A Randomized, Double-Masked, Vehicle-Controlled Parallel Group Clinical Trial to Assess Efficacy and Safety of 0.25% Reproxalap Ophthalmic Solution Compared to Vehicle in Subjects With Dry Eye Disease
Phase: PHASE3
Conditions: Dry Eye Disease
Sponsor: Aldeyra Therapeutics, Inc.

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Clinical Trial Protocol: ADX-102-DED-032 
Protocol Title: 
A Randomized, Double-Masked, Parallel-Group, 
Vehicle-Controlled Phase 3 Clinical Trial to 
Assess the Efficacy and Safety of 0.25% 
Reproxalap Ophthalmic Solution Compared to 
Vehicle in Subjects with Dry Eye Disease 
Protocol Number: 
ADX-102-DED-032  
Study Phase: 
3 
Test Article Name: 
0.25% Reproxalap Ophthalmic Solution  
IND Number: 
134734 
Indication: 
Dry Eye Disease 
Sponsor: 
Aldeyra Therapeutics, Inc. 
131 Hartwell Ave. 
Lexington, MA 02421 USA 
IRB/IEC: 
 
 
 
 
 
 
Date 
Original Protocol: 
19Apr2024 
 
 
Confidentiality Statement 
This protocol contains confidential, proprietary information 
 
 and Aldeyra 
Therapeutics, Inc. Further dissemination, distribution, or copying of this protocol or its 
contents is strictly prohibited. 
 

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STUDY PERSONNEL 
SPONSOR PERSONNEL 
Chief Development Officer: 
 
 
 
 
 
Department Senior Vice 
President: 
 
 
 
 
Department Senior Director: 
 
  
 
Clinical Project Manager: 
 
 
 
MEDICAL MONITOR 
Medical Monitor: 
 
 
 
 

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SYNOPSIS 
Protocol Title: 
A Randomized, Double-Masked, Parallel-Group, 
Vehicle-Controlled Phase 3 Clinical Trial to Assess 
the Efficacy and Safety of 0.25% Reproxalap 
Ophthalmic Solution Compared to Vehicle in 
Subjects with Dry Eye Disease 
Protocol Number: 
ADX-102-DED-032 
Test Article: 
0.25% Reproxalap Ophthalmic Solution (reproxalap) 
Study Phase: 
3 
Primary Objective(s): 
 
To evaluate the efficacy of reproxalap, as assessed by 
an ocular symptom during exposure to the 
 
 (CAE) in subjects with dry 
eye disease 
Overall Study Design: 
Structure: 
Double-masked, randomized, parallel-group trial 
Duration: 
Approximately 16-32 days per subject 
Controls: 
Vehicle Ophthalmic Solution (vehicle) 
Dosage: 
Vehicle will be administered once approximately 5 
minutes prior to the CAE entry and once 
approximately 50 minutes after initiation of the CAE 
at Visit 1.  
 
Test article will be dosed topically in both eyes. Test 
article will be administered four times (QID) at Visit 
2. At Visit 3, test article will be administered once 
approximately 5 minutes prior to CAE entry and 
once approximately 50 minutes after initiation of the 
CAE. 
Summary of Visit Schedule: 
Three visits over the course of approximately 2 
weeks: 
• 
Visit 1 = Day -14 -16/+2, screening, vehicle 
CAE  
• 
Visit 2 = Day 1, randomization, QID test article 
administration 
• 
Visit 3 = Day 2,test article CAE, trial exit 
At Visit 2, subjects will be randomized 1:1 to receive 
either reproxalap or vehicle for Visit 2 and Visit 3. 
Measures Taken to Reduce Bias: 
ADX-102-DED-032 is a randomized treatment 
assignment, double-masked trial. 
Study Population Characteristics: 

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7. Use of topical ocular cyclosporine, lifitegrast, or 
corticosteroid within 90 days of Visit 1; 
8. Systemic corticosteroid or other 
immunomodulator therapy (not including 
inhaled corticosteroids) within 14 days of Visit 
1, or any planned immunomodulatory therapy 
throughout the clinical trial;  
9. Planned ocular and/or lid surgeries throughout 
the clinical trial or any ocular surgery within 6 
months of Visit 1; 
10. Temporary punctal plugs during the trial that 
have not been stable within 30 days of Visit 1; 
11. Use of and unwillingness to discontinue topical 
ophthalmic prescriptions (including medications 
for glaucoma) or over-the-counter solutions (not 
including artificial tears), gels, or scrubs for the 
duration of the trial (excluding medications 
allowed for the conduct of the trial); 
12. Corrected visual acuity greater than or equal to 
logarithm of the minimum angle of resolution 
(logMAR) + 0.7 as assessed by Early Treatment 
of Diabetic Retinopathy Study (ETDRS) scale in 
both eyes at Visit 1; 
13. Pregnancy, nursing, or planned pregnancy 
during the conduct of the trial; 
14. Unwillingness to submit a urine pregnancy test 
at Visit 1 and Visit 3 (or early termination visit) 
if of childbearing potential (non-childbearing 
potential is defined as a woman who is 
permanently sterilized [e.g., has had a 
hysterectomy or tubal ligation], or is post-
menopausal [without menses for 12 consecutive 
months].); 
15. If of childbearing potential (female or male), 
unwillingness to use an acceptable means of 
birth control (Acceptable methods of 
contraception include: hormonal – oral, 
implantable, injectable, or transdermal 
contraceptives; mechanical – spermicide in 
conjunction with a barrier such as a diaphragm 
or condom; intrauterine device [IUD]; or 
surgical sterilization of partner. For non-sexually 
active males or females, abstinence may be 
regarded as an adequate method of birth control; 
however, if the subject becomes sexually active 
during the trial, he/she must agree to use 
adequate birth control as defined above for the 
remainder of the trial.); 

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TABLE OF CONTENTS 
Clinical Trial Protocol: ADX-102-DED-032 ....................................................................1 
SYNOPSIS ..........................................................................................................................3 
TABLE OF CONTENTS ..................................................................................................8 
List of Abbreviations .......................................................................................................11 
1 
INTRODUCTION...................................................................................................12 
2 
STUDY OBJECTIVE .............................................................................................13 
3 
CLINICAL HYPOTHESES ..................................................................................13 
4 
OVERALL STUDY DESIGN ................................................................................13 
5 
STUDY POPULATION .........................................................................................13 
5.1 
Number of Subjects (approximate) .............................................................13 
5.2 
Study Population Characteristics ...............................................................13 
5.3 
Inclusion Criteria .........................................................................................13 
5.4 
Exclusion Criteria .........................................................................................14 
5.5 
Withdrawal Criteria (if applicable) ............................................................15 
6 
STUDY PARAMETERS ........................................................................................15 
6.1 
Primary Endpoint .........................................................................................15 
6.2 
Safety Endpoints ...........................................................................................15 
7 
STUDY MATERIALS ............................................................................................16 
7.1 
Study Treatment(s) .......................................................................................16 
7.1.1 
Test Article and Vehicle Packaging Configuration ..........................16 
7.1.2 
Test Article Storage and Accountability ...........................................16 
7.1.3 
Instructions for Dispensation, Use, and Administration ...................16 
7.2 
Other Study Supplies ...................................................................................16 
8 
STUDY METHODS AND PROCEDURES .........................................................17 
8.1 
Subject Entry Procedures ............................................................................17 
8.1.1 
Overview ...........................................................................................17 
8.1.2 
Informed Consent..............................................................................17 
8.1.3 
Washout Intervals .............................................................................17 
8.1.4 
Procedures for Final Study Entry ......................................................17 
8.1.5 
Methods for Assignment to Treatment Groups: ...............................17 
8.2 
Concurrent Therapies ..................................................................................17 
8.2.1 
Prohibited Medications/Treatments ..................................................17 
8.2.2 
Escape Medications ..........................................................................18 
8.2.3 
Special Diet or Activities ..................................................................18 
8.3 
Examination Procedures ..............................................................................18 
8.3.1 
Procedures to be Performed at the Study Visit with Regard to Trial 
Objective(s) ....................................................................................................18 
8.4 
Early Termination/Discontinuation ............................................................19 
8.5 
Schedule of Visits, Measurements, and Dosing .........................................20 
8.5.1 
Scheduled Visits................................................................................20 
8.5.2 
Unscheduled Visits ...........................................................................20 

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8.6 
Subject Disposition .......................................................................................20 
8.6.1 
Completed Subjects ..........................................................................20 
8.6.2 
Discontinued Subjects .......................................................................20 
8.7 
Study Duration .............................................................................................20 
8.8 
Monitoring and Quality Assurance ............................................................20 
9 
ADVERSE EVENTS ..............................................................................................21 
9.1 
Adverse Event ...............................................................................................21 
9.1.1 
Severity .............................................................................................21 
9.1.2 
Relationship to Study Procedures .....................................................21 
9.1.3 
Expectedness .....................................................................................22 
9.2 
Serious Adverse Events ................................................................................22 
9.3 
Procedures for Reporting Adverse Events .................................................23 
9.3.1 
Reporting a Suspected Unexpected Adverse Reaction .....................23 
9.3.2 
Reporting a Serious Adverse Event ..................................................23 
9.4 
Procedures for Unmasking Test Article .....................................................24 
9.5 
Procedures for Reporting Adverse Events .................................................24 
10 
STATISTICAL HYPOTHESES AND METHODS OF ANALYSES................25 
10.1 Analysis Populations ....................................................................................25 
10.2 Statistical Hypotheses ...................................................................................25 
10.3 Sample Size ...................................................................................................25 
10.4 General Considerations ...............................................................................25 
10.5 Unit of Analysis .............................................................................................26 
10.6 Missing Data .................................................................................................26 
10.7 Multiplicity Considerations .........................................................................26 
10.8 Primary Efficacy Analysis ...........................................................................26 
10.9 Safety Variables ............................................................................................27 
11 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES ................................27 
11.1 Protection of Human Subjects.....................................................................27 
11.1.1 Subject Informed Consent.................................................................27 
11.1.2 Institutional Review Board Approval ...............................................28 
11.2 Ethical Conduct of the Clinical Trial .........................................................28 
11.3 Subject Confidentiality ................................................................................28 
11.4 Documentation ..............................................................................................28 
11.4.1 Retention of Documentation .............................................................28 
11.5 Labeling, Packaging, Storage, Accountability, and Return or Disposal of 
Test Article ....................................................................................................29 
11.5.1 Labeling/Packaging...........................................................................29 
11.5.2 Storage of Test Article ......................................................................29 
11.5.3 Accountability of Test Article ..........................................................29 
11.5.4 Return or Disposal of Test Article ....................................................29 
11.6 Recording of Data on Source Documents and Electronic Case Report 
Forms .............................................................................................................29 
12 
REFERENCES ........................................................................................................30 

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Appendix 1: Schedule of Visits and Measurements ......................................................31 
Appendix 2: Prohibited Medications List .............................................................32 
Appendix 3: Examination Procedures, Tests, Equipment, and Techniques .....35 
Appendix 4: Amendment Summary of Changes Table ................................................39 
Appendix 5: Sponsor and
 Approvals .....................................................................40 
Appendix 6: Investigator’s Signature ............................................................................41 
 
 

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List of Abbreviations 
 
 
CFR 
Code of Federal Regulations 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
HIPAA 
Health Information Portability and Accountability Act 
ICF 
informed consent form 
IEC 
Independent Ethics Committee 
IRB 
institutional/independent review board 
ITT 
intent-to-treat 
LogMAR 
logarithm of the minimum angle of resolution 
MMRM 
mixed model repeated measures 
 
 
OTC 
over the counter 
PP 
per protocol 
QID 
four times daily 
RASP 
reactive aldehyde species 
TEAE 
treatment-emergent adverse event 
VAS 
visual analog scale 
 
 

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15. If of childbearing potential (female or male), unwillingness to use an 
acceptable means of birth control. (Acceptable methods of contraception 
include: hormonal – oral, implantable, injectable, or transdermal 
contraceptives; mechanical – spermicide in conjunction with a barrier such 
as a diaphragm or condom; intrauterine device [IUD]; or surgical 
sterilization of partner. For non-sexually active males or females, 
abstinence may be regarded as an adequate method of birth control; 
however, if the subject becomes sexually active during the trial, he/she 
must agree to use adequate birth control as defined above for the 
remainder of the trial); 
16. Known allergy and/or sensitivity to the test article or test article 
components; 
17. A condition that the investigator feels may put the subject at significant 
risk, may confound the trial results, or may interfere significantly with 
participation in the trial; 
18. Current enrollment in an investigational drug or device trial or previous 
use of an investigational drug or device within 30 days of Visit 1; 
 
20. Current use of any medication known to cause ocular drying that is not 
used on a stable dosing regimen for at least 30 days prior to Visit 1; or 
21. Inability or unwillingness to follow instructions, including participation in 
all assessments and visits. 
5.5 
Withdrawal Criteria (if applicable) 
Subjects may voluntarily withdraw from the trial at any time. Additionally, 
subjects may be discontinued for safety reasons as determined by the 
investigator and/or Medical Monitor. 
6 
STUDY PARAMETERS 
6.1 
Primary Endpoint  
Ocular discomfort symptom score (0 – 100 VAS) over 100 minutes in the 
CAE at Visit 1 and Visit 3  
6.2 
Safety Endpoints 
• Visual acuity 
• Slit lamp examination 
• Adverse event query 
• Intraocular pressure 

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8 
STUDY METHODS AND PROCEDURES 
8.1 
Subject Entry Procedures 
8.1.1 Overview 
Subjects as defined by the criteria in section 5.2, 5.3, and 5.4 will be 
considered for entry into the trial. 
8.1.2 Informed Consent 
Prior to participation in the clinical trial, the clinical trial will be discussed 
with the subjects, and subjects wishing to participate must give written 
informed consent using an informed consent form. The informed consent 
form must be the most recent version that has received approval/favorable 
review by a properly constituted Independent Review Board. 
8.1.3 Washout Intervals 
Prohibited medications, treatments, and activities are outlined in the 
exclusion criteria. 
8.1.4 Procedures for Final Study Entry 
Subjects must satisfy all of the inclusion criteria and none of the exclusion 
criteria in order to be entered into the trial. 
8.1.5 Methods for Assignment to Treatment Groups: 
At Visit 1 each subject who signs the informed consent will be assigned a 
screening number. All screening numbers will be assigned in strict 
numerical sequence at each site and no numbers will be skipped or 
omitted. 
At Visit 2, a subject who meets all the eligibility criteria will be 
randomized to receive reproxalap or vehicle in a 1:1 ratio. Subjects will be 
assigned a randomization number and kit number via interactive web 
response system. 
Both the randomization number and the assigned test article kit number 
will be recorded on the patient’s source document and electronic Case 
Report Form (eCRF). 
8.2 
Concurrent Therapies 
The use of any applicable concurrent medications (prescription or OTC) is to 
be recorded on the subject source document along with the reason the 
medication was taken. 
Concurrent enrollment in an investigational drug or medical device trial is not 
permitted. 
8.2.1 Prohibited Medications/Treatments 
Prohibited medications, treatments, and activities are outlined in the 
exclusion criteria and Appendix 2. 

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• In-office Dose # 2 
 
• In-office Dose #3 
 
• In-office Dose #4 
• Subjects will return to clinic the following day 
Visit 3 (Day 2, test article CAE, trial exit) 
• Medical/medication update 
• Adverse event query 
• Urine pregnancy test (as needed) 
• Visual acuity (ETDRS) 
• Slit lamp examination 
• Subject-reported ocular discomfort (0-100 VAS) 
• In-office test article instillation by trained site staff (approximately 5 
minutes prior to CAE entry) 
• CAE exposure (100 minutes, test article administration at 
approximately 50 minutes) with subject-reported ocular discomfort 
collected at 10, 15, 20, 25, 30, 35, 40, 45, 65, 70, 75, 80, 85, 90, 95, 
and 100 minutes in the CAE  
• CAE exit  
• Slit lamp examination 
• Intraocular pressure 
• Trial exit 
8.4 
Early Termination/Discontinuation  
If a subject is discontinued from the trial prior to Visit 3, then all safety 
evaluations that are to be performed at Visit 3 should be performed on the day 
of discontinuation (early termination) or at the discretion of the investigator. 
Adverse events (both elicited and observed) and serious adverse events will be 
monitored throughout the trial. The investigator will promptly review all 
adverse events (both elicited and observed) for accuracy and completeness. 
All adverse events will be documented on the appropriate source document 
and case report form. 
If a positive pregnancy test is observed during the trial, the investigator will 
notify 
 immediately. The investigator shall request from the subject and/or 
the subject’s physician copies of all related medical reports during the 
pregnancy and shall document the outcome of the pregnancy. The investigator 
will retain the reports together with the subject’s source documents and will 
provide a copy of all documentation to 
. Pregnant subjects will be 
discontinued from the trial as per the exclusion criteria. 

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8.5 
Schedule of Visits, Measurements, and Dosing 
8.5.1 Scheduled Visits 
Appendix 1 details the schedule of visits and measurements. 
8.5.2 Unscheduled Visits 
Unscheduled visits may be performed in order to ensure subject safety. All 
procedures performed at an unscheduled visit will be recorded in the 
source documents and on the Unscheduled Visit eCRF pages. Any 
procedure indicated in the eCRF that is not performed should be indicated 
as “Not done.” 
Evaluations that may be conducted at an unscheduled visit include: 
• Slit lamp examination; 
• Visual acuity; 
• Intraocular pressure; 
• Urine pregnancy test; 
• Assessment of adverse events; 
• Assessment of concurrent medications and/or treatments; and 
• Any other assessments needed in the judgment of the investigator. 
8.6 
Subject Disposition 
8.6.1 Completed Subjects 
A completed subject is one who has not been discontinued from the trial 
and has completed all applicable assessments. 
8.6.2 Discontinued Subjects 
Subjects may be discontinued prior to the completion of the trial for 
reason, which may include: 
• Adverse events, 
• Protocol violations, 
• Administrative reasons (e.g., inability to continue), or 
• Sponsor termination of the trial. 
Notification of subject discontinuations and reasons for discontinuation 
will be made to 
 and will be clearly documented on the source 
document. 
8.7 
Study Duration 
Participation in the clinical trial is estimated to be approximately 2 weeks per 
subject.  
8.8 
Monitoring and Quality Assurance 
During the course of the trial, a monitor, or designee, will make routine site 
visits to review protocol compliance; assess test article accountability, storage 
conditions, and subject safety; and ensure the trial is being conducted 

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factors for the assessment of causal relationship of an adverse event to the 
study procedures include, but are not limited to, temporal relationship 
between the adverse event and the procedure, known side effects of the 
procedure medical history, and/or concomitant medication: 
• Definite: When there are good reason and sufficient documentation to 
demonstrate a direct causal relationship between study procedure and 
adverse event; 
• Probable: When there are good reasons and sufficient documentation 
to assume a causal relationship in the sense of plausible, conceivable, 
or likely, but not necessarily highly probable. 
• Possible: When there is sufficient information to accept the possibility 
of a causal relationship in the sense of not impossible and not unlikely, 
although the connection is uncertain or doubtful (e.g., missing data or 
insufficient evidence). 
• None: When there is sufficient information to accept a lack of a causal 
relationship, in the sense of impossible and improbable. 
• Unclassified: When the causal relationship is not assessable for 
whatever reason due to insufficient evidence, conflicting data, or poor 
documentation. 
9.1.3 Expectedness 
The expectedness of an adverse event should be determined based upon 
existing safety information about the study procedures. Therefore, the 
following definition will be used: 
• Unexpected: An adverse event that is not listed in the safety 
information available for the study procedure at the specificity or 
severity that has been observed. 
• Expected: An adverse event that is listed in the safety information 
available for the study procedure at the specificity and severity that has 
been observed. 
• Not Applicable: Any adverse event that is unrelated to the study 
procedure. 
9.2 
Serious Adverse Events 
An adverse event is considered serious if, in the view of either the investigator 
or Sponsor, the adverse event results in any of the following outcomes: 
• Death; 
• A life-threatening adverse event; 
o Note: An adverse event is considered “life-threatening” if, in the 
view of either the investigator or Sponsor, the occurrence of the 
adverse event places the subject at immediate risk of death. A life-
threatening adverse event does not include an adverse event that, 
had it occurred in a more severe form, might have caused death. 

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• Inpatient hospitalization or prolongation of existing hospitalization; 
o Note: The term “inpatient hospitalization” refers to any inpatient 
admission (even if less than 24 hours). For chronic or long-term 
inpatients, inpatient admission includes transfer within the hospital 
to an acute/intensive care inpatient unit. Inpatient hospitalization 
does not include: emergency room visits, outpatient/same-
day/ambulatory procedures, observation/short stay units, 
rehabilitation facilities, hospice facilities, nursing homes, or clinical 
research/Phase 1 units. 
o Note: The term “prolongation of existing hospitalization” refers to 
any extension of an inpatient hospitalization beyond the stay 
anticipated or required for the reason for the initial admission as 
determined by the investigator or treating physician. 
• A persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions; 
o Note: A serious adverse event specifically related to visual threat 
would be interpreted as any potential ocular impairment or ocular 
damage (e.g., hemorrhage, retinal detachment, central corneal ulcer, 
or damage to the optic nerve). 
• A congenital anomaly/birth defect in the fetus or child of a female 
subject if the subject was exposed to test article when pregnant with 
the fetus or child. 
Important medical events that may not result in death, are life-threatening, or 
require hospitalization may be considered serious when, based upon 
appropriate medical judgment, the subject may be jeopardized or may require 
medical or surgical intervention to prevent one of the outcomes listed above. 
9.3 
Procedures for Reporting Adverse Events 
All adverse events and associated outcomes must be reported to 
and the 
Institutional Review Board (IRB, as required by the IRB; federal, state, or 
local regulations; and governing health authorities) and recorded on the 
appropriate source document. 
9.3.1 Reporting a Suspected Unexpected Adverse Reaction 
All adverse events that are related (definite, probable, possible) and 
unexpected are to be reported to 
and the IRB, as required by the 
IRB; federal, state, or local regulations; and governing health 
authorities. 
9.3.2 Reporting a Serious Adverse Event 
To ensure subject safety, all serious adverse events, regardless of relationship 
to the test article, must be immediately reported. All information relevant to 
the serious adverse event must be recorded on the appropriate source 

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the amended informed consent is reviewed and approved by the Sponsor 
prior to submission to the governing IRB and that the amended informed 
consent is read, signed, and dated by all subjects currently and 
subsequently enrolled. If informed consent is taken under special 
circumstances (e.g., oral informed consent), then the consent procedures to 
be followed must be determined by 
and provided in writing by 
 
prior to the consent process. 
11.1.2 Institutional Review Board Approval 
The ADX-102-DED-032 clinical trial is to be conducted in accordance 
with IRB regulations (U.S. 21 CFR Part 56.103). The investigator must 
obtain appropriate IRB approval before initiating the trial, and must obtain 
re-approval at least annually. 
Only an IRB-approved version of the informed consent form will be used. 
11.2 Ethical Conduct of the Clinical Trial 
The ADX-102-DED-032 clinical trial will be conducted in accordance with 
the ethical principles that originated with the Declaration of Helsinki. 
11.3 Subject Confidentiality 
All personal subject data collected and processed should be maintained by the 
investigator and staff with adequate precautions as to ensure the 
confidentiality of the data in accordance with local, state, and federal laws and 
regulations. 
Monitors, auditors, and other authorized representatives of 
, the IRB 
approving the trial, the United States Food and Drug Administration, the 
United States Department of Health and Human Services, other domestic 
government agencies, and other foreign regulatory agencies will be granted 
direct access to original medical and study records for verification of the data 
and clinical trial procedures. Access to records will be permitted for the 
aforementioned individuals only to the extent permitted by law. 
11.4 Documentation 
Source documents may include medical records, hospital charts, clinic charts, 
subject files, and the results of diagnostic tests such as X-rays, laboratory 
tests, and electrocardiograms. The investigator source documents serves as the 
investigator record of study-related data. 
11.4.1 Retention of Documentation 
All trial-related correspondence, subject records, consent forms, and 
copies of source documents should be maintained on file for at least two 
years or longer, if required by the applicable regulatory requirements or by 
an agreement with the Sponsor.  
If an investigator retires, relocates, or for other reasons withdraws from 
the responsibility of keeping study records, custody must be transferred to 

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Appendix 4: Amendment Summary of Changes Table  
 
Not applicable.

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Appendix 5: Sponsor and 
 Approvals 
Protocol Title: 
A Randomized, Double-Masked, Parallel Group, Vehicle-
Controlled Phase 3 Clinical Trial to Assess the Efficacy and 
Safety of 0.25% Reproxalap Ophthalmic Solution Compared to 
Vehicle in Subjects with Dry Eye Disease 
Protocol Number: 
ADX-102-DED-032 
Protocol Date: 
19 Apr 2024 
The clinical trial protocol was subject to critical review and has been approved by the 
Sponsor. The following personnel contributed to writing and/or approving the protocol. 
 
 
 
 
 
 

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Appendix 6: Investigator’s Signature 
Protocol Title: 
A Randomized, Double-Masked, Parallel Group, Vehicle-Controlled 
Phase 3 Clinical Trial to Assess the Efficacy and Safety of 0.25% 
Reproxalap Ophthalmic Solution Compared to Vehicle in Subjects 
with Dry Eye Disease 
Protocol Number: 
ADX-102-DED-032 
Protocol Date: 
19 Apr 2024 
I agree to implement and conduct the study diligently and in strict compliance with the 
protocol, good clinical practices, and all applicable laws and regulations. I agree to 
maintain all information supplied by 
 in confidence and, when the information is 
submitted to an Institutional Review Board (IRB) or another group, it will be submitted 
with a designation that the material is confidential. 
I have read this protocol in its entirety, including the above statement, and I agree to all 
aspects. 
Signed: 
 
 
Date:  
 
 
Name:  
 
Title: Principal Investigator 
 
Site:  
 
Address:  
 
Phone Number: