Phase 1/2a, Proof-of-Concept, Multicenter, Parallel, Vehicle-Controlled, Double-Masked, Randomized Study Evaluating the Safety, Tolerability, and Efficacy of IVW-1001 Ophthalmic Eyelid Wipe in Subjects With Dry Eye Disease
Phase: PHASE1
Conditions: Dry Eye Disease
Sponsor: IVIEW Therapeutics Inc.

Study Title: Phase 1/2a, Proof-of-Concept, Multicenter, Parallel, Vehicle-Controlled, Double-
Masked, Randomized Study Evaluating the Safety, Tolerability, and Efficacy of IVW-1001 
Ophthalmic Eyelid Wipe in Subjects With Dry Eye Disease 
 
Study Number: IVW-1001-CS-101 
 
CTG Number: NCT06400459 
 
Document Date: 17 April 2024 

IVW-1001 Ophthalmic Eyelid Wipe 
 
IVIEW Therapeutics, Inc. 
Clinical Trial Protocol: IVW-1001-CS-101 
 
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CONFIDENTIAL 
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Version 1.1 
PROTOCOL: IVW-1001-CS-101 
Study Title: 
Phase 1/2a, Proof-of-Concept, Multicenter, Parallel, Vehicle-Controlled, 
Double-Masked, Randomized Study Evaluating the Safety, Tolerability, 
and Efficacy of IVW-1001 Ophthalmic Eyelid Wipe in Subjects With Dry 
Eye Disease 
Study Number: 
IVW-1001-CS-101 
Study Phase: 
Phase 1/2a 
IND: 
164036 
Product Name: 
IVW-1001 Ophthalmic Eyelid Wipe 
Sponsor: 
IVIEW Therapeutics, Inc. 
Sponsor Contact: 
 
  
Sponsor Medical 
Monitor: 
 
 
 
 
Date 
Original Protocol: 
Version 1.0; 22 January 2024 
Amended Protocol 
Version 1.1; 17 April 2024 
 
 
 
 
Confidentiality Statement 
The information in this document contains trade secrets and commercial information that are 
privileged or confidential and may not be disclosed unless such disclosure is required by federal or 
state law or regulations. In any event, persons to whom the information is disclosed must be informed 
that the information is privileged or confidential and may not be disclosed by them. These restrictions 
on disclosure will apply equally to all future information supplied to you, which is indicated as 
privileged or confidential. 

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Clinical Trial Protocol: IVW-1001-CS-101 
 
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SYNOPSIS 
Sponsor 
IVIEW Therapeutics, Inc. 
Study Title 
Phase 1/2a, Proof-of-Concept, Multicenter, Parallel, Vehicle-Controlled, 
Double-Masked, Randomized Study Evaluating the Safety, Tolerability, 
and Efficacy of IVW-1001 Ophthalmic Eyelid Wipe in Subjects With 
Dry Eye Disease 
Protocol Number 
IVW-1001-CS-101 
Indication 
Dry eye disease (DED) 
Sites 
Up to approximately 10 sites throughout the United States (US) 
Phase of Development 
Phase 1/2a 
Objectives  
The objectives of this study are to assess the safety and efficacy of 
IVW-1001 Ophthalmic Eyelid Wipe in subjects with DED.  
Primary Safety 
Outcome Measures 
The primary safety measures are: 
• 
Mean change from baseline in:  
o Best-corrected visual acuity (BCVA) 
o Slit lamp biomicroscopy 
o Intraocular pressure (IOP) 
o Dilated ophthalmoscopy 
• 
Visual analog scale (VAS) of investigational product (IP) 
tolerability 
• 
Adverse events (AEs)  
 
Primary Efficacy  
Outcome Measures 
The primary efficacy endpoint is: 
• 
Mean change from baseline at Day 29 (Week 4/End of Study) 
in the study eye in unanesthetized Schirmer’s test 
Exploratory Efficacy 
Outcome Measures 
The exploratory efficacy endpoints are: 
• 
Mean change from baseline in: 
o Unanesthetized Schirmer’s test (Weeks 1, 2, and 3) 
o VAS of IP comfort (ASHRAE 7-Point Scale) 
o VAS of Eye Dryness Score (EDS) 
o VAS of Ocular Discomfort Score (ODS) 
o Symptom Assessment in Dry Eye (SANDE) 
questionnaire 
o Corneal fluorescein staining (inferior zone) 
o Corneal fluorescein staining (total of all zones) 
o Anesthetized Schirmer’s test 
• 
Proportion of subjects ≥10 mm increase in unanesthetized 
Schirmer’s test score  

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Clinical Trial Protocol: IVW-1001-CS-101 
 
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• 
Proportion of subjects ≥10 mm increase in anesthetized 
Schirmer’s test score  
Study Design 
This is a randomized (1:1:1), multicenter, parallel, vehicle-controlled, 
double-masked study to evaluate the safety, tolerability, and efficacy of 
IVW-1001 Ophthalmic Eyelid Wipes in subjects with DED. Treatments 
will be IVW-1001 Ophthalmic Eyelid Wipe 0.2% (high dose), 
IVW-1001 0.1% (low dose), or IVW-1001 Ophthalmic Eyelid Wipe 
Placebo (vehicle). Subjects will participate in a 7-day, single-masked 
vehicle run-in period followed by a 28-day, double-masked treatment 
period. 
Inclusion Criteria 
Each subject must meet the following criteria to be randomized in this 
study. 
1. Subjects of any gender at least 18 years of age at the Screening 
Visit 
2. Able to voluntarily provide written informed consent to 
participate in the study 
3. Able and willing to comply with all study procedures and 
restrictions, follow study instructions, and complete required 
study visits 
4. Self-reported diagnosis of DED in one or both eyes 
5. BCVA +0.70 logMAR (Snellen equivalent 20/100) or better in 
each eye at the Screening Visit 
6. For women of childbearing potential, confirmed negative 
pregnancy test at the Screening Visit and the Baseline Visit, not 
nursing a child, and willing to comply with one of the 
acceptable methods of birth control described in the protocol  
7. History (by subject recollection) of artificial tear use within 
30 days prior to the Screening Visit  
8. Willingness to suspend use of artificial tears during study 
participation 
9. Willingness to suspend use of contact lenses during study 
participation 
10. Able to demonstrate adequate self-administration of the run-in 
eyelid wipe to upper eyelid at the Screening Visit 
11. Unanesthetized Schirmer’s test score between 5 and 10 mm 
(inclusive) in at least 1 eye (same eye) at the Screening Visit 
and the Baseline Visit 
12. Total corneal fluorescein staining score between 5 and 13, 
representing the sum of scores of all 5 regions (inferior, 
superior, nasal, temporal, and central) using the National Eye 
Institute (NEI) grading system (0-4 scale) in at least one eye at 
the Screening Visit and the Baseline Visit 
13. EDS VAS ≥40 at the Screening Visit and the Baseline Visit, 
with ≤20 units of improvement from the Screening Visit to the 
Baseline Visit 

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Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from 
randomization. 
Ocular history – medical 
1. Corneal fluorescein staining score of 4 in either eye in any zone 
using the NEI grading system at either the Screening Visit or 
the Baseline Visit 
2. IOP ≥23 mmHg  in either eye at either the Screening Visit or 
the Baseline Visit  
3. History of glaucoma or ocular hypertension in either eye 
requiring past or current medical or surgical intervention 
4. History of contact or scleral lens use in either eye within 30 
days prior to the Screening Visit or anticipated use during the 
study 
5. Subjects with ocular inflammatory conditions (eg, 
conjunctivitis, keratitis, severe anterior blepharitis, etc.) not 
related to DED at the Screening Visit or the Baseline Visit 
6. Suspected ocular fungal, viral, or bacterial infection at the 
Screening Visit or the Baseline Visit. Note: Mild blepharitis is 
permitted 
7. Presence of trigger factors that, in the opinion of the 
Investigator, may confound the study data, including but not 
limited to conjunctivochalasis, allergic conjunctivitis, trichiasis, 
epithelial basement membrane dystrophy, infectious keratitis, or 
conjunctivitis 
Ocular history – surgical/procedural 
8. Routine use (as defined by the Investigator) of lid hygiene 
products (warm compresses, medicinal eyelid wipes, eyelid 
scrubs, mechanical eyelid cleaning therapy) within 30 days 
prior to the Screening Visit or inability or unwillingness to 
withhold use during study participation. Note: Makeup removal 
products are permitted  
9. Treatments for meibomian gland dysfunction (MGD) within 
30 days prior to the Screening Visit or anticipated use during 
the study, including but not limited to thermal pulsation 
(Lipiflow®, iLux2®), debridement of lid margin (BlephEx®), 
moisture chamber goggles, or thermal application (MiBoFlo 
Thermoflo®, TearCare®) 
10. Cauterization of the punctum within 90 days prior to the 
Screening Visit or anticipated during study participation 
11. Non-dissolvable punctal plugs inserted within 90 days prior to 
the Screening Visit or, in the opinion of the Investigator, 
considered unstable and likely to become displaced 
12. Long-term dissolvable punctal plugs inserted within 90 days 
prior to the Screening Visit 
Prior medications and therapies in either eye 

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13. Use of artificial tears within 2 hours prior to the Screening Visit 
or anticipated use during study participation 
14. Use of the following therapies within 30 days prior to the 
Screening Visit or anticipated use during study participation: 
a. Topical cyclosporine (Restasis®, Cequa®, or Vevye™ 
[previously known as CyclASol®]) 
b. Topical brimonidine (prescription or over-the-counter 
[OTC]) 
c. Topical lifitegrast (Xiidra®) 
d. Topical perfluorohexyloctane (Miebo™) 
e. Topical ocular corticosteroids or nonsteroidal anti-
inflammatory drugs (NSAIDs) 
f. Any other prescription or OTC topical eye lid (including 
wipes) or ocular medications for DED and/or MGD or 
any other indication that, in the opinion of the 
Investigator,  might interfere with study assessments  
Prior non-ocular medications  
15. Use of medications for the treatment of DED and/or MGD such 
as oral tetracyclines, oral tetracycline derivatives, oral or topical 
macrolides (such as azithromycin), and oral retinoids (Note: 
Current or past isotretinoin use is exclusionary) within 30 days 
prior to the Screening Visit or anticipated use during the study 
16. Initiation, discontinuation, or change in dosing of any systemic 
corticosteroid within 30 days prior to the Screening Visit or an 
anticipated change in dosage during the study 
a. Topical non-ocular dermal corticosteroids may be used up 
to 3 times per week in no more than 3 locations 
simultaneously. No periocular use is permitted 
b. Intranasal corticosteroids are permitted with a stable 
dosing history during the 30 days prior to the Screening 
Visit and without an anticipated change in dosage during 
the study 
17. Use of NSAIDs, including aspirin, unless: 
a. Used with a stable dosing history during the 30 days prior 
to the Screening Visit without an anticipated change in 
dosage during the study 
b. Used as needed (PRN) no more than 3 times weekly 
c. Note: Acetaminophen has no restrictions on its use 
18. Initiation, discontinuation, or change in dose of a systemic 
medication (oral or topical) known to cause ocular drying (eg, 
antihistamines or tricyclic antidepressants) within 30 days prior 
to the Screening Visit or an anticipated change in dosage during 
the study. Note: These agents are permitted when used PRN to 
treat insomnia 
19. Initiation, discontinuation, or change in dose of any systemic 
immunomodulator (eg, hydroxychloroquine, methotrexate, 

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cyclosporine) within 30 days prior to the Screening Visit or an 
anticipated change during the study. Note: Treatment with 
vaccines is allowed during study participation 
20. Use of Tyrvaya® (varenicline solution, nasal spray) within 
30 days prior to the Screening Visit or anticipated use during 
the study 
21. Any prior use of isotretinoin (Accutane®) or anticipated use 
during the study  
Systemic conditions or procedures 
22. History of allergic conjunctivitis requiring use of prescription or 
OTC topical antihistamine therapy within the last 14 days 
23. History or presence of significant (in the opinion of the 
Investigator) systemic (eg, cardiovascular, pulmonary, hepatic, 
renal, hematologic, immunologic) conditions 
24. Any significant physical or mental condition that, in the opinion 
of the Investigator, could interfere with study participation 
25. Any planned surgical procedure that could interfere with study 
participation 
Lifestyle related 
26. Participation in any interventional investigational drug or 
device trial within 30 days prior to the Screening Visit 
27. Employed by study site, or an immediate family member of site 
staff, and directly involved in clinical activities related to this 
study 
Study Population 
The subject population to be studied is comprised of subjects with DED 
confirmed at the Screening Visit who, after a 7-day, single (subject)-
masked vehicle run-in period, continue to meet eligibility requirements 
at the Baseline Visit. 
Investigational Product, 
Dose, and Mode of 
Administration 
The IPs to be administered in this study are IVW-1001 Ophthalmic 
Eyelid Wipe 0.1%, IVW-1001 Ophthalmic Eyelid Wipe 0.2%, and 
IVW-1001 Ophthalmic Eyelid Wipe Placebo (vehicle) for eyelid 
application.  
Each unit dose will contain 2 polyester wipes saturated with a solution 
containing active ingredient (except vehicle, which contains no active 
ingredient), sodium hyaluronate, mannitol, and water for injection in a 
clear glass bottle. 
One unique wipe will be used for the application to the upper eyelid of 
each eye, moving in a nasal to temporal direction while applying 
modest pressure. 
Duration of Study 
This study has a duration of approximately 5 weeks, with a 7-day run-in 
period and a 28-day treatment period. 
Number of Subjects 
Approximately 150 subjects are targeted for enrollment. 
Safety Assessments 
The safety assessments to be used in this study are: 
• 
BCVA 

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• 
Slit lamp biomicroscopy 
• 
IOP 
• 
Dilated ophthalmoscopy 
• 
VAS of IP tolerability  
• 
AEs 
Efficacy Assessments 
The efficacy assessments to be used in this study are: 
• 
Unanesthetized Schirmer’s test  
• 
VAS of IP comfort (ASHRAE 7-Point Scale) 
• 
VAS of EDS 
• 
VAS of ODS 
• 
SANDE questionnaire 
• 
Corneal fluorescein staining (inferior zone) 
• 
Corneal fluorescein staining (total of all zones) 
• 
Anesthetized Schirmer’s test 
Statistical Methods 
The analysis of safety and efficacy will be performed after all subjects 
have completed the Day 29 Visit or been discontinued prior to Day 29, 
and after the study database has been cleaned, verified, and locked. It is 
planned that the data from all clinical sites participating in this study 
will be combined so that the target sample size will be available for 
analysis. For each efficacy parameter measured on a per-eye basis, the 
primary analysis will be done using data from the study eye (ie, the eye 
that satisfies all of the enrollment criteria). If both eyes satisfy all 
enrollment criteria, then a predefined method will be used to select the 
study eye. 
Analyses will be implemented using SAS® version 9.4 or later. More 
details regarding the analysis of the safety and efficacy data will be 
described in the Statistical Analysis Plan. 
Sample size determination 
Approximately 150 subjects will be enrolled (50/group) in order to 
obtain approximately 138 subjects who complete the study (46/group). 
For the primary efficacy endpoint, this sample size of 46 subjects per 
group should provide at least 80% power to detect a difference between 
the placebo group and each of the IVW-1001 groups of 3.3 mm or 
greater, assuming a standard deviation of 5.0 mm and a 0.025 two-sided 
significance level. 
Interim Analysis  
None 

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Table of Contents 
PROTOCOL: IVW-1001-CS-101 .............................................................................................1 
SUMMARY OF CHANGES .....................................................................................................2 
SYNOPSIS .................................................................................................................................3 
TABLE OF CONTENTS ...........................................................................................................9 
LIST OF ABBREVIATIONS ..................................................................................................14 
1 
INTRODUCTION .................................................................................................15 
1.1 
Indication .........................................................................................................15 
1.2 
Investigational Products ...................................................................................16 
1.3 
Nonclinical Experience ....................................................................................16 
1.4 
Clinical Experience ..........................................................................................16 
1.5 
Risks and Benefits............................................................................................16 
2 
STUDY OBJECTIVES AND MEASURES ..........................................................17 
2.1 
Objective ..........................................................................................................17 
2.2 
Measures ..........................................................................................................17 
2.2.1 
Safety ...................................................................................................17 
2.2.2 
Efficacy ................................................................................................17 
3 
INVESTIGATIONAL PLAN ................................................................................18 
3.1 
Overall Study Design .......................................................................................18 
3.2 
Number of Subjects..........................................................................................18 
3.3 
Study Duration .................................................................................................18 
3.4 
Rescue Treatment.............................................................................................18 
3.5 
Study Treatments .............................................................................................18 
3.6 
Rationale for Study Design and Control Group ...............................................18 
3.7 
Dose and Dosing Regimen...............................................................................18 
3.8 
Study Oversight ...............................................................................................19 
4 
STUDY POPULATION SELECTION AND WITHDRAWAL ...........................20 
4.1 
Study Population ..............................................................................................20 
4.2 
Inclusion Criteria .............................................................................................20 
4.3 
Exclusion Criteria ............................................................................................20 
4.4 
Discontinuation of Treatment and Withdrawal of Subjects .............................23 
4.4.1 
Early Termination Visit .......................................................................23 
4.5 
Subject Replacement ........................................................................................23 
5 
STUDY TREATMENTS .......................................................................................24 
5.1 
Investigational Products ...................................................................................24 
5.2 
Packaging and Labeling ...................................................................................24 
5.3 
Supply, Storage, and Administration of Investigational Product ....................24 
5.3.1 
Supply ..................................................................................................24 

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5.3.2 
Storage .................................................................................................24 
5.3.3 
Administration .....................................................................................25 
5.4 
Accountability, Retention, and Destruction (or Return) ..................................25 
6 
ALLOCATION AND DOSING OF INVESTIGATIONAL PRODUCT .............26 
6.1 
Allocation to Treatment Groups ......................................................................26 
6.1.1 
Subject Assignment .............................................................................26 
6.1.2 
Study Eye Selection .............................................................................26 
6.1.3 
Randomization Procedures ..................................................................26 
6.1.4 
Masking................................................................................................26 
6.1.4.1 
Masking Method ................................................................................26 
6.1.4.2 
Emergency Unmasking ......................................................................26 
7 
PERMITTED MEDICATIONS AND THERAPIES AND 
CONTRAINDICATIONS .....................................................................................27 
7.1 
Concomitant Therapy.......................................................................................27 
7.1.1 
Permitted Therapies .............................................................................27 
7.1.2 
Prohibited Ocular Medications and Therapies .....................................27 
7.1.3 
Prohibited Non-ocular Therapies .........................................................27 
7.1.4 
Concomitant Medication Assessments ................................................28 
7.1.5 
Makeup and Eyelid Hygiene ................................................................28 
7.2 
Lifestyle Restrictions .......................................................................................28 
7.2.1 
Reproductive Restrictions ....................................................................28 
7.3 
Informed Consent.............................................................................................28 
7.4 
Clinical Assessments .......................................................................................29 
7.4.1 
Demographics ......................................................................................29 
7.4.2 
Medical and Ophthalmic History .........................................................29 
7.4.3 
Prior and Concomitant Medications ....................................................29 
7.4.4 
Pregnancy Test .....................................................................................29 
7.4.5 
In-Office Investigational Product Administration ...............................29 
7.4.6 
Investigational Product Tolerability Visual Analog Scale ..................29 
7.4.7 
Investigational Product Comfort Visual Analog Scale ........................29 
7.4.8 
Eye Dryness Score Visual Analog Scale .............................................30 
7.4.9 
Ocular Discomfort Score Visual Analog Scale ...................................30 
7.4.10 
Symptom Assessment in Dry Eye Questionnaire ................................30 
7.4.11 
Unanesthetized Schirmer’s Test ..........................................................30 
7.4.12 
Best-Corrected Visual Acuity (and Refraction) ...................................30 
7.4.13 
Slit Lamp Biomicroscopy ....................................................................30 
7.4.14 
Corneal Fluorescein Staining (CFS) ....................................................31 
7.4.15 
Intraocular Pressure .............................................................................31 
7.4.16 
Anesthetized Schirmer’s Test ..............................................................31 

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7.4.17 
Fundoscopy (Dilated Ophthalmoscopy) ..............................................31 
7.4.18 
Adverse Events ....................................................................................32 
7.5 
Study Activities ................................................................................................32 
7.5.1 
Screening Visit (Day -7 to 1 +2 days) .................................................32 
7.5.2 
Baseline/Randomization Visit (Day 1) ................................................33 
7.5.3 
Visit 3 (Day 8 ±1 day), Visit 4 (Day 15 ±2 days), and Visit 5 (Day 
22 ±2 days) ...........................................................................................34 
7.5.4 
Visit 6/End of Study (Day 29 -3 to +1 days) .......................................35 
8 
ADVERSE EVENTS .............................................................................................36 
8.1 
Definition of an Adverse Event .......................................................................36 
8.2 
Definition of a Serious Adverse Event ............................................................36 
8.3 
Assessment of Relationship to Investigational Product or Procedure .............36 
8.4 
Assessment of Severity ....................................................................................37 
8.5 
Recording of Adverse Events ..........................................................................37 
8.6 
Recording of Serious Adverse Events .............................................................38 
8.7 
Reporting of Serious Adverse Events ..............................................................38 
8.8 
Pregnancy .........................................................................................................38 
8.9 
Appropriateness of Measurements ...................................................................39 
9 
PLANNED STATISTICAL METHODS ..............................................................40 
9.1 
General Considerations ....................................................................................40 
9.2 
Determination of Sample Size .........................................................................40 
9.3 
Analysis Populations ........................................................................................40 
9.4 
Demographics and Baseline Characteristics ....................................................40 
9.5 
Safety Analyses ................................................................................................40 
9.6 
Efficacy Analyses ............................................................................................41 
10 
QUALITY CONTROL AND ASSURANCE .......................................................42 
11 
REGULATORY AND ETHICAL CONSIDERATIONS .....................................43 
11.1 
Institutional Review Board ..............................................................................43 
11.2 
Ethical Conduct of the Study ...........................................................................43 
11.3 
Subject Information and Consent.....................................................................43 
11.4 
Subject Confidentiality ....................................................................................43 
12 
ADMINISTRATIVE CONSIDERATIONS ..........................................................44 
12.1 
Access to Source Documentation ....................................................................44 
12.2 
Retention of Data .............................................................................................44 
12.3 
Study Termination ...........................................................................................44 
12.4 
Financial Disclosure.........................................................................................44 
12.5 
Publication and Disclosure Policy ...................................................................44 
13 
REFERENCE LIST ...............................................................................................45 

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14 
APPENDICES .......................................................................................................46 
 
 
 

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List of Appendices 
Appendix 1 
Schedule of Events............................................................................................... 46 
Appendix 2 
Investigational Product Tolerability Visual Analog Scale ................................... 48 
Appendix 3 
Investigational Product ASHRAE 7-Point Comfort Visual Analog Scale .......... 49 
Appendix 4 
Eye Dryness Score Visual Analog Scale ............................................................. 50 
Appendix 5 
Ocular Discomfort Score Visual Analog Scale ................................................... 51 
Appendix 6 
Symptom Assessment in Dry Eye Questionnaire ................................................ 52 
Appendix 7 
Unanesthetized Schirmer’s Test .......................................................................... 53 
Appendix 8 
Fluorescein Solution Administration Using Strips .............................................. 54 
Appendix 9 
Corneal Fluorescein Staining Grading ................................................................. 55 
Appendix 10 
Anesthetized Schirmer’s Test .............................................................................. 56 
Appendix 11 
Sponsor Approval Signature ................................................................................ 57 
Appendix 12 
Investigator’s Signature ....................................................................................... 58 
 
 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition or Explanation 
AE 
adverse event 
ASHRAE 
American Society of Heating, Refrigerating and Air-conditioning Engineers 
BCVA 
best-corrected visual acuity 
C3 
cryosim-3; IVW-1001 
CFS 
corneal fluorescein staining 
DED 
dry eye disease 
eCRF 
electronic case report form 
EDS 
Eye Dryness Score 
EOS 
End of Study 
ET 
Early Termination 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Information Portability and Accountability Act 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IOP 
intraocular pressure 
IP 
investigational product 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
MedDRA 
Medical Dictionary for Regulatory Activities 
MGD 
meibomian gland dysfunction 
mITT 
Modified Intention-to-Treat 
NEI 
National Eye Institute 
NSAID 
nonsteroidal anti-inflammatory drug 
ODS 
Ocular Discomfort Score 
OTC 
over-the-counter 
OU 
oculus uterque; both eyes 
PP 
Per Protocol 
PRN 
pro re nata; as needed 
SAE 
serious adverse event 
SANDE 
Symptom Assessment in Dry Eye 
SD 
standard deviation 
US 
United States 
VA 
visual acuity 
VAS 
visual analog scale 
WOCBP 
women of childbearing potential 

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1 
INTRODUCTION 
In 2017, the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS-DEWS II) defined 
dry eye disease (DED) as “…a multifactorial disease of the ocular surface characterized by a loss of 
homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and 
hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play 
etiological roles” (Craig 2017). TFOS-DEWS II goes on to state, “The management of DED is 
complicated, due to its multifactorial etiology…The ultimate aim of DED management is to restore 
the homeostasis of the ocular surface and tear film, through breaking the vicious cycle of the disease.” 
A wide range of treatments are available based upon the nature and severity of the patient’s DED. 
Management of DED generally begins with conventional, low-risk self-administered therapies, 
including over-the-counter (OTC) lubricant eye drops, and progresses to more advanced therapies as 
severity increases (Craig 2017). However, many patients are still not optimally treated despite the 
availability of numerous approved therapeutic products.  
As recently reviewed, researchers have discovered that thermal changes at the ocular surface activate 
cool neurons and may affect surface wetness (Yang 2018). TRPM8 receptors, which are located on 
the cornea and eyelid at the base of eyelash follicles (Yang 2017), appear to be first activated after 
evaporation of the tear film (Belmonte 2017); these may be associated with the detection of “dryness” 
on the eye surface (Parra 2014; Quallo 2015). TRPM8 may also be a direct stimulator of tear 
secretion from the lacrimal gland (Parra 2010).  
In order to test this hypothesis, a TRPM8 agonist was synthesized (IVW-1001; cryosim-3; C3; 
1-diisopropyl-phosphinoyl-nonae; Yang 2017). In nonclinical models of mouse DED, single topical 
ocular doses of C3 0.2% showed activity (Yang 2017). IVW-1001 0.2% singly applied ocular 
topically increased tear secretion in healthy rabbits.  
In clinical C3 studies conducted in Korea in subjects with DED, 60 subjects (n=30 per group) 
participated in a single-dose study, and 40 subjects (n=20 per group) completed a 2-week, repeat-dose 
study. Cryosim-3 or vehicle (water) was applied with a cotton gauze pad to upper eyelids of subjects 
with DED (n=30). Cooling sensation, tear film break-up time (TBUT), basal tear secretion, and 
corneal staining were evaluated. Cryosim-3 was then applied 4 times daily (QID) for 2 weeks to 
subjects using a pre-loaded single-unit applicator containing C3 2 mg/mL (0.2%) in water (n=20) or 
water only. After 2 weeks of QID dosing with C3 0.2% as an eyelid wipe, subjects experienced 
improved signs and symptoms relative to the control (water) group (Yang 2017). An open-label, non-
comparative pilot study was also conducted in Korea in 20 subjects with neuropathic ocular pain 
(Yoon 2021). After 1 month of treatment with C3 0.2% eyelid wipes, subjects experienced 
improvement in ocular pain symptoms, quality of life, and Schirmer’s test scores. 
In this protocol, IVW-1001 Ophthalmic Eyelid Wipe is being evaluated for the treatment of subjects 
with DED. The final drug product is a single-use, preservative-free, sterile eyelid wipe that is 
saturated with either C3 0.1% ophthalmic solution, C3 0.2% ophthalmic solution, or a vehicle 
ophthalmic solution on a polyester cloth. Two wipes (1 for each eye) are sealed into a glass vial. Also 
provided are tweezers to extract the wipe from the vial. IVW-1001 is a new drug substance, and there 
is no previous human experience in the United States (US).  
 
1.1 
Indication 
In this clinical trial, the population to be studied is subjects with DED confirmed by Screening Visit 1 
assessments. 
 

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1.2 
Investigational Products 
IVW-1001 Ophthalmic Eyelid Wipe is a single-use, preservative-free, sterile eyelid wipe that is 
saturated with C3 0.1% ophthalmic solution, C3 0.2% ophthalmic solution, or a vehicle ophthalmic 
solution on a polyester cloth. Two wipes (1 for each eye) are sealed into a glass vial. Also provided 
are tweezers to extract the wipe from the vial.  
 
1.3 
Nonclinical Experience 
Please see the Investigator’s Brochure for this information.  
 
1.4 
Clinical Experience 
IVW-1001 is a new drug substance, and there is no previous human experience in the US. 
 
1.5 
Risks and Benefits 
Based upon previous human evaluation and this class of compounds, the primary potential risk of 
IVW-1001 is ocular discomfort. The potential benefits are improvements in signs and symptoms of 
ocular surface disease.  

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2 
STUDY OBJECTIVES AND MEASURES 
2.1 
Objective  
The objectives of this study are to assess the safety and efficacy of IVW-1001 Ophthalmic Eyelid 
Wipe in subjects with DED. 
 
2.2 
Measures 
2.2.1 
Safety 
The primary safety measures are: 
• 
Mean change from baseline in:  
o Best-corrected visual acuity (BCVA) 
o Slit lamp biomicroscopy 
o Intraocular pressure (IOP) 
o Dilated ophthalmoscopy 
• 
Visual analog scale (VAS) of investigational product (IP) tolerability  
• 
Adverse events (AEs)  
 
2.2.2 
Efficacy 
The primary efficacy endpoint is  
• 
Mean change from baseline at Day 29 (Week 4/End of Study [EOS]) in the study eye in 
unanesthetized Schirmer’s test  
The exploratory efficacy endpoints are: 
• 
Mean change from baseline in: 
o Unanesthetized Schirmer’s test (Weeks 1, 2, and 3) 
o Visual analog scale of IP comfort (ASHRAE 7-Point Scale) 
o Visual analog scale of Eye Dryness Score (EDS) 
o Visual analog scale of Ocular Discomfort Score (ODS) 
o Symptom Assessment in Dry Eye (SANDE) questionnaire 
o Corneal fluorescein staining (inferior zone) 
o Corneal fluorescein staining (total of all zones) 
o Anesthetized Schirmer’s test 
• 
Proportion of subjects ≥10 mm increase in unanesthetized Schirmer’s test score 
• 
Proportion of subjects ≥10 mm increase in anesthetized Schirmer’s test score 

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3 
INVESTIGATIONAL PLAN 
This study will be conducted in strict accordance with the Council for International Organizations of 
Medical Sciences International Ethical Guidelines, International Council for Harmonisation of 
Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Good Clinical 
Practice (GCP) guidelines, and all applicable laws and regulations.  
 
3.1 
Overall Study Design 
This is a randomized (1:1:1), multicenter, parallel, vehicle-controlled, double-masked study to 
evaluate the safety, tolerability, and efficacy of IVW-1001 Ophthalmic Eyelid Wipes in subjects with 
DED. Treatments will be IVW-1001 Ophthalmic Eyelid Wipe 0.2% (high dose), IVW-1001 0.1% 
(low dose), or IVW-1001 Ophthalmic Eyelid Wipe Placebo (vehicle). Subjects will participate in a 
7-day, single-masked vehicle run-in period followed by a 28-day, double-masked treatment period. 
 
3.2 
Number of Subjects 
A total of approximately 150 subjects are planned to be randomized.  
 
3.3 
Study Duration 
The study is divided into 2 periods: 
• 
Seven-day, single (subject)-masked vehicle run-in period  
• 
Twenty-eight–day, active, double-masked treatment period commencing on Day 1, when the 
assigned treatment will be administered 
 
3.4 
Rescue Treatment 
Subjects will not be eligible to receive rescue treatment during the study.  
 
3.5 
Study Treatments 
This study will evaluate IVW-1001 Ophthalmic Eyelid Wipe 0.2% and IVW-1001 Ophthalmic Eyelid 
Wipe 0.1% compared to IVW-1001 Ophthalmic Eyelid Wipe Placebo (vehicle) for the treatment of 
DED.  
3.6 
Rationale for Study Design and Control Group 
This Phase 1/2a study, which utilizes a vehicle comparator design, will evaluate the safety, 
tolerability, and efficacy of 2 different concentrations of IVW-1001 in a population of subjects with 
active DED to inform the clinical development of IVW-1001 Ophthalmic Eyelid Wipes.  
This study includes treatment-experienced subjects, particularly those with a prior suboptimal 
response to artificial tear therapy. 
 
3.7 
Dose and Dosing Regimen 
This study assesses twice daily (BID) administration to the upper eyelid of both eyes of 2 different 
doses of the IVW-1001 Ophthalmic Eyelid Wipe compared to vehicle. Subjects are not to use wipes 

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the morning of Visits 3 (Day 8), 4 (Day 15), 5 (Day 22), or 6 (Day 29), as they will be used during the 
visit. 
 
3.8 
Study Oversight 
Study oversight will be the responsibility of the Sponsor, in conjunction with the clinical trial contract 
research organization and the study medical monitor. 
 

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STUDY POPULATION SELECTION AND WITHDRAWAL 
4.1 
Study Population 
The subject population to be studied is comprised of subjects with DED confirmed at the Screening 
Visit who, after a 7-day, single (subject)-masked vehicle run-in period, continue to meet eligibility 
requirements at the Baseline Visit. 
Subjects will be recruited from among the population of individuals with DED within the clinical 
practices of study Investigators and from among treatment-experienced patients with DED referred to 
the clinical practices of study Investigators. Potential subjects will be identified by appropriate study 
site personnel and will be approached by care providers known to the patients to discuss study 
participation. Patients who are potentially eligible for the clinical study will be referred to the study 
for screening and formal determination of study eligibility.  
 
4.2 
Inclusion Criteria 
Each subject must meet the following criteria to be randomized in this study. 
1. Subjects of any gender at least 18 years of age at the Screening Visit 
2. Able to voluntarily provide written informed consent to participate in the study 
3. Able and willing to comply with all study procedures and restrictions, follow study 
instructions, and complete required study visits 
4. Self-reported diagnosis of DED in one or both eyes 
5. Best-corrected visual acuity (VA) +0.70 logMAR (Snellen equivalent 20/100) or better in 
each eye at the Screening Visit 
6. For women of childbearing potential (WOCBP), confirmed negative pregnancy test at the 
Screening Visit and the Baseline Visit, not nursing a child, and willing to comply with one of 
the acceptable methods of birth control described in the protocol (see Section 7.2.1) 
7. History (by subject recollection) of artificial tear use within 30 days prior to the Screening 
Visit  
8. Willingness to suspend use of artificial tears during study participation 
9. Willingness to suspend use of contact lenses during study participation 
10. Able to demonstrate adequate self-administration of the run-in eyelid wipe to upper eyelid at 
the Screening Visit 
11. Unanesthetized Schirmer’s test score between 5 and 10 mm (inclusive) in at least 1 eye (same 
eye) at the Screening Visit and the Baseline Visit 
12. Total corneal fluorescein staining score between 5 and 13, representing the sum of scores of 
all 5 regions (inferior, superior, nasal, temporal, and central) using the National Eye Institute 
(NEI) grading system (0-4 scale) at the Screening Visit and the Baseline Visit 
13. Eye Dryness Score VAS ≥40 at the Screening Visit and the Baseline Visit, with ≤20 units of 
improvement from the Screening Visit to the Baseline Visit 
 
4.3 
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from randomization. 

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Ocular history – medical 
1. Corneal fluorescein staining score of 4 in either eye in any zone using the NEI grading 
system at either the Screening Visit or the Baseline Visit 
2. Intraocular pressure ≥23 mmHg in either eye at either the Screening Visit or the Baseline 
Visit  
3. History of glaucoma or ocular hypertension in either eye requiring past or current medical or 
surgical intervention 
4. History of contact or scleral lens use in either eye within 30 days prior to the Screening Visit 
or anticipated use during the study 
5. Subjects with ocular inflammatory conditions (eg, conjunctivitis, keratitis, severe anterior 
blepharitis, etc.) not related to DED at the Screening Visit or the Baseline Visit 
6. Suspected ocular fungal, viral, or bacterial infection at the Screening Visit or the 
Baseline Visit. Note: Mild blepharitis is permitted 
7. Presence of trigger factors that, in the opinion of the Investigator, may confound the study 
data, including but not limited to conjunctivochalasis, allergic conjunctivitis, trichiasis, 
epithelial basement membrane dystrophy, infectious keratitis, or conjunctivitis 
Ocular history – surgical/procedural 
8. Routine use (as defined by the Investigator) of lid hygiene products (warm compresses, 
medicinal eyelid wipes, eyelid scrubs, mechanical eyelid cleaning therapy) within 30 days 
prior to the Screening Visit or inability or unwillingness to withhold use during study 
participation. Note: Makeup removal products are permitted  
9. Treatments for meibomian gland dysfunction (MGD) within 30 days prior to the Screening 
Visit or anticipated use during the study, including but not limited to thermal pulsation 
(Lipiflow®, iLux2®), debridement of lid margin (BlephEx®), moisture chamber goggles, or 
thermal application (MiBoFlo Thermoflo®, TearCare®) 
10. Cauterization of the punctum within 90 days prior to the Screening Visit or anticipated during 
study participation 
11. Non-dissolvable punctal plugs inserted within 90 days prior to the Screening Visit or, in the 
opinion of the Investigator, considered unstable and likely to become displaced 
12. Long-term dissolvable punctal plugs inserted within 90 days prior to the Screening Visit 
Prior medications and therapies in either eye 
13. Use of artificial tears within 2 hours prior to the Screening Visit or anticipated use during 
study participation 
14. Use of the following therapies within 30 days prior to the Screening Visit or anticipated use 
during study participation: 
a. Topical cyclosporine (Restasis®, Cequa®, or Vevye™ [previously known as 
CyclASol®]) 
b. Topical brimonidine (prescription or OTC) 
c. Topical lifitegrast (Xiidra®) 
d. Topical perfluorohexyloctane (Miebo™) 
e. Topical ocular corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) 

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f. Any other prescription or OTC topical eye lid (including wipes) or ocular medications 
for DED and/or MGD or any other indication that, in the opinion of the Investigator, 
might interfere with study assessments 
 
Prior non-ocular medications  
15. Use of medications for the treatment of DED and/or MGD such as oral tetracyclines, oral 
tetracycline derivatives, oral or topical macrolides (such as azithromycin), and oral retinoids 
(Note: Current or past isotretinoin use is exclusionary) within 30 days prior to the Screening 
Visit or anticipated use during the study 
16. Initiation, discontinuation, or change in dosing of any systemic corticosteroid within 30 days 
prior to the Screening Visit or an anticipated change in dosage during the study 
a. Topical non-ocular dermal corticosteroids may be used up to 3 times per week in no 
more than 3 locations simultaneously. No periocular use is permitted 
b. Intranasal corticosteroids are permitted with a stable dosing history during the 30 days 
prior to the Screening Visit and without an anticipated change in dosage during the 
study 
17. Use of NSAIDs, including aspirin, unless: 
a. Used with a stable dosing history during the 30 days prior to the Screening Visit 
without an anticipated change in dosage during the study 
b. Used as needed (PRN) no more than 3 times weekly  
c. Note: Acetaminophen has no restrictions on its use 
18. Initiation, discontinuation, or change in dose of a systemic medication (oral or topical) known 
to cause ocular drying (eg, antihistamines or tricyclic antidepressants) within 30 days prior to 
the Screening Visit or an anticipated change in dosage during the study. Note: These agents 
are permitted when used PRN to treat insomnia 
19. Initiation, discontinuation, or change in dose of any systemic immunomodulator (eg, 
hydroxychloroquine, methotrexate, cyclosporine) within 30 days prior to the Screening Visit 
or an anticipated change during the study. Note: Treatment with vaccines is allowed during 
study participation 
20. Use of Tyrvaya® (varenicline solution, nasal spray) within 30 days prior to the Screening 
Visit or anticipated use during the study 
21. Any prior use of isotretinoin (Accutane®) or anticipated use during the study  
Systemic conditions or procedures 
22. History of allergic conjunctivitis requiring use of prescription or OTC topical antihistamine 
therapy within the last 14 days 
23. History or presence of significant (in the opinion of the Investigator) systemic (eg, 
cardiovascular, pulmonary, hepatic, renal, hematologic, immunologic) conditions 
24. Any significant physical or mental condition that, in the opinion of the Investigator, could 
interfere with study participation 
25. Any planned surgical procedure that could interfere with study participation 
Lifestyle related 

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26. Participation in any interventional investigational drug or device trial within 30 days prior to 
the Screening Visit 
27. Employed by study site, or an immediate family member of site staff, and directly involved in 
clinical activities related to this study 
 
4.4 
Discontinuation of Treatment and Withdrawal of Subjects  
The Investigator may withdraw a subject from the study for any of the following reasons: 
• 
A serious or intolerable AE occurs 
• 
A clinically significant change in systemic health 
• 
The Sponsor or Investigator terminates the study 
• 
The subject requests to be discontinued from the study 
Withdrawal of subjects from the study will occur with completion of an Early Termination (ET) Visit 
to collect EOS data. 
Subjects who use prohibited concomitant medications during the study will not be withdrawn from 
the trial. The data from subjects who use prohibited concomitant medications during the study will be 
included in the Modified Intention-to-Treat (mITT) analysis and excluded from the per-protocol 
analysis. 
 
4.4.1 
Early Termination Visit 
Subjects who are withdrawn from the study should complete an ET Visit, with assessments 
completed in a comparable manner to an EOS Visit. 
 
4.5 
Subject Replacement 
Subjects who are withdrawn from the study will not be replaced.  

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5 
STUDY TREATMENTS 
5.1 
Investigational Products 
The IPs to be administered in this study are IVW-1001 Ophthalmic Eyelid Wipe 0.1%, IVW-1001 
Ophthalmic Eyelid Wipe 0.2%, and IVW-1001 Ophthalmic Eyelid Wipe Placebo (hereinafter vehicle) 
for eyelid application.  
Each unit dose will contain 2 polyester wipes saturated with a solution containing active ingredient 
(except vehicle, which contains no active ingredient), sodium hyaluronate, mannitol, and water for 
injection in a clear glass bottle. 
One unique wipe will be used for the application to the upper eyelid of each eye, moving in a nasal to 
temporal direction while applying modest pressure. 
 
5.2 
Packaging and Labeling 
Two polyester IVW-1001 Ophthalmic Eyelid Wipes (0.1% or 0.2%) are contained within each 20 mL 
clear glass bottle. The sterile, packaged bottles are contained within secondary packaging―a white 
carton with a unique identifier for IP for tracking and dispensing purposes―that does not reveal the 
specific identity of the IP. The cartons are contained within a larger kit package―a white carton with 
a unique identifier for tracking and dispensing purposes. 
Vehicle is packaged and labeled in the same manner as IVW-1001 Ophthalmic Eyelid Wipes 0.1% 
and 0.2%.  
Collectively, this approach will avoid revealing the specific identity of the IP (IVW-1001 Ophthalmic 
Eyelid Wipe 0.1%, IVW-1001 Ophthalmic Eyelid Wipe 0.2%, or vehicle) by the external appearance 
or external labeling of the packaging, ensuring that study personnel are not unmasked in the handling 
of the packaged drug products.  
Separately, subjects will be provided with tweezers to aid in removing the wipes from the vial and 
decapper pliers (or similar) to aid in removing the rubber stoppers and aluminum-plastic caps. 
 
5.3 
Supply, Storage, and Administration of Investigational Product 
5.3.1 
Supply 
Investigational products will be supplied to study sites in the packaging described above by an IP 
distribution vendor. Study site personnel will be responsible for receiving and recording the 
identification numbers and dates received for all IPs, and the supply will be masked as described 
above using appropriate packaging without identifying names or attributes and by use of appropriate 
unique identifiers on the external packaging. 
 
5.3.2 
Storage 
Investigational product and comparator control are to be stored within the refrigerated (between 2°C 
and 8°C inclusive) temperature range at all times prior to dispensation to subjects. After dispensation 
to the subject, store IP at room temperature for up to 30 days. 
 

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5.3.3 
Administration  
Upon qualification, study site personnel will dispense vehicle using the Interactive Web Response 
System (IWRS) to each subject for the run-in period. Upon randomization, study site personnel will 
dispense IP (IVW-1001 Ophthalmic Eyelid Wipe 0.1%, IVW-1001 Ophthalmic Eyelid Wipe 0.2%, or 
vehicle) using the IWRS to each subject for the treatment period. 
Site personnel will instruct subjects verbally on the eyelid administration procedures and frequency of 
use and provide written instructions that will document use of 1 unique wipe for application to the 
upper eyelid of each eye, moving in a nasal to temporal direction while applying modest pressure. 
Subjects will be instructed about best practices, i.e., storing IP with bottle cap positioned upwards, 
and shaking the IP bottle approximately 10 times prior to use. Subjects will be instructed to wait at 
least 15 minutes after eye makeup removal before application of the IP. Site personnel will oversee 
the first IP use while the subject is at the site. 
Subjects are not to use wipes the morning of Visits 3 (Day 8), 4 (Day 15), 5 (Day 22), or 6 (Day 29).  
 
5.4 
Accountability, Retention, and Destruction (or Return) 
Investigational products will be tracked at the study site. Subjects will be instructed to replace used IP 
wipes into the clear glass bottles and to retain all used vials. Subjects will be instructed to return all 
used and unused vials to the investigational site at each visit. Each subject’s returned used and unused 
vials will be counted as a surrogate measure of compliance. Subjects will be queried as to how many 
doses they recall missing since the prior visit. 
Unused IP unit packaging will be maintained at the site until the conclusion of the study, when 
appropriate destruction and disposal instructions will be provided. Study site personnel will be 
required to maintain drug accountability records as per GCP requirements for study record 
maintenance. 

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ALLOCATION AND DOSING OF INVESTIGATIONAL PRODUCT 
6.1 
Allocation to Treatment Groups 
After the vehicle run-in period, during which all subjects receive vehicle, qualified subjects will be 
randomized 1:1:1 to 1 of 3 treatment groups to receive one of the following: IVW-1001 Ophthalmic 
Eyelid Wipe 0.1%, IVW-1001 Ophthalmic Eyelid Wipe 0.2%, or vehicle. 
 
6.1.1 
Subject Assignment 
All subjects will receive the same vehicle control run-in at the Screening Visit (single-masked), and at 
the Baseline Visit, subjects will receive and be dispensed IP according to the treatment group to 
which they are assigned. 
 
6.1.2 
Study Eye Selection 
The study eye will be designated by Data Management at randomization at the Baseline Visit. If both 
eyes have an unanesthetized Schirmer’s test score between 5 and 10 mm inclusive, the study eye will 
be the one with the lower score. If both eyes have the same an unanesthetized Schirmer’s test score, 
the study eye will be the one with the highest qualifying total CFS score. However, if both eyes have 
the same total qualifying CFS score, the right eye will be designated as the study eye. Site personnel 
are not required to designate the study eye. 
Note that dosing of study medication will be in both eyes (OU). 
 
6.1.3 
Randomization Procedures 
Central randomization using the IWRS will be utilized to provide assignment of a specific 
anonymized code, corresponding to vehicle during the run-in period at the Screening Visit and 
separately to the IP to which the subject is randomized (IVW-1001 Ophthalmic Eyelid Wipe 0.1%, 
IVW-1001 Ophthalmic Eyelid Wipe 0.2%, or vehicle) at the Baseline Visit.  
Trial treatment randomization codes and procedures for breaking codes will be maintained by the 
central randomization provider.  
 
6.1.4 
Masking 
6.1.4.1 
Masking Method 
Specific procedures used for masking include anonymized codes and barcoding of IP without 
identifiable names, marking, or labels.  
In rare cases, masking can be broken for an individual subject in the event of an unexpected serious 
adverse event (SAE) necessitating identification of the specific IP received. 
 
6.1.4.2 
Emergency Unmasking 
Only in case of medical emergency or occurrence of SAEs will the code be unmasked via the central 
randomization service. The code may then be made available to the Investigator, the Sponsor, and/or 
other personnel involved in the monitoring or conduct of this study as applicable. 

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PERMITTED MEDICATIONS AND THERAPIES AND CONTRAINDICATIONS 
7.1 
Concomitant Therapy 
Ongoing medications are concomitant from the Screening Visit until the final study visit. 
 
7.1.1 
Permitted Therapies 
Subjects are permitted to take necessary prescription and OTC systemic medications for the 
management of ongoing medical conditions unless prohibited by specific exclusion criteria. 
• 
Intranasal corticosteroids with a stable dosing history during the 30 days prior to the 
Screening Visit without an anticipated change in dosage during the study are permitted 
• 
Nonsteroidal anti-inflammatory drugs, including aspirin, with a stable dosing history during 
the 30 days prior to Screening Visit 1 without an anticipated change in dosage during the 
study are permitted. As-needed use is permitted if no more than 3 doses weekly are used 
• 
Acetaminophen has no restrictions on its use 
 
7.1.2 
Prohibited Ocular Medications and Therapies 
Subjects are not permitted to the following ocular medications and/or therapies during study 
participation and for specified periods of time noted below prior to the Screening Visit since usage 
could confound the study assessments. 
Within 30 days prior to the Screening Visit and during study participation: 
• 
Lid hygiene products (warm compresses, medicinal eyelid wipes, eyelid scrubs, mechanical 
eyelid cleaning therapy). Note: Makeup removal products are permitted  
• 
MGD treatments including but not limited to thermal pulsation (Lipiflow®, iLux2®), 
debridement of lid margin (BlephEx®), moisture chamber goggles, or thermal application 
(MiBoFlo Thermoflo®, TearCare®) 
• 
Cauterization of the punctum 
• 
Topical cyclosporine (Restasis, Cequa, or Vevye) 
• 
Topical brimonidine (prescription or OTC) 
• 
Topical lifitegrast (Xiidra) 
• 
Topical perfluorohexyloctane (Miebo) 
• 
Topical ocular corticosteroids or NSAIDs 
• 
Any other prescription or OTC topical eye lid (including wipes) or ocular medications for 
DED or MGD or any other indication that, in the opinion of the Investigator, might interfere 
with study assessments 
 
7.1.3 
Prohibited Non-ocular Therapies 
Subjects are not permitted to take the following non-ocular medications during study participation 
and for specified periods of time noted below prior to the Screening Visit since usage could confound 
the study assessments. 

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Within 30 days prior to the Screening Visit and during study participation: 
• 
Medications for the treatment of DED or MGD such as oral tetracyclines, oral tetracycline 
derivatives, oral or topical macrolides (such as azithromycin), and oral retinoids 
• 
Medications (oral or topical) known to cause ocular drying (eg, antihistamines or tricyclic 
antidepressants). Note: These agents are permitted when used PRN to treat insomnia. 
• 
Tyrvaya (varenicline solution, nasal spray)  
• 
Isotretinoin (Accutane; any prior use) 
o Topical non-ocular dermal products may be used up to 3 times per week in no more 
than 3 locations simultaneously. No periocular use is permitted 
 
7.1.4 
Concomitant Medication Assessments 
The study site clinical research coordinator will be responsible for recording the subject’s 
concomitant prescription and OTC medication use under the supervision of the Investigator. 
Diagnostic eye drops do not need to be recorded. 
 
7.1.5 
Makeup and Eyelid Hygiene  
Subjects meeting exclusion criterion #5 (ie, unable or unwilling to refrain from eyelid hygiene 
[mechanical cleaning of the lid/lash margin] during study participation) must be excluded from study 
participation. Makeup removal is allowed. Sites should remove any residual eye makeup 20 minutes 
or more prior to study examinations at the beginning of a study visit using the eye makeup remover 
provided by the Sponsor.  
 
7.2 
Lifestyle Restrictions 
7.2.1 
Reproductive Restrictions 
All WOCBP must have a negative urine pregnancy test at the Screening Visit and the Baseline Visit 
prior to randomization in the study and must not intend to become pregnant during the study. 
Women of childbearing potential must use an effective method of birth control during study 
participation. Acceptable methods include the use of at least one of the following: intrauterine device, 
hormonal (oral, injection, patch, implant, ring) contraception, barrier with spermicide (condom, 
diaphragm), a vasectomized partner, or abstinence.  
Refer to Section 8.8 for more information on management of subjects who become pregnant during 
the study or up until 30 days after the last dose of the IP. 
 
7.3 
Informed Consent 
The study will be introduced to potentially eligible treatment-experienced patients with DED by a 
care provider known to the patient. Prior to conducting any screening activities, a complete discussion 
of the purpose of the study, IPs to be tested, and study activities and assessments will be explained 
and reviewed with the patient. The patient will be given ample time to ask any questions and will 
undergo a formal informed consent process, to discuss potential benefits and risks of study 
participation. The patient will sign and receive a copy of an informed consent form (ICF) that was 
approved by the Institutional Review Board (IRB) before any study-specific procedure is performed. 

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An original signed ICF will be retained in the patient’s source documentation at the site and a copy 
will be provided to the patient. 
Written informed consent must be obtained from the patient before any study-related procedures are 
performed, and if there is a change in the study procedures during study participation. 
 
7.4 
Clinical Assessments 
All clinical assessments will be collected as indicated in the Schedule of Events (Appendix 1).  
 
7.4.1 
Demographics 
Demographic data including sex, age, race, and ethnicity will be collected.  
 
7.4.2 
Medical and Ophthalmic History 
A complete medical history that includes all relevant medical and surgical history will be collected. A 
complete ophthalmic history will be collected. 
  
7.4.3 
Prior and Concomitant Medications 
The name, dose, and frequency of all prescription and OTC medications that the subject is taking or 
has taken within 30 days prior to the Screening Visit must be recorded. All allowed and excluded 
medications should be recorded, including all prescription drugs, vitamins, supplements, and OTC 
medications. Generic drug names should be used preferentially. 
  
7.4.4 
Pregnancy Test 
A urine pregnancy test will be performed at the Screening and Baseline Visits for WOCBP. 
 
7.4.5 
In-Office Investigational Product Administration 
Refer to Section 5.3.3 for a description of IP administration procedures. 
IP administration must be performed at least 20 minutes after completion of CFS. 
 
7.4.6 
Investigational Product Tolerability Visual Analog Scale 
Investigational product tolerability will be measured on a scale ranging from 0 (no discomfort) to 100 
(severe discomfort; Appendix 2). Study staff will measure and record the VAS scores. Score cards 
will be retained for measurement confirmation. 
 
7.4.7 
Investigational Product Comfort Visual Analog Scale 
Investigational product comfort will be measured using the American Society of Heating, 
Refrigerating and Air-conditioning Engineers (ASHRAE) 7-point VAS (Beizaee 2012) ranging from 
-3 to +3 (Appendix 3). The assessment will be conducted before IP administration (pre-dose) and 5, 
15, 30, and 60 minutes post-IP administration, unless the score at 5 and 15 minutes is 0, in which case 

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the 30- and 60-minute assessments can be omitted. Study staff will measure and record the VAS 
scores. Score cards will be retained for measurement confirmation. 
 
7.4.8 
Eye Dryness Score Visual Analog Scale 
Eye dryness will be measured using the EDS VAS ranging from 0 to 100 (Appendix 4). Study staff 
will measure and record the VAS scores. Score cards will be retained for measurement confirmation. 
 
7.4.9 
Ocular Discomfort Score Visual Analog Scale 
Ocular discomfort will be measured using the ODS VAS ranging from 0 to 100 (Appendix 5). Study 
staff will measure and record the VAS scores. Score cards will be retained for measurement 
confirmation. 
 
7.4.10 
Symptom Assessment in Dry Eye Questionnaire 
A modified SANDE instrument (Schaumberg, 2007) will be used to evaluate dry eye symptoms 
(Appendix 6). Subjects will respond to separate questions assessing frequency and severity of 
symptoms over the past week. Study staff will measure and record the SANDE. Score cards will be 
retained for measurement confirmation. 
 
7.4.11 
Unanesthetized Schirmer’s Test 
At all visits an unanesthetized Schirmer’s test will be initiated in each eye at least 15 minutes after 
CFS. At Visits 1, 2 and 6 it will be repeated at least 20 ± 5 minutes after IP administration. (Appendix 
7) 
Strips should be placed in each eye, right before left. After placement OU the 5-minute testing period 
will be initiated. Strips will be removed after 5 minutes, and the amount of wetting marked and the 
measurement recorded in mm by comparison to a ruler. Strips should be preserved to allow for 
measurement confirmation. 
 
7.4.12 
Best-Corrected Visual Acuity (and Refraction) 
LogMAR VA must be assessed for each eye using a standard Early Treatment Diabetic Retinopathy 
Study (ETDRS) illuminated chart (on wall or stand) at 4 m. The procedure used will be consistent 
with the recommendations provided for using the ETDRS eye chart, which will be provided 
separately to the clinical site. Visual acuity should be evaluated at the beginning of each visit in the 
study (ie, prior to slit lamp examination). Visual acuity testing should be done with the most recent 
correction. Subjects will undergo manifest refraction at Screening according to the Investigator’s 
standard of care. At any study visit if there is a 3-line or more reduction in VA since the prior BCVA 
was performed, a repeat refraction and BCVA should be performed. 
 
7.4.13 
Slit Lamp Biomicroscopy 
The anterior-segment examination of each eye will be performed according to the Investigator’s usual 
clinical technique. Magnification, lighting, and examiner should be consistent for each subject 
throughout the study. Biomicroscopy should be performed prior to pupil dilation. The examination 
should include an evaluation of the lids, conjunctiva, cornea, anterior chamber, iris/pupil (Screening 

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Visit only), and lens using a 4-point grading scale (0, none; 1, mild; 2, moderate; and 3, severe, as 
applicable).  
 
7.4.14 
Corneal Fluorescein Staining (CFS) 
Sodium fluorescein will be delivered according to the instructions in into the conjunctival cul-de-sac 
of each eye followed by adequate blinking (Appendix 8). Staining will be measured 2 to 2½ minutes 
after instillation using the cobalt blue light of the slit lamp and a yellow Tiffen lens (Appendix 9). The 
modified NEI Grading Scale will be used to grade each of the 5 corneal zones using a 0 to 4 scale 
(Lemp 1995). The Investigator must review the grading scale at every examination when scoring the 
amount of staining.  
 
7.4.15 
Intraocular Pressure 
All IOP assessments must be measured by Goldmann applanation tonometry. The tonometer 
calibration should be checked for accuracy within 1 month before screening the first subject for the 
study with measurements recorded and filed before the first subject is screened; calibration must be 
checked monthly thereafter throughout the study. Variation within ±2 mmHg is acceptable. The 
fluorescein and anesthetic agents should remain consistent throughout the study. Intraocular pressure 
will be measured following biomicroscopy and always prior to dilation. 
Two consecutive IOP measurements should be taken, with the right eye measured first. The 
applanation probe should be withdrawn between measurements. If the first 2 measurements differ by 
>2 mmHg, a third measurement will be taken. Repeat for the left eye. 
At the Screening Visit, Goldmann applanation tonometry must be performed after the completion of 
the unanesthetized Schirmer’s test and prior to randomization to run-in IP. 
At the Baseline Visit, Goldmann applanation tonometry must be performed after the completion of 
the unanesthetized Schirmer’s test and prior to randomization to IP assignment. 
At Visit 6, Goldmann applanation tonometry must be performed after the completion of the 
anesthetized Schirmer’s test. 
 
7.4.16 
Anesthetized Schirmer’s Test 
 
Five minutes after the instillation of anesthetic drops strips should be placed in each eye, right before 
left. After placement OU the 5-minute testing period will be initiated. Strips will be removed after 5 
minutes, and the amount of wetting marked and the measurement recorded in mm by comparison to a 
ruler. Strips should be preserved to allow for measurement confirmation. 
 
7.4.17 
Fundoscopy (Dilated Ophthalmoscopy) 
Indirect dilated ophthalmoscopy will be performed on all subjects, UNLESS one of the below 
scenarios occur:  
• 
Indirect dilated ophthalmoscopy was performed by a licensed eye professional within 
6 months prior to Visit 1. In that case, it is not necessary to repeat ophthalmoscopy 

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• 
Indirect dilated ophthalmoscopy was performed by a licensed eye professional between 6 and 
12 months prior to Visit 1. In that case, either direct undilated or indirect dilated 
ophthalmoscopy will be performed 
Posterior segment examination of each eye will be performed according to the Investigator’s 
preferred procedure. Magnification, lighting, and examiner should be consistent for each subject 
throughout the study. Ophthalmoscopy should be performed after pupil dilation. The examination 
should include evaluation and grading of the vitreous, macula, retinal vessels, peripheral retina, and 
optic disc using a normal/abnormal grading scale, as applicable.  
 
7.4.18 
Adverse Events  
At each visit, the subject should be asked general questions such as, “How are you/your eyes feeling 
today? Have you had any changes since the last study visit?” 
Any AE occurring after the first dose of IP will be recorded as an AE. Adverse events occurring 
during the Screening Visit prior to the first dose of IP will be noted in the medical history. 
 
7.5 
Study Activities 
The Schedule of Events (Appendix 1) outlines the below events and procedures. 
 
7.5.1 
Screening Visit (Day -7 to 1 +2 days) 
Procedures should be conducted in the following order: 
• Informed consent 
• Eligibility determination 
• Demographics 
• Medical/Ophthalmic history 
• Concomitant medications  
• Urine pregnancy test (WOCBP only) 
• Eye Dryness Score VAS  
• Ocular Discomfort Score VAS 
• Investigational product ASHRAE 7-point comfort VAS (pre-dose) 
• Best-corrected VA and refraction OU 
• Slit lamp biomicroscopy OU 
• Corneal fluorescein staining OU 
• First unanesthetized Schirmer’s test OU (≥15 minutes post-CFS) 
• Intraocular pressure OU 

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• Assign run-in IP (vehicle) 
• In-office IP (vehicle) administration OU (≥20  minutes post-CFS) 
• Investigational product ASHRAE 7-point comfort VAS (5 ±2 minutes post-dose) 
• Symptom Assessment in Dry Eye questionnaire (5 +10 minutes post-dose) 
• Investigational product tolerability VAS (5 +10 minutes post-dose) 
• Investigational product ASHRAE 7-point comfort VAS (15 ±2 minutes post-dose) 
• Second unanesthetized Schirmer’s test OU (≥20 ±5 minutes post-dose) 
• Investigational product ASHRAE 7-point comfort VAS (30 ±5 and 60 ±5 minutes post-dose) 
• Fundoscopy (indirect dilated ophthalmoscopy) OU 
• Dispense run-in vehicle  
• Adverse event assessment 
 
7.5.2 
Baseline/Randomization Visit (Day 1) 
Procedures should be conducted in the following order: 
• Eligibility determination 
• Medical/Ophthalmic history 
• Concomitant medications  
• Collect run-in vehicle/compliance assessment 
• Urine pregnancy test (WOCBP only) 
• Eye Dryness Score VAS 
• Ocular Discomfort Score VAS 
• Investigational product ASHRAE 7-point comfort VAS (pre-dose) 
• Best-corrected VA OU 
• Slit lamp biomicroscopy OU 
• Corneal fluorescein staining OU 
• First unanesthetized Schirmer's test OU (≥15 minutes post-CFS)  
• Anesthetized Schirmer’s test OU 
• Intraocular pressure OU 

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• Randomization 
• In-office IP administration OU (≥20  minutes post-CFS) 
• Investigational product ASHRAE 7-point comfort VAS (5 ±2 minutes post-dose) 
• Symptom Assessment in Dry Eye questionnaire (5 +10 minutes post-dose) 
• Investigational product tolerability VAS (5 +10 minutes post-dose) 
• Investigational product ASHRAE 7-point comfort VAS (15 ±2 minutes post-dose) 
• Second unanesthetized Schirmer’s test OU (≥20 ±5 minutes post-dose)Investigational 
product ASHRAE 7-point comfort VAS (30 ±5 and 60 ±5 minutes post-dose) 
• Anesthetized Schirmer’s test OU (post final Investigational Product ASHRAE 7-point 
comfort VAS) 
• Dispense IP 
• Adverse event assessment 
 
7.5.3 
Visit 3 (Day 8 ±1 day), Visit 4 (Day 15 ±2 days), and Visit 5 (Day 22 ±2 days) 
Procedures should be conducted in the following order: 
• Concomitant medications 
• Collect IP/compliance assessment/dispense IP 
• Eye Dryness Score VAS 
• Ocular Discomfort Score VAS 
• Investigational product ASHRAE 7-point comfort VAS (pre-dose) 
• Best-corrected VA OU 
• Slit lamp biomicroscopy OU 
• Corneal fluorescein staining OU 
• Unanesthetized Schirmer's test OU (≥15 minutes post-CFS) 
• In-office IP administration OU (≥20  minutes post-CFS) 
• Investigational product ASHRAE 7-point comfort VAS (5 ±2 minutes post-dose) 
• Symptom Assessment in Dry Eye questionnaire (5 +10 minutes post-dose) 
• Investigational product tolerability VAS (5 +10 minutes post-dose) 
• Investigational product ASHRAE 7-point comfort VAS (15 ±2 minutes post-dose) 

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• Investigational product ASHRAE 7-point comfort VAS (30 ±5 and 60 ±5 minutes post-dose) 
• Adverse event assessment 
 
7.5.4 
Visit 6/End of Study (Day 29 -3 to +1 days) 
Procedures should be conducted in the following order: 
• Concomitant medications 
• Collect IP/compliance assessment/dispense IP 
• Eye Dryness Score VAS 
• Ocular Discomfort Score VAS 
• Investigational product ASHRAE 7-point comfort VAS (pre-dose) 
• Best-corrected VA OU 
• Slit lamp biomicroscopy OU 
• Corneal fluorescein staining OU 
• First unanesthetized Schirmer's test OU (≥15 minutes post-CFS) 
• In-office IP administration OU (≥20  minutes post-CFS) 
• Investigational product ASHRAE 7-point comfort VAS (5 ±2 minutes post-dose) 
• Symptom Assessment in Dry Eye questionnaire (5 +10 minutes post-dose) 
• Investigational product tolerability VAS (5 +10 minutes post-dose) 
• Investigational product ASHRAE 7-point comfort VAS (15 ±2 minutes post-dose) 
• Second unanesthetized Schirmer’s test OU (≥20 ±5 minutes post-dose) 
• Investigational product ASHRAE 7-point comfort VAS (30 ±5 and 60 ±5 minutes post-dose) 
• Anesthetized Schirmer’s test OU (post final Investigational Product ASHRAE 7-point 
comfort VAS) 
• Intraocular pressure OU to be performed post anesthetized Schirmer’s 
• Adverse event assessment 
 

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8 
ADVERSE EVENTS 
8.1 
Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence in a subject regardless of its causal 
relationship to the IP. An AE can be any unfavorable and unintended sign (including any clinically 
significant laboratory test result), symptom, or disease temporally associated with the use of the IP, 
whether or not it is considered related to IP administration. Included in this definition is any newly 
occurring event or previous condition that has increased in severity or frequency since the 
administration of the IP. 
 
8.2 
Definition of a Serious Adverse Event 
An SAE is any AE occurring at any dose and regardless of causality that: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant incapacity or a substantial disruption of the ability to 
conduct normal life functions 
• 
Is a congenital anomaly or birth defect in an offspring of a subject taking the IP 
• 
Is an important medical event 
The term ‘hospitalization’ refers to any surgery or treatment that requires a formal admission into the 
hospital regardless of length of stay. The term does not include an emergency room visit or admission 
to an outpatient facility.  
The term ‘life-threatening’ refers to an event in which the subject was at immediate risk of death at 
the time of the event. It does not refer to an event that hypothetically might have caused death if it 
were more severe. 
Important medical events are those that may not meet any of the criteria defined above; however, they 
may be considered serious when, based upon appropriate medical judgement, they may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the other outcomes listed 
in the SAE definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
8.3 
Assessment of Relationship to Investigational Product or Procedure 
The Investigator must determine the relationship (if any) between an AE and the IP or procedure, as 
applicable. The Investigator should decide whether, in their medical judgment, there is a reasonable 
possibility that the event may have been caused by the IP (IVW-1001 Ophthalmic Eyelid Wipe) or 
the administration procedure (execution of wiping the upper eyelid with the IP wipe). The 
Investigator should use the following classifications and criteria to characterize the relationship or 
association of the IP or procedure in causing or contributing to the AE:  
• 
Unrelated – This relationship suggests that there is no association between the IP and the 
reported event  

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• 
Related – This relationship suggests that there is a reasonable possibility of association 
between the IP and the reported event 
 
8.4 
Assessment of Severity 
The Investigator must use the following criteria to rate the intensity of the AE as mild, moderate, or 
severe. Adverse events will be reported at the highest intensity experienced.  
• 
Mild: Symptoms causing no or minimal interference with usual social and functional 
activities 
• 
Moderate: Symptoms causing greater than minimal interference with usual social and 
functional activities  
• 
Severe: Symptoms causing inability to perform usual social and functional activities 
 
8.5 
Recording of Adverse Events 
All AEs should be reported starting after the first IP dose is administered (during the run-in period) 
and through 30 days after last dose of IP. The Sponsor may request follow-up on any unresolved AEs 
within 30 days after the final study visit. 
All conditions present prior to receiving the IP should be documented as medical history. Information 
to be collected includes type of event, date of onset, date of resolution, and Investigator-specified 
assessment of severity and relationship to the IP. 
While an AE is ongoing, changes in the severity (eg, worsening and improving) should be noted in 
the source documents but, when documenting the AE, only the total duration and greatest severity 
should be recorded in the electronic case report form (eCRF). Adverse events characterized as 
intermittent require documentation of onset and duration.  
Pre-existing conditions (present before the start of the AE collection period) are considered 
concurrent medical conditions and should NOT be recorded as AEs. If the subject, however, 
experiences a worsening or complication of such a concurrent condition, the worsening or 
complication should be recorded as an AE. The Investigator should ensure that the AE term recorded 
captures the change in the condition (eg, ‘worsening of ……’).  
Each AE should be recorded as a single diagnosis. Accompanying signs (including abnormal 
laboratory test values) or symptoms should NOT be recorded as additional AEs. Changes in 
laboratory test values are only considered to be AEs if they are judged to be clinically significant (ie, 
if some action or intervention is required or if the Investigator judges the change to be beyond the 
range of normal physiological fluctuation). If abnormal laboratory test values are the result of 
pathology for which there is an overall diagnosis (eg, increased creatinine in renal failure), only the 
diagnosis should be reported as an AE.  
Pre-planned elective procedures (surgeries or therapies) known at the time of randomization that are 
performed to manage/treat conditions that existed prior to the subjects’ enrolling in the study (eg, 
elective periodontal surgery, elective hernia repair) should not be recorded as AEs but should be 
documented in the subject’s source documents. If a pre-planned procedure is performed early (eg, as 
an emergency) because the pre-existing condition worsens, the worsening condition should be 
captured as an AE. 
 

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8.6 
Recording of Serious Adverse Events 
The Investigator is responsible for reporting to the Sponsor or designee all SAEs that are observed or 
reported by the subject during the study regardless of their relationship to the IP or their clinical 
significance. All SAEs reported or observed during the study must be followed to resolution or until 
the Investigator deems the event to be chronic or the subject to be stable. The Sponsor or designee 
may contact the Investigator to obtain additional information on any SAE that has not resolved at the 
time the subject completes the study. The Investigator may wish to contact the medical monitor to 
discuss the details of an SAE.  
Medical monitor contact information: 
 
 
 
 
8.7 
Reporting of Serious Adverse Events 
Any AE that the Investigator considers serious according to the previously described criteria must be 
reported within 24 hours from the time when site personnel first learn about the event. Serious AEs 
occurring after the subject receives the first dose of the IP will be reported to the Sponsor or its 
representative. The SAE should be reported using the SAE Report Form within 24 hours of 
knowledge of the event. This can be done by emailing a completed SAE Report Form to:  
 
 
 
   
 
   
 
  
 
   
 
 
 
 
 
Any additional information that becomes available later should be submitted through a follow-up 
report within 1 working day of receipt.  
The Sponsor or designee will notify the regulatory agencies of any fatal or life-threatening 
unexpected events associated with the use of the IP as soon as possible but no later than 7 calendar 
days after the initial receipt of the information. Initial notification will be followed by a written report 
within the timeframe established by the appropriate regulatory agency. For SAEs that do not meet the 
fatal or life-threatening unexpected criteria but are reported to be associated with the use of the IP, the 
Sponsor or designee will notify the appropriate regulatory agencies in writing with the timeframe 
established by those regulatory agencies. The Sponsor or designee will provide copies of any reports 
to regulatory agencies regarding serious and unexpected SAEs to the Investigators for review and 
submission to their IRBs or Ethics Committees.  
 
8.8 
Pregnancy 
If a subject becomes pregnant during the study or up until 30 days after the last dose of the IP, the 
Investigator must notify the Sponsor or its representative immediately. The Pregnancy Report Form 
should be completed within 24 hours of learning of the pregnancy and sent to the Sponsor or its 
representative. The pregnancy should be followed up to determine outcome, including spontaneous or 
voluntary termination, details of the birth, and the presence or absence of any birth defects, congenital 
abnormalities, or maternal and/or newborn complications. Any complications during pregnancy 

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should be recorded as an AE and may constitute an SAE if they fulfill any of the specified criteria for 
an SAE. If upon outcome, the pregnancy meets one of the serious criteria (eg, spontaneous 
miscarriage, congenital anomaly, or birth defect), it will then be considered an SAE and full details 
will be requested. 
 
8.9 
Appropriateness of Measurements 
The measures selected to assess signs and symptoms of DED as well as ocular and systemic safety are 
consistent with standard of care.  
 

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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
The analysis of safety and efficacy will be performed after all subjects have completed the Day 29 
Visit or been discontinued prior to Day 29, and after the study database has been cleaned, verified, 
and locked. It is planned that the data from all clinical sites participating in this study will be 
combined so that the target sample size will be available for analysis. For each efficacy parameter 
measured on a per-eye basis, the primary analysis will be done using data from the study eye (ie, the 
eye that satisfies all of the enrollment criteria). If both eyes satisfy all enrollment criteria, then a 
predefined method will be used to select the study eye (Section 6.1.2). 
Analyses will be implemented using SAS® version 9.4 or later. More details regarding the analysis of 
the safety and efficacy data will be described in the Statistical Analysis Plan. 
 
9.2 
Determination of Sample Size 
Approximately 150 subjects will be enrolled (50/group) in order to obtain approximately 138 subjects 
who complete the study (46/group). For the primary efficacy endpoint, this sample size of 46 subjects 
per group should provide at least 80% power to detect a difference between the placebo group and 
each of the IVW-1001 groups of 3.3 mm or greater, assuming a standard deviation (SD) of 5.0 mm 
and a 0.025 two-sided significance level.  
 
9.3 
Analysis Populations 
The safety and tolerability endpoints will be analyzed using the Safety Set, and the primary and 
secondary efficacy endpoints will be analyzed using the mITT and Per Protocol (PP) Sets. The Safety 
and mITT Sets will include all randomized subjects who receive at least 1 dose of the IP. The PP Set 
will include all randomized subjects who meet all of the enrollment criteria and complete the efficacy 
evaluations at Day 29 without any significant protocol deviations that could impact the integrity of 
the data. As a sensitivity analysis, the primary and secondary efficacy endpoints will be analyzed 
using the PP Set. 
For the Safety Set, subjects will be analyzed in the group according to the treatment received during 
the majority of the study, irrespective of the group to which they were randomized, and no subjects 
will be excluded from this study population because of protocol deviations. For the mITT Set, 
subjects will be analyzed in the group to which they were randomized, irrespective of what they 
actually received, and no subjects will be excluded from this study population because of protocol 
deviations. The analysis sets will be determined prior to unmasking the treatment assignments. 
 
9.4 
Demographics and Baseline Characteristics 
Subject demographic and baseline disease characteristics will be summarized by treatment group for 
all subjects. Continuous variables will be summarized using descriptive statistics (number of subjects, 
mean, SD, median, minimum, and maximum), and categorical variables will be summarized using the 
count and percentage of subjects in each category. 
 
9.5 
Safety Analyses 
The assessment of safety will be based on the summaries of ocular and non-ocular AEs and 
ophthalmic examination findings. Adverse events reported during the study will have their verbatim 

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terms mapped to the corresponding thesaurus terms from the most current version of the Medical 
Dictionary for Regulatory Activities (MedDRA) coding dictionary. All summaries of AEs will be 
based on the assigned MedDRA preferred term and system organ class, and summaries will be given 
for each of the randomized treatment groups. 
Separate summaries of AEs related to treatment (as reported by the Investigator) and by severity will 
be prepared. The number of SAEs will also be presented, and events leading to discontinuation from 
the study will be listed and tabulated. 
Other safety assessments will be presented descriptively (absolute values and changes from baseline). 
These will include BCVA, IOP, slit lamp biomicroscopy, dilated ophthalmoscopy, and tolerability 
assessment. Continuous variables will be summarized by descriptive statistics, and categorical 
variables will be summarized using the count and percentage of subjects in each category. Shift tables 
will be prepared by treatment group showing all categorical changes from baseline to each study visit. 
 
9.6 
Efficacy Analyses  
In this exploratory study, several measures of efficacy are being evaluated at the study visits. The 
populations will include mITT and PP Sets. In general, the high dose (0.2%) will be compared to 
vehicle, then the low dose (0.1%) will be compared to vehicle. The final on-drug visit, Week 4/EOS, 
will be evaluated, and then the other visits. Missing data for the test score will be imputed using last 
observation carried forward. From a statistical perspective, evaluations include: 
• 
Unanesthetized Schirmer’s test (mean change from baseline at Week 4/EOS)  
• 
Unanesthetized Schirmer’s tests (mean change from baseline at Weeks 1, 2, and 3) 
• 
Visual analog scale of IP ASHRAE 7-point comfort (mean change from baseline) 
• 
Visual analog scale of EDS (mean change from baseline) 
• 
Visual analog scale of ODS (mean change from baseline) 
• 
Symptom Assessment in Dry Eye (mean change from baseline) 
• 
Corneal fluorescein staining (inferior zone) (mean change from baseline) 
• 
Corneal fluorescein staining (total of all zones) (mean change from baseline) 
• 
Anesthetized Schirmer’s test (mean change from baseline)  
• 
Anesthetized Schirmer’s test (proportion of subjects with ≥10 mm increase) 
• 
Unanesthetized Schirmer’s test (proportion of subjects with ≥10 mm increase)  
Each endpoint will be presented descriptively by visit (absolute values and changes from baseline as 
appropriate). Variables will be summarized by descriptive statistics (number of subjects, mean, SD, 
median, minimum, and maximum). 
The efficacy parameters will be analyzed using appropriate statistical methods (eg, mixed-effects 
models for repeated measures, analysis of covariance, etc.) to compare IVW-1001 to vehicle. 
Appropriate methods will be used to control the Type I error rate for multiple comparisons of the 
2 dose groups versus the control group. 

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10 QUALITY CONTROL AND ASSURANCE 
Investigators will be trained by the Sponsor or designee prior to conducting study activities and are 
responsible for training site staff to whom they delegate authority to conduct any study-related 
procedures. 
Routine study monitoring will be conducted at each site at appropriate intervals to assure accurate, 
consistent, complete, and reliable data. 
The Sponsor or designee may conduct site quality assurance audits at their discretion. 

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11 REGULATORY AND ETHICAL CONSIDERATIONS 
11.1 Institutional Review Board  
This protocol, the informed consent document, and all subject recruitment or advertising must be 
submitted to the IRB for review and must be approved before clinical use. Any amendments to the 
protocol must also be approved by the IRB prior to implementing changes in study conduct. The 
Investigator is responsible for keeping the IRB apprised of the progress of the study, SAEs, and any 
changes made to the protocol according to the requirements of the site’s IRB. 
 
11.2 Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that have their origins in the 
Declaration of Helsinki and are consistent with ICH/GCP and applicable regulatory requirements. 
 
11.3 Subject Information and Consent 
The subject must sign the ICF before participation in the study; once the ICF is signed, the subject is 
enrolled in the study. A copy of the ICF must be provided to the subject or the subject's legal 
guardian. Each subject will receive oral and written information about the study in their functional 
language, given the opportunity to ask questions, and allowed time to consider the information 
provided. 
 
11.4 Subject Confidentiality 
The information obtained during the conduct of this clinical study is confidential, and disclosure to 
third parties other than those noted below is strictly prohibited. Information obtained during the 
conduct of this study will be used by IVIEW Therapeutics, Inc. in connection with the development 
of the IP. The study Investigator is obliged to provide IVIEW Therapeutics, Inc. or designee with 
complete test results and all data developed in this study. This information may be disclosed to other 
physicians who are participating in this trial, and to the US Food and Drug Administration (FDA) as 
deemed necessary by IVIEW Therapeutics, Inc. Subject-specific information may be provided to 
other appropriate medical personnel only with the subject’s permission. 
Subjects will provide consent to the disclosure of protected health information as required under the 
Health Information Portability and Accountability Act (HIPAA). 

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12 ADMINISTRATIVE CONSIDERATIONS 
12.1 Access to Source Documentation 
Study monitoring visits will be conducted by an authorized Sponsor representative to inspect study 
data, participants’ medical records, and eCRFs in accordance with current GCP and the respective 
local, national government, and international regulations and guidelines. 
The Investigator will permit authorized representatives of the Sponsor or its representative, the FDA, 
and any appropriate health authorities to inspect facilities and records relevant to this study. 
 
12.2 Retention of Data 
The Principal Investigator must maintain all study records according to ICH guidelines and according 
to the record retention policies of the country in which the study is being conducted. The FDA 
requires that records be retained for at least 2 years after the last marketing application approval, or if 
not approved, 2 years after the FDA has been notified of the discontinuance of the investigational use 
of the IP (21 CFR 312.57). 
 
12.3 Study Termination 
This study may be terminated by the Sponsor if deemed appropriate. 
 
12.4 Financial Disclosure 
Investigators will comply with applicable financial disclosure requirements in the country in which 
the study is being conducted. 
 
12.5 Publication and Disclosure Policy 
The Sponsor has proprietary interest in this study. Any authorship and manuscript composition 
resulting from the study will reflect cooperation between the Sponsor and multiple Investigators. 
Authorship will be established prior to the writing of the manuscript. No individual publication will 
be allowed prior to completion of the final study report except as agreed with the Sponsor. 

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13 REFERENCE LIST 
Beizaee A, Firth SK, Vadodaria K, Loveday D. Assessing the ability of PMV model in predicting 
thermal sensation in naturally ventilated buildings in UK. Proceedings of 7th Windsor Conference. 
Windsor, UK; 12–15 April 2012.  
Belmonte C, Nichols JJ, Cox SM, Brock JA, Begley CG, Bereiter DA, et al. TFOS DEWS II pain and 
sensation report. Ocul Surf. 2017;15(3):404–37. 
Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II Report Executive Summary. Ocul Surf. 
2017;15(4):802–12. 
Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. 
CLAO J 1995;21(4):221–32. 
Parra A, Gonzalez-Gonzalez O, Gallar J, Belmonte C. Tear fluid hyperosmolality increases nerve 
impulse activity of cold thermoreceptor endings of the cornea. Pain. 2014;155:1481–91. 
Parra A, Madrid R, Echevarria D, del Olmo S, Morenilla-Palao C, Acosta MC, et al. Ocular surface 
wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea. Nat Med. 
2010;16:1396–9. 
Quallo T, Vastani N, Horridge E, Gentry C, Parra A, Moss S, et al. TRPM8 is a neuronal osmosensor 
that regulates eye blinking in mice. Nat Commun. 2015;6:7150. 
Schaumberg DA, Gulati A, Mathers WD, et al. Development and validation of a short global dry eye 
symptom index. Ocul Surf. 2007;5(1):50–7.  
Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II Diagnostic Methodology report. Ocul Surf. 
2017;15(3):539–74. 
Yang JM, Li F, Liu Q, Ruedi M, Wei ET, Lentsman M, et al. A novel TRPM8 agonist relieves dry 
eye discomfort. BMC Ophthalmol. 2017;17(1):101. 
Yang JM, Wei ET, Kim SJ, Yoon KC. TRPM8 channels and dry eye. Pharmaceuticals (Basel). 
2018;11(4):125. 
Yoon HJ, Kim J, Yang JM, Wei ET, Kim SJ, Yoon KC. Topical TRPM8 agonist for relieving 
neuropathic ocular pain in patients with dry eye: A pilot study. J ClinMed. 2021;10(2):250. 

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14 APPENDICES 
Appendix 1 
Schedule of Events 
Study Period 
Screening [a] 
Baseline/ 
Randomization [b] 
Week 1 [b] Week 2 [b] Week 3 [b] 
Week 4/ 
EOS/ET [b] 
Visit 
1 
2 
3 
4 
5 
6 
Procedures         Visit Timing (Window) Day -7 to 1 (+2) 
Day 1 
Day 8 (±1) Day 15 (±2) Day 22 (±2) Day 29 (-3 to +1) 
Informed consent 
X 
 
 
Eligibility determination 
(inclusion/exclusion criteria) 
X 
X 
 
 
Demographics 
X 
 
 
 
 
 
Medical/Ophthalmic history 
X 
X 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
Urine pregnancy test (WOCBP only [c]) 
X 
X 
 
 
EDS VAS  
X 
X 
X 
X 
X 
X 
ODS VAS  
X 
X 
X 
X 
X 
X 
IP ASHRAE 7-point comfort VAS [d] 
X 
X 
X 
X 
X 
X 
BCVA (and refraction [e]) OU 
X 
X 
X 
X 
X 
X 
Slit lamp biomicroscopy OU 
X 
X 
X 
X 
X 
X 
Corneal fluorescein staining OU 
X 
X 
X 
X 
X 
X 
Unanesthetized Schirmer’s test OU [f, g] 
X [f, g] 
X [f, g] 
X [f] 
X [f] 
X [f] 
X [f, g] 
Anesthetized Schirmer’s test OU [h, i] 
 
X [h, i] 
 
 
 
X [i] 
IOP OU 
X 
X 
 
 
 
X [j] 
Randomization/assignment 
X[k] 
X 
 
 
In-office IP administration OU [l] 
X 
X [l] 
X [l] 
X [l] 
X [l] 
X [l] 
SANDE questionnaire [m] 
X 
X 
X 
X 
X 
X 
IP tolerability VAS [m]  
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Fundoscopy (dilated ophthalmoscopy) OU 
X 
 
X 
Dispense/Return IP with 
accountability/compliance 
X 
X 
X 
X 
X 
X 

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Study Period 
Screening [a] 
Baseline/ 
Randomization [b] 
Week 1 [b] Week 2 [b] Week 3 [b] 
Week 4/ 
EOS/ET [b] 
Visit 
1 
2 
3 
4 
5 
6 
Procedures         Visit Timing (Window) Day -7 to 1 (+2) 
Day 1 
Day 8 (±1) Day 15 (±2) Day 22 (±2) Day 29 (-3 to +1) 
AE assessment 
X 
X 
X 
X 
X 
X 
AE, adverse event; BCVA, best-corrected visual acuity; EDS, Eye Dryness Score; EOS, End of Study; ET, Early Termination; IOP, intraocular pressure; IP, investigational 
product; ODS, Ocular Discomfort Score; OU, both eyes; SANDE, Symptom Assessment in Dry Eye; VAS, visual analog scale; WOCBP, women of childbearing potential. 
[a] The Screening Visit can occur any time of the day. 
[b] The Baseline, Week 1, Week 2, Week 3, and EOS Visits should be conducted between 7:00 am and 12:00 pm. 
[c] All WOCBP must have a negative pregnancy test result at Screening Visit 1 and Baseline Visit 2 prior to randomization in the study. 
[d] IP ASHRAE 7-point comfort VAS to be performed pre-dose and 5 ±2, 15 ±2, 30 ±5, and 60 ±5 minutes post-dose, unless the score at 5 and 15 minutes is 0, in which case the 
30- and 60-minute assessments can be omitted. 
[e] Refraction at Visit 1 only unless ≥ 3 line reduction in VA. 
[f] Unanesthetized Schirmer’s to be performed at least 15 minutes post-CFS. 
[g] Unanesthetized Schirmer’s to be performed 20 ±5 minutes post-IP administration. 
[h] Anesthetized Schirmer’s to be performed after unanesthetized Schirmer’s. 
[i] Anesthetized Schirmer’s to be performed post final IP ASHRAE 7-point comfort VAS. [j] IOP to be performed post anesthetized Schirmer’s. 
[k] Assignment of run-in IP (vehicle). 
[l] IP administration must be performed at least 20 minutes after completion of CFS. Subjects should not dose IP at home the morning of Visits 2, 3, 4, 5, or 6. 
 
[m] SANDE questionnaire and IP tolerability VAS to be performed between 5 and 15 minutes post-dose. 
 
 
 
 

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Appendix 3 
Investigational Product ASHRAE 7-Point Comfort Visual Analog Scale 
Representation of the IP ASHRAE 7-Point Comfort VAS. Subjects will rate the comfort of the eyelid 
wipes using the ASHRAE 7-point scale (-3 to +3) by placing a vertical mark on the horizontal line. 
Study staff will measure and record the VAS. 
 
 
 
 
 
 
 

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Appendix 4 
Eye Dryness Score Visual Analog Scale 
Representation of the EDS VAS. Subjects will grade their symptoms on a scale of 0 (no symptoms) to 
100 (severe symptoms) by placing a vertical mark on the horizontal line. Study staff will measure and 
record the VAS score. 
 
 
 

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Appendix 5 
Ocular Discomfort Score Visual Analog Scale 
Representation of the ODS VAS. Subjects will grade their symptoms at this moment on a scale of 0 
(no symptoms) to 100 (severe symptoms) by placing a vertical mark on the horizontal line. Study 
staff will measure and record the VAS score. 
 
 
 
 
 

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Appendix 7 
Unanesthetized Schirmer’s Test 
Initiate unanesthetized Schirmer’s Test in each eye at least 15 minutes after CFS at all visits. 
At Visits 1, 2, and 6 initiate additional unanesthetized Schirmer’s test OU at least 20 ±5 minutes after 
Investigational Product dose). 
Unanesthetized Schirmer’s test instructions: 
• 
While still inside the plastic sheath, fold the rounded end of the Schirmer’s test strip at the 
first line on the strip (closest to the rounded end). 
• 
Remove the right eye strip from the sheath. 
• 
Ask the subject to look up and gently draw the right lower lid of the unanesthetized eye in a 
downward and temporal direction. 
• 
Place the rounded end of the strip toward the temporal one-third of the lower eyelid. 
• 
Repeat this procedure in the left unanesthetized eye. 
• 
Darken the room. 
• 
Instruct the subject to focus on the 20/400 E letter on the eye chart.  
• 
Start the timer. 
• 
Remove strips after 5 minutes. 
• 
After removing the strips, place each strip on a flat surface beside a ruler. 
• 
Visualize the leading edge and the lowest point of moisture and, using the ruler, measure a 
point halfway between the 2 points. Record this value as the amount of wetting. 
• 
Retain Schirmer’s test strips in source documentation for confirmatory measurement 
purposes. 
 
  
 

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Appendix 8 
Fluorescein Solution Administration Using Strips 
Use Sponsor-supplied unpreserved sterile saline (if not available, unpreserved sterile water may be 
used) to moisten the dye on the fluorescein-impregnated strip supplied by the Sponsor. 
Remove any excess fluid by shaking fluid from the strip to ensure a consistent amount of dye is 
dispensed at each assessment.  
Instill the dye onto the inferior cul-de-sac of the first eye by touching the strip to the palpebral 
conjunctiva. Wait approximately 1 minute. Repeat the procedure for the second eye using the same 
strip. Ask the subject to blink several times to spread the dye. 
For corneal fluorescein staining, assess the staining approximately 2 to 2½ minutes after the dye 
instillation. 
The 1-minute waiting period between dye instillation into each eye will allow the evaluator to 
complete the assessment of the first eye before the 2- to 2½-minute waiting period has elapsed after 
dye instillation in the second eye. 
Use a slit lamp with cobalt blue illumination (465–490 nm) and a Wratten #12 yellow filter to 
improve the ability to grade fluorescein staining. Grade the 5 areas of the cornea according to the 
scale for each zone (Appendix 9).  
 
 

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Appendix 9 
Corneal Fluorescein Staining Grading 
This scale is modified from the corneal grading scale presented in the Tear Film & Ocular Surface 
Society Dry Eye Workshop II report (Wolffsohn 2017). 
Expanded NEI/Industry Workshop model (Lemp 1995): 
• 
Cornea is divided into five (5) zones: inferior, nasal, central, temporal, superior; the central 
zone diameter should be 1/3 the cornea diameter with the 4 equally sized outer zones. 
• 
Score each zone using a scale of 0 to 4 based upon the PREDOMINANT finding within the 
zone. Note: The presence of an isolated small area of coalescent staining should be graded 
according to the predominant appearance in the entire zone. 
o 0= 
no staining 
o 1= 
few/rare punctate lesions 
o 2= 
discrete and countable lesions 
o 3= 
lesions too numerous to count, but not coalescent 
o 4= 
coalescent 
• 
Total maximum score equals 20 
 
 
 
 
 
 

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Appendix 10 
Anesthetized Schirmer’s Test 
Perform anesthetized Schirmer’s Test after unanesthetized Schirmer’s Test at Visit 2. 
 
Perform anesthetized Schirmer’s Test after the final IP ASHRAE 7-point comfort VAS (Visits 2 and 
6). 
 
Anesthetized Schirmer’s test instructions: 
• 
Instill proparacaine 0.5% drops bilaterally.  
• 
Blot excess from ocular cul-de-sac and periorbital area; wait 5 minutes. 
• 
While still inside the plastic sheath, fold the rounded end of the Schirmer’s test strip at the 
first line on the strip (closest to the rounded end). 
• 
Remove the right eye strip from the sheath. 
• 
Ask the subject to look up and gently draw the right lower lid of the anesthetized eye in a 
downward and temporal direction. 
• 
Place the rounded end of the strip toward the temporal one-third of the lower eyelid. 
• 
Repeat this procedure in the left anesthetized eye. 
• 
Darken the room. 
• 
Instruct the subject to focus on the 20/400 E letter on the eye chart.  
• 
Start the timer. 
• 
Remove strips after 5 minutes. 
• 
After removing the strips, place each strip on a flat surface beside a ruler. 
• 
Visualize the leading edge and the lowest point of moisture and, using the ruler, measure a 
point halfway between the 2 points. Record this value as the amount of wetting. 
• 
Retain Schirmer’s test strips in source documentation for confirmatory measurement 
purposes. 
 
 

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Appendix 11 
Sponsor Approval Signature 
Study Title: 
Phase 1/2a, Proof-of-Concept, Multicenter, Parallel, Vehicle-Controlled, 
Double-Masked, Randomized Study Evaluating the Safety, Tolerability, 
and Efficacy of IVW-1001 Ophthalmic Eyelid Wipe in Subjects With 
Dry Eye Disease 
Study Number: 
IVW-1001-CS-101 
Version: 
1.1 
Final Date: 
17 April 2024 
 
This clinical study protocol has been approved by the Sponsor. 
 
 
 
 
 
. 
 
 
 

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Appendix 12 
Investigator’s Signature 
Study Title: 
Phase 1/2a, Proof-of-Concept, Multicenter, Parallel, Vehicle-Controlled, 
Double-Masked, Randomized Study Evaluating the Safety, Tolerability, 
and Efficacy of IVW-1001 Ophthalmic Eyelid Wipe in Subjects With 
Dry Eye Disease 
Study Number: 
IVW-1001-CS-101 
Version: 
1.1 
Final Date: 
10 April 2024 
By signing below, the Investigator agrees to adhere to the protocol as outlined and agrees that any 
changes to the protocol must be approved by IVIEW Therapeutics, Inc. prior to seeking approval 
from the Institutional Review Board. 
The Investigator also agrees to conduct the study in accordance with current United States Food and 
Drug Administration regulations, International Council for Harmonisation guidelines, Good Clinical 
Practice standards, the Declaration of Helsinki, and local ethical and legal requirements. 
 
 
 
 
Investigator Signature: 
 
 
 
 
 
Date: 
 
 
 
 
 
Printed Name: 
 
 
 
 
 
Name of Institution: