Clinical trial NCT04747808
Conditions: Primary Open Angle Glaucoma Ocular Hypertension
Keywords: Glaucoma Prostaglandin Intraocular pressure
Sponsor: MediPrint Ophthalmics, Inc.
Start date: 2021-01-08; Completion date: 2021-02-16
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is an open-label, Phase 2a clinical study of LL-BMT1 in patients with primary open-angle glaucoma and ocular hypertension. Study subjects will be treated for 7 days with a single dose of LL-BMT1.

Detailed description:

Arms: arm 1: Group 4 extended-wear contact lens printed with bimatoprost
Interventions: intervention 1: LL-BMT1
Intervention descriptions: intervention 1: Drug-printed contact lens in both eyes

Protocol documents:
Prot_000.pdf: 
NCT04747808 
Study LL-BMT10001 
 
A Phase 2a Study of Safety, Tolerability, and Efficacy of Drug-Delivering Contact Lens LL-BMT1 
in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension 
 
Protocol V 1.2 
Date: 21 December 2020 


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LL-BMT10001                                                                            CONFIDENTIAL
Version 1.1
Leo Lens Technology Co., Inc.
19 November 2020
A Phase 2a Study of Safety, Tolerability, and Efficacy 
of Drug-Delivering Contact Lens LL-BMT1 in 
Patients With Primary Open-Angle Glaucoma or 
Ocular Hypertension
Protocol Number: 
LL-BMT10001
Investigational Device Exemption  
Sponsor: 
Leo Lens Technology Co., Inc.
9899 Hibert Street, Suite A
San Diego, CA 92131
Phone: 
Version Number: 
v1.2 
Date: 
21 December 2020
Confidential Information
The information contained in this protocol is the property LEO LENS TECHNOLOGY and is intended for the use 
of clinical investigators. It should not be copied by or distributed to persons not involved in the clinical 
investigation unless disclosure is required by law or such persons are bound by a non-disclosure agreement with 
LEO LENS TECHNOLOGY CO., INC


9 
LEO LENS 
1FCHN0L0{;V 
Protocol Signature Page 
I confirm that I have read this protocol, I nnderstand it, and I will work according to this protocol 
and to the ethical principles stated in the applicable Declaration of Helsinki and in accordance 
with 21 CFR's 50, 54, 56,812 or the applicable guidelines for good clinical practices or the 
applicable laws and regulations of the country of the study site for which I am responsible, 
whichever provides the greater protection of the individual. 
I agree to maintain all information supplied by Leo Lens Technology Co., Inc. in confidence and 
when this information is submitted to an Institutional Review Board, Independent Ethics 
Committee, or other review board, it will be submitted with a designation that the material is 
confidential. 
0A J1.2 
vJ Vl-5'\-v,.i 
('AO 
Investigator Printed Name 
Acknowledged by: 
Praful Doshi 
Sponsor Representative Name 
Return signed page to Trial Runners 
LL-BMTl000I 
Leo Lens Technology Co., Inc. 
3 
CONFIDENTIAL 
12/21/2020 
Date 
Version 1.2 
21 December 202b 


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LL-BMT10001                                                                            CONFIDENTIAL
Version 1.2 
Leo Lens Technology Co., Inc.
21 December 2020
Version 1.2 
21 December 2020
No subjects enrolled.
No effect on subject exposure or safety.
Based upon input from the Investigational Review Board, best corrected visual acuity and slit lamp exam 
were added to all visits prior to the baseline visit. This impacts several sections of the protocol including 
the Schema and Schedule of Activities section.  


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LL-BMT10001                                                                            CONFIDENTIAL
Version 1.2 
Leo Lens Technology Co., Inc.
21 December 2020
STUDY TITLE
A Phase 2a Study of Safety, Tolerability, and Efficacy of Drug-Delivering Contact Lens 
LL-BMT1 in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension 
PROTOCOL NUMBER
LL-BMT10001 


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LL-BMT10001                                                                            CONFIDENTIAL
Version 1.2 
Leo Lens Technology Co., Inc.
21 December 2020
Table of Contents
STATEMENT OF COMPLIANCE.............................................................................................................................. 7
1
PROTOCOL SUMMARY.................................................................................................................................. 8
1.1
Synopsis....................................................................................................................................................... 8
1.2
Schema ........................................................................................................................................................ 9
1.3
Schedule of Activities................................................................................................................................13
2
INTRODUCTION ............................................................................................................................................15
2.1
Study Rationale..........................................................................................................................................15
2.2
Background................................................................................................................................................15
2.3
Potential Risks and Benefits to Human Patients........................................................................................16
3
OBJECTIVES AND ENDPOINTS...................................................................................................................17
4
STUDY DESIGN..............................................................................................................................................17
4.1
Overall Design...........................................................................................................................................17
4.2
Scientific Rationale for Study Design........................................................................................................18
4.3
Justification for Dose................................................................................................................................. 18
4.4
End of Study Definition.............................................................................................................................19
5
STUDY POPULATION ...................................................................................................................................19
5.1
Inclusion Criteria .......................................................................................................................................19
5.2
Exclusion Criteria......................................................................................................................................20
5.3
Lifestyle Considerations ............................................................................................................................21
5.4
Screen Failures ..........................................................................................................................................21
5.5
Strategies for Recruitment and Retention..................................................................................................21
6
STUDY INTERVENTION...............................................................................................................................21
6.1
Study Interventions Administration...........................................................................................................21
6.1.1
Study Intervention Description.......................................................................................................22
6.1.2
Dosing and Administration ............................................................................................................23
6.2
Preparation/Handling/Storage/Accountability...........................................................................................23
6.2.1
Acquisition and Accountability......................................................................................................23
6.2.2
Formulation, Appearance, Packaging, and Labeling......................................................................24
6.2.3
Product Storage and Stability.........................................................................................................24
6.2.4
Preparation
24
6.3
Measures to Minimize Bias: Randomization and Blinding .......................................................................24
6.4
Study Intervention Compliance .................................................................................................................24
6.5
Concomitant Therapy ................................................................................................................................24
6.5.1
Rescue Medicine 25
7
STUDY INTERVENTION DISCONTINUATION AND PATIENT DISCONTINUATION.........................25
7.1
Discontinuation of Study Intervention.......................................................................................................25
7.2
Patient Discontinuation From the Study....................................................................................................26
7.3
Lost to Follow-Up......................................................................................................................................26
8
STUDY ASSESSMENTS AND PROCEDURES ............................................................................................27
8.1
Efficacy Assessments ................................................................................................................................27
8.2
Safety and Other Assessments...................................................................................................................27
8.3
Adverse Events and Serious Adverse Events ............................................................................................28
8.3.1
Definition of Adverse Events.........................................................................................................28
8.3.2
Definition of Serious Adverse Events ............................................................................................28
8.3.3
Classification of an Adverse Event ................................................................................................28


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LL-BMT10001                                                                            CONFIDENTIAL
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8.3.4
Time Period and Frequency for Event Assessment and Follow-Up...............................................29
8.3.5
Adverse Event Reporting ...............................................................................................................30
8.3.6
Serious Adverse Event Reporting ..................................................................................................30
8.3.7
Reporting Events to Patients ..........................................................................................................31
8.3.8
Events of Special Interest...............................................................................................................31
8.3.9
Reporting of Pregnancy..................................................................................................................31
8.4
Unanticipated Problems.............................................................................................................................31
8.4.1
Definition of Unanticipated Problems............................................................................................31
8.4.2
Unanticipated Problem Reporting..................................................................................................32
8.4.3
Reporting Unanticipated Problems to Patients...............................................................................32
9
STATISTICAL CONSIDERATIONS..............................................................................................................32
9.1
Statistical Hypotheses................................................................................................................................32
9.2
Sample Size Determination .......................................................................................................................33
9.3
Populations for Analyses ...........................................................................................................................33
9.4
Statistical Analyses....................................................................................................................................33
9.4.1
General Approach 33
9.4.2
Safety Analyses
33
9.4.3
Efficacy Analyses 34
9.4.4
Baseline Descriptive Statistics .......................................................................................................34
9.4.5
Planned Interim Analyses...............................................................................................................34
9.4.6
Sub-Group Analyses ......................................................................................................................35
9.4.7
Tabulation of Individual Patient Data ............................................................................................35
9.4.8
Other Exploratory Analyses ...........................................................................................................35
10
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.....................................35
10.1
Regulatory, Ethical, and Study Oversight Considerations.........................................................................35
10.1.1
Informed Consent Process..............................................................................................................35
10.1.2
Study Discontinuation and Closure................................................................................................36
10.1.3
Confidentiality and Privacy............................................................................................................36
10.1.4
Future Use of Stored Specimens and Data .....................................................................................36
10.1.5
Key Roles and Study Governance..................................................................................................36
10.1.6
Safety Oversight
37
10.1.7
Clinical Monitoring........................................................................................................................37
10.1.8
Quality Assurance and Quality Control..........................................................................................37
10.1.9
Data Handling and Record Keeping...............................................................................................37
10.1.10
Protocol Deviations........................................................................................................................39
10.1.11
Publication and Data Sharing Policy..............................................................................................39
10.1.12
Conflict of Interest Policy ..............................................................................................................39
10.2
Additional Considerations .........................................................................................................................39
10.3
Abbreviations.............................................................................................................................................40
10.4
Protocol Amendment History....................................................................................................................41
11
REFERENCES..................................................................................................................................................42
12
Attachments ......................................................................................................................................................44


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LL-BMT10001                                                                            CONFIDENTIAL
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Leo Lens Technology Co., Inc.
21 December 2020
STATEMENT OF COMPLIANCE
The trial will be conducted in accordance with International Conference on Harmonisation (ICH) 
Good Clinical Practice (GCP), applicable United States (US) Code of Federal Regulations 
(CFR), the Health Insurance Portability and Accountability Act (HIPAA), and local regulatory 
guidelines. The Principal Investigator will assure that no deviation from, or changes to the 
protocol will take place without prior agreement from the Investigational New Drug (IND) 
Sponsor, funding agency and documented approval from the Institutional Review Board (IRB), 
except where necessary to eliminate an immediate hazard(s) to the trial patients. All personnel 
involved in the conduct of this study have completed Human Subjects Protection and ICH GCP 
Training. 
The protocol, informed consent form(s), recruitment materials, and all patient materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent 
form must be obtained before any patient is enrolled. Any amendment to the protocol will 
require review and approval by the IRB before the changes are implemented to the study. All 
changes to the consent form will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from patients who provided consent, using a 
previously approved consent form. 
 
 


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LL-BMT10001                                                                            CONFIDENTIAL
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1
PROTOCOL SUMMARY
1.1
SYNOPSIS 
Title: 
A Phase 2a Study of Safety, Tolerability, and Efficacy of Drug-
Delivering Contact Lens LL-BMT1 in Patients With Primary Open-
Angle Glaucoma or Ocular Hypertension 
Study Description: 
This will be an open-label, phase 2a clinical study. Beginning 
2 weeks prior to the Baseline Visit, all patients will have a 2-week 
run-in acclimation screening with a nonmedicated contact lens in 
each eye to ensure contact lens tolerability. Five patients with treated 
or treatment-naïve primary open-angle glaucoma (POAG) or ocular 
hypertension (OHT) in both eyes who have successfully passed the 
acclimation screening will be enrolled. All previously treated eyes 
will have a washout period prior to enrollment. At least one eye 
(called the study eye) will have untreated (after washout, if 
applicable) intraocular pressure (IOP) between 22 mmHg and 34 
mmHg (inclusive). If the fellow eye does not meet this IOP criterion, 
it must have an untreated IOP (following washout, if applicable) 
within 5 mmHg of the study eye without exceeding the 34-mmHg 
maximum. Five patients will be enrolled to receive LL-BMT1 
(medicated) contact lenses placed in a packaging solution containing 
. During the 7-day treatment 
period, patients will be assessed for safety and IOP reduction. 
Adverse events (AEs) and treatment-related serious adverse event 
[SAE] will be monitored, as will other safety measures, including 
best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, and 
contact lens protein deposit. The study hypothesis is that no safety 
concerns are revealed. 
Objectives: 
The primary objective of this study is to evaluate the safety of 
LL-BMT1 in patients with POAG or OHT. Additional objectives of 
this study are to evaluate the tolerability and IOP-lowering effects of 
LL‑BMT1 in patients with POAG or OHT. 
Endpoints: 
Primary safety endpoint: AE rate 
Secondary safety endpoints: percent of patients with ≥5-mmHg 
increase from baseline in IOP at each visit; abnormal slit-lamp 
biomicroscopy findings at the Baseline, Day 1, and Day 7 Visits; 
contact lens protein deposits at the Day 7 Visit; and change from 
baseline in Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) 
results at the Day 7 Visit 
Secondary efficacy endpoints: change from baseline in IOP at each
visit 


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LL-BMT10001                                                                            CONFIDENTIAL
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Leo Lens Technology Co., Inc.
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Study Population: 
Five patients who are at least 18 years of age of either sex with 
POAG or OHT in both eyes 
Phase: 
2a 
Description of Site 
Enrolling Patients:
Up to 2 sites within the United States (US)  
Description of Study 
Intervention: 
LL-BMT1 is a US Food and Drug Administration (FDA)-classified 
Group 4 extended-wear contact lens that has bimatoprost printed onto 
the anterior surface of the contact lens in one set concentration. The 
coating of the anterior surface does not obstruct the optic zone, and 
the bimatoprost elutes from both the concave and convex surfaces of 
the lens. LL-BMT1 is designed to lower the IOP of patients with 
POAG or OHT and be worn for 1 week (7 days, 6 nights). Patients 
will wear LL-BMT1 lenses for 1 week. 
Study Duration: 
3 to 4 months 
Patient Treatment 
Duration: 
1 week for each patient  
1.2
SCHEMA
Day -45 to -14 (Visit 1): Screening 
•
Total n=5 to 7 (If all 7 patients successfully complete the acclimation screening, only 5 
patients will be enrolled to receive LL-BMT1. If dropouts occur during acclimation 
screening resulting in less than 5 patients successfully completing the acclimation 
screening, then that patient(s) will be replaced until at least 5 patients have been enrolled 
to receive LL-BMT1) 
•
Obtain informed consent 
•
Screen potential patients by inclusion and exclusion criteria, including: 
•
Ultrasound pachymetry to assess corneal thickness  
•
Humphrey visual field to assess visual field loss (If Humphrey visual field 
assessment has been completed within 6 months of Screening Visit, it does not 
have to be repeated at the Screening Visit)
•
Obtain medical history
•
Concomitant medications - Systemic treatments that the patient has been receiving for at 
least 30 days prior to study initiation will be collected
•
If on any IOP-lowering medication, start washout according to the period required for the 
current medication, timed to end at the Baseline Visit 
•
Two weeks prior to the Baseline Visit, start 2-week acclimation screening with insertion 
of nonmedicated lenses 
Day -14 (Visit 2): Acclimation (first nonmedicated lens insertion) 


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LL-BMT10001                                                                            CONFIDENTIAL
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Leo Lens Technology Co., Inc.
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•
Concomitant medications - The medical monitor should be informed of any new systemic 
medications that cannot be delayed until the end of the study to determine if the patient 
can participate and/or continue in the study
•
AEs
•
BCVA 
•
Biomicroscopy 
•
Nonmedicated lens insertion  
Day -7 (Visit 3): Acclimation (first nonmedicated lens removal) 
•
Concomitant medications 
•
AEs - The patient will also be questioned about AEs related to the contact lens wear by 
the investigator. Eligibility for the treatment portion of the study will be at investigator’s 
discretion. 
•
Nonmedicated lens removal  
•
BCVA 
•
Biomicroscopy 
Day -6 (Visit 4): Acclimation (second nonmedicated lens insertion) 
•
Concomitant medications 
•
AEs
•
BCVA 
•
Biomicroscopy 
•
Nonmedicated lens insertion (new lens)  
Day 0 (Visit 5): Baseline 
•
Concomitant medications 
•
AEs - The patient will also be questioned about AEs related to the contact lens wear by 
the investigator. Eligibility for the treatment portion of the study will be at investigator’s 
discretion. 
•
Remove nonmedicated lenses 
•
Verify inclusion/exclusion criteria 
•
CLDEQ-8 
•
Heart rate and blood pressure 
•
Urine pregnancy test for women of childbearing potential 
•
BCVA 
•
Biomicroscopy  
•
IOP (measured at 9 am ±1 hour) 
•
IOP (measured at 4 pm ±1 hour) 
Day 1 (Visit 6): Lens insertion  
•
Concomitant medications 
•
AEs
•
Heart rate and blood pressure - procedure should be performed before study intervention
•
BCVA - procedure should be performed before study intervention
•
Biomicroscopy - procedure should be performed before study intervention


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LL-BMT10001                                                                            CONFIDENTIAL
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Leo Lens Technology Co., Inc.
21 December 2020
•
IOP (measured at 8 am ±1 hour) - procedure should be performed before study 
intervention
•
LL-BMT1 insertion of new lens 
•
Contact lens assessment 
•
LL-BMT1 removal (directly before 4 pm IOP assessment) - If a lens is damaged during 
removal, a new lens cannot be inserted in the patient’s eye. Patients can remain on the 
study if at least one LL-BMT1 lens is able to be reinserted.
•
IOP (measured at 4 pm ±1 hour) 
•
LL-BMT1 reinsertion (directly after 4 pm IOP assessment)  
Day 4 (Visit 7): On-treatment assessment  
•
Concomitant medications 
•
AEs
•
Heart rate and blood pressure 
•
BCVA 
•
Biomicroscopy  
•
LL-BMT1 removal (directly before 8 am IOP assessment) - If a lens is damaged during 
removal, a new lens cannot be inserted in the patient’s eye. Patients can remain on the 
study if at least one LL-BMT1 lens is able to be reinserted.
•
IOP (measured at 8 am ±1 hour) 
•
LL-BMT1 reinsertion (directly after 8 am IOP assessment)  
Day 7 (Visit 8): End of treatment assessment  
•
Concomitant medications 
•
AEs
•
Heart rate and blood pressure 
•
BCVA 
•
Biomicroscopy 
•
LL-BMT1 removal - Lens will be removed prior to IOP assessment, but the lens will not 
be reinserted
•
Contact lens protein deposit assessment 
•
IOP (measured at 4 pm ±1 hour) 
•
CLDEQ-8  
Day 8 (Visit 9): Follow-up assessment / End of study 
•
Concomitant medications 
•
AEs 
•
BCVA 
•
Heart rate and blood pressure 
•
IOP (measured at 8 am ±1 hour) 
•
If patient’s IOP is decreased by ≥3 mmHg from baseline, schedule Visit 10. If not, Visit 9 
is the end of the study 
Day 9 (Visit 10): Conditional follow-up assessment (If a patient’s IOP is decreased from 
baseline by ≥3 mmHg at the Day 8 Visit) / End of study  
•
Concomitant medications 
•
AEs 


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LL-BMT10001                                                                            CONFIDENTIAL
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•
Heart rate and blood pressure 
•
IOP (measured at 8 am ±1 hour) 


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LL-BMT10001                                                                            CONFIDENTIAL
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Leo Lens Technology Co., Inc.
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1.3
SCHEDULE OF ACTIVITIES 
Procedures
Screening 
Visit 1
Day -45 to -14
Acclimation 
Visit 2
Day -14
Acclimation 
Visit 3 
Day -7
Acclimation
Visit 4 
Day -6
Baseline 
Visit 5 
Day 0
Lens 
Insertion
Visit 6 
Day 1
On-
Treatment
Visit 7 
Day 4
End of 
Treatment
Visit 8 
Day 7 
Follow-Up 
Visit 9
Day 8 
Conditional 
Follow-Up/
End of 
Study
Visit 10
Day 9
Early 
Termination 
Visit
Informed consent
X
Inclusion/exclusion criteria
X 
X 
Ultrasound pachymetry
X
Humphrey visual field 
assessmenta
X 
Demographics
X
Medical history
X 
Insertion of nonmedicated 
lensesb,c
X 
X 
X 
Removal of nonmedicated 
lensesb
X 
X 
Heart rate and blood 
pressure
X 
X 
Xd
X 
X 
X 
X 
X 
Urine pregnancy teste
X
X
BCVA
X
X
X
X
X
Xd
X
X
X
X
Biomicroscopy
X 
X 
X 
X 
X 
Xd
X
X 
X 
IOPf,q
X
Xg
Xd,h
Xi
Xj
Xi
Xi
X
CLDEQ-8 
Xk
X 
X 
Insertion of new LL-BMT1 
lensb,c
Xl
Removal/reinsertion of 
LL-BMT1 lensc 
Xm
Xm
Xn
X 
CL assessmento
X 
X 
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
AEs
X 
X 
Xp
X 
Xp
X 
X 
X 
X 
X 
X 
Abbreviations: AEs, adverse event; BCVA, best-corrected visual acuity; CL, contact lens; CLDEQ-8, Contact Lens Dry Eye Questionnaire-8; IOP, intraocular pressure. 
aIf Humphrey visual field assessment has been completed within 6 months of Screening Visit, it does not have to be repeated at the Screening Visit.
bAll lens insertions and removals will be conducted by the investigator. 
cAt the discretion of the investigator, topical anesthesia can be applied to patient’s eyes prior to lens insertion. 
dThese procedures should be performed before study intervention. 
eUrine pregnancy test will be performed on women of childbearing potential. 


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LL-BMT10001                                                                            CONFIDENTIAL
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fIOP will be assessed 3 minutes after lens removal, with the goal of reinserting the lens within 2-3 minutes after IOP assessment. Three measurements will be taken at each visit and these results will be 
averaged.
gIOP will be performed at 9 am ±1 hour and 4 pm ±1 hour.
hIOP will be performed at 8 am ±1 hour and 4 pm ±1 hour. 
iIOP will be performed at 8 am ±1 hour. 
jIOP will be performed at 4 pm ±1 hour.
kQuestionnaire to be given at the end of the acclimation screening. 
lLens will be inserted by the investigator after all assessments (except 4 pm IOP assessment) are complete. 
mLens will be removed prior to and reinserted following IOP assessment. If a lens is damaged during removal, a new lens cannot be inserted in the patient’s eye. Patients can remain on the study if at 
least one LL-BMT1 lens is able to be reinserted.
nLens will be removed prior to IOP assessment, but the lens will not be reinserted. 
oAssessments will include contact lens centration, movement with blinking, and lens surface wettability/deposits, as described in ISO 11980:2012.  
pThe patient will also be questioned about AEs related to the contact lens wear by the investigator. Eligibility for the treatment portion of the study will be at investigator’s discretion.  
qShould the IOP at any time during the study be elevated 10 mmHg above baseline (after washout, if applicable), the lens will be removed and a different IOP-lowering medication should be prescribed 
at the discretion of the investigator. The patient will be discontinued from study intervention but will continue in the study 


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LL-BMT10001                                                                            CONFIDENTIAL
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2
INTRODUCTION
2.1
STUDY RATIONALE  
Therapy for glaucoma and ocular hypertension today includes pharmaceuticals, laser 
trabeculoplasty, and surgery. Each of these treatments has been shown to be effective in lowering 
elevated IOP as well as to slow the progression of glaucomatous visual field loss (Kass 2002;
Lichter 2001; AGIS Investigators 2000; CNTGSG 1998). 
Pharmacotherapy with eye drops requires patients, or their care givers, to be adherent to the 
dosing schedule, as well as to be able to appropriately instill eyedrops. Even experienced patients 
at a private practice clinic are less than perfect in both adherence and performance (Robin 2007; 
Stone 2009).  
In order to optimize therapy, a wide range of drug delivery technologies have been evaluated in 
ophthalmology (Novack 2009). Recently, an intracameral drug delivery system using 
bimatoprost (Durysta®, Allergan) was approved by the US FDA (Craven 2020; Lewis 2017). 
While providing ocular hypotensive efficacy for at least 3 months, use of this product has been 
associated with concerns about the health of the corneal endothelium (Durysta prescribing 
information [PI]).
Thus, there is a continuing need for safe and effective pharmacotherapeutic delivery systems for 
the treatment of elevated IOP.
2.2
BACKGROUND  
Leo Lens Technology Co., Inc. has developed the MediPrint™ process that allows active 
pharmaceutical ingredients to be inkjet printed onto FDA-approved, Group 4 extended-wear 
contact lenses (eg, BIOMEDICS® 55 [ocufilcon D] soft [hydrophilic] contact lenses). Currently, 
Leo Lens Technology is developing a lens that has bimatoprost digitally printed onto the anterior 
surface of the contact lens at one strength. This product, called LL-BMT1, is designed to reduce 
elevated IOP in patients with open-angle glaucoma (OAG) or OHT. LL-BMT1 is a preservative-
free, continuous wear (7-day and 6-night) contact lens that delivers sustained-release bimatoprost 
to the eye. This product is intended to provide a novel, sustained delivery mechanism for 
bimatoprost and has the potential to reduce progression of glaucoma and the rate of vision loss in 
patients with glaucoma or OHT, compared to the current standard of care.  
Bimatoprost has been approved by the FDA as bimatoprost ophthalmic solution (Lumigan® New 
Drug Application [NDA] 021275 and NDA 022184; Lumigan PI), several abbreviated NDAs, 
Latisse® NDA 022369, and Durysta® NDA 211911. NDA 021275 has been discontinued by its
Sponsor, Allergan. However, it is Sponsor’s understanding that this was not for safety or efficacy 
reasons.  
The bimatoprost in LL-BMT1 is printed on a contact lens that is an FDA-approved, Group 4 
extended-wear contact lenses (eg, BIOMEDICS® 55 [ocufilcon D] soft [hydrophilic] contact 


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LL-BMT10001                                                                            CONFIDENTIAL
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lenses). The contact lens used in LL-BMT1 was approved by the US FDA as PMA P890023. 
Information on this product is provided in the instructions for use (Biomedics 55 PI). 
2.3
POTENTIAL RISKS AND BENEFITS TO HUMAN PATIENTS   
Adverse reactions of greatest concern reported with bimatoprost eyedrops include pigmentation 
(including blepharal pigmentation and iris hyperpigmentation), eyelash changes, intraocular 
inflammation, macular edema, and hypersensitivity. In controlled clinical trials, the most 
common adverse reaction was conjunctival hyperemia (31%). Approximately 1.6% of patients 
discontinued therapy due to conjunctival hyperemia. Other adverse drug reactions (reported in 
1% to 4% of patients) with Lumigan® 0.01% included conjunctival edema, conjunctival 
hemorrhage, eye irritation, eye pain, eye pruritus, erythema of eyelid, eyelids pruritus, growth of 
eyelashes, hypertrichosis, instillation site irritation, punctate keratitis, skin hyperpigmentation, 
vision blurred, and visual acuity reduced. In post-marketing use, AEs reported also include 
asthma-like symptoms, dizziness, dry eye, dyspnea, eye discharge, eye edema, foreign body 
sensation, headache, hypersensitivity (including signs and symptoms of eye allergy and allergic 
dermatitis), lacrimation increased, and periorbital and lid changes (including deepening of the 
eyelid sulcus; Lumigan PI). 
The bimatoprost in LL-BMT1 is printed on Group 4 extended-wear contact lenses. Risks to 
patients in the present study are those typical of contact lenses. 
The potential benefit to patients in this study is the lowering of IOP without the use of daily 
eyedrops.  


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LL-BMT10001                                                                            CONFIDENTIAL
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3
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Justification for Endpoints
Primary safety 
To evaluate the safety 
of LL-BMT1 in 
patients with POAG 
or OHT
AE rate
AE collection is necessary to 
determine the safety of this 
intervention. AEs will be 
collected at each visit to 
maximize safety during the 
study.
Secondary safety
To evaluate the safety 
and tolerability of 
LL-BMT1 in patients 
with POAG or OHT
The secondary safety endpoints are: 
•
Percent of patients with ≥10-mmHg 
increase from baseline in IOP at each visit
•
Abnormal slit-lamp biomicroscopy 
findings at the Baseline, Day 1, and Day 7
Visits  
•
Contact lens protein deposits at the Day 7 
Visit
•
Change from baseline in CLDEQ-8 results 
at the Day 7 Visit  
These safety endpoints will 
provide additional safety 
information during the 
course of the study.
Secondary efficacy
To evaluate IOP-
lowering effects of 
LL-BMT1 in patients 
with POAG or OHT
The secondary efficacy endpoint is: 
•
Change from baseline in IOP at each visit
IOP assessment is necessary 
to determine the efficacy of 
an IOP-lowering device.
4
STUDY DESIGN 
4.1
OVERALL DESIGN
This will be an open-label, phase 2a clinical study. Five patients with treated or treatment-naïve 
POAG or OHT in both eyes will be enrolled. All previously treated eyes will have a washout 
period prior to enrollment. At least one eye (called the study eye) will have untreated (after 
washout, if applicable) IOP between 22 mmHg and 34 mmHg (inclusive). If both eyes meet this 
criterion, then the eye with the higher IOP will be selected as the study eye. If the IOP in both 
qualified eyes is the same, then the right eye will be selected as the study eye. If the fellow eye 
does not meet this IOP criterion, it must have an untreated IOP (following washout, if 
applicable) within 5 mmHg of the study eye without exceeding the 34-mmHg maximum. For all 
enrolled patients, both eyes will be treated, and all tests will be performed separately on both 
eyes, but only the study eye will be included for efficacy analysis.  


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LL-BMT10001                                                                            CONFIDENTIAL
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Beginning 2 weeks prior to the Baseline Visit, all patients will have a 2-week run-in acclimation 
period with a nonmedicated contact lens in each eye to ensure contact lens tolerability. The 
patient will be questioned about AEs related to the contact lens wear. The patient must have 
experienced no contact lens-related AEs in order to be eligible for the study. If a patient does not 
successfully complete the 2-week acclimation screening, that patient will be replaced until at 
least 5 patients successfully complete the acclimation screening. Those patients who have 
completed acclimation screening will be enrolled as patients for dosing with LL-BMT1. After 
insertion of the LL-BMT1 (medicated) lens, patients will be followed for 7 or 8 days for 
assessments of safety and IOP reduction.  
Five (5) patients will receive LL-BMT1 contact lenses 
inserted into each eye at the Day 1 visit, where they will remain until 
the Day 7 Visit, at which time the lenses will be removed. Patients will not remove the lenses 
themselves during the study. During the 7-day treatment period, patients will be assessed for 
safety and IOP reduction which requires removal and reinsertion of LL-BMT1 on Day 1 and Day 
4. AEs will be monitored, as will other safety measures, including BCVA, slit-lamp 
biomicroscopy, and contact lens protein deposit. Patients will attend a follow-up visit on Day 8, 
during which heart rate/blood pressure, BCVA, and IOP will be assessed. If a patient’s IOP is 
decreased from baseline by ≥3 mmHg at the Day 8 Visit, a Day 9 Visit will be performed in 
order to reassess IOP. 
The primary focus of this safety study will be a comprehensive descriptive assessment of safety 
endpoints. No formal study hypothesis will be tested. 
4.2
SCIENTIFIC RATIONALE FOR STUDY DESIGN
This study is designed to examine the use of bimatoprost delivered via extended-wear contact 
lenses and assess the safety and efficacy of this drug device in a sample of patients. Both 
bimatoprost and the contact lens (as a nonmedicated lens) are FDA-approved, long-standing 
commercial products with well-characterized safety and effectiveness profiles. All patients will 
attend a follow-up visit on Day 8, and if IOP at that visit is decreased from baseline by ≥3 
mmHg, patients will attend a conditional follow-up visit on Day 9 in order to reassess IOP. 
4.3
JUSTIFICATION FOR DOSE
LL-BMT1 is an investigational device composed of an FDA-approved Group 4 extended-wear 
contact lens that has been has had bimatoprost coated onto the anterior surface of the lens via an 
inkjet printer. Once LL-BMT1 is inserted in the eye, the bimatoprost will elute uniformly from 
both the concave and convex surfaces of the lens. In vitro studies have shown that the LL-BMT1 
lens 
releases approximately 26 μg 
bimatoprost over the 7-day wearing period. Given the fact that over a 7-day period, patients 
using bimatoprost eye drops would receive approximately 105 μg of bimatoprost, LL-BMT1 
releases approximately 25% of the total amount of bimatoprost compared with the eye drops. 
However, because of the continuous elution of drug from the lens, the LL-BMT1 lens is 
expected to have increased bioavailability compared with topical bimatoprost administration, 
possibly resulting in a safer, more efficacious treatment. 


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LL-BMT10001                                                                            CONFIDENTIAL
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4.4
END OF STUDY DEFINITION
A patient is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities, 
Section 1.3.
The end of the study is defined as completion of the last visit or procedure shown in the Schedule 
of Activities, Section 1.3, in the last patient.  
5
STUDY POPULATION
5.1
INCLUSION CRITERIA
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
1. Male or female, at least 18 years of age at the Screening Visit
2. Diagnosed with POAG or OHT in both eyes 
3. At least one eye (called the study eye) must have an untreated IOP between 22 mmHg 
and 34 mmHg (inclusive) as measured at 9 am during the Baseline Visit. For eyes 
receiving IOP treatment, untreated IOP will be assessed following a required washout 
period as outlined below: 
•
4 days washout for parasympathomimetic and topical or systemic carbonic 
anhydrase inhibitors 
•
2 weeks washout for sympathomimetics and alpha agonists  
•
4 weeks washout for beta adrenergic blocking agents, combination product, Rho 
kinase (ROCK) inhibitors, and prostaglandin agonists 
4. If the fellow eye does not meet inclusion criterion #3 above, it must have an untreated 
IOP (following washout, if applicable) within 5 mmHg of the study eye without 
exceeding the 34 mmHg maximum (eg, a study eye IOP of 22 mmHg and a fellow eye 
IOP of 17 mmHg are allowed).  
5. BCVA of Early Treatment Diabetic Retinopathy Study (ETDRS) of 50 letters or better 
(Snellen equivalent of 20/100 or better) in each eye 
6. Women of child-bearing potential must not be pregnant or lactating, must have a negative 
pregnancy test at screening and must be practicing an adequate method of birth control, 
including intrauterine device (IUD); oral, dermal (“patch”), implant or injected 
contraceptives; tubal ligation; or barrier methods with spermicide 
7. No adverse reactions to nonmedicated contact lenses during the 2-week acclimation 
screening  
8. Score of 0-11 on CLDEQ-8, administered at the end of the 2-week acclimation screening 
9. Willing and able to comply with the study procedure and sign a written informed consent 


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LL-BMT10001                                                                            CONFIDENTIAL
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5.2
EXCLUSION CRITERIA
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1. Glaucoma or optic neuropathy due to anything other than POAG or OHT 
2. Cup-to-disc ratio of >0.8 in either eye 
3. Corneal thickness <480 or >620 μm 
4. IOP >34 mmHg in either eye at the Screening Visit or Baseline Visit  
5. Significant visual field loss, in the opinion of the investigator 
6. Uncontrolled systemic disease, such as poorly controlled hypertension or poorly 
controlled diabetes 
7. An active ocular infection (ie, bacterial, viral, parasitic, or fungal) in either eye at the 
Screening Visit
8. Current contact lens use for vision correction (unless willing to switch to glasses for the 
duration of the study) 
9. Current contact lens use for cosmetic purposes (unless willing to discontinue use for the 
duration of the study) 
10. Clinically significant dry eye 
11. History of treated allergic, vernal, or atopic conjunctivitis 
12. History of contact lens intolerance, corneal scarring, corneal neovascularization, giant 
papillary conjunctivitis, or any other corneal pathology that is deemed by the investigator 
to constitute a contraindication for applying contact lenses 
13. Aphakia or presence of anterior chamber intraocular lens in either eye 
14. History of clinically significant macular pathology (ie, progressive age-related macular 
degeneration, diabetic macular edema, proliferative diabetic retinopathy, etc.)  
15. History of corneal refractive surgery (ie, laser-assisted in situ keratomileusis [LASIK], 
photorefractive keratectomy [PRK], radial keratotomy [RK], small incision lenticule 
extraction [SMILE], or corneal inlay, etc.)  
16. History of prior incisional glaucoma surgery (ie, bleb, shunt, seton, etc.)  
17. History within past 6 months of any ocular anterior segment laser or other intraocular 
surgery 
18. Use of laser of any type on retina in either eye within 3 months prior to the Screening 
Visit
19. History of punctal cautery or planned use of punctal plugs during the study  
20. Cataract surgery in either eye within 3 months, or other intraocular surgery in either eye 
within 6 months prior to the Screening Visit or planned during the course of the study 


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LL-BMT10001                                                                            CONFIDENTIAL
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21. Anticipated need for ocular surgery in either eye during the study period 
22. Required chronic use of topical or injectable ocular medications other than IOP-lowering 
medication, including artificial tears, or currently receiving chronic intravitreal injections  
23. Known allergy or hypersensitivity to the study medications or its components 
24. Treatment with an investigational drug within 60 days prior to the Baseline Visit (when 
treatment is given) 
25. Any participation in a clinical trial within 30 days of the Screening Visit or during the 
course of the study  
26. Patient has a condition or is in a situation that, in the investigator’s opinion, will interfere 
with the patient’s ability to comply with the dosing and visit schedules and the protocol 
evaluations or may not be suitable for this study 
5.3
LIFESTYLE CONSIDERATIONS
During this study, participants will be instructed to refrain from using a sauna, hot tub, and 
partaking in any water-related activities, including swimming, snorkeling and scuba diving. All 
participants will be instructed to avoid consuming fluids for 1 hour prior to each study visit.  
5.4
SCREEN FAILURES
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently assigned to the study intervention or entered in the study. Screen failures can be 
identified at the Screening Visit, at either of the Acclimation Visits, or at the Baseline Visit. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAEs. 
Individuals who do not meet the criteria for participation in this trial (screen failure) may not be 
rescreened.  
5.5
STRATEGIES FOR RECRUITMENT AND RETENTION
Because this study will enroll only 5 patients with a duration of less than 6 weeks (including 
washout), no particular recruitment or retention strategies are expected to be necessary. Enrolled 
patients who fail acclimation screening will be replaced until at least 5 patients successfully 
complete the acclimation screening. Enrolled patients who exit the study early due to related or 
unrelated reasons will not be replaced. 
6
STUDY INTERVENTION
6.1
STUDY INTERVENTIONS ADMINISTRATION


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LL-BMT10001                                                                            CONFIDENTIAL
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6.1.1
STUDY INTERVENTION DESCRIPTION
LL-BMT1 is an investigational device composed of an FDA-approved Group 4 extended-wear 
contact lens (marketed as ocufilcon D; Figure 1) that has had bimatoprost coated onto the 
anterior surface of the lens via an inkjet printer.
Figure 1. Ocufilcon D Chemical Structure
Chemical Formula: C10-H14-O4.C6-H10-O3.C4-H6-O2)x- 
Before printing, the unmodified Group 4 lens has the following parameters (Table 1): 
Table 1. Parameters of the nonmedicated Group 4 lens
Base Curve
8.6 ± 0.2 mm
Diameter
14 ± 0.2 mm
Water Content
55%
Spherical Power
+10.00 to -10.00
Optic Zone
6 mm to 9 mm
Lens Thickness
60 μm to 150 μm 
In order to coat the lens, bimatoprost is diluted in a proprietary mixture, which is then placed in 
an inkjet cartridge and printed onto the contact lens surface, without obstructing the optic zone.  
The LL-BMT1 lenses are supplied freely floating in individual vials of basic saline solution 
. Once the LL-BMT1 lens is inserted in the eye, the 
bimatoprost will elute from both the concave and convex surfaces of the lens at a descending 
release rate over the next 7 days.  
The Sponsor has determined the dosing of LL-BMT1 
. For this study, there will be one dose
. In vitro studies have shown 


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LL-BMT10001                                                                            CONFIDENTIAL
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that an LL-BMT1 lens 
releases approximately 26 μg
bimatoprost over the 7-day wearing period.  
After the printing process, the LL-BMT1 lens was tested to verify that it maintained its integrity 
through physical, chemical, and biological (toxicity) testing. Results are shown below (Table 2).
Table 2. Parameters of the LL-BMT1 (medicated) Group 4 lens
Base Curve
8.6 ± 0.2 mm
Diameter
14 ± 0.2 mm
Power
Labeled power ± 0.125
Refractive Index
1.41 
Water Content
56.7%
Light Transmission
97%
ISO-3993 Cytotoxicity
Non-toxic
ISO-3993 Systemic toxicity
Non-toxic
ISO-3993 Ocular irritation
Non-toxic
ISO-3993 Histopathology
Non-toxic
6.1.2
DOSING AND ADMINISTRATION
Patients will have LL-BMT1 lenses inserted by the investigator at the Day 1 Visit, and they will 
remain in the patients’ eyes (except during IOP assessment) until the Day 7 Visit (end of 
treatment), at which time the investigator will remove the lenses. Patients will not remove the 
lenses themselves during the study. 
6.2
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY
6.2.1
ACQUISITION AND ACCOUNTABILITY
LL-BMT1 lenses will be shipped to the investigator from the Sponsor’s manufacturing site. The 
lenses should be handled according to normal Group 4 lens procedures 
  


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LL-BMT10001                                                                            CONFIDENTIAL
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If a LL-BMT1 lens is damaged during removal from the storage vial or during the thorough 
rinsing procedure, then a new LL-BMT1 lens can be used by the investigator.  
  
When lenses are removed and handled during the study period while the patient’s IOP is 
measured, the lens should be held by the Principal Investigator or staff with a sterile plastic 
tweezer with a soft tip. When the lens is reinserted in the patient’s eye, one drop of sterile saline 
solution should be added to the bowl of the lens prior to reinsertion in the eye. 
Investigator should take care with lens handling, especially during removal of the lens for IOP 
assessment. If a lens is damaged during removal, a new lens cannot be inserted in the patient’s 
eye. Patients can remain on the study if at least one LL-BMT1 lens is able to be reinserted in one 
of the patient’s eyes.  
Any unused contact lenses should be returned to the Sponsor at the completion of the study. 
6.2.2
FORMULATION, APPEARANCE, PACKAGING, AND LABELING
The LL-BMT1 lenses, manufactured by Leo Lens Technology Co., Inc., are supplied freely 
floating in individual vials of basic saline solution 
. The peel-off cap 
and rubber stopper will be removed from the vial prior to use. The extended-wear contact lenses
have had bimatoprost coated onto the anterior surface of the lens. 
6.2.3
PRODUCT STORAGE AND STABILITY
The study lenses must be stored in a secure, locked location accessible only to authorized study 
personnel and maintained at a temperature of 2˚-8˚C (35.6˚-46.4˚F), with excursion permitted to 
25˚C (77˚F). The lenses should also be kept away from light when stored. 
6.2.4
PREPARATION
Not applicable. 
6.3
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING
Not applicable. 
6.4
STUDY INTERVENTION COMPLIANCE
Not applicable. 
6.5
CONCOMITANT THERAPY
Aside from study medication, antihistamines and all topical ocular medications are prohibited 
during the study. In addition, marijuana and any other recreational drugs are prohibited. Systemic 
treatments that the patient has been receiving for at least 30 days prior to study initiation are 


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LL-BMT10001                                                                            CONFIDENTIAL
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acceptable. The medical monitor should be informed of any new systemic medications that 
cannot be delayed until the end of the study to determine if the patient can participate and/or 
continue in the study. Prior to study treatment initiation, any current glaucoma medications must 
be washed out using the below schedule (but washout should not commence until after written 
informed consent has been obtained): 
•
4 days washout for parasympathomimetic and topical or systemic carbonic anhydrase 
inhibitors 
•
2 weeks washout for sympathomimetics and alpha agonists  
•
4 weeks washout for beta adrenergic blocking agents, combination product, ROCK 
inhibitors, and prostaglandin agonists 
6.5.1
RESCUE MEDICINE
The Sponsor will not supply rescue medication. Should the IOP at any time during the study be 
elevated 10 mmHg above baseline (after washout, if applicable), the lens will be removed and a 
different IOP-lowering medication should be prescribed at the discretion of the investigator. The 
patient will be discontinued from study intervention but will continue in the study. 
The date and time of rescue medication administration as well as the name and dosage regimen 
of the rescue medication must be recorded in the electronic Case Report Form (eCRF).  
7
STUDY INTERVENTION DISCONTINUATION AND PATIENT
DISCONTINUATION
7.1
DISCONTINUATION OF STUDY INTERVENTION
Patients may be discontinued from study intervention for any of the following reasons: 
•
Investigator decision: The investigator can decide that the patient should be discontinued 
from study intervention for any reason. 
•
Patient decision: Patients who decide to discontinue study intervention should be 
explicitly asked about the contribution of possible AEs to their decision, and any AE 
information elicited should be documented. Preferably the patient should withdraw 
consent in writing and, if the patient refuses or is physically unavailable, the site should 
document and sign the reason for the patient’s failure to withdraw consent in writing. The 
patient is lost to follow-up after a reasonable number of attempts to contact the patient 
(including documented phone calls and/or emails, and a certified letter) have been 
completed. 
•
Sponsor decision: The Sponsor or its designee can stop the patient’s participation in the 
study for medical, safety, regulatory, or other reasons consistent with applicable laws, 
regulations, and GCP guidelines. 
•
Pregnancy: If a patient becomes pregnant during the study, the patient will be 
immediately discontinued from study intervention. Only pregnancies considered by the 


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LL-BMT10001                                                                            CONFIDENTIAL
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investigator as related to study drug (e.g., resulting from an interaction between study 
drug and a contraceptive drug) are considered AEs unto themselves. However, all 
pregnancies with an estimated conception date that occurred during the study must be 
recorded in the AE section of the eCRF and investigators must actively follow up, 
document, and report on the outcome of all pregnancies. 
•
AE: If the investigator decides that the study intervention should be discontinued because 
of an AE, the investigational product is to be discontinued and appropriate measures are 
to be taken. The Sponsor or its designee is to be alerted immediately. 
•
Damage to both LL-BMT1 lenses: The investigator should take care with lens handling, 
especially during removal of the lens for IOP assessment. If a lens is damaged during 
removal, a new lens cannot be inserted in the patient’s eye. Patients can remain on the 
study if at least one LL-BMT1 lens is able to be reinserted in one of the patient’s eyes. If 
both lenses are damaged during removal, then the patient will not be allowed to continue 
with study procedures.  
In all of these circumstances, patients should continue to attend all remaining study visits and 
undergo all scheduled testing. 
7.2
PATIENT DISCONTINUATION FROM THE STUDY
Patients will be discontinued from the study in the cases of patient death or lost to follow-up.  
Patients may decide to discontinue participation in the study; any such patient withdrawing from 
the study will be asked to complete the Early Termination Visit assessments. The reason for 
patient discontinuation from the study will be recorded on the eCRF. No patients who 
discontinue from the study will be replaced under any circumstances. 
7.3
LOST TO FOLLOW-UP 
A patient will be considered lost to follow-up per Principal Investigator discretion and upon 
consultation with the Sponsor upon failure to adhere to the protocol. 
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit:
o
The site will attempt to contact the patient and reschedule the missed visit on the 
following day and counsel the patient on the importance of maintaining the assigned 
visit schedule and ascertain if the patient wishes to and/or should continue in the 
study.
o
Before a patient is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the patient (where possible, 3 telephone calls and a 
certified letter to the patient’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the patient’s medical 
record or study file.


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LL-BMT10001                                                                            CONFIDENTIAL
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o
Should the patient continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.
8
STUDY ASSESSMENTS AND PROCEDURES
8.1
EFFICACY ASSESSMENTS 
•
Goldmann applanation tonometry. Intraocular pressure will be measured with a 
Goldmann applanation tonometer that is calibrated pre-study and monthly during study 
participation.
8.2
SAFETY AND OTHER ASSESSMENTS
Abnormal findings that are of clinical significance will be recorded as AEs on the eCRFs.  
•
Ultrasound pachymetry. Corneal thickness will be measured using an ultrasound 
pachymeter.
•
Humphrey visual field assessment. Visual field (perimetry) will be assessed using a 
Humphrey Field Analyzer. If Humphrey visual field assessment has been completed 
within 6 months of Screening Visit, it does not have to be repeated at the Screening Visit 
•
Contact Lens (CL) Assessment: Assessments will include contact lens centration, 
movement with blinking, and lens surface wettability/deposits, as described in ISO 
11980:2012.
•
Heart rate and blood pressure. Heart rate and blood pressure will be measured by a 
manual or automated sphygmomanometer. 
•
Pregnancy testing. Pregnancy testing will be performed using a human chorionic 
gonadotropin pregnancy urine dipstick test on women of childbearing potential. 
•
Best-corrected visual acuity. BCVA will be quantified using the ETDRS visual acuity 
protocol (at a distance of 3 m) and the number of letters read correctly will be recorded 
on the eCRF. 
•
Biomicroscopy. Biomicroscopy will be performed by slit-lamp examination of 
conjunctiva, cornea, and iris with findings reported on a scale of 0 = none, 0.5 = trace, 1 
= mild, 2 = moderate, and 3 = severe. The status of the lens will be assessed using the 
Age-Related Eye Disease Study scale. 
•
Goldmann applanation tonometry. IOP will be measured with a Goldmann applanation 
tonometer. During the study, the LL-BMT1 contact lens will be removed in order to 
perform IOP assessment. Of particular significance, all lens insertions and removals will 
be conducted by the investigator. IOP will be assessed 3 minutes after lens removal, with 
the goal of reinserting the lens within 5 minutes of removal. Two consecutive IOP 
measurements of each eye were obtained. If the 2 measurements differed by more than 2 
mmHg, a third measurement was obtained. For each eye, IOP was analyzed as the mean 


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LL-BMT10001                                                                            CONFIDENTIAL
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of 2 measurements or as the median of 3 measurements. For each patient, change from 
baseline IOP was determined by averaging the values for each eye (Sherwood 2006). 
•
Conjunctival hyperemia. The Efron Grading Scales for Contact Lens Complications 
will be performed using a conjunctival hyperemia scale.
Unscheduled visits can be included if safety concerns arise. Additional examinations may be 
performed as necessary to ensure the safety and wellbeing of patients during the study. eCRFs 
should be completed for each unscheduled visit. 
  
8.3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
8.3.1
DEFINITION OF ADVERSE EVENTS
An AE is any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to that product. Worsening of the 
pterygium is not an AE, unless the lesion growth is greater than expected. 
Treatment-emergent AEs are any AEs with an onset date equal to or after the date of the first 
insertion of the study lens and during the treatment. A pre-existing event that worsens after the 
first treatment date is considered a treatment-emergent event. 
8.3.2
DEFINITION OF SERIOUS ADVERSE EVENTS
An SAE is any AE occurring at any dose that results in any of the following outcomes: death, a 
life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important 
medical events that may not result in death, be life-threatening, or require hospitalization may be 
considered an SAE when, based upon appropriate medical judgment, they may jeopardize the 
patient and may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition. See Section 8.3.6 for procedures for reporting an SAE. 
8.3.3
CLASSIFICATION OF AN ADVERSE EVENT
8.3.3.1 SEVERITY OF EVENT
For AEs not included in the protocol-defined grading system, the following guidelines will be 
used to describe severity.  
•
Mild:  Event requires minimal or no treatment and do not interfere with the patient’s 
daily activities 
•
Moderate:  Event results in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning 


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LL-BMT10001                                                                            CONFIDENTIAL
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•
Severe:  Event interrupts a patient’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. Of note, the term “severe” does not necessarily equate to “serious” 
8.3.3.2
RELATIONSHIP TO STUDY INTERVENTION
A determination will be made of the relationship (if any) between an AE and the study drug. A 
causal relationship is present if a determination is made that there is a reasonable possibility that 
the AE may have been caused by the drug and/or the lens. 
•
Unrelated:  A causal relationship can be excluded and another documented cause of the 
AE is most plausible 
•
Unlikely related: A causal relationship is improbable, and another documented cause of 
the AE is most plausible 
•
Possibly related: A causal relationship is clinically/biologically plausible and there is a 
plausible time sequence between onset of the AE and administration of the study drug
•
Probably related:  A causal relationship is clinically/biologically highly plausible, there 
is a plausible time sequence between onset of the AE and administration of the study 
drug, and there is a reasonable response on withdrawal 
8.3.4
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP 
Any medical condition that is present at the time that the patient is screened will be considered as 
medical history and not reported as an AE. However, if the study patient’s condition deteriorates 
at any time after enrollment, it will be recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The investigator or qualified designee will record all reportable events with start dates occurring 
any time after informed consent is obtained until 7 days (for non-serious AEs) or 30 days (for 
SAEs) after the last day of study participation. Patient will be told to call and notify the 
investigator of such events that occur during this period after the end of study visit. Events will 
be followed for outcome information until resolution or stabilization. 
AEs will be monitored throughout the study beginning at the time the patient signs the informed 
consent for this study. At each post-Baseline visit, the investigator will begin by querying for 
AEs by asking each patient a general, non-directed question, such as “How have you been 
feeling since the last visit?” Directed questioning and examination will then be done as 
appropriate. All reported AEs will be documented on the appropriate eCRF, including 
seriousness, severity, relationship to study drug, action taken, and outcome (including date of 
resolution or stabilization, if AE is not ongoing). If AEs occur, the first concern will be the safety 
of the study patients.  


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LL-BMT10001                                                                            CONFIDENTIAL
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If a patient becomes pregnant during the study, the investigator must inform the Sponsor and 
collect follow-up data regarding the pregnancy, birth, and status of the child. The Sponsor will 
provide special CRFs for data collection in the case of pregnancy. Follow-up should be 
continued until study close-out at the study center. After close-out, the Sponsor's Safety designee 
will continue to obtain follow-up information. Pregnancy should be recorded as a protocol 
deviation. Pregnancy is not an AE; however, any complication related to pregnancy would be 
considered an AE. 
8.3.5
ADVERSE EVENT REPORTING 
Any AE should be recorded on the appropriate eCRF. 
8.3.6
SERIOUS ADVERSE EVENT REPORTING 
Any SAE occurring during the study period should be immediately (ie, within 24 hours of 
learning of the event) reported to a Trial Runners representative listed on the protocol cover 
page. The SAE is recorded on the appropriate eCRFs. In the event of an early termination within 
8 days after study drug administration, the occurrence of an SAE within 8 weeks from Baseline 
(Day 0) should be reported immediately to Trial Runners personnel. All patients with an SAE 
that is related to study drug must be followed for at least 30 days and the outcomes reported until 
the event is resolved or stabilized. The investigator should supply the Sponsor and the IRB with 
any additional requested information (e.g., autopsy reports and terminal medical reports). 
In the event of an SAE, the investigator must:
•
Notify the Trial Runners safety office and the medical monitor immediately by fax using 
the SAE reporting forms provided by Trial Runners (see first page of the protocol for the 
SAE fax number). Emergency phone numbers and relevant personnel contacts are below: 
o


o
  

  
•
Obtain and maintain in the patient’s files all pertinent medical records, information, and 
medical judgments from colleagues who assisted in the treatment and follow-up of the 
patient 
•
Provide Leo Lens Technology with a complete, written case history (AE report form) 
which includes a statement as to whether the event was or was not related to the use of 
the investigational drug 
•
Promptly inform the governing IRB of the SAE if it is drug-related. For other SAEs, 
notify the governing IRB as required by the IRB, local regulations, and the governing 
health authorities 


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LL-BMT10001                                                                            CONFIDENTIAL
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Adverse drug reactions that are both serious and unexpected (suspected unexpected serious 
adverse reactions) will be subject to expedited reported to the IRB as required by the relevant 
regulations. Reporting must occur within 15 calendar days of first knowledge, or for fatal or life-
threatening events, an initial or full report must be made within 7 calendar days and a follow-up 
report must be made, if necessary, within the 15-calendar day timeframe. 
8.3.7
REPORTING EVENTS TO PATIENTS  
Not applicable.
8.3.8
EVENTS OF SPECIAL INTEREST 
Not applicable. 
8.3.9
REPORTING OF PREGNANCY 
If a female patient becomes pregnant during the study, the investigator will notify Trial Runners 
and the medical monitor immediately after the pregnancy is confirmed and the patient will be 
exited from the study. The investigator will (1) notify the patient’s physician that the patient was 
being treated with LL-BMT1 or bimatoprost, as appropriate, and (2) follow the progress of the 
pregnancy to term on the patient providing written informed consent for release of this data. The 
investigator should document the outcome of the pregnancy and provide a copy of the 
documentation to Leo Lens Technology. 
8.4
UNANTICIPATED PROBLEMS
8.4.1
DEFINITION OF UNANTICIPATED PROBLEMS 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving 
risks to patients or others to include, in general, any incident, experience, or outcome that meets 
all of the following criteria: 
•
Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the patient 
population being studied 
•
Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research) 
•
Suggests that the research places patients or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized 
This definition could include an unanticipated adverse device effect, any serious adverse effect 
on health or safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary plan or 


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application), or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of patients (21 CFR 812.3(s)). 
8.4.2
UNANTICIPATED PROBLEM REPORTING 
The investigator will report unanticipated problems or events as outlined in the Safety 
Management Plan. The unanticipated problem report will include the following information: 
•
Protocol identifying information: protocol title and number, Principal Investigator’s 
name, and the IRB project number 
•
A detailed description of the event, incident, experience, or outcome  
•
An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an unanticipated problem 
•
A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the unanticipated problem 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported using 
the following timeline:   
•
Unanticipated problems that are SAEs will be reported to the IRB and to the study 
Sponsor within 24 hours of the investigator becoming aware of the event.  
•
Any other unanticipated problem will be reported to the IRB and to the study Sponsor 
within 7 days of the investigator becoming aware of the problem.  
•
All unanticipated problems should be reported to appropriate institutional officials (as 
required by an institution’s written reporting procedures), the supporting agency head (or 
designee), and the OHRP within 10 days of the IRB’s receipt of the report of the problem 
from the investigator. 
An investigator shall submit to the Sponsor and to the reviewing IRB a report of any 
unanticipated adverse device effect occurring during an investigation as soon as possible, but in 
no event later than 10 working days after the investigator first learns of the effect (21 CFR 
812.150(a)(1)). A Sponsor who conducts an evaluation of an unanticipated adverse device effect 
under 812.46(b) shall report the results of such evaluation to the FDA and to all reviewing IRB's 
and participating investigators within 10 working days after the Sponsor first receives notice of 
the effect. Thereafter the Sponsor shall submit such additional reports concerning the effect as 
FDA requests (21 CFR 812.150(b)(1)).  
8.4.3
REPORTING UNANTICIPATED PROBLEMS TO PATIENTS  
Not applicable. 
9
STATISTICAL CONSIDERATIONS  
9.1
STATISTICAL HYPOTHESES


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LL-BMT10001                                                                            CONFIDENTIAL
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There are no formal study hypotheses to be tested in this study. We hypothesize that no safety 
concerns are revealed in eyes receiving LL-BMT1. 
9.2
SAMPLE SIZE DETERMINATION
Due to the exploratory nature of this study, no formal power sample size calculation has been 
performed. An empirical sample size of at least 5 evaluable patients is planned. Assuming a 
10%-20% drop-out non-evaluable rate, up to 7 patients (7 study eyes) will be consented to begin 
acclimation screening. Those who are consented but fail acclimation screening will be replaced 
until at least 5 patients successfully complete the acclimation screening. Five patients who pass 
acclimation screening will be enrolled as patients for study treatment.  
9.3
POPULATIONS FOR ANALYSES
The following populations will be analyzed: 
•
Safety population: Includes all patients whose eyes are in contact with LL-BMT1 lenses. 
•
Intent-to-treat (ITT) population: Includes all patients who have LL-BMT1 lenses 
successfully inserted. 
•
Modified intent-to-treat (mITT) population: Includes all patients who have LL-BMT1 
lenses successfully inserted and complete at least 1 on-therapy follow-up assessment; 
only the study eye from each patient will be included in this analysis. 
9.4
STATISTICAL ANALYSES
9.4.1
GENERAL APPROACH
The database will be locked after all patients exit the study and all data clarification forms or 
queries have been resolved. Prior to database lock, a detailed Statistical Analysis Plan (SAP) will 
be finalized and approved. Final analysis will occur after database lock.  
Wherever appropriate, summary statistics will include the frequency, mean, standard deviation, 
median, minimum, and maximum for continuous and ordinal variables, and frequency counts 
and percent for categorical variables. Graphical representations of the results may also be 
provided.  
In general, unless otherwise specified, eyes will be the analytical unit and a formal statistical test 
will only be conducted for exploratory purposes when sample size is deemed appropriate. All 
testing will be two-sided with a 95% confidence level. Due to the small sample size in this study, 
nonparametric approach will be applied. For quantitative variables, within-eye before-and-after 
comparisons will be assessed using one-sample Wilcoxon test. For qualitative variables, Fisher’s 
Exact test will be used.  
9.4.2
SAFETY ANALYSES
Analysis of treatment-emergent AEs will be conducted based on the safety population. Safety 
endpoints include: 


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LL-BMT10001                                                                            CONFIDENTIAL
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•
AEs
•
Concomitant medications 
•
Heart rate and blood pressure 
•
BCVA 
•
IOP  
•
Biomicroscopy  
•
Conjunctival hyperemia 
Ocular events will be reported on an eye level, while non-ocular events will be on a patient level. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). For each 
AE reported, the number and percent of patients/eyes will be tabulated based on the preferred 
term and ocular and non-ocular AEs will be reported separately. The tables will be generated by 
relationship to treatment as well as by system organ class and severity. 
The primary safety endpoint is the AE rate (100 × [number of AEs / number of eyes exposed to 
treatment]). The modified safety set will be used for a sensitivity analysis of the primary safety 
endpoint. 
Secondary safety endpoints: 
•
Percent of patients with ≥5-mmHg increase from baseline in IOP at each visit 
•
Abnormal slit-lamp biomicroscopy findings at the Baseline, Day 1, and Day 7 Visits 
•
Contact lens protein deposits at the Day 7 Visit
•
Change from baseline in CLDEQ-8 results at the Day 7 Visit
Pre-existing AEs, those identified after enrollment but before treatment with LL-BMT1, will be 
tabulated for all consented patients. 
9.4.3
EFFICACY ANALYSES 
The secondary efficacy endpoint is the change from baseline in IOP at each visit. 
The efficacy analyses will be based on the mITT population and only the study eyes will be used. 
Statistical analyses will be performed using methods described in Section 9.4.1.
9.4.4
BASELINE DESCRIPTIVE STATISTICS
Baseline and demographic assessments will be presented descriptively. 
9.4.5
PLANNED INTERIM ANALYSES 
No interim analysis will be performed. 


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LL-BMT10001                                                                            CONFIDENTIAL
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9.4.6
SUB-GROUP ANALYSES
No subgroup analyses are planned. 
9.4.7
TABULATION OF INDIVIDUAL PATIENT DATA
Line listings will be provided for each patient. 
9.4.8 OTHER EXPLORATORY ANALYSES
No other exploratory analyses are planned.
10
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS
10.1.1 INFORMED CONSENT PROCESS
10.1.1.1 CONSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PATIENTS 
Consent forms describing in detail the study intervention, study procedures, and risks, that have 
been reviewed and approved by the relevant IRB, will be given to the patient and written 
documentation of informed consent will be required prior to starting study intervention. An 
informed consent form will be submitted with this protocol.
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. Consent forms will be 
IRB-approved, and the patient will be asked to read and review the document. The investigator 
will explain the research study to the patient and answer any questions that may arise. A verbal 
explanation will be provided in terms suited to the patient’s comprehension of the purposes, 
procedures, and potential risks of the study and of their rights as research patients. Patients will 
have the opportunity to carefully review the written consent form and ask questions prior to 
signing. The patients should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. Patients must be informed that 
participation is voluntary and that they may withdraw from the study at any time, without 
prejudice.  
A copy of the informed consent document will be given to the patients for their records. The 
informed consent process will be conducted and documented in the source document (including 
the date), and the form signed, before the patient undergoes any study-specific procedures. The 
rights and welfare of the patients will be protected by emphasizing to them that the quality of 
their medical care will not be adversely affected if they decline to participate in this study. 


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LL-BMT10001                                                                            CONFIDENTIAL
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10.1.2 STUDY DISCONTINUATION AND CLOSURE
Recruitment may be halted by the site investigator at any time for safety reasons. If this occurs, 
the IRB and any other investigators will be immediately notified. 
  
Leo Lens Technology may stop the study (and/or the study site) for any reason with appropriate 
notification. If the study is prematurely terminated or suspended, the Principal Investigator will 
promptly inform study patients, the IRB, and Sponsor and will provide the reason(s) for the 
termination or suspension. Study patients will be contacted, as applicable, and be informed of 
changes to study visit schedule. 
  
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB, and/or FDA. 
10.1.3 CONFIDENTIALITY AND PRIVACY 
A report of the results of this study may be published or sent to the appropriate health authorities 
in any country in which the study drug may ultimately be marketed, but the patient’s name will 
not be disclosed in these documents. The patient's name may be disclosed to Leo Lens 
Technology, the governing health authorities, or the FDA if they inspect the study records as 
required by law. Appropriate precautions will be taken to maintain confidentiality of medical 
records and personal information. 
In accordance with HIPAA requirements, additional purposes of this study include (1) the 
publishing of anonymous patient data from the study, and (2) the creation and maintenance of a 
data repository.  
All study-related correspondence, patient records (ie, source documents listed in Section 11.4.1), 
informed consent forms, patient privacy documentation, records of the distribution and use of all 
investigational products, and patient questionnaires, correspondence with IRB, and other 
essential documents should be maintained on file. Local regulatory requirements should be 
followed regarding the retention of clinical study documentation. 
Leo Lens Technology requires that it be notified in writing if the investigator wishes to 
relinquish ownership of the data so that mutually agreed-upon arrangements can be made for 
transfer of ownership to a suitably qualified, responsible person. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA 
Not applicable.
10.1.5 KEY ROLES AND STUDY GOVERNANCE
Medical Monitor


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LL-BMT10001                                                                            CONFIDENTIAL
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10.1.6 SAFETY OVERSIGHT
No internal data review committee will be used during this study. 
10.1.7 CLINICAL MONITORING
Clinical site monitoring is conducted to ensure that the rights and well-being of trial patients are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the trial is in compliance with the currently approved protocol/amendment(s), with ICH GCP, 
and with applicable regulatory requirement(s).  
•
Monitoring for this study will be performed by an employee of Trial Runners on a 
periodic basis. The determination of the extent and nature of monitoring will be based on 
considerations, such as the objective, purpose, design, complexity, masking, size, and 
endpoints of the study. 
•
An employee of Trial Runners or regulatory authority representatives will conduct on-site 
visits to review, audit, and copy study-related documents. These representatives will meet 
with the investigator and appropriate staff at mutually convenient times to discuss study-
related data and questions. 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL
Each clinical site will perform internal quality management of study conduct, data collection, 
documentation and completion.  
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site for clarification/resolution. 
Following written Standard Operating Procedures, the monitors will verify that the clinical trial 
is conducted and data are generated and biological specimens are collected, documented 
(recorded), and reported in compliance with the protocol, ICH GCP, and applicable regulatory 
requirements (eg, Good Laboratory Practices, Good Manufacturing Practices).  
The investigational site will provide direct access to all trial-related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the Sponsor, and inspection by local 
and regulatory authorities.
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 


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LL-BMT10001                                                                            CONFIDENTIAL
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legibility, and timeliness of the data reported. All source documents should be completed in a 
neat, legible manner to ensure accurate interpretation of data.  
•
Clinical data will be entered into eCRFs. Data entered into the eCRF will correspond 
with and be supported by source documentation maintained at the site. A final report of 
all patient data will be provided to each site at the end of the study to serve as eCRF 
documentation. 
Source documents may include a patient's medical records, diaries, hospital charts, clinic charts, 
the investigator's patient study files, as well as the results of diagnostic tests and laboratory tests. 
The investigator's copy of the eCRFs serves as part of the investigator's record of a patient's 
study-related data.  
The following information should be entered into the patient's medical record: 
•
Patient’s name (this information will not be included in the study database) 
•
Patient’s contact information (this information will not be included in the study database) 
•
Date that the patient entered the study, patient number, and patient medication kit number 
•
Study title and/or the protocol number of the study and the name of Leo Lens Technology 
•
Statement that informed consent was obtained (including the date) prior to any study 
procedures being performed and that the patient was provided a copy of the signed 
informed consent. A statement that country and local patient privacy-required 
documentation for this study has been obtained (including the date) 
•
Dates of all patient visits 
•
All concurrent medications (List all prescription and non-prescription medications being 
taken at the time of enrollment. At each subsequent visit, changes to the list of 
medications should be recorded.) 
•
Occurrence and status of any AEs (including any procedure-related AEs) 
•
The date the patient exited the study, and a notation as to whether the patient completed 
the study or reason for discontinuation 
•
The results, if applicable, of any procedures performed to confirm eligibility criteria  
•
Documentation of the patient’s medical history 
•
Heart rate and blood pressure  
•
Results of biomicroscopy/ophthalmoscopy exams 
•
Documentation of whether any procedure, including study treatment administration, was 
performed according to the protocol, noting any deviations (if applicable) 
•
Study drug accountability and reconstitution records 
10.1.9.2 STUDY RECORDS RETENTION 


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LL-BMT10001                                                                            CONFIDENTIAL
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Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be 
destroyed without the written consent of the Sponsor, if applicable. It is the responsibility of the 
Sponsor to inform the investigator when these documents no longer need to be retained. 
10.1.10
PROTOCOL DEVIATIONS 
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or Project 
Management Plan requirements. The noncompliance may be either on the part of the patient, the 
investigator, or the study site staff. As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly.  
These practices are consistent with ICH GCP: 
•
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
•
5.1 Quality Assurance and Quality Control, section 5.1.1  
•
5.20 Noncompliance, sections 5.20.1, and 5.20.2 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation, or within 10
working days of the scheduled protocol-required activity. All deviations must be addressed in 
study medical records, reported to Leo Lens Technology or its designee. Protocol deviations 
must be sent to the reviewing IRB per their policies. The site investigator is responsible for 
knowing and adhering to the reviewing IRB requirements. Further details about the handling of 
protocol deviations will be included in the Project Management Plan. 
10.1.11
PUBLICATION AND DATA SHARING POLICY
Leo Lens Technology, as the Sponsor, has proprietary interest in this study. Authorship and 
manuscript composition will reflect joint cooperation between the Principal Investigator and Leo 
Lens Technology personnel. Authorship will be established prior to the writing of the 
manuscript. No individual publications will be allowed prior to completion of the final report of 
the study, except as agreed with Leo Lens Technology. 
This study will be registered on the ClinicalTrials.gov registry.  
10.1.12
CONFLICT OF INTEREST POLICY
Due to potential conflict of interest, patients or members of the patient’s household who are 
employees of the investigative site are not eligible for enrollment in the study. 
10.2 ADDITIONAL CONSIDERATIONS


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Investigational site staff will be instructed to follow their institutional infection control standard 
procedures and to consider additional measures during periods of community transmission of 
conditions, such as COVID-19. These additional measures may include: 
•
Contacting patients the day before a scheduled appointment for a number of reasons, 
including: 
o
To determine if they are experiencing any signs or symptoms of possible 
infections. Such COVID-19-related symptoms include fever, cough, shortness of 
breath, and sore throat 
o
To determine if the patient has tested positive for COVID-19, been in contact with 
someone who is known or suspected to be positive for COVID-19, or traveled to 
an area of in which there is or has been an outbreak of COVID-19 cases 
o
To reschedule patients who are experiencing respiratory symptoms and 
instructing them to seek appropriate medical attention. This requires removal of 
the LL-BMT1 contact lenses if they are in the on-treatment portion of the study. 
Removal under these circumstances can done by the subject or by site personnel. 
o
To remind patients to contact the investigational site if they develop respiratory or 
other COVID-related symptoms on the morning before a scheduled examination 
of if they have had changes to their health status since their last visit 
Upon arrival at the investigational site, patients should be assessed for fever and provided with 
proper protective equipment (PPE; eg, face masks), if they are not already using PPE. 
Equipment that is meant to be used on more than one person should be draped to prevent 
possible contamination and appropriately cleaned before and after each use. Additional measures 
should also be considered, including: 
•
Posting guidelines for the reduction of risk of coronavirus transmission 
•
Reminding patients of the need for social distancing/ consider having patients wait 
outside of the investigational site (eg, in their vehicles until they are ready to be seen) 
•
Restricting non-essential individuals accompanying patients from patient areas 
•
Providing supplies for respiratory hygiene and cough etiquette, including 60% to 95% 
alcohol-based hand sanitizer, no-touch receptacles for waste disposal, face masks, and 
tissues at healthcare facility entrances, waiting rooms, patient check-ins, etc. 
•
Reminding patients to wash hands and/or use hand sanitizer frequently 
Study visits and assessments should be rescheduled at the discretion of the Investigator when 
there is a perceived increased risk of coronavirus transmission to patients and/or investigational 
site staff. 
10.3 ABBREVIATIONS
AE
adverse event
BCVA
best-corrected visual acuity
CFR
Code of Federal Regulations


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LL-BMT10001                                                                            CONFIDENTIAL
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CLDEQ-8
Contact Lens Dry Eye Questionnaire-8
CONSORT
Consolidated Standards of Reporting Trials
eCRF
electronic Case Report Forms
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act 
ICH
International Conference on Harmonisation 
IFU
instructions for use
IND
Investigational New Drug
IOP
intraocular pressure
IRB
Institutional Review Board
ITT
intent-to-treat
IUD
intrauterine device
IWRS
interactive web response system
LASIK
laser-assisted in situ keratomileusis
MedDRA
Medical Dictionary for Regulatory Activities
NDA
New Drug Application
OAG
open-angle glaucoma
OHRP
Office for Human Research Protections
OHT
ocular hypertension
PI
prescribing information
POAG
primary open-angle glaucoma
PP
per-protocol
PPE
proper protective equipment
PRK
photorefractive keratectomy
ROCK
Rho kinase
QC
quality control
RK
radial keratotomy
SAE
serious adverse event
SAP
statistical analysis plan
SMILE
small incision lenticule extraction
US
United States
10.4 PROTOCOL AMENDMENT HISTORY
Version
Date
Description of Change 
Brief Rationale
1.1
11/19/20
Based upon input from the U.S. Food 
and Drug Administration, the 
numbers of subjects to be entered and 
dosed in the study was changed 
FROM “5-7” TO “5”.  This impacts 
several sections of the protocol 
including the Synopsis, Schema, 
Overall Design, and Sample Size 
Determination section. Further, 
clarifications were added to the 
Schema and Safety and Other 
Assessment sections to assist the 
Investigator. 
Amendment based on input 
from U.S. Food and Drug 
Administration.


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LL-BMT10001                                                                            CONFIDENTIAL
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1.2
12/21/20
Based upon input from the IRB, the 
protocol was amended to include best 
corrected visual acuity and slit lamp 
exam to all visits prior to the baseline 
visit.
Amendment based on input 
from IRB.
11
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2. BIOMEDICS® 55 (ocufilcon D) soft (hydrophilic) contact lenses [prescribing 
information]. Scottsville, NY: CooperVision; 2019 Accessed July 13, 2020. 
3. CLASSIC Sphere soft contact lens for daily wear [prescribing information]. Lancaster, 
NY: Alden Optical; 2016. Accessed February 9, 2019. 
4. Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular 
pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 
1998;126:498–505. 
5. Craven ER, Walters T, Christie WC, Day DG, Lewis RA, Goodkin ML, et al. 24-Month 
phase I/II clinical trial of bimatoprost sustained-release implant (Bimatoprost SR) in 
glaucoma patients. Drugs. 2020;80(2):167–179. 
6. Durysta [prescribing information]. Madison, NJ: Allergan, Inc.; 2020. Accessed July 7, 
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7. Frequency 55 soft contact lenses for daily and extended wear [prescribing information]. 
Scottsville, NY: CooperVision; 2004. Accessed February 9, 2019. 
8. Horizon contact lenses [prescribing information]. Grand Junction, CO: Westcon Contact 
Lens Co., Inc.; 2005. Accessed February 9, 2019. 
9. Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular hypertension treatment study: a 
randomized trial determines that topical ocular hypotensive medication delays or prevents 
the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–713. 


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LL-BMT10001                                                                            CONFIDENTIAL
Version 1.2 
Leo Lens Technology Co., Inc.
21 December 2020
10. Lewis RA, Christie WC, Day DG, Craven ER, Walters T, Bejanian M, et al. Bimatoprost 
sustained-release implants for glaucoma therapy: 6-month results from a phase I/II 
clinical trial. Am J Ophthalmol. 2017;175:137–147. 
11. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the 
collaborative initial glaucoma treatment study comparing initial treatment randomized to 
medications or surgery. Ophthalmology. 2001;108:1943–1953. 
12. Lumigan (bimatoprost ophthalmic solution) 0.01% [prescribing information]. Irvine, CA: 
Allergan, Inc.; 2020. Accessed October 1, 2020. 
13. Novack GD. Ophthalmic drug delivery: development and regulatory considerations. Clin 
Pharmacol Ther. 2009;85(5):539–543. 
14. Robin AL, Novack GD, Covert DW, Crockett RS, Marcic TS. Adherence in glaucoma: 
Objective measurements of once-daily and adjunctive medication use. Am J Ophthalmol.
2007;144(4):533–540. 
15. Stone JL, Robin AL, Novack GD, Covert D, Cagle GD. An objective evaluation of eye-
drop instillation in glaucoma patients. Arch Ophthalmol. 2009;127(6):732–736. 
16. Sherwood MB, Craven ER, Chou C, DuBiner HB, Batoosingh AL, Schiffman RM, et al. 
Twice-daily 0.2% brimonidine-0.5% timolol fixed-combination therapy vs monotherapy 
with timolol or brimonidine in patients with glaucoma or ocular hypertension: a 12-
month randomized trial. Arch Ophthalmol. 2006;124(9):1230–1238. 


44
LL-BMT10001                                                                            CONFIDENTIAL
Version 1.2 
Leo Lens Technology Co., Inc.
21 December 2020
12 ATTACHMENTS  

SAP_001.pdf: 
NCT04747808 
Study LL-BMT10001 
 
A Phase 2a Study of Safety, Tolerability, and Efficacy of Drug-Delivering Contact Lens LL-BMT1 
in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension 
 
Statistical Analysis Plan 
Date: 11 February 2021 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
Statistical Analysis Plan 
Statistical Analysis Plan 
Version 1.0-11-FEB-2021 
A Phase 2a Study of Safety, Tolerability, and Efficacy of Drug-Delivering Contact Lens L~SMTl in Patie,1s• 
with Primary Open-Angle Glaucoma or Ocular Hypertension 
• 
• 
Prepared for: 
MediPrint Ophthalmics, Inc. 
9899 Hibert Street, Suite A 
San Diego, CA 92131 
Protocol details: 
Name: 
Version: 
Date: 
Author details: 
Version: 
Version Date: 
"•h 11 
LL-BMT10001 
1.2 
21-DEC-2020 
1.0 
11-FEB-2021 
i1 t I a 
CONFIDENTIAL 
... 
. 
~-
.,.,. ti ', .. ,..,~ J 
Page 1 of 8 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
Review and Approval 
Statistical Analysis Plan 
Version l.0- ll-FEB-2021 
The undersigned have approved this Statistical Analysis Plan for use in this study. 
Trial Runners, LLC Approval: 
· i :e-------
Biostatistician 
Feb 12, 2021 
Date 
--------
Feb 12, 2021 
Date 
Project Manager 
-~---
Feb 12, 2021 
Date 
Data Manager 
MediPrint Ophthalmics, Inc. Approval: 
-11111111·,l .. m.-i .. l'-4'-•-•----------
Feb 12, 2021 
chiet Operating Officer 
CONFIDENTIAL 
Page2of8 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
Statistical Analysis Plan 
Version 1.0 - ll-FEB-2021 
Table of Contents 
1 
INTRODUCTION ..................................................................................................................................... 5 
1.1 
Changes from Protocol ................................................................................................................. 5 
2 
STUDY OBJECTIVES ................................................................................................................................ 5 
2.1 
Primary Objective .......................................................................................................................... 5 
2.2 
Secondary Objective ..................................................................................................................... 5 
3 
STUDY DESIGN ....................................................................................................................................... 5 
3.1 
Sample Size Considerations .......................................................................................................... 5 
3.2 
Randomization .............................................................................................................................. 5 
3.3 
Schedule of Evaluations and Analysis Visit Windows ................................................................... 5 
4 
ANALYSIS POPULATIONS ....................................................................................................................... 6 
4.1 
Intent-to-Treat Population ............................................................................................................ 6 
4.2 
Safety Population .......................................................................................................................... 6 
5 
STUDY VARIABLES/PARAMETERS .......................................................................................................... 6 
5.1 
Primary Endpoints ......................................................................................................................... 6 
5.2 
Secondary Endpoints .................................................................................................................... 6 
6 
STATISTICAL ANALYSIS METHODS ......................................................................................................... 7 
6.1 
Subject Disposition ........................................................................................................................ 7 
6.2 
Protocol Deviations ....................................................................................................................... 7 
6.3 
Missing Data and Imputation ........................................................................................................ 7 
6.4 
Demographics and Baseline Characteristics ................................................................................. 7 
6.5 
Prior and Concomitant Medications ............................................................................................. 7 
6.6 
Medical History ............................................................................................................................. 7 
A I . 
. .................................. 8 
6. 7 
Primary na ys1s .................................................. •······ .............................. .. 
6.8 
Secondary Analysis ........................................................................................................................ 8 
7 
INTERIM ANALYSIS ................................................................................................................................ B 
8 
G 
.......................... 8 
VERSION HISTORY LO 
.............................................................................................. . 
GLOSSARY OF ABBREVIATIONS 
CONFIDENTIAL 
Page 3 of 8 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
Abbreviation 
Meaning 
AE 
Adverse Event 
BCVA 
Best-corrected visual acuity 
CLDEQ-8 
Contact Lens Dry Eye Questionnaire-8 
IOP 
lntraocular Pressure 
ITT 
Intent-to-treat 
min 
Modified intent-to-treat 
OHT 
Ocular hypertension 
POAG 
Primary open-angle glaucoma-999 
TEAE 
Treatment-emergent adverse event 
CONFIDENTIAL 
Statistical Analysis Plan 
Version 1.0-11-FEB-2021 
Page 4of 8 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
1 
INTRODUCTION 
Statistical Analysis Plan 
Version 1.0 - ll-FEB-2021 
This statistical analysis plan (SAP) provides a comprehensive and detailed description of analyses and 
reporting of data for LL-BMT1 study protocol LL-BMTl000l. The purpose ofthe SAP is to ensure the 
credibility of the study findings by pre-specifying the statistical approaches to the analysis of study data 
prior to data base lock. 
1.1 
Changes from Protocol 
Not applicable. 
2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to evaluate the safety of LL-BMTl in patients with POAG or OHT. 
2.2 
Secondary Objective 
The secondary objectives of this study are: 
• 
To evaluate the safety and tolerability of LL-BMTl in patients with POAG or OHT, and 
• 
To evaluate efficacy by !OP-lowering effects of LL-BMTl in patients with POAG or OHT. 
3 
STUDY DESIGN 
This study is an open-label, phase 2a clinical study consisting of 5 patients at up to 2 sites within the 
United States, each with a treatment duration of 1 week. All patients will be assigned to the study 
intervention (LL-BMTl lenses) and will wear then for 1 week. 
3.1 
Sample Size Considerations 
Due to the exploratory nature of this study, no formal power sample size calculation has been 
performed. An empirical sample size of at least 5 evaluable patients is planned. Assuming a 10-20% 
drop-out non-evaluable rate, up to 7 patients (7 study eyes) will be consented to begin acclimation 
screening. Those who are consented but fail acclimation screening will be replaced until at least 5 
patients successfully complete the acclimation screening. Five patients who pass acclimation screening 
will be enrolled as patients for study treatment. 
3.2 
Randomization 
Not applicable, as all study subjects will be assigned to a single treatment, LL-BMTl lenses. 
3.3 
Schedule of Evaluations and Analysis Visit Windows 
The schedule of visits and procedures are provided in the study protocol, LL-BMTl000l, version 1.2, 
section 1.3. The study consists of a screening period, 2 acclimation periods where the subject wears 2 
sets of nonmedicated lens for 1 week each, 1 treatment week where the subject wears 1 set of LL-BMTl 
CONFIDENTIAL 
Page 5 of8 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
Statistical Analysis Plan 
Version l.O- ll-FEB-2021 
lenses for 1 week, and a follow-up visit after lens removal. Visit days and windows are summarized in 
the table below: 
Target Day of the 
Visit Windows (Days) for 
Visit 
Visit 
Analyses 
Visit 1 - Screening 
-45 to -14 
<-14 
Visit 2 -Acclimation 
-14 
-14 
Visit 3 -Acclimation 
-7 
-7 
Visit 4 -Acclimation 
-6 
-6 
Visit 5 - Baseline 
0 
0 
Visit 6- LL-BMTl Lens Insertion 
1 
1 
Visit 7 - On-treatment 
4 
4 
Visit 8 - End of treatment 
7 
7 
Visit 9 - Follow-up 
8 
8 
Visit 10 - Conditional Follow-up/ End of study 
9 
9 
4 
ANALYSIS POPULATIONS 
4.1 
Intent-to-Treat Population 
The intent-to-treat (ITT) population includes all patients who have LL-BMTl lenses successfully inserted. 
This population of patients will be used to summarize protocol deviations. 
4.2 
Safety Population 
The safety population includes all patients who have LL-BMT1 lenses successfully inserted. 
5 
STUDY VARIABLES/PARAMETERS 
5.1 
Primary Endpoints 
The primary safety endpoint is the adverse event (AE) rate, defined to be 100 x [number of AEs / 
number of eyes exposed to treatment]. 
5.2 
Secondary Endpoints 
The secondary safety endpoints include the following: 
• 
AEs 
• 
Concomitant medications 
• 
Heart rate and blood pressure 
• 
BCVA 
• 
IOP 
• 
Biomicroscopy 
• 
Conjunctiva! hyperemia 
• 
Percent of patients with .:: 5 mm Hg increase from baseline in IOP at each visit 
• 
Abnormal slit-lamp biomicroscopy findings at the Baseline, Day 1, and Day 7 Visits 
• 
Contact lens protein deposits at the Day 7 Visit 
• 
Change from Baseline in CLDEQ-8 results at the Day 7 Visit 
CONFIDENTIAL 
Page6of8 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
Statistical Analysis Plan 
Version 1.0 -11-FEB-2021 
The secondary efficacy endpoint will be the change from baseline in IOP at each visit. 
6 
STATISTICAL ANALYSIS METHODS 
There are no formal study hypotheses to be tested in this study. Safety and efficacy endpoints will be 
summarized using frequency, mean, median, standard deviation, min and max for continuous variables, 
and frequency and percentage for categorical variables. 
6.1 
Subject Disposition 
The number and percentage of subjects screened, enrolled, completed treatment, completed study, and 
within each population will be summarized. 
Individual subject disposition data will be listed. 
6.2 
Protocol Deviations 
The number and percentage of protocol deviations will be presented using the intent-to-treat 
population. 
6.3 
Missing Data and Imputation 
No Imputation will be conducted for this study. 
6.4 
Demographics and Baseline Characteristics 
Baseline and demographic assessments will be presented descriptively using the safety population. 
Mean, median, standard deviation, min and max will be used for continuous variables, while number 
and percentage will be used to describe categorical variables. 
6.5 
Prior and Concomitant Medications 
Prior and concomitant medication will be coded using the World Health Organization Drug Dictionary 
(WHO DD), September 2020. The number and percentage of subjects who reported taking prior and/or 
concomitant medications will be summarized using the safety population. 
Individual subject prior and concomitant medication data will be listed. 
6.6 
Medical History 
The number and percentage of past and concurrent medical conditions will be summarized using the 
safety population. 
Individual subject medical history data will be listed. 
CONFIDENTIAL 
Page 7 of8 


MediPrint Ophthalmics, Inc. 
LL-BMT10001 
6.7 
Primary Analysis 
Statistical Analysis Plan 
Version 1.0-11-FEB-2021 
The primary safety analysis will be treatment-emergent adverse events, defined to be any AE with an 
onset date equal to or after the date of the first insertion of the study lens and during the treatment, 
using the safety population. 
Pre-existing AEs, those identified after enrollment but before treatment with LL-BMTl, will be tabulated 
for all consented patients. The rate of adverse events will be defined as 100 x [number of AEs / number 
of eyes exposed to treatment]. 
6.8 
Secondary Analysis 
There will be both safety and efficacy assessments in the secondary analysis. 
The secondary safety analysis will consist of identifying the following: 
• 
Percent of patients with ;;: 5 mm Hg increase from baseline in IOP at each visit 
• 
"Abnormal" and "Severe" slit-lamp biomicroscopy findings at the Baseline, Day 1, and Day 7 
Visits 
• 
Contact lens protein deposits at the Day 7 Visit 
• 
Change from Baseline in CLDEQ-8 results at the Day 7 Visit 
The secondary efficacy analysis will consist of identifying the change from baseline in IOP at each visit. 
Study eyes only within the modified intent-to-treat population will be used for this part of the analysis. 
7 
INTERIM ANALYSIS 
No interim analysis is planned for this study. 
8 
VERSION HISTORY LOG 
Version 
Date 
Implemented Changes 
Author 
1.0 
11-FEB-2021 
First Approved Version 
Lauren Mudd 
CONFIDENTIAL 
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