Adaptation To and Satisfaction With Contact Lens Wear In Myopic Young Adults
Conditions: Myopia
Sponsor: CooperVision, Inc.



 
Mulberry Protocol V2 11mar2021 
2 
 
Clinical site address :  
 
CORE 
 
 
 
 
 
School of Optometry & Vision Science 
 
 
 
 
 
University of Waterloo 
 
 
 
 
 
200 Columbia Street West 
 
 
 
 
 
Waterloo, Ontario N2L 3G1 
 
 
 
 
 
CANADA 
 

 
Mulberry Protocol V2 11mar2021 
3 
 
DOCUMENT CHANGE HISTORY 
 
Version 
date 
Author 
Description of change(s) 
21Dec2020 
 
Original protocol 
11mar2021 
 
Section 6 (Risk section): 
Addition of risk details concerning COVID-19 
 
 
 
 
 
 

 
Mulberry Protocol V2 11mar2021 
4 
Table of contents 
Document change history ................................................................................................................ 3 
1 
Introduction ............................................................................................................................... 8 
2 
Objectives ................................................................................................................................. 8 
3 
Hypothesis ................................................................................................................................ 9 
4 
Materials and methods ............................................................................................................. 9 
4.1 
Study design ...................................................................................................................... 9 
4.1.1 
Overall design ............................................................................................................ 9 
4.1.2 
Masking .................................................................................................................... 10 
4.2 
Study population .............................................................................................................. 10 
4.2.1 
Sample size calculation............................................................................................ 10 
4.2.2 
Number of participants ............................................................................................. 10 
4.2.3 
Inclusion and exclusion criteria ................................................................................ 10 
4.2.4 
Repeated screenings ............................................................................................... 12 
4.3 
Study materials ................................................................................................................ 12 
4.3.1 
Lenses ...................................................................................................................... 12 
4.3.2 
Ordering consumables ............................................................................................. 12 
4.3.3 
Disposing of consumables ....................................................................................... 13 
4.3.4 
Product accountability .............................................................................................. 13 
4.4 
Scheduled and unscheduled visits .................................................................................. 13 
4.4.1 
Study visits ............................................................................................................... 13 
4.4.2 
Visit 1, Screening ..................................................................................................... 14 
4.4.3 
Visit 2, Baseline & Dispense (Day 0) ....................................................................... 15 
4.4.4 
Visit 3, 2 week Follow-up ......................................................................................... 15 
4.4.5 
Visit 4, 1 month Follow-up ........................................................................................ 16 
4.4.6 
Visit 5, 2 month Follow-up ........................................................................................ 16 

 
Mulberry Protocol V2 11mar2021 
5 
4.4.7 
Visit 6, 3 month follow up visit and exit .................................................................... 16 
4.4.8 
Study Exit ................................................................................................................. 17 
4.4.9 
Unscheduled visits ................................................................................................... 17 
4.5 
Study procedures ............................................................................................................ 18 
4.5.1 
Case history ............................................................................................................. 19 
4.5.2 
Quality of life (CLIQ) and Quality of Vision Questionnaires (QoV): ........................ 20 
4.5.3 
Visual acuity ............................................................................................................. 20 
4.5.4 
Autorefraction ........................................................................................................... 20 
4.5.5 
Subjective refraction ................................................................................................. 20 
4.5.6 
Slit lamp biomicroscopy ........................................................................................... 20 
4.5.7 
Contact Lens fit ........................................................................................................ 21 
 
 
 
 
 
 
 
 
 
 
5 
Monitoring protocol adherence .............................................................................................. 22 
6 
Potential risks and benefits to human participants ................................................................ 22 
7 
Adverse events ....................................................................................................................... 24 
7.1 
Normal or adaptive symptoms......................................................................................... 26 
7.2 
Procedures for adverse events ....................................................................................... 26 
7.3 
Reporting adverse events ............................................................................................... 26 
8 
Discontinuation from the study............................................................................................... 27 
9 
Study completion and remuneration ...................................................................................... 28 
10 
Statistical analysis and data management ............................................................................ 29 
10.1 
Statistical analysis ........................................................................................................ 29 

 
Mulberry Protocol V2 11mar2021 
6 
10.2 
Data management ....................................................................................................... 29 
10.3 
Comments on source documents ................................................................................ 29 
11 
Protocol training ..................................................................................................................... 30 
12 
Study monitoring .................................................................................................................... 30 
13 
Study management ................................................................................................................ 30 
13.1 
Statement of compliance ............................................................................................. 30 
13.2 
Ethics review ................................................................................................................ 30 
13.3 
Clinical trial registration ................................................................................................ 31 
13.4 
Protocol deviations....................................................................................................... 31 
13.4.1 
Major protocol deviations ......................................................................................... 31 
13.4.2 
Minor protocol deviations ......................................................................................... 31 
13.4.3 
Reporting and documenting protcol deviations ....................................................... 32 
13.5 
Premature termination of the study ............................................................................. 32 
13.6 
Study participant records ............................................................................................. 32 
13.7 
Retention of study records and data ........................................................................... 32 
14 
Report ..................................................................................................................................... 33 
15 
References ............................................................................................................................. 33 
 
 

 
Mulberry Protocol V2 11mar2021 
7 
 
 
 Confidentiality 
This is a private document and the property of the Centre for Ocular Research & Education. It 
is therefore confidential to the recipient and must not be quoted from or distributed beyond the 
company to which it is sent without the express written permission of the Director (or her/his 
designate) of the Centre for Ocular Research & Education. Release of information from this 
document is governed by the research agreement on file. 
 
Disclaimer 
This study will be conducted for research purposes only. 
 
 
 

 
Mulberry Protocol V2 11mar2021 
8 
1 
INTRODUCTION 
Myopia is a significant public health problem, it has been predicted that by 2050, 50% of the 
word population will be myopic. (1) Myopia can be defined as an eye that is excessively long 
and with the increase in axial length comes an increased risk of developing ocular pathology. 
This increased risk is directly related to the amount of myopia, individuals with high myopia 
being as much as 40x more likely to have pathology that can result in loss of vision compared to 
individuals with low amounts of myopia.(2)  There is very good evidence in the literature that 
there are interventions that can slow down the  progression of myopia and hence reduce the risk 
of ocular pathology.  One such intervention is the MiSight contact lens. In a three year study, the 
MiSight lens reduced the myopic progression of a group of subjects by 59% compared with their 
control group counterparts.(3) Subjects for the original MiSight study were aged 8-12 at 
recruitment,  this being a typical age group when myopia is first seen.  There is a cohort of 
patients who experience later onset of myopia and progression into early adult hood. The 
COMET study demonstrated that on average, myopia stabilizes by age 15 (48%), however, 90% 
of the cohort had stable myopia by age 21 and 96% by age 24.(4) Therefore it is clear that there 
is a proportion of the population whose myopic prescription continues to progress into early 
adulthood. To date there is no evidence in the literature that commencing a myopia control 
program in young adult myopes would have an impact on the progression of their myopia. The 
purpose of this study is to assess whether young adults can adapt to and achieve satisfaction 
with the MiSight lens. The results from this short term study may contribute towards the planning 
for longer term studies for the same population sample.  
2 
OBJECTIVES 
The objectives of the study are: 
x 
To measure objective and subjective visual performance, patient satisfaction and to 
determine if these aspects change over time as myopic young adults adapt to MiSight 
soft contact lenses. 
 
Primary outcome variable: 
• 
Subjective quality of vision (QoV) 
Secondary outcome variable: 
x 
Contact lens Impact on Quality of Life (CLIQ) 

 
Mulberry Protocol V2 11mar2021 
9 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
  
 
3 
HYPOTHESIS 
Young adults will achieve good subjective quality of vision (QoV) scores with the MiSight lenses. 
4 
MATERIALS AND METHODS 
4.1 STUDY DESIGN 
4.1.1 OVERALL DESIGN 
This is a prospective, single group, dispensing clinical trial to determine subjective and objective 
visual performance measures, patient satisfaction and adaptability to commercially available 
myopia control contact lenses (MiSight 1-day) in myopic young adults over 3 months of daily 
lens wear. There will be 4 scheduled in-office sessions and one remote/at home session 
spanning a total commitment time of 5.5 hours over the 3 months. The first session is anticipated 
to include the screening visit, visit 1 (V1) and, if eligible, visit 2 (V2) will be conducted in 
immediate succession. Visit 2 may be conducted on a separate day if necessary, but should be 
scheduled within 10 days of visit 1. 
 
x 
Visit 1 (V1): Screening and Baseline (75 mins) 
x 
Visit 2 (V2): Fitting/Dispensing of study lenses (15 mins if immediately following V1 on the 
same day)  
Note – V2 can take place on a separate day, if necessary, but should be scheduled within 
10 days of V1. Entrance acuity and biomicroscopy will be required in this case, and time 
required would be increased to 30 minutes.  
x 
Visit 3 (V3): Day 7, Follow-up (60 mins) 

 
Mulberry Protocol V2 11mar2021 
10 
x 
Visit 4 (V4): 1 month, Follow-up (75 mins) 
x 
Visit 5 (V5): 2 month, Remote at home questionnaires (15 mins) 
x 
Visit 6 (V6): 3 month, Follow up and exit (90 mins) 
 
4.1.2 MASKING 
This is an open-label study that will not involve masking.  
4.2 STUDY POPULATION 
4.2.1 SAMPLE SIZE CALCULATION 
Using a conservative estimate for repeated measure ANOVA paradigm, with 1 group, with 3 
measurements (baseline, 1 month, 2 months) and f effect size of 0.25 (cumulative probability 
75%), and 1-beta 0.95, the minimum sample size is n = 43.  Using an attributed drop-out rate of 
10-15%, the required sample size to be dispensed will be 50 participants.  
4.2.2 NUMBER OF PARTICIPANTS 
Participants will be recruited using CORE database and advertising approved by the UW Office 
of Research Ethics. Up to 50 participants who meet all eligibility criteria may be dispensed with 
MiSight study lenses and asked to wear these lenses for 3 months (± 7 days), with a target of 43 
completing the study. Participants who were screened but did not meet all eligibility criteria are 
not included in the number of participants (n=50) to be dispensed. Informed consent will be 
obtained for all participants prior to their enrolment in the study and prior to collecting any study 
data (Appendix 1). 
4.2.3 INCLUSION AND EXCLUSION CRITERIA 
A person is eligible for inclusion in the study if he/she: 
1. Is between 17 and 25 years of age (inclusive) and has full legal capacity to volunteer; 
2. Has read and signed an information consent letter; 
3. Is willing and able to follow instructions and maintain the appointment schedule; 
4. Has a vertex corrected spherical equivalent distance refraction that ranges between -
0.75D to -6.00D in each eye;  
5. Has astigmatism ≤ -0.75 DC in either eye, by refraction; 
 
6. Be correctable to better than 0.20 logMAR in each eye by refraction; 
 
7. Has habitually worn spherical soft contact lenses to correct for distance vision (i.e. no 
multifocal or monovision) for the past 3 months; 

 
Mulberry Protocol V2 11mar2021 
11 
 
8. Is willing to wear contact lenses for at least 10 hours a day, 6 days a week while in the 
study; 
9. Demonstrates an acceptable fit with the study lenses; 
10. Has ocular health findings considered to be “normal” and which would not prevent the 
participant from safely wearing contact lenses. 
 
A person will be excluded from the study if he/she: 
1. Is participating in any concurrent clinical or research study; 
2. Has a history of amblyopia; 
3. Has TNO Stereoacuity worse than 120” arc / or Titmus worse than 100” arc; 
4. Has any known active* ocular disease and/or infection; 
5. Has a systemic condition that in the opinion of the investigator may affect a study 
outcome variable; 
6. Is using any systemic or topical medications that in the opinion of the investigator may 
affect a study outcome variable; 
7. Has known sensitivity to the diagnostic pharmaceutical (sodium fluorescein) to be used in 
the study; 
8. Is pregnant, lactating or planning a pregnancy at the time of enrolment (verbal 
confirmation at the screening visit); 
9. Is pseudophakic; 
10. Has undergone refractive error surgery; 
11. Has one of following experiences with MiSight lenses: 
x 
Is currently wearing MiSight lenses or 
x 
Has worn MiSight lenses for more than one week at any given time or 
x 
Has worn MiSight lenses for any more than 30 minutes in the past 30 days; 
12. Has had orthokeratology treatment within the last 3 months. 
* For the purposes of this study, active ocular disease is defined as infection or inflammation, which requires 
therapeutic treatment. Mild (i.e. not considered clinically relevant) lid abnormalities (blepharitis, meibomian gland 
dysfunction, papillae), corneal and conjunctival staining and dry eye are not considered active ocular disease. 
Neovascularization and corneal scars are the result of previous hypoxia, infection or inflammation and are therefore 
not active. 
Pregnant and lactating women are not being excluded from the study due to safety concerns but due to changes in 
physiology that occur secondary to systemic hormonal changes which may impact refractive error and visual acuity.  

 
Mulberry Protocol V2 11mar2021 
14 
 
4.4.2 VISIT 1, SCREENING  
A documented informed consent process will be conducted with all participants prior to their 
enrolment in the study and prior to any data collection or measurements.  
Participants will be assigned a study ID number after they sign the consent documentation process 
i.e. before their eligibility for the study has been confirmed. The investigator will determine 
participant eligibility using the inclusion and exclusion criteria. Ineligible participants will be 
discontinued from the study. The procedures to be performed are outlined below:  
1. Informed consent 
2. Participant demographics and medical history: 
x 
Age, Sex 
x 
Medical history/medications, Allergies 
3. CL wear history 
x 
Habitual contact lens wear (CL type, cleaning solution (if applicable), wear time) 
4. Subjective questionnaires (QoV and CLIQ) with habitual lenses within the last month of 
lens wear experience 
5. Presenting visual acuity 
6. Auto refraction/auto keratometry 
7. Sphero-cylindrical refraction, monocular & binocular logMAR distance HIHC VA 
 
 
 
 
 
13. Slit lamp biomicroscopy 
14. MiSight study lens fitting 
a. The contact lens power will be chosen based on the vertex best sphere refraction. 
b. The participant will insert the lenses. 

 
Mulberry Protocol V2 11mar2021 
15 
c. Acceptability of lens fit (centration, movement, limbal coverage, overall; YES/NO) 
will be confirmed. 
d. Monocular over-refraction will be performed to determine if a different power is 
needed. If any changes are made, the above procedures will be repeated. 
e. The final lens powers for OD and OS and monocular & binocular logMAR 
distance HIHC VA will be recorded. 
15. Confirm eligibility. 
 
4.4.3 VISIT 2, BASELINE & DISPENSE (DAY 0) 
Participants who successfully met all eligibility criteria in Visit 1 will directly transition to Visit 2, 
while continuing to wear the pair of study lenses that has just been fitted. 
1. Lens dispense: Participants will be provided with a supply of MiSight CLs to last them for 
the period of the study.   
2. Participant instructions. The participants will be asked to: 
x 
Wear the lenses at least 6 days per week and 10 hours per day throughout the 
study; 
x 
Attend V3 after 2 hours or more of MiSight study lens wear on that day; 
 
4.4.4 VISIT 3, 2 WEEK FOLLOW-UP  
Participant to attend visit after 2 hours or more of MiSight study lens wear. 
1. Changes in medical history/medications; 
2. Compliance with # of CL wear days/hours per day  
3. Presenting VA 
 
5. Spherical over-refraction 
6. Slit lamp biomicroscopy 
7. Questionnaires (CLIQ, QoV) 
8. Lens removal 

 
Mulberry Protocol V2 11mar2021 
16 
9. Biomicroscopy examination  
 
4.4.5 VISIT 4, 1 MONTH FOLLOW-UP  
Participant to attend visit after 2 hours or more of MiSight study lens wear. 
1. Changes in medical history/medications; 
2. Compliance with # of CL wear days/hours per day  
3. Presenting VA 
 
 
6. Slit lamp biomicroscopy 
7. Questionnaires (CLIQ, QoV) 
8. Lens removal 
9. Biomicroscopy examination  
10. Instructions on completing QoV and CLIQ surveys within the V5 time window 
 
4.4.6 VISIT 5, 2 MONTH FOLLOW-UP  
This visit will be conducted remotely to reduce the number of study visits. 
Participants will be sent a link to an electronic questionnaire which will include version questions 
to confirm their contact lens wearing time (i.e. typical hours per day and days per week) plus the 
QoV and CLIQ surveys. If electronic access is not available or fails then the questions can be 
emailed or provided in paper form. 
 
4.4.7 VISIT 6, 3 MONTH FOLLOW UP VISIT AND EXIT  
Participant to attend visit after 2 hours or more of MiSight  study lens wear. 
1. Collect unused study CLs; 
2. Changes in medical history/medications; 
3. Compliance with # of CL wear days/hours per day  

 
Mulberry Protocol V2 11mar2021 
17 
4. Presenting VA 
 
 
 
8. Spherical over-refraction 
9. Slit lamp biomicroscopy 
10. Questionnaires (CLIQ, QoV) 
11. Lens removal 
12. Biomicroscopy examination 
 
14. Exit visual acuity with habitual correction 
 
4.4.8 STUDY EXIT 
The study exit form will be completed when a participant exits the study. This form will be 
completed either at study completion, or if the participant is discontinued from the study at 
another time. A study exit form must be completed for all participants who have taken a study ID 
number. If in the opinion of the investigator post-study follow-up visits are required, the exit form 
will be completed after the last follow-up visit.  
Exit monocular and binocular distance vision will be recorded with either the participant’s 
spectacles, refraction or habitual contact lenses. An exit biomicroscopy assessment will be 
conducted if not already completed on the same day for a concurrent study visit. 
After the exit assessments have been completed, the participant and investigator will complete 
the study completion and remuneration forms. At this time the participant will be considered as 
having exited the study. 
 
4.4.9 UNSCHEDULED VISITS 
An unscheduled visit is defined as an interim visit requested by the participant or investigator 
due to an unanticipated problem. Data recorded at these visits will be entered into the database. 

 
Mulberry Protocol V2 11mar2021 
19 
 
 
 
- 
- 
 
- 
 
- 
Spherical Over-
refraction 
+ VA 
- 
- 
 
- 
- 
 
- 
Wear time review 
- 
- 
 
 
 
 
* 
Compliance 
assessment / Lens 
and solution returns 
- 
- 
 
 
- 
 
* 
Slit-lamp 
biomicroscopy: 
Assessment of lenses 
worn at visit and 
ocular assessment 
 
 
 
 
- 
 
 
Questionnaires 
(including QOL/OOV 
questionnaires) 
*** 
+ 
 
 
 
 
- 
Photos / video 
* 
* 
* 
* 
- 
* 
* 
Adverse event 
assessment 
 
 
 
 
- 
 
 
Visit summary 
 
 
 
 
- 
 
 
* 
At investigators’ discretion 
** 
If visual acuity (VA) is decreased by 2 lines or more from BL or LD 
*** 
With habitual lenses 
+ 
If lenses dispensed 
 
 
4.5.1 CASE HISTORY 
Demographics: 
Demographic information from the participant will be obtained, including age and sex. 
Medical History: 
At screening, information will be obtained from participants about the current medication, allergies, 
and any medical conditions. At visits 2 (if applicable),3, 4 and 6 participants will be asked about 
changes in their medication or health. 

 
Mulberry Protocol V2 11mar2021 
20 
Contact Lens History: 
Information will be obtained from the participant about the current contact lens type (lens name, 
brand), lens power and use of artificial tears. Participants will be asked their typical lens wear time 
(hours/day and days/week). 
4.5.2 QUALITY OF LIFE (CLIQ) AND QUALITY OF VISION QUESTIONNAIRES 
(QOV): 
Participants will be asked to complete questionnaires based on the time period of contact lens 
wear specified in the questionnaire. 
4.5.3 VISUAL ACUITY 
Visual acuity for distance will be measured using high contrast computer-generated acuity charts 
in high illumination. Participants will be asked to read letters that progressively decrease in size 
on a computer screen located at a distance of 6 meters.  
4.5.4 AUTOREFRACTION 
Participants will be asked to focus on a target while seated at an instrument that measures their 
approximate spectacle prescription and corneal shape. 
4.5.5 SUBJECTIVE REFRACTION 
Participants will be asked to read a letter chart from a distance through lenses placed in front of 
their eyes. They will also be asked to compare clarity of their vision between different lenses 
placed in front of their eyes. This procedure aids to determine their spectacle and/or contact lens 
prescription. 
4.5.6 SLIT LAMP BIOMICROSCOPY 
The participant will be seated behind a slit lamp and the following may be assessed at any visit: 
External adnexa anomalies: 
Any observations of the anterior eye (e.g. pterygium, pinguecula, etc) will be recorded. 
Cornea:  
Any corneal observations (such as infiltrates, old scars, etc) will be documented.  
Conjunctival redness: 

 
Mulberry Protocol V2 11mar2021 
21 
Ocular redness will be assessed for the bulbar and limbal conjunctiva using the EFRON grading 
scale (0 to 4, 0 = normal; 0.1 increments).  
Corneal and conjunctival staining with fluorescein:  
Corneal staining will be assessed for 5 zones, by grading type (0-4, 0.5 steps), extent (0-4, 0.5 
steps) and depth (0-4, integer steps); 
Lens edge related conjunctival staining and conjunctival indentation will be assessed for 4 zones 
(0-4, 0.5 steps). 
Palpebral conjunctival hyperemia and roughness: 
The redness and roughness of the upper and lower eyelids (tarsal plate zone 2) will be assessed 
using the Efron grading scale (0 to 4, 0 = normal/ uniform satin appearance; 0.25 steps). 
 
4.5.7 CONTACT LENS FIT  
Contact lens fit: 
Lens fit will be assessed to ensure acceptable lens fit with study lenses at the screening visit. 
At V2 and V3, lens centration and movement will be assessed as follows 
x 
Lens centration (scale: optimal, slight decentration, moderate decentration but not 
encroaching limbus, excessive & occasionally encroaching limbus); 
x 
Lens movement for primary gaze (-2 = Unacceptably tight; -1 = Slightly tight but 
acceptable; 0 = Optimal; +1 = Slightly loose but acceptable; +2 = Unacceptably loose); 
lens tightness on push-up test (0-100 scale, with 50 being optimal; 5-point steps). 
 
 
 
 
 
 

 
Mulberry Protocol V2 11mar2021 
23 
incidence of infection due to daily-wear soft lenses is 0.035%. Almost always an infection will occur 
only in one eye. Thirty five million Americans who currently wear contact lenses assume this risk.  
When contact lenses are worn on a daily wear basis there is a small risk of an adverse event 
compared to not wearing contact lenses. When contact lenses are worn on an extended wear 
basis, there is a significantly increased risk of an adverse reaction compared with wearing contact 
lenses on a daily wear basis. 
A dye (fluorescein) normally used for eye exams is being used in this study. Although rare, it is 
possible that participants may have an allergic reaction to the dye. This could cause discomfort to 
their eye.   
Participants are advised to inform the investigator of any sensitivities to the study products. 
Parts or all of this study will be conducted during the COVID-19 pandemic. Therefore, risks 
exists with the infection with COVID-19. The risks of infection with COVID-19 arise due to 
possible exposure during commute to and from the study visit as well as during the study visit, 
particularly due to the closeness of the investigator and participant (within 2m for some 
assessments). The potential effects of COVID-19 are not yet fully known and may include long-
term health consequences. In a small percentage, infection with COVID-19 can lead to serious 
illness, hospitalization, and in rare cases to complications leading to death. Individuals aged 60 
and above and those with underlying medical conditions are considered at a greater risk for 
severe illness from the COVID-19 virus.   
In consideration of risks associated with COVID-19, CORE has implemented a series of on-site 
safety procedures which have been reviewed and approved by the University of Waterloo. 
These include, but are not limited to, self-screening of investigators and participants prior to 
entering the building, maintaining physical distancing as much as possible, frequent 
handwashing, wearing of face masks by the investigator and participant, and frequent room and 
equipment hygiene and decontamination. 
Participants will not benefit directly from taking part in this study.  
Information from this study may help researchers come up with new soft contact lens designs to 
help others in the future. This study may help the study sponsor to better understand the 
performance of the products being used in this study in a different age cohort from that 
previously studied. 
 

 
Mulberry Protocol V2 11mar2021 
26 
23 
Asymptomatic corneal infiltrative events 
reporting as per 
requirements 
24 
Any sign and/or symptom for which temporary lens discontinuation for > 1 day 
is recommended (if not already classified) 
20 
Other sign and/or symptom warranting classification as a non-significant 
adverse event 
 
7.1 NORMAL OR ADAPTIVE SYMPTOMS 
Transient symptoms such as end-of-day dryness, lens awareness, itching or burning or other 
discomfort may occur with contact lens wear and may occasionally reduce wearing time. These 
are not reported as adverse events unless in the investigator’s opinion they are unexpected in 
nature, severe or have a high rate of occurrence.  
 
7.2 PROCEDURES FOR ADVERSE EVENTS 
Treatment of an adverse event will depend on its nature and severity. Based on the clinical 
judgment of the investigator the participant may be referred to an ophthalmologist for treatment. 
The investigator will attempt to determine whether the reaction is related to the test device or a 
result of other factors. An adverse event form will be completed for each adverse event. Whenever 
possible, the adverse event will be photo-documented.  
Expenses incurred for medical treatment as part of study participation will be paid by the sponsor 
(bills and prescription receipts kept). The participant must be followed until resolution or no further 
change is anticipated and/or referred for further care with the appropriate health care professional 
and/or recorded as being under appropriate health care as per investigator’s discretion. A written 
report will be completed indicating the subsequent treatment and resolution of the condition. 
 
7.3 REPORTING ADVERSE EVENTS 
All potential Serious and Unanticipated Adverse Device Effects that are related or possibly related 
to participant’s participation will be reported to the Principal Investigator and the sponsor within 24 
hours of the investigator becoming aware of the event. The Investigator will report the event to the 
University of Waterloo’s Office of Research Ethics (ORE) within 24 hours of becoming aware, as 

 
Mulberry Protocol V2 11mar2021 
27 
per their requirements (by fax, mail/delivery, phone, or email).  All fatal or life threatening events 
will be reported immediately to the ORE. 
Significant and Non-Significant Adverse Events will be reported to the sponsor as soon as 
possible, but no later than 5 working days after the occurrence. The Investigator will report the 
event to the ORE as per ORE requirements (by fax, mail/delivery, phone, or email). 
 
  
  
 
  
 
  
 
  
  
 
 
 
 
 
Details of all adverse events will be included in the study report. 
 
8 
DISCONTINUATION FROM THE STUDY 
Participants may be discontinued at the discretion of the investigator or sponsor in consideration 
of participant safety or protocol compliance, or at discretion of the participant.  Participants 
discontinued from a study will be reimbursed $20 per hour for their active involvement in the 
study (including the initial screening visit).  Upon discontinuing, a participant will be offered the 
option of their data being withdrawn from future statistical analysis. The following is a list of 
possible reasons for discontinuation from the study: 
x 
Screening failure: Participants will be discontinued if they do not meet the inclusion and 
exclusion criteria outlined in section 4.2.2. 
x 
Unacceptable performance with products to be used in study: Participants may be 
discontinued if they are unable to achieve acceptable comfort and /or vision with the 
study products. 
x 
Positive slit lamp finding:  Participants may be permanently discontinued from the study 
depending on the severity of the condition and on the judgement of the investigator.   

 
Mulberry Protocol V2 11mar2021 
28 
x 
Adverse event: If a participant experiences an adverse event during the study they may 
be discontinued based on the clinical judgement of the investigator. 
x 
Symptoms: If the participant has persistent symptoms they may be discontinued based 
on the clinical judgement of the investigator. 
x 
Disinterest, relocation or illness: The participant may choose to discontinue due to 
reasons within or beyond their control. 
x 
Violation of protocol or non-compliance:  The participant will be discontinued if they are 
unable or unwilling to follow the protocol specified visit schedules and/or study 
procedures. 
x 
Instillation of topical ocular medication:  The participant will be discontinued if they elect 
to use a topical ocular medication during the study unless that topical ocular medication 
is prescribed for a limited duration (less than two weeks) to treat a transient condition; in 
this case the participant may remain an active participant (at the discretion of the 
investigator) after stopping topical ocular medication following resolution of the ocular 
condition). 
x 
Lost to follow-up:  The participant will be discontinued if they cannot be contacted and do 
not return for a final exit visit, and if the investigator has made a reasonable effort to 
contact the participant for a final study visit. 
x 
Premature termination of the study by the sponsor, CORE or the Office of Research 
Ethics at the University of Waterloo. 
A discontinuation form , stating the reason for discontinuation will be completed, which requires 
the signatures of both the participant and the investigator except where the participant is lost to 
follow-up in which case only the signature of the investigator is required.   
All discontinuations including their reasons will be included in the final report. 
9 
STUDY COMPLETION AND REMUNERATION 
At the last scheduled protocol visit a study completion form will be completed, which requires the 
signatures of both the participant and the investigator.   
Once their involvement in the study is complete, participants will be informed about receiving 
feedback following study completion in the Letter of Appreciation. 

 
Mulberry Protocol V2 11mar2021 
29 
 
 
 
10 STATISTICAL ANALYSIS AND DATA MANAGEMENT 
10.1 STATISTICAL ANALYSIS 
All data will be analyzed by CORE at the University of Waterloo.  Data analysis will be 
conducted using Statistica, SPSS, or other appropriate software. 
Descriptive statistics will be provided for all primary outcome variables as well as information 
regarding baseline variables (e.g. age, sex).  
QoV and CLIQ ratings will be compared between visits using either Paired t-tests or Wilcoxon 
matched pairs, or using ANOVA, as applicable; statistical significance will be set at 5%. The 
appropriate tests will be selected based on tests of normality - non-parametric tests will be used 
for data not showing a normal distribution. For assessments conducted for each eye separately, 
the right eye will be used for analysis if there is no difference between eyes. 
Additional analysis may be conducted. 
10.2 DATA MANAGEMENT 
All study data will be recorded on paper CRFs. Data from this study will be entered in an 
electronic database and retained by CORE for a minimum of 25 years on a password-protected 
server. After 25 years, data will be disposed of in accordance with the guidelines laid out by the 
University of Waterloo.  
At the completion of the study CORE may provide a copy of the study data to the funding 
company. Data will typically be sent using a secure file share system operated by the University 
of Waterloo called Sendit which uses 128bit (or 256bit) SSL encryption.  This system provides a 
secure way to transfer files when email is not appropriate, whether because of file size, file type 
or concerns over security. Sendit includes features such as password protection, a restricted 
time period for download, IP logging and email notification of download. Files may be encrypted 
prior to transmission. Using this method means that data files are only stored on University of 
Waterloo servers during the transfer. 
10.3 COMMENTS ON SOURCE DOCUMENTS 

 
Mulberry Protocol V2 11mar2021 
30 
Data analysis will not be conducted on comments which have been recorded in the source 
documents. Only relevant and applicable comments will be included in the final report as 
deemed necessary by the lead investigator. 
11 PROTOCOL TRAINING 
All study personnel will be required to complete training prior to their involvement in the study. 
Records of training will be kept at CORE. 
12 STUDY MONITORING 
Study monitoring will be conducted throughout the study. In addition study records may be 
inspected at CORE by the Office of Research Ethics at the University of Waterloo, and by 
regulatory authorities in Canada and the United States, namely Health Canada and the United 
States Food and Drug Administration (FDA); however, no records containing 
identifiable/personal information will be permitted to leave the custody of CORE. 
Study monitoring will include, but may not be limited to: 
x 
The number of participants screened, enrolled, and randomized (i.e. assigned a study ID 
number), discontinued and completed; 
x 
Consent documentation; 
x 
Details of adverse events and protocol deviations; 
x 
Reports of unintended events. 
13 STUDY MANAGEMENT 
13.1 STATEMENT OF COMPLIANCE 
This clinical study is designed to be in compliance with the ethical principles in the Declaration of 
Helsinki, with the ICH guidelines for Good Clinical Practice (GCP), with the University of 
Waterloo’s Guidelines for Research with Human Participants and with the Tri-Council Policy 
Statement: Ethical Conduct for Research Involving Humans, 2nd Edition. 
x 
Declaration of Helsinki 
x 
ICH E6 - International Conference on Harmonisation; Good Clinical Practice 
x 
http://iris.uwaterloo.ca/ethics/human/guidelines/index.htm 
x 
http://iris.uwaterloo.ca/ethics/human/ethicsReview/UWStatement.htm 
x 
http://www.pre.ethics.gc.ca/eng/policy-politique/initiatives/tcps2-eptc2/Default/ 
 
13.2 ETHICS REVIEW 

 
Mulberry Protocol V2 11mar2021 
31 
This protocol will be submitted to and reviewed through the Office of Research Ethics (ORE) at 
the University of Waterloo. Notification of ethics clearance of the application is required prior to 
the commencement of the study. 
13.3 CLINICAL TRIAL REGISTRATION 
The sponsor will register this study with clinicaltrials.gov.  
13.4 PROTOCOL DEVIATIONS 
Protocol deviations are unanticipated or unintentional changes to a study after it has received 
prior sponsor approval and ethics clearance. Protocol deviations can be major or minor.  
13.4.1 MAJOR PROTOCOL DEVIATIONS 
Major protocol deviations may impact the research protocol, information consent document or 
other study materials, usually cannot be anticipated ahead of time and are often necessary to 
ensure the safety and welfare of the participants. 
The following are examples of protocol deviations that must be reported to the ORE: 
x 
Changes in procedures initiated to eliminate immediate risks/hazards to participants; 
x 
Enrollment of participants outside the protocol inclusion/exclusion criteria whether agreed 
to or not by the sponsor; 
x 
Medication / device / intervention errors (i.e. incorrect drug or dosage of drug / incorrect 
contact lens(es) dispensed / incorrect care system dispensed); 
x 
Inadvertent deviation in specific research intervention procedures or timing of the 
research intervention which could impact upon the safety or efficacy of the study-related 
intervention or upon the experimental design; 
x 
Information consent documentation violations: no documentation of informed consent; 
incorrect version of, or incomplete, informed consent documentation used. 
13.4.2 MINOR PROTOCOL DEVIATIONS 
Protocol deviations caused by or which originate with research participants are considered 
minor, and normally are not reported to the ORE unless these result in increased risk to the 
participant(s). The following are examples of protocol deviations that are considered minor and 
do not require reporting to the ORE: 
x 
Logistical or administrative aspects of the study (e.g., study participant missed 
appointment, change in appointment date); 

 
Mulberry Protocol V2 11mar2021 
32 
x 
Inadvertent deviation in specific research intervention procedures or timing of the 
research intervention which would not impact upon the safety or efficacy of the study-
related intervention or upon the experimental design (i.e., missing a measurement during 
a session that is not considered critical for the study).  
13.4.3 REPORTING AND DOCUMENTING PROTCOL DEVIATIONS 
Major protocol deviations must be reported to the ORE and the sponsor within 7 days of the 
deviation occurring (or its discovery) using the Protocol Deviation Report Form 107 (PDRF).  
Information from the PDRF is provided to the Clinical Research Ethics Committee (CREC) at the 
next monthly meeting. 
All protocol deviations (major and minor) occurring during the study will be documented and 
included in the final report. 
13.5 PREMATURE TERMINATION OF THE STUDY 
The sponsor, CORE or the Office of Research Ethics at the University of Waterloo may 
terminate the study at any time for any reason. 
13.6 STUDY PARTICIPANT RECORDS 
Study participant records will be completed to comply with GCP guidelines. Records will contain: 
x 
Unique study acronym and/or code; 
x 
Participant ID; 
x 
Date enrolled; 
x 
Confirmation by investigator that participant met eligibility criteria; 
x 
Confirmation that participant received a signed and dated copy of informed consent; 
x 
Exit date; 
x 
Investigator’s signature confirming study exit. 
13.7 RETENTION OF STUDY RECORDS AND DATA 
Records and data from this study will be retained for a minimum of 25 years. Details regarding 
storage procedures are given in CORE SOP014_v02 Clinical data management.  
 

 
Mulberry Protocol V2 11mar2021 
33 
14 REPORT 
A draft report will be provided according to the timeline specified in the contract. 
15 REFERENCES 
 
1. 
Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global 
Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. 
Ophthalmology. 2016;123(5):1036-42. 
2. 
Flitcroft DI. The complex interactions of retinal, optical and environmental factors in 
myopia aetiology. Prog Retin Eye Res. 2012;31(6):622-60. 
3. 
Chamberlain P, Peixoto-de-Matos SC, Logan NS, Ngo C, Jones D, Young G. A 3-year 
Randomized Clinical Trial of MiSight Lenses for Myopia Control. Optom Vis Sci. 2019;96(8):556-
67. 
4.         Myopia stabilization and associated factors among participants in the Correction of 
Myopia Evaluation Trial (COMET). Invest Ophthalmol Vis Sci. 2013;54(13):7871-84.