VA. The investigational lens will be 
declared statistically significantly lower than 0.17 logMAR if the one-sided p-values is below 
0.025.  
 
The null and alternative hypothesis for binocular near HLHC visual performance to test for 
superiority of the investigational lens relative to the pre-defined threshold of 0.17 logMAR is 
as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇≥ 0.17 logMAR 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇< 0.17 logMAR 
 
 
Where 𝜇𝜇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 represents the population mean for the investigational lens after 2-weeks lens 
wear with respect to near binocular HLHC VA. The investigational lens will be declared 
statistically significantly lower than 0.17 logMAR if the one-sided p-values is below 0.025.  
 
 
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CLUE Vision Scores 
CLUE Vision Scores after approximately 2-Weeks in the optimized lenses will be analyzed 
using a linear mixed model adjusting for baseline scores as a covariate. Strata (hyperope and 
myope) will be included as the only fixed effect. Other baseline characteristics known of 
importance such as age, gender and Additional (ADD) power may be included as covariates 
when appropriate. Site will be included as random effect (G-side). The Kenward and Roger 
method will be used for the calculation of the denominator of degrees of freedom15. Mean 
estimates will be conducted using two-sided confidence intervals (CI) constructed for the least 
square mean. One-sided p-values will also be calculated.      
 
The null and alternative hypothesis to test for superiority of the myopic subjects relative to the 
pre-defined threshold of 41 for the investigational lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀≤ 41 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀> 41 
 
 
Where 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 represents the population mean for the investigational lens after 2-Weeks lens 
wear with respect to CLUE Visions scores for myopic subjects. The investigational lens will 
be declared statistically significantly greater than 41 if the one-sided p-values is below 0.025.  
 
The null and alternative hypothesis to test for superiority of the hyperopic subjects relative to 
the pre-defined threshold of 36 for the investigational lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻≤ 36 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻> 36 
 
Where 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻 represents the population mean for the investigational lens after 2-weeks 
lens wear with respect to CLUE Visions scores for hyperopic subjects. The investigational lens 
will be declared statistically significantly greater than 36 if the one-sided p-values is below 
0.025.  
 
Toric Lens Orientation and Rotational Stability at least 15-minutes Following Settling 
Absolute toric lens orientation (degrees) will be dichotomized as 𝑌𝑌= 1 if absolute toric lens 
rotation (degrees) ≤10°) and 𝑌𝑌= 0 otherwise. Rotational stability will be quantified by lens 
stability with blinks (degrees). Lens stability will be dichotomized as 𝑋𝑋= 1 if the lens stability 
with blinks (degrees) ≤5° and 𝑋𝑋= 0 otherwise.  
 
Absolute toric lens orientation and rotational stability will be analyzed separately using a 
Bayesian beta-binomial model with correlated binary data14. 
 
 
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The Model: 
Let Y (the percentage of eyes with grade 3 or higher SLFs) be the sum of equicorrelated binary 
responses ( 𝑌𝑌1 and 𝑌𝑌2 denotes left and right eyes, respectively) with probability of success p 
and correlation coefficient 𝜌𝜌. 
The probability distribution of 𝑌𝑌= 𝑌𝑌1 + 𝑌𝑌2 is obtained by the mixture of two variables. One 
of them follow a binomial distribution 𝐵𝐵𝐵𝐵𝐵𝐵(2, 𝑝𝑝) with probability of success p and mixing 
probability (1 −𝜌𝜌), and the other follows a modified Bernoulli distribution 𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀(𝑝𝑝), taking 
values 0 and 2, with probability of success p and mixing probability 𝜌𝜌: 
𝑃𝑃(𝑌𝑌= 𝑦𝑦 |𝑝𝑝, 𝜌𝜌) = (1 −𝜌𝜌) 𝐵𝐵𝐵𝐵𝐵𝐵(2, 𝑝𝑝)𝐼𝐼𝐴𝐴1 + 𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌(𝑝𝑝)𝐼𝐼𝐴𝐴2 
where 𝐼𝐼𝐴𝐴1 = {0, 1, 2}, 𝐼𝐼𝐴𝐴2 = {0, 2} and 𝑝𝑝 is the probability of success (i.e. proportion of eyes 
with Grade 3 or Higher SLFs).  
To overcome the complexity of the mixture likelihood, a latent variable 𝑍𝑍𝑖𝑖, 𝑖𝑖= 1, 2 is 
introduced in the model to indicate in which component of the correlated binary model the 
observation 𝑦𝑦𝑖𝑖, 𝑖𝑖= 1, 2 belongs to, that is,  
𝑍𝑍𝑖𝑖= ൜1
if the observation belong to 𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀(𝑝𝑝)
0
if the observation belong to 𝐵𝐵𝐵𝐵𝐵𝐵(2, 𝑝𝑝)   
The joint distribution of the augmented data (𝑌𝑌𝑖𝑖, 𝑍𝑍𝑖𝑖), 𝑖𝑖= 1, 2, is given by  
𝑃𝑃(𝑌𝑌= 𝑦𝑦𝑖𝑖, 𝑍𝑍= 𝑧𝑧𝑖𝑖| 𝑝𝑝, 𝜌𝜌)
= 𝜌𝜌𝑧𝑧𝑖𝑖 𝑝𝑝
𝑦𝑦𝑖𝑖𝑧𝑧𝑖𝑖
2  (1 −𝑝𝑝)(2−𝑦𝑦𝑖𝑖)𝑧𝑧𝑖𝑖
2 (1 −𝜌𝜌)1−𝑧𝑧𝑖𝑖 ൬2
𝑦𝑦𝑖𝑖൰ 𝑝𝑝𝑦𝑦𝑖𝑖 (1−𝑧𝑧𝑖𝑖) (1 −𝑝𝑝)(2−𝑦𝑦𝑖𝑖)(1−𝑧𝑧𝑖𝑖)   
The probability p links to the regression variables through a logit transformation as follow: 
logit(𝑝𝑝) = 𝛽𝛽𝑜𝑜+ 𝛽𝛽1lens 
It is assumed that 𝛽𝛽𝑜𝑜, 𝛽𝛽1 and 𝜌𝜌 to be independent with a non-informative prior N(0, 1000) for 
𝛽𝛽𝑜𝑜 and 𝛽𝛽1, and beta(0.5, 0.5) for 𝜌𝜌. The Metropolis sampler algorithm as implemented in the 
SAS/STAT MCMC procedure11 will be used to estimate the posterior distributions of the 
parameters (𝛽𝛽𝑜𝑜, 𝛽𝛽1, 𝜌𝜌). Inferences will be made based on a posterior credible interval for the 
relevant parameters.  
 
The null and alternative hypotheses for evaluating superiority of the Test lens relative to 0.80 
for are as follows: 
𝐻𝐻𝑜𝑜: 𝑝𝑝𝑇𝑇≤80% 
𝐻𝐻1: 𝑝𝑝𝑇𝑇> 80% 
 
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where 𝑝𝑝𝑇𝑇 is the percentage of eyes with absolute toric rotation ≤ 10° (or lens stability ≤ 5°) for 
the investigational lens. Based on Bayesian posterior probability distribution of the proportion 
𝑝𝑝𝑇𝑇, superiority is interpreted as 95% probability of the investigational lens being statistically 
higher than the threshold of 80% (i.e., 𝑝𝑝𝑇𝑇> 80%). If the lower bound of the 95% central 
posterior credible interval is above 80%, it will be concluded that there is 95% probability that 
the investigational lens is statistically significantly higher than 80% based on observed sample. 
14.5.2. Co-Primary Safety Analyses 
The primary safety analyses will be conducted on the safety population. 
 
Grade 3 or Higher SLFs and Unacceptable Lens Fitting 
Grade 3 of Higher SLFs (or Unacceptable lens fitting) will be analyzed using a Bayesian beta-
binomial model with correlated binary data14. 
The Model: 
Let Y (the percentage of eyes with grade 3 or higher SLFs [or unacceptable lens fitting]) be 
the sum of equicorrelated binary responses ( 𝑌𝑌1 and 𝑌𝑌2 denotes left and right eyes, respectively) 
with probability of success p and correlation coefficient 𝜌𝜌. 
The probability distribution of 𝑌𝑌= 𝑌𝑌1 + 𝑌𝑌2 is obtained by the mixture of two variables. One 
of them follow a binomial distribution 𝐵𝐵𝐵𝐵𝐵𝐵(2, 𝑝𝑝) with probability of success p and mixing 
probability (1 −𝜌𝜌), and the other follows a modified Bernoulli distribution 𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀(𝑝𝑝), taking 
values 0 and 2, with probability of success p and mixing probability 𝜌𝜌: 
𝑃𝑃(𝑌𝑌= 𝑦𝑦 |𝑝𝑝, 𝜌𝜌) = (1 −𝜌𝜌) 𝐵𝐵𝐵𝐵𝐵𝐵(2, 𝑝𝑝)𝐼𝐼𝐴𝐴1 + 𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌𝜌(𝑝𝑝)𝐼𝐼𝐴𝐴2 
where 𝐼𝐼𝐴𝐴1 = {0,1,2}, 𝐼𝐼𝐴𝐴2 = {0, 2} and 𝑝𝑝 is the probability of success (i.e. proportion of eyes 
with Grade 3 or Higher SLFs).  
To overcome the complexity of the mixture likelihood, a latent variable 𝑍𝑍𝑖𝑖, 𝑖𝑖= 1, 2 is 
introduced in the model to indicate in which component of the correlated binary model the 
observation 𝑦𝑦𝑖𝑖, 𝑖𝑖= 1, 2 belongs to, that is,  
𝑍𝑍𝑖𝑖= ൜1
if the observation belong to 𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀(𝑝𝑝)
0
if the observation belong to 𝐵𝐵𝐵𝐵𝐵𝐵(2, 𝑝𝑝)   
The joint distribution of the augmented data (𝑌𝑌𝑖𝑖, 𝑍𝑍𝑖𝑖), 𝑖𝑖= 1, 2, is given by  
𝑃𝑃(𝑌𝑌= 𝑦𝑦𝑖𝑖, 𝑍𝑍= 𝑧𝑧𝑖𝑖| 𝑝𝑝, 𝜌𝜌)
= 𝜌𝜌𝑧𝑧𝑖𝑖 𝑝𝑝
𝑦𝑦𝑖𝑖𝑧𝑧𝑖𝑖
2  (1 −𝑝𝑝)(2−𝑦𝑦𝑖𝑖)𝑧𝑧𝑖𝑖
2 (1 −𝜌𝜌)1−𝑧𝑧𝑖𝑖 ൬2
𝑦𝑦𝑖𝑖൰ 𝑝𝑝𝑦𝑦𝑖𝑖 (1−𝑧𝑧𝑖𝑖) (1 −𝑝𝑝)(2−𝑦𝑦𝑖𝑖)(1−𝑧𝑧𝑖𝑖)   
The probability p links to the regression variables through a logit transformation as follow: 
logit(𝑝𝑝) = 𝛽𝛽𝑜𝑜+ 𝛽𝛽1lens 
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It is assumed that 𝛽𝛽𝑜𝑜, 𝛽𝛽1 and 𝜌𝜌 to be independent with a non-informative prior N(0, 1000) for 
𝛽𝛽𝑜𝑜 and 𝛽𝛽1, and beta(0.5, 0.5) for 𝜌𝜌. The Metropolis sampler algorithm as implemented in the 
SAS/STAT MCMC procedure11 will be used to estimate the posterior distributions of the 
parameters (𝛽𝛽𝑜𝑜, 𝛽𝛽1, 𝜌𝜌). Inferences will be made based on a posterior credible interval for the 
relevant parameters.  
 
Bayesian Estimation and Statistical Evaluation of Hypothesis: 
The null and alternative hypotheses for Grade 3 or higher SLFs of the investigational lens 
compared to the threshold of 5% are as follows: 
𝐻𝐻𝑜𝑜: 𝑝𝑝𝑇𝑇≥5% 
𝐻𝐻1: 𝑝𝑝𝑇𝑇< 5% 
 
where 𝑝𝑝𝑇𝑇 is the probability of a grade 3 or higher SLF across all study visits for test lens. Based 
on Bayesian posterior probability distribution of the proportion 𝑝𝑝𝑇𝑇, superiority is interpreted 
as 95% probability of test being statistically lower than the threshold of 5% (i.e., 𝑝𝑝𝑇𝑇< 5%). 
If the upper bound of the 95% central posterior credible interval is below 5%, it will be 
concluded that there is 95% probability that the investigational lens is statistically significantly 
lower than 5% based on observed sample. 
 
Bayesian Estimation and Statistical Evaluation of Hypothesis: 
The null and alternative hypotheses for unacceptable lens fitting of the investigational lens 
compared to the threshold of 20% are as follows: 
𝐻𝐻𝑜𝑜: 𝑝𝑝𝑇𝑇≥20% 
𝐻𝐻1: 𝑝𝑝𝑇𝑇< 20% 
 
where 𝑝𝑝𝑇𝑇 is the probability of an unacceptable lens fitting across all study visits for test lens. 
Based on Bayesian posterior probability distribution of the proportion 𝑝𝑝𝑇𝑇, superiority is 
interpreted as 95% probability of test being statistically lower than the threshold of 20% (i.e., 
𝑝𝑝𝑇𝑇< 20%). If the upper bound of the 95% central posterior credible interval is below 20%, it 
will be concluded that there is 95% probability that the investigational lens is statistically 
significantly lower than 20% based on observed sample. 
 
In the case of zero clinically significant SLF (or unacceptable lens fitting), a Bayesian 
hierarchical model accounting for zero-event problem will be considered16.  
 
14.6. Secondary Analyses  
CLUE Vision, Comfort and, Handling  
Secondary endpoints for CLUE vision, comfort and handling, scores after 2-weeks of lens wear 
will be analyzed separately using the same model as described above for primary analysis of 
CLUE vision scores.  
 
 
 
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The null and alternative hypothesis to test for superiority of the hyperopic subjects relative to 
the pre-defined threshold of 46 for the investigational lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻≤ 46 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻> 46 
 
Where 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻 represents the population mean for the investigational lens after 2-weeks 
lens wear with respect to CLUE handling scores for hyperopic subjects. The Test lens will be 
declared statistically significantly greater than 46 if the one-sided p-values is below 0.025.  
 
 
The null and alternative hypothesis to test for superiority of the hyperopic subjects relative to 
the pre-defined threshold of 38 for the investigational lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻≤ 38 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻> 38 
 
Where 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻 represents the population mean for the investigational lens after 2-weeks 
lens wear with respect to CLUE comfort scores for hyperopic subjects. The Test lens will be 
declared statistically significantly greater than 38 if the one-sided p-values is below 0.025.  
 
 
The null and alternative hypothesis to test for superiority of the myopic subjects relative to the 
pre-defined threshold of 55 for the investigational lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀≤ 55 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀> 55 
 
 
Where 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 represents the population mean for the investigational lens after 2-weeks lens 
wear with respect to CLUE handling scores for myopic subjects. The investigational lens will 
be declared statistically significantly greater than 55 if the one-sided p-values is below 0.025.  
 
The null and alternative hypothesis to test for superiority of the hyperopic subjects relative to 
the pre-defined threshold of 41 for the Test lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻≤ 41 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻> 41 
 
Where 𝜇𝜇𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻 represents the population mean for the investigational lens after 2-weeks 
lens wear with respect to CLUE vision scores for hyperopic subjects. The investigational lens 
will be declared statistically significantly greater than 41 if the one-sided p-values is below 
0.025.  
 
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The null and alternative hypothesis to test for superiority of the myopic subjects relative to the 
pre-defined threshold of 51 for the investigational lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀≤ 51 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀> 51 
 
 
Where 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 represents the population mean for the investigational lens after 2-weeks lens 
wear with respect to CLUE comfort scores for myopic subjects. The investigational lens will 
be declared statistically significantly greater than 51 if the one-sided p-values is below 0.025.  
 
 
The null and alternative hypothesis to test for superiority of the myopic subjects relative to the 
pre-defined threshold of 46 for the investigational lens is as follows:  
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀≤ 46 
𝐻𝐻𝐴𝐴: 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀> 46 
 
 
Where 𝜇𝜇𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 represents the population mean for the investigational lens after 2-weeks lens 
wear with respect to CLUE vision scores for myopic subjects. The Test lens will be declared 
statistically significantly greater than 46 if the one-sided p-values is below 0.025.  
 
 
Lens Fit Success (Number of lenses required to achieve lens optimization) 
 
Number of lenses required to achieve lens optimization will be analyzed using a Bayesian beta-
binomial model with correlated binary data14.  
 
Bayesian Estimation and Statistical Evaluation of Hypothesis: 
Superiority of the Test lens relative to the pre-defined threshold with respect to unacceptable 
lens fitting will be evaluated using Bayesian statistics. The null and alternative hypotheses for 
evaluating superiority of the investigational lens relative to 90% are as follows:  
 
𝐻𝐻0: 𝑝𝑝T ≤90%   
 𝐻𝐻𝐴𝐴: 𝑝𝑝T > 90%, 
 
where 𝑝𝑝T is the probability of event (i.e., proportion of subjects to achieve optimization in 4 
lenses or less while wearing the test lens). Based on Bayesian posterior probability distribution 
of the proportion 𝑝𝑝𝑇𝑇, superiority is interpreted as 95% probability of the Test lens being 
statistically greater than the pre-defined threshold of 90% (i.e., 𝑝𝑝T > 0.90) with respect to 
unacceptable lens fitting rate. If the upper bound of the 95% central posterior credible interval 
is above 0.90, it can be concluded that there is 95% probability that the investigational lens is 
superior to the 90% threshold (statistically better) based on the observed sample.  
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In the event that all subjects’ vision was optimized in 4 lenses (2 pairs) or less (i.e., zero  
optimization events), a Bayesian hierarchical model accounting for zero event problem will be 
considered16.  
 
14.7. Exploratory Analyses 
Not Applicable. 
 
14.8. Interim Analysis 
Not Applicable. 
 
14.9. Procedure for Handling Missing Data and Drop-Outs 
Missing values will not be imputed. The count of missing values will be included in the 
summary tables and listings. Subjects who drop-out early may be replaced to ensure that at 
least 140 subjects complete the study.  
 
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 (Clario).  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. 
 
The clinical data will be recorded on dedicated eCRFs specifically designed to match the study 
procedures for each visit. Only specifically delegated staff can enter data on a CRF.  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 
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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. 1 
15.2. Subject Record 
At a minimum, subject record should be available for the following:  
• subject identification 
• eligibility 
• study identification 
• study discussion 
• provision of and date of informed consent 
• visit dates 
• results of safety and efficacy parameters as required by the protocol 
• a record of all adverse events 
• follow-up of adverse events 
• medical history and concomitant medication 
• test article receipt/dispensing/return records 
• date of study completion 
• reason for early discontinuation of test article or withdrawal from the study, if 
applicable 
 
The subject record is the eCRF or an external record. The author of an entry in the subject 
record must be identifiable. The first point of entry is considered to be the source record. 
 
Adverse event notes must be reviewed and initialed by the Investigator. 
 
15.3. Trial Registration on ClinicalTrials.gov  
This study will be registered on ClinicalTrials.gov based on the following: The purpose of the 
study is for design confirmation, not feasibility. 
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. 
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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-
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. 
16.4. Data Monitoring Committee  
Not applicable. 
17. CLINICAL 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 versions, 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. 
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• 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. 
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, ISO14155:20201, 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 20132 and that the clinical study 
data are credible. The Investigator must maintain clinical study files in accordance with 
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. 
• Sponsor-approved informed consent form (and any other written materials to be 
provided to the subjects) 
• Investigator’s Brochure (or equivalent information). 
• 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. 
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This study will be undertaken only after IEC/IRB has given full approval of the final protocol, 
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 revisions 
• 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 revisions  
• Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB) 
• Reports of adverse events that are serious, unanticipated, and associated with the test 
articles, according to the IRB’s requirements 
• New information that may adversely affect the safety of the subjects or the conduct of 
the study 
• Major protocol deviations as required by the IEC/IRB 
• Report of deaths of subjects under the Investigator's care 
• Notification if a new Investigator is responsible for the study at the clinical site 
• Any other requirements of the IEC/IRB 
 
For protocol revisions that increase subject risk, the revisions 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 or their representative, 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 Helsinki2, ISO14155:20201 guidelines,  
applicable regulatory requirements, and Sponsor Policy. 
 
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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 Health Information Portability and Accountability Act (HIPAA) in the 
United States17  and other applicable personal data protection and security laws and regulations. 
Appropriate measures will be employed to safeguard these data, to maintain the confidentiality 
of the person’s related health and medical information, to properly inform the concerned 
persons about the collection and processing of their personal data, to grant them reasonable 
access to their personal data and to prevent access by unauthorized persons. 
 
All information obtained during the course of the investigation will be regarded as confidential. 
All personal data gathered in this trial will be treated in strictest confidence by Investigators, 
monitors, Sponsor’s personnel and IEC/IRB. No data will be disclosed to any third party 
without the express permission of the subject concerned, with the exception of Sponsor 
personnel (monitor, auditor), IEC/IRB and regulatory organizations in the context of their 
investigation related activities that, as part of the investigation will have access to the CRFs 
and subject records. 
 
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to investigate the efficacy, safety, quality, and utility of 
the investigational product(s) used in this study. 
 
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. 
The Sponsor ensures that the personal data will be: 
• processed fairly and lawfully. 
• collected for specified, explicit, and legitimate purposes and not further processed in a 
way incompatible with these purposes. 
• adequate, relevant, and not excessive in relation to said purposes. 
• accurate and, where necessary, kept current. 
 
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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 ISO 14155:20201 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 ISO 14155:20201 and all study documents as specified by 
the applicable regulatory requirement(s). The Investigator/Institution will take measures to 
prevent accidental or premature destruction of these documents. 
 
Essential documents must be retained until at least two (2) years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least two (2) years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents will be retained for a longer period if required by the applicable regulatory 
requirements or instructed by the Sponsor. It is the responsibility of the Sponsor to inform the 
Investigator/Institution as to when these documents no longer need to be retained. 
 
If the responsible Investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The Sponsor must be notified in writing of the name and address of 
the new custodian. Under no circumstance shall the Investigator relocate or dispose of any 
study documents before having obtained written approval from the Sponsor. 
 
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the Investigator must permit access to such reports.  
If the Investigator has a question regarding retention of study records, he/she should contact 
JJVC. 
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20. FINANCIAL CONSIDERATIONS 
Remuneration for study services and expenses will be set forth in detail in the Clinical Research 
Agreement. The Research Agreement will be signed by the Principal Investigator and a JJVC 
management representative prior to study initiation. 
 
JJVC reserves the right to withhold remuneration for costs associated with protocol violations 
such as: 
• Continuing an ineligible subject in the study. 
• Scheduling a study visit outside the subject’s acceptable visit range. 
 
JJVC reserves the right to withhold final remuneration until all study related activities have 
been completed, such as: 
• Query resolution. 
• Case Report Form signature. 
• Completion of any follow-up action items. 
21. PUBLICATION 
There is no plan to publish the outcome of this investigation, but the study sponsor may choose 
to publish study results if this is needed to support future regulatory submissions or marketing 
activities. 
22. REFERENCES 
1 ISO 14155:2020: Clinical investigation of medical devices for human subjects — Good 
clinical practice, Available at: https://www.iso.org/standard/71690.html 
2 Declaration of Helsinki – Ethical principles for Medical Research Involving Human 
Subjects, 
Available 
at: 
https://www.wma.net/policies-post/wma-declaration-of-
helsinki-ethical-principles-for-medical-research-involving-human-subjects/  
3 United States (US) Code of Federal Regulations (CFR). Available at: 
https://www.gpo.gov/fdsys/browse/collectionCfr.action?collectionCode=CFR 
4 Franklin R. Investigator's Brochure CR-6542, v1.0 (
): Evaluation of 
the clinical performance of Daily Disposable Silicone Hydrogel Multifocal Toric 
Contact Lenses. 
5 Franklin R. Clinical Study Protocol 
 v4. (
). Pilot 
Evaluation of a Silicone Hydrogel Daily Disposable Toric Multifocal Contact Lens. 
August 6, 2020. 
6 Franklin R. Clinical Study Protocol 
, v6. (
). Evaluation of 
Silicone Hydrogel Multifocal Toric Contact Lenses in a Hyperopic Population. January 
11, 2021. 
7 Franklin R. Clinical Study Protocol 
, v1. (
). Evaluation of 
Daily Disposable Silicone Hydrogel Multifocal Toric Contact Lenses. May 12, 2021. 
8 Franklin R. Clinical Study Protocol 
, v1.0 (
). Evaluation 
of Rotation with a Multifocal Toric Contact Lens. June 02, 2022. 
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9 Wirth RJ, Edwards MC, Henderson M, Henderson T, Olivares G, Houts CR. 
Development of the contact lens user experience: CLUE scales . Optometry and Vision 
Science. 2016;93(8):801. Available at: https://pubmed.ncbi.nlm.nih.gov/27383257/ 
10 Project Aurora for Astigmatism Customer Requirements Document (CRD), 
 
11 SAS Institute Inc: SAS® 9.4 Statements: Reference, Third Edition. Cary, NC SAS 
Institute Inc; 2014. 
12 Cannon J. Technical Report 
. Post-Marketing CLUE Scores Analysis 
of Toric and Multifocal Toric CL Wearers.  April 14, 2022. 
13 PASS. Power Analysis and Sample Size Software. Kaysville, Utah, USA: NCSS, LLC; 
2021. https://www.ncss.com/software/pass/pass-documentation  
14 Diniz CAR, Tutia MH, Leite JG. Bayesian analysis of a correlated binomial model. 
Brazilian Journal of Probability and Statistics. 2010;24(1):68-77.  
15 Kenward MG, Roger JH. Small Sample Inference for Fixed Effects from Restricted 
Maximum Likelihood. Biometrics. 1997;53(3):983-997.  
16 Jovanovic BD. and Levy PS. A Look at the Rule of Three. The American Statistician. 
1997;51(2):137-139. 
17 Health Information Portability and Accountability Act (HIPAA), Available at: 
https://www.hhs.gov/hipaa/for-professionals/privacy/index.html  
 
 
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APPENDIX B: PATIENT INSTRUCTION GUIDE 
Will be provided separately.  
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APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) 
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APPENDIX D: TEST LENS FITTING GUIDE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
   
 
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APPENDIX E: PRESBYOPIC SYMPTOMS QUESTIONNAIRE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Document Number:  
 
Revision Number:  5 
 
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NEAR LOGMAR VISUAL ACUITY MEASUREMENT PROCEDURE 
 
 
 
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DETERMINATION 
OF 
DISTANCE 
SPHEROCYLINDRICAL 
REFRACTIONS 
 
 
 
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Revision Number:  5 
 
  
 
 
 
 
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BIOMICROSCOPY SCALE 
 
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 KERATOMETRY 
 
 
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DISTANCE AND NEAR VISUAL ACUITY EVALUATION 
 
 
 
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Document Type:       
 
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Revision Number:  5 
 
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DISTANCE 
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VISUAL 
ACUITY 
MESAUREMENT 
PROCEDURE  
 
 
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Clinical Study Protocol 
Johnson & Johnson Vision Care, Inc. 
 
  
VISUAL ACUITY CHART LUMINANCE AND ROOM ILLUMINATION     
TESTING 
 
 
CR-6542, v 4.0 
 
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Revision Number:  4 
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Clinical Study Protocol 
Johnson & Johnson Vision Care, Inc. 
 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE 
Protocol Number and Title: CR-6542 Evaluation of the clinical performance of Daily Disposable 
Silicone Hydrogel Multifocal Toric Contact Lenses 
 
Version and Date: 4.0,  25 March 2024 
 
I have read and understand the protocol specified above and agree on its content.   
 
I agree to conduct this study according to ISO 14155:20201, the Declaration of Helsinki2, United States 
(US) Code of Federal Regulations (CFR)3, and the pertinent individual country laws/regulations and to 
comply with its obligations, subject to ethical and safety considerations.  I, as the Principal Investigator, 
am responsible for ensuring that all clinical site personnel, including Sub-Investigators, adhere to all 
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. 
 
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 
 
 
 
 
 
CR-6542, v 4.0 
 
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