A Single-Center, Phase 2a, Randomized, Double Masked, Clinical Study to Assess the Safety, Tolerability, and Pharmacodynamic Activity of ADX-102 Ophthalmic Solution in Subjects With Dry Eye Syndrome
Phase: PHASE2
Conditions: Dry Eye Syndromes
Sponsor: Aldeyra Therapeutics, Inc.

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 1 of 67 
Clinical Trial Protocol 
Protocol Title: 
A Single-Center, Phase 2a, Randomized, 
Double-Masked, Clinical Study to Assess the Safety, 
Tolerability, and Pharmacodynamic Activity of 
ADX-102 Ophthalmic Solution in Subjects with Dry 
Eye Syndrome  
Protocol Number: 
ADX-102-DES-007 
Study Phase: 
2a 
Product Name: 
ADX-102 Ophthalmic Solution (0.5% and 0.1%) 
 
 
Indication: 
Dry Eye Syndrome (DES) 
Sponsor: 
Aldeyra Therapeutics, Inc. 
131 Hartwell Ave. 
Lexington, MA 02421 USA 
Contract Research 
Organization: 
Ora. Inc. 
300 Brickstone Square, 3rd Floor 
Andover, MA 01810 USA 
 
 
 
 
 
Date 
Original Protocol: 
27 March 2017 
Confidentiality Statement 
This protocol contains confidential, proprietary information of Ora, Inc. and/or Aldeyra Therapeutics, Inc. 
Further dissemination, distribution or copying of this protocol or its contents is strictly prohibited. 

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 2 of 67 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 3 of 67 
SYNOPSIS 
Protocol Title: 
A Single-Center, Phase 2a, Randomized, 
Double-Masked, Clinical Study to Assess the Safety, 
Tolerability, and Pharmacodynamic Activity of ADX-
102 Ophthalmic Solution in Subjects with Dry Eye 
Syndrome  
Protocol Number: 
ADX-102-DES-007 
Study Drug: 
1) ADX-102 Ophthalmic Solution (0.5%)
2) ADX-102 Ophthalmic Solution (0.1%)
3) ADX-102 Ophthalmic Lipid Solution (0.5%)
Study Phase: 
2a 
Study Objective: 
The objective of this study is to evaluate the safety, 
tolerability, and pharmacodynamic activity of ADX-102 
Ophthalmic Solutions and ADX-102 Ophthalmic Lipid 
Solution in subjects with dry eye syndrome. 
Overall Study Design 
Structure: 
Single-center, double-masked, randomized study 
Duration: 
An individual subject’s participation is estimated to be 
approximately 4 weeks (28 days). 
Dosage/Dose Regimen: 
Subjects eligible to be randomized will receive one of 
the following treatments to be administered bilaterally 
four times daily (QID) for 28 days (from Visit 1 to Visit 
3). 
1) ADX-102 Ophthalmic Solution (0.5%)
2) ADX-102 Ophthalmic Solution (0.1%)
3) ADX-102 Ophthalmic Lipid Solution (0.5%)
Summary of Visit 
Schedule: 
3 visits over the course of approximately 4 weeks 

Visit 1 = Day 1, Screening and Enrollment

Visit 2 = Day 8 ± 1, 1-Week Follow-Up

Visit 3 = Day 29 ± 2, 4-Week Follow-Up
Measures Taken to 
Reduce Bias: 
This is a randomized treatment assignment, 
double-masked study. 
Study Population 
Characteristics 
Number of Subjects: 
Approximately 60 subjects will be screened to enroll 45 
subjects (15 per treatment arm). 
Condition/Disease: 
Dry Eye Syndrome (DES) 

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 4 of 67 
Inclusion Criteria: 
Subjects must: 
1. Be at least 18 years of age of either gender and any
race;
2. Provide written informed consent and sign the
Health Information Portability and Accountability
Act (HIPAA) form;
3. Have a reported history of dry eye for at least
 prior to Visit 1; 
4. Have a history of use or desire to use eye drops for
dry eye symptoms within 
 of Visit 1; 
5. Report a score of
 on the Ora Calibra® Ocular 
Discomfort & 4-symptom questionnaire in at least 
one symptom at Visit 1; 
6. Have a Schirmer’s Test score of
 at Visit 1; 
7. Have a tear film break-up time (TFBUT©)
 at Visit 1; 
8. Have a corneal fluorescein staining score of 
 in
at least one region (e.g. inferior, superior, or central)
at Visit 1;
9. Have a sum corneal fluorescein staining score of
, based on the sum of the inferior, superior, and
central regions, at Visit 1;
10. Have a total lissamine green conjunctival score of
, based on the sum of the temporal and nasal
regions at Visit 1;
11. Have at least one eye satisfy all criteria for 6, 7, 8,
9, and 10 above.
Exclusion Criteria: 
Subjects must not: 
1. Have any clinically significant slit lamp findings at
Visit 1 that may include active blepharitis,
meibomian gland dysfunction (MGD), lid margin
inflammation, or active ocular allergies that require
therapeutic treatment, and/or in the opinion of the
investigator may interfere with study parameters;

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 5 of 67 
2. Be diagnosed with an ongoing ocular infection
(bacterial, viral, or fungal), or active ocular
inflammation at Visit 1;
3. Have worn contact lenses within 7 days of Visit 1 or
anticipate using contact lenses during the study;
4. Have used any eye drops within 2 hours of Visit 1;
5. Have previously had laser-assisted in situ
keratomileusis (LASIK) surgery within the last 12
months;
6. Have used cyclosporine 0.05% or lifitigrast 5.0%
ophthalmic solution within 45 days of Visit 1;
7. Have any planned ocular and/or lid surgeries over
the study period or any ocular surgery within the
last 6 months;
8. Be using or anticipate using temporary punctal
plugs during the study that have not been stable
within 30 days of Visit 1;
9. Be currently taking any topical ophthalmic
prescription (including medications for glaucoma)
or over-the-counter (OTC) solutions, artificial tears,
gels or scrubs, and cannot discontinue these
medications for the duration of the trial (excluding
medications allowed for the conduct of the study);
10. Have 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;
11. Be a woman who is pregnant, nursing, or planning a
pregnancy;
12. Be unwilling 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);

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 6 of 67 
13. Be a man or woman of childbearing potential who is
not using 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
study, he/she must agree to use adequate birth
control as defined above for the remainder of the
study;
14. Have a known allergy and/or sensitivity to the test
article or its components;
15. Have a condition or be in a situation which the
investigator feels may put the subject at significant
risk, may confound the study results, or may
interfere significantly with the subject’s
participation in the study;
16. Be currently enrolled in an investigational drug or
device study or have used an investigational drug or
device within 30 days of Visit 1;
17. Have previously used ADX-102 ophthalmic
solution;
18. Be currently using 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;
19. Be unable or unwilling to follow instructions,
including participation in all study assessments and
visits.
Study Formulations: 

ADX-102 Ophthalmic Solution (0.5%)

ADX-102 Ophthalmic Solution (0.1%)

ADX-102 Ophthalmic Lipid Solution (0.5%)

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 7 of 67 
Evaluation Criteria 
Safety Measures: 

Visual acuity

Slit-lamp evaluation

Adverse event query

Intraocular Pressure (IOP)

Undilated fundoscopy
Exploratory 
Pharmocodynamic 
Measures: 

Ora CalibraTM Drop Comfort assessment;
 
 
 
 
 
 
Other: 
Not applicable. 
General Statistical Methods and Types of Analyses 
Analysis Populations 

Intent-to-Treat Population – The intent-to-treat (ITT) population includes all
randomized subjects.  Subjects in the ITT population will be analyzed as
randomized.

Per-Protocol Population – The per-protocol (PP) population includes subjects
in the ITT population who do not have significant protocol deviations and
who complete the study.  Protocol deviations will be assessed prior to
database lock and unmasking.  Subjects in the PP population will be
analyzed as treated.

Safety Population – The safety population includes all randomized subjects
who have received at least one dose of the investigational product.  Subjects
in the Safety population will be analyzed as treated.

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 8 of 67 
 
 
 
 
 
 
 
 
 
 
Primary Efficacy Analyses: 
There are no primary endpoints in this Phase 2a study. 
Secondary Efficacy Analyses: 
There are no secondary endpoints in this Phase 2a study. 
Safety Variables: 
Adverse events (AEs) will be coded using the MedDRA dictionary. Frequencies 
and percentages of subjects with treatment-emergent adverse events (TEAEs), 
serious TEAEs, and TEAEs causing premature discontinuation will be provided 
by treatment group. An AE is treatment emergent if it occurs or worsens after the 
first dose of study treatment. Furthermore, frequencies will be given of subjects 
with TEAEs by system organ class, by system organ class and preferred term, by 
system organ class, preferred term and maximal severity, by system organ class, 
preferred term and strongest relationship, and by system organ class, preferred 
term, maximal severity, and strongest relationship. Separate summaries will be 
performed for ocular and non-ocular AEs.  
Other safety endpoints including visual acuity, slit-lamp biomicroscopy, 
undilated fundoscopy, and intraocular pressure will be summarized by treatment 
group and visit using descriptive statistics. Changes or shifts from baseline will 
also be summarized where appropriate. For assessments performed by eye, study 
eye and fellow eye will be summarized separately.  
 
 
 
 
 
  

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 9 of 67 
  
 
Summary of Known and Potential Risks and Benefits to Human Subjects 
Refer to Investigator’s Brochure. 

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 10 of 67 
TABLE OF CONTENTS 
SYNOPSIS ..........................................................................................................................3 
TABLE OF CONTENTS ................................................................................................10 
LIST OF ABBREVIATIONS .........................................................................................13 
1 
INTRODUCTION...................................................................................................15 
2 
CLINICAL STUDIES OF ADX-102 OPHTHALMIC SOLUTION..................16 
2.1 
Phase 1 Clinical Trial ...................................................................................16 
2.2 
Phase 2 Clinical Trial of ADX-102 in Allergic Conjunctivitis ..................16 
2.3 
Phase 2 Clinical Trial of ADX-102 in Non-infectious Anterior Uveitis ...17 
2.4 
Minimization of Risk ....................................................................................17 
3 
STUDY OBJECTIVES ...........................................................................................18 
4 
DESIGN ...................................................................................................................18 
5 
STUDY POPULATION .........................................................................................19 
5.1 
Number of Subjects ......................................................................................19 
5.2 
Study Population Characteristics ...............................................................20 
5.3 
Inclusion Criteria .........................................................................................20 
5.4 
Exclusion Criteria .........................................................................................20 
5.5 
Withdrawal Criteria (if applicable) ............................................................22 
6 
STUDY PARAMETERS ........................................................................................22 
6.1 
Efficacy Measures .........................................................................................22 
 
 
6.2 
Safety Measures ............................................................................................23 
7 
STUDY MATERIALS ............................................................................................23 
7.1 
Study Drug(s) ................................................................................................23 
7.1.1 
Formulations .....................................................................................23 
7.1.2 
Dispensation Schedule ......................................................................23 
7.1.3 
Instructions for Use ...........................................................................23 
7.2 
Other Study Supplies ...................................................................................24 
8 
STUDY METHODS AND PROCEDURES .........................................................24 
8.1 
Subject Entry Procedures ............................................................................24 
8.1.1 
Overview ...........................................................................................24 
8.1.2 
Informed Consent..............................................................................24 
8.1.3 
Washout Intervals .............................................................................24 
8.1.4 
Procedures for Final Study Entry ......................................................24 
8.1.5 
Methods for Assignment to Treatment Groups ................................24 
8.2 
Concurrent Therapies ..................................................................................25 
8.2.1 
Prohibited Medications/Treatments ..................................................25 
8.2.2 
Escape Medications ..........................................................................25 
8.2.3 
Special Diet or Activities ..................................................................25 
8.3 
Examination Procedures ..............................................................................25 
8.3.1 
Procedures to be Performed at Each Study Visit with Regard to 
Study Objective(s) ..........................................................................................25 
8.4 
Schedule of Visits, Measurements, and Dosing .........................................28 
8.4.1 
Scheduled Visits................................................................................28 
8.4.2 
Unscheduled Visits ...........................................................................28 
8.5 
Compliance with Protocol ............................................................................28 

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 11 of 67 
8.6 
Subject Disposition .......................................................................................29 
8.6.1 
Completed Subjects ..........................................................................29 
8.6.2 
Discontinued Subjects .......................................................................29 
8.7 
Study Termination .......................................................................................29 
8.8 
Study Duration .............................................................................................29 
8.9 
Monitoring and Quality Assurance ............................................................29 
9 
ADVERSE EVENTS ..............................................................................................31 
9.1 
Adverse Event ...............................................................................................31 
9.1.1 
Severity .............................................................................................31 
9.1.2 
Relationship to Study Drug ...............................................................31 
9.1.3 
Expectedness .....................................................................................32 
9.2 
Serious Adverse Events ................................................................................32 
9.3 
Procedures for Reporting Adverse Events .................................................33 
9.3.1 
Reporting a Suspected Unexpected Adverse Reaction .....................33 
9.3.2 
Reporting a Serious Adverse Event ..................................................34 
9.4 
Procedures for Unmasking of Study Drug .................................................34 
9.5 
Type and Duration of the Follow-up of Subjects after Adverse Events ..35 
10 
STATISTICAL HYPOTHESES AND METHODS OF ANALYSES................35 
10.1 Analysis Populations ....................................................................................35 
10.2 Statistical Hypotheses ...................................................................................35 
10.3 Sample Size ...................................................................................................36 
10.4 Statistical Analysis ........................................................................................36 
10.4.1 General Considerations .....................................................................36 
10.4.2 Unit of Analysis ................................................................................36 
10.4.3 Missing Data .....................................................................................37 
10.4.4 Multiplicity Consideration ................................................................37 
10.4.5 Primary Efficacy Analyses ...............................................................37 
10.4.6 Secondary Efficacy Analyses ...........................................................37 
10.4.7 Safety Variables ................................................................................37 
10.4.8 Exploratory Pharmacodynamic (Efficacy) Measures .......................37 
10.4.9 Interim Analyses ...............................................................................38 
11 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES ................................38 
11.1 Protection of Human Subjects.....................................................................38 
11.1.1 Subject Informed Consent.................................................................38 
11.1.2 Institutional Review Board (IRB) Approval .....................................38 
11.2 Ethical Conduct of the Study ......................................................................39 
11.3 Subject Confidentiality ................................................................................39 
11.4 Documentation ..............................................................................................39 
11.4.1 Retention of Documentation .............................................................39 
11.5 Labeling, Packaging, Storage, Accountability, and Return or Disposal of 
Study Drug ....................................................................................................40 
11.5.1 Labeling/Packaging...........................................................................40 
11.5.2 Storage of Study Drug ......................................................................40 
11.5.3 Accountability of Study Drug ...........................................................40 
11.5.4 Return or Disposal of Study Drug ....................................................40 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 12 of 67 
 
11.6 Recording of Data on Source Documents and Electronic Case Reports 
Forms (eCRFs)..............................................................................................40 
11.7 Handling of Biological Specimens ...............................................................41 
11.8 Publications ...................................................................................................41 
12 
REFERENCES ........................................................................................................42 
13 
APPENDICES .........................................................................................................44 
Appendix 1:  Schedule of Visits and Measurements ...................................................44 
Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques ...........46 
Appendix 3:  Amendment Summary of Changes........................................................65 
Appendix 4:  Sponsor and Ora Approvals ..................................................................66 
Appendix 5:  Investigator’s Signature .........................................................................67 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 13 of 67 
 
LIST OF ABBREVIATIONS 
AE 
adverse event 
BCVA 
best-corrected visual acuity 
CFR 
Code of Federal Regulations 
CRF 
case report form 
DES 
Dry Eye Syndrome 
DHHS 
Department of Health and Human Services 
eCRF 
electronic case report form 
EKG 
Electrocardiograph 
ERC 
ethical review committee 
ETDRS 
Early Treatment of 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 Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
investigational new drug application 
IOP 
intraocular pressure 
IRB 
institutional/independent review board 
ITT 
intent-to-treat 
IUD 
Intra-uterine device 
IWRS 
interactive web response system 
LASIK 
laser in situ keratomileusis 
LOCF 
last observation carried forward 
LPS 
lipopolysaccharide 
logMAR 
logarithm of the minimum angle of resolution 
MDA 
Malondialdehyde; malonaldehyde 
MedDRA 
Medical Dictionary for Regulatory Activities 
MGD 
meibomian gland dysfunction 
mL 
Milliliter 
mm 
Millimeter 
µg  
microgram  
µL  
microliter  
µm 
Micrometer 
mmHg 
millimeters of mercury 
OD 
right eye 
OS 
left eye 
 
 
OU 
both eyes 
OTC 
over-the-counter 
PP 
per protocol 
QID 
four times a day 
SAE 
serious adverse event 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 14 of 67 
 
 
 
TEAEs 
treatment emergent adverse events 
VA 
visual acuity 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 15 of 67 
 
1 INTRODUCTION 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
   
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 16 of 67 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
2 CLINICAL STUDIES OF ADX-102 OPHTHALMIC SOLUTION 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 17 of 67 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 18 of 67 
 
3 STUDY OBJECTIVES  
The objective of this study is to evaluate the safety, tolerability and pharmacodynamic 
activity of ADX-102 Ophthalmic Solutions (0.5% and 0.1%) and ADX-102 Ophthalmic 
Lipid Solution (0.5%) in subjects with dry eye. 
 
CLINICAL HYPOTHESIS 
 
 
  
4 DESIGN 
This is a Phase 2a, single-center, randomized, double-masked study designed to evaluate 
the safety, tolerability and pharmacodynamic activity of ADX-102 Ophthalmic Solution 
(0.5%), ADX-102 Ophthalmic Solution (0.1%), and ADX-102 Ophthalmic Lipid 
Solution (0.5%) in subjects with dry eye. Approximately 45 male and female subjects at 
least 18 years of age with a subject-reported history of dry eye in both eyes and meeting 
all other study eligibility criteria will be randomized to receive treatment ADX-102 
Ophthalmic Solution (0.5%), ADX-102 Ophthalmic Solution (0.1%), or ADX-102 
Ophthalmic Lipid Solution (0.5%) in a 1:1:1 ratio (approximately 15 subjects in each 
treatment group). 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 20 of 67 
 
5.2 Study Population Characteristics 
All subjects must be at least 18 years of age, of either gender, and of any race, and must 
meet all inclusion criteria and none of the exclusion criteria. 
5.3 Inclusion Criteria 
Subjects must: 
 
1. Be at least 18 years of age of either gender and any race; 
 
2. Provide written informed consent and sign the Health Information Portability 
and Accountability Act (HIPAA) form; 
 
3. Have a reported history of dry eye for at least 
prior to Visit 1; 
 
4. Have a history of use or desire to use eye drops for dry eye symptoms within  
 of Visit 1; 
 
5. Report a score of 
 on the Ora Calibra® Ocular Discomfort & 4-symptom 
questionnaire in at least one symptom at Visit 1; 
 
6. Have a Schirmer’s Test score of 
 at Visit 1; 
 
7. Have a tear film break-up time (TFBUT©) 
 at Visit 1;  
 
8. Have a corneal fluorescein staining score of 
 in at least one region (e.g. 
inferior, superior, or central) at Visit 1; 
 
9. Have a sum corneal fluorescein staining score of 
 based on the sum of the 
inferior, superior, and central regions, at Visit 1;  
 
10. Have a total lissamine green conjunctival score of 
 based on the sum of the 
temporal and nasal regions at Visit 1; 
 
11. Have at least one eye satisfy all criteria for 6, 7, 8, 9, and 10 above. 
5.4 Exclusion Criteria 
Subjects must not: 
1. Have any clinically significant slit lamp findings at Visit 1 that may 
include active blepharitis, meibomian gland dysfunction (MGD), lid 
margin inflammation, or active ocular allergies that require therapeutic 
treatment, and/or in the opinion of the investigator may interfere with 
study parameters; 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 21 of 67 
 
2. Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), 
or active ocular inflammation at Visit 1; 
3. Have worn contact lenses within 7 days of Visit 1 or anticipate using 
contact lenses during the study; 
4. Have used any eye drops within 2 hours of Visit 1; 
5. Have previously had laser-assisted in situ keratomileusis (LASIK) surgery 
within the last 12 months; 
6. Have used cyclosporine 0.05% or lifitigrast 5.0% ophthalmic solution 
within 45 days of Visit 1; 
7. Have any planned ocular and/or lid surgeries over the study period or any 
ocular surgery within the last 6 months; 
8. Be using or anticipate using temporary punctal plugs during the study that 
have not been stable within 30 days of Visit 1; 
9. Be currently taking any topical ophthalmic prescription (including 
medications for glaucoma) or over-the-counter (OTC) solutions, artificial 
tears, gels or scrubs, and cannot discontinue these medications for the 
duration of the trial (excluding medications allowed for the conduct of the 
study); 
10. Have 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; 
11. Be a woman who is pregnant, nursing, or planning a pregnancy; 
12. Be unwilling 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); 
13. Be a man or woman of childbearing potential who is not using 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 study, he/she 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 22 of 67 
 
must agree to use adequate birth control as defined above for the 
remainder of the study; 
14. Have a known allergy and/or sensitivity to the test article or its 
components; 
15. Have a condition or be in a situation which the investigator feels may put 
the subject at significant risk, may confound the study results, or may 
interfere significantly with the subject’s participation in the study; 
16. Be currently enrolled in an investigational drug or device study or have 
used an investigational drug or device within 30 days of Visit 1; 
17. Have previously used ADX-102 ophthalmic solution; 
18. Be currently using 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; 
19. Be unable or unwilling to follow instructions, including participation in all 
study assessments and visits. 
5.5 Withdrawal Criteria (if applicable) 
If at any time during the study the investigator determines that a subject’s safety has 
been compromised, the subject may be withdrawn from the study. 
Subjects may withdraw consent from the study at any time. 
Sponsor and/or investigator may discontinue any subject for non-compliance or any 
valid medical reason (see Section 8.6.2). 
6 STUDY PARAMETERS 
6.1 Efficacy Measures  
6.1.1 Exploratory Pharmacodynamic Variables 
The following exploratory endpoints will be tested: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Ora CalibraTM Ocular Discomfort Scale; 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 23 of 67 
 
 
 
 
 
 
 
 
 
 
 
6.2 Safety Measures 
 Visual acuity (ETDRS); 
 Slit-lamp biomicroscopy; 
 Adverse event query; 
 Undilated Fundoscopy;  
 Intraocular Pressure; 
7 STUDY MATERIALS 
7.1 Study Drug(s) 
7.1.1 Formulations 
Randomized Study Treatments 
 ADX-102 Ophthalmic Solution (0.5%) 
 ADX-102 Ophthalmic Solution (0.1%) 
 ADX-102 Ophthalmic Lipid Solution (0.5%) 
7.1.2 Dispensation Schedule 
 At the end of Visit 1, qualified subjects will be randomized and the first 
dose of study drug will be administered in office. A supply of ADX-102 
Ophthalmic Solution (0.5%), ADX-102 Ophthalmic Solution (0.1%), or 
ADX-102 Ophthalmic Lipid Solution (0.5%) will be dispensed for 
dosing QID. 
 At the end of Visit 2, the unused vials from their Visit 1 kit will be re-
dispensed to subjects, and a second kit for dosing through Visit 3 will 
also be dispensed.  
 At Visits 2 and 3, remaining/used study drug will be collected from 
subjects for drug accountability.  
 Subjects will be instructed to not use study drug on the day of visits 
(Visit 2 and 3) prior to the visit. 
7.1.3 Instructions for Use 
Subjects will be instructed to dose in each eye QID (morning, noon, 
afternoon, and in the evening before bed). 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 24 of 67 
 
7.2 Other Study Supplies 
Other study supplies include urine pregnancy tests, 
 
 
 
8 STUDY METHODS AND PROCEDURES 
8.1 Subject Entry Procedures 
8.1.1 Overview 
Subjects, as defined by the criteria in Sections 5.2, 5.3, and 5.4, will be 
considered for entry into this study. 
8.1.2 Informed Consent 
Prior to a subject’s participation in the trial (i.e., prior to changes in a 
subject’s medical treatment and/or prior to study related procedures), the 
study will be discussed with each subject, and subjects wishing to 
participate must give written informed consent using an informed consent 
form (ICF). The ICF must be the most recent version that has received 
approval/favorable review by a properly constituted Institutional Review 
Board (IRB). 
8.1.3 Washout Intervals 
Prohibited medications, treatments, and activities are outlined in the 
exclusion criteria (Section 5.4). 
8.1.4 Procedures for Final Study Entry 
Subjects must meet all inclusion and none of the exclusion criteria. 
8.1.5 Methods for Assignment to Treatment Groups 
Prior to initiation of study drug (at Visit 1), each subject who qualifies for 
entry will be assigned a screening number. All screening numbers will be 
assigned in strict numerical sequence at a site and no numbers will be 
skipped or omitted. If all inclusion and exclusion criteria are met at 
Visit 1, each qualifying subject will then be assigned a randomization 
number at the end of Visit 1.  
A randomization schedule will be provided to the investigational site. The 
randomization schedule will use block randomization, such that there will 
be an approximate equal number of subjects assigned to each of the three 
treatment arms at the site. The site staff will dispense to the patient the 
study kit labeled with the corresponding randomization number. The 
randomization number will be recorded on the patient’s source document 
and electronic case report form (eCRF). A new kit will be dispensed at 
Visit 2 based on the subject’s randomization. The Sponsor, Investigators, 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 25 of 67 
 
and study staff will be masked during the randomization process and 
throughout the study.  
8.2 Concurrent Therapies 
The use of any concurrent medication, prescription or over-the-counter, is to be 
recorded on the subject’s source document and corresponding eCRF along with the 
reason the medication was taken. 
Concurrent enrollment in another investigational drug or device study is not 
permitted. 
8.2.1 Prohibited Medications/Treatments 
Disallowed medications/treatments during the study are outlined in the 
Exclusion Criteria (Section 5.4).  
8.2.2 Escape Medications 
No escape medications are required for this study. 
8.2.3 Special Diet or Activities 
No special diets or activities are required for this study. 
8.3 Examination Procedures 
8.3.1 Procedures to be Performed at Each Study Visit with Regard to Study 
Objective(s) 
The following procedures will be performed (see Appendix 2 for 
description): 
Visit 1 (Day 1):  Screening & Enrollment 
 Informed consent / HIPAA; 
 Demographic data and medical / medication history; 
 Review of qualification criteria; 
 Urine pregnancy test (for females of childbearing potential); 
 Ora Calibra® Ocular Discomfort; 
 
 
 
 
 
 
 
 Visual Acuity (ETDRS); 
 Slit-lamp Biomicroscopy; 
 
 
 
 
 At least 20-minute wait; 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 26 of 67 
 
 Fluorescein staining – Ora Calibra®;  
 Lissamine Green staining – Ora Calibra®; 
 
 
 
 
 Intraocular Pressure; 
 Undilated Fundoscopy; 
 Adverse event query; 
 Review of qualification criteria; 
 Randomization & Dispensation of study drug kit according to 
randomization for QID dosing until Visit 2; 
 
 
 
 
 Subjects will be instructed to dose in each eye four times daily 
(morning, noon, afternoon, and in the evening before bed); 
o Subjects will be instructed to dose in each eye before bed in the 
evening of Visit 2; 
o Subjects will be instructed to not dose with study drug on the 
morning of their next visit (Visit 2); 
 Qualified subjects will be scheduled for Visit 2. 
Visit 2 (Day 8 ± 1):  1-Week Follow-Up  
 Collection and review of study drug; 
 Subject will be asked if he/she dosed with study drug on the morning 
of the visit; if the subject indicates he/she dosed that morning, he/she 
should wait at least 4 hours from the time of dosing before efficacy 
assessments are performed; 
 Medical/medication history update; 
 Adverse event query; 
 Ora Calibra® Ocular Discomfort; 
 
 
 
 
 
 
 Visual Acuity (ETDRS); 
 Slit-lamp Biomicroscopy; 
 
 
 
  
 Dispensation of study drug kits for QID dosing until Visit 3; 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 27 of 67 
 
 Subjects will be instructed to dose in each eye four times daily 
(morning, noon, afternoon, and in the evening before bed); 
o Subjects will be instructed to dose in each eye before bed the 
evening of Visit 3; 
o Subjects will be instructed to not dose with study drug on the 
morning of their next visit (Visit 3); 
 Subjects will be scheduled for Visit 3. 
Visit 3 (Day 29 ± 2): 4-Week Follow-Up and Study Exit 
 Collection and review of study drug; 
 Subject will be asked if he/she dosed with study drug on the morning 
of the visit; if the subject indicates he/she dosed that morning, he/she 
should wait at least 4 hours from the time of dosing before efficacy 
assessments are performed; 
 Medical/medication history update; 
 Adverse event query; 
 Urine pregnancy test (for females of childbearing potential); 
 Ora Calibra® Ocular Discomfort; 
 
 
 
 
 
 
 
 Visual Acuity (ETDRS); 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 Intraocular Pressure; 
 Undilated Fundoscopy; 
 Adverse event query; 
 Study Exit. 
Early Termination/Discontinuation  
If a subject is discontinued from the study prior to Visit 3 (Day 29 ± 2), 
then all safety evaluations that are to be performed at Visit 3 (Day 29 ± 2) 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 28 of 67 
 
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 
(SAEs) will be monitored throughout the study.  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 female reports a pregnancy or has a positive pregnancy test during the 
study the investigator will notify Ora 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 these reports together with 
the subject’s source documents and will provide a copy of all 
documentation to Ora. The pregnant subjects will be discontinued from 
the study as per the exclusion criteria. 
8.4 Schedule of Visits, Measurements, and Dosing 
8.4.1 Scheduled Visits 
Refer to Appendix 1 for a schedule of visits and measurements. 
8.4.2 Unscheduled Visits 
These 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 Biomicroscopy; 
 Visual Acuity; 
 Intraocular Pressure; 
 Urine Pregnancy Test; 
 Undilated Fundoscopy; 
 Assessment of Adverse Events; 
 Assessment of concurrent medications and/or treatments; and 
 Any other assessments needed in the judgment of the investigator. 
8.5 Compliance with Protocol 
Subjects will be instructed on proper instillation and storage of study drug at the end 
of Visits 1 and 2, and given written instructions. The used and unused study drug 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 29 of 67 
 
vials will be collected at each visit from Visit 2 up to and including Visit 3 to assess 
dosing and symptom assessment compliance. 
 
 
 
  
8.6 Subject Disposition 
8.6.1 Completed Subjects 
A completed subject is one who has not been discontinued from the study. 
8.6.2 Discontinued Subjects 
Subjects may be discontinued at any time prior to their completion of the 
study due to: 
 adverse events; 
 unmasking when medically necessary; 
 protocol violations; 
 administrative reasons (e.g., inability to continue, lost to follow 
up); 
 sponsor termination of study; 
 subject choice (e.g., withdrawal of consent); and 
 other. 
Note: In addition, any subject may be discontinued for any sound medical 
reason at the discretion of the investigator. 
Notification of a subject discontinuation and the reason for discontinuation 
will be made to Ora and/or study sponsor and will be clearly documented 
on the eCRF. 
Discontinued subjects will not be replaced. 
8.7 Study Termination 
The study may be stopped at any time by the investigator, the Sponsor, and/or Ora 
with appropriate notification. 
8.8 Study Duration 
An individual subject’s participation will involve 3 visits over approximately a 
4-week period (28 days). 
8.9 Monitoring and Quality Assurance 
During the course of the study a monitor, or designee, will make routine site visits to 
review protocol compliance, assess study drug accountability, subject safety, and 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 30 of 67 
 
ensure the study is being conducted according to the pertinent regulatory 
requirements.  The review of the subjects’ medical records will be performed in a 
manner that adequately maintains subject confidentiality. Further details of the study 
monitoring will be outlined in a monitoring plan. 
Regulatory authorities of domestic and foreign agencies, Ora, Inc. quality assurance 
and or its designees may carry out on-site inspections and/or audits, which may 
include source data checks.  Therefore, direct access to the original source data will 
be required for inspections and/or audits.  All inspections and audits will be carried 
out giving consideration to data protection as well as subject confidentiality to the 
extent that local, state, and federal laws apply. 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 31 of 67 
 
9 ADVERSE EVENTS 
9.1 Adverse Event 
An adverse event is defined as any untoward medical occurrence associated with the 
use of a drug in humans, whether or not the event is considered drug-related.  An 
adverse event can therefore be any unfavorable and unintended sign (e.g., an 
abnormal laboratory finding), symptom, or disease occurring after the subject started 
dosing with the study drug, without any judgment about causality.  Any pre-existing 
medical condition that worsens after administration of the study drug will also be 
considered a new adverse event.   
If there is a worsening of a medical condition that was present prior to the 
administration of the study drug, this should also be considered a new adverse event 
and reported.  Any medical condition present prior to the administration of the study 
drug that remains unchanged or improved should not be recorded as an adverse event 
at subsequent visits. 
Study drug includes the investigational drug under evaluation. 
Documentation regarding the adverse event should be made as to the nature, date of 
onset, end date, severity, relationship to study drug, action(s) taken, seriousness, and 
outcome of any sign or symptom observed by the physician or reported by the subject 
upon indirect questioning. 
9.1.1 Severity 
Severity of an adverse event is defined as a qualitative assessment of the 
degree of intensity of an adverse event as determined by the investigator 
or reported to him/her by the patient/subject.  The assessment of severity 
is made irrespective of relationship to study drug or seriousness of the 
event and should be evaluated according to the following scale: 
 
 
 
 
 
 
 
 
 
 
9.1.2 Relationship to Study Drug 
The relationship of each adverse event to the investigational product 
should be determined by the investigator (in a blinded manner) using 
these explanations: 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 32 of 67 
 
 Definite: When there are good reason and sufficient 
documentation to demonstrate a direct causal relationship 
between investigational product and adverse event. 
 Probable: When there are good reasons and sufficient 
documentation to assume a causal relationship in the sense of 
plausible, conceivable, 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, 
for example; due to 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 drug using these explanations: 
 Unexpected: An adverse event that is not listed in the 
Investigator’s brochure or is not listed at the specificity or severity 
that has been observed. 
 Expected: An adverse event that is listed in the Investigator’s 
brochure at the specificity and severity that has been observed. 
 Not Applicable: Any adverse event that is unrelated to the study 
drug. 
Adverse events that are mentioned in the Investigator’s brochure as 
occurring with a class of drugs or as anticipated from the pharmacological 
properties of the drug, but are not specifically mentioned as occurring with 
the particular drug under investigation are to be considered unexpected. 
The investigator should initially classify the expectedness of an adverse 
event, but the final classification is subject to the Medical Monitor’s 
determination. 
9.2 Serious Adverse Events 
An adverse event is considered serious if, in the view of either the investigator or 
Sponsor, it results in any of the following outcomes: 
 Death; 
 A life-threatening adverse event; 
Note:  An adverse event is considered “life-threatening” if, in the view of 
either the investigator or Sponsor, its occurrence places the patient or subject 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 33 of 67 
 
at immediate risk of death.  It does not include an adverse event that, had it 
occurred in a more severe form, might have caused death. 
 Inpatient hospitalization or prolongation of existing hospitalization; 
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. 
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; 
Note:  A serious adverse event specifically related to visual threat would be 
interpreted as any potential impairment or damage to the subject’s eyes (e.g., 
hemorrhage, retinal detachment, central corneal ulcer or damage to the optic 
nerve). 
 A congenital anomaly/birth defect. 
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, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
9.3 Procedures for Reporting Adverse Events 
All adverse events and their outcomes must be reported to Ora, the study sponsor, and 
the institutional review board (IRB)/independent ethics committee (IEC) as required 
by the IRB/IEC, federal, state, or local regulations and governing health authorities 
and recorded on the appropriate eCRF. 
9.3.1 Reporting a Suspected Unexpected Adverse Reaction 
All adverse events that are ‘suspected’ and ‘unexpected’ are to be reported 
to Ora, the study sponsor and the IRB/IEC as required by the IRB/IEC, 
federal, state, or local regulations and governing health authorities. 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 34 of 67 
 
9.3.2 Reporting a Serious Adverse Event 
To ensure subject safety, all serious adverse events, regardless of 
relationship to the study drug, must be immediately reported.  All 
information relevant to the serious adverse event must be recorded on the 
appropriate case report forms.  The investigator is obligated to pursue 
and obtain information requested by Ora and/or the sponsor in addition to 
that information reported on the case report form.  All subjects 
experiencing a serious adverse event must be followed up and the outcome 
reported. 
In the event of a serious adverse event, the investigator must notify Ora 
and the Sponsor immediately; obtain and maintain in his/her files all 
pertinent medical records, information, and medical judgments from 
colleagues who assisted in the treatment and follow-up of the subject; 
provide Ora and the study sponsor with a complete case history, which 
includes a statement as to whether the event was or was not suspected to 
be related to the use of the study drug; and inform the IRB of the adverse 
event within their guidelines for reporting serious adverse events. 
Contact information for reporting Serious Adverse Events:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.4 Procedures for Unmasking of Study Drug 
All subjects, investigators, and study personnel involved with the conduct of the study 
will be masked with regard to treatment assignments. When medically necessary, the 
investigator may need to determine what treatment arm has been assigned to a 
subject. When possible (i.e., in non-emergent situations), Ora and/or the study 
sponsor should be notified before unmasking study drug. The unmasked subject will 
be discontinued from the study.  

Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Final V1.0 27Mar2017 
Confidential 
Page 35 of 67 
9.5 Type and Duration of the Follow-up of Subjects after Adverse 
Events 
The investigator will follow unresolved AEs to resolution until the subject is lost to 
follow-up or until the AE is otherwise classified. Resolution means the subject has 
returned to baseline state of health or the Investigator does not expect any further 
improvement or worsening of the AE. If the patient is lost to follow-up, the 
Investigator should make 3 reasonable attempts to contact the patient via telephone, 
post, or certified mail. All follow-up will be documented in the subject’s source 
document. Non-serious AEs identified on the last scheduled contact must be recorded 
on the AE eCRF with the status noted.  
If the investigator becomes aware of any new information regarding an existing SAE 
(i.e., resolution, change in condition, or new treatment), a new SAE/Unanticipated 
Report Form must be completed and faxed to Ora within 24 hours of the site’s 
awareness of the new information. The original SAE form is not to be altered. The 
report should describe whether the event has resolved or continues and how the event 
was treated. 
10 STATISTICAL HYPOTHESES AND METHODS OF ANALYSES 
10.1 Analysis Populations 
The following analysis populations will be considered: 

Intent-to-Treat Population – The intent-to-treat (ITT) population includes all
randomized subjects. Subjects in the ITT population will be analyzed as
randomized.

Per-Protocol Population – The per-protocol (PP) population includes subjects
in the ITT population who do not have significant protocol deviations and
who complete the study. Protocol deviations will be assessed prior to database
lock and unmasking. Subjects in the PP population will be analyzed as treated.

Safety Population – The safety population includes all randomized subjects
who have received at least one dose of the investigational product. Subjects in
the Safety population will be analyzed as treated.
 
 
 
10.2 
Statistical Hypotheses 
This is a Phase 2a study to assess the safety, tolerability and pharmacodynamic 
activity of ADX-102 Ophthalmic Solution in subjects with dry eye syndrome. 
There are no primary endpoints and no formal statistical hypotheses. 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 36 of 67 
 
10.3  Sample Size 
 
 
 
 
 
10.4 Statistical Analysis 
 
 
 
 
  
 
 
 
 
 
  
 
 
  
 
  
 
 
 
10.4.2 Unit of Analysis 
 
 
  
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 37 of 67 
 
10.4.3 Missing Data 
 
 
 
 
 
10.4.4 Multiplicity Consideration 
 
 
 
10.4.5 Primary Efficacy Analyses 
There are no primary endpoints in this Phase 2a study. 
10.4.6 Secondary Efficacy Analyses 
There are no secondary endpoints in this Phase 2a study. 
10.4.7 Safety Variables 
Adverse events will be coded using the MedDRA dictionary. Frequencies 
and percentages of subjects with treatment-emergent adverse events 
(TEAEs), serious TEAEs, and TEAEs causing premature discontinuation 
will be provided by treatment group. An AE is treatment emergent if it 
occurs or worsens after the first dose of study treatment. Furthermore, 
frequencies will be given of subjects with TEAEs by system organ class; 
by system organ class and preferred term; by system organ class, preferred 
term and maximal severity; by system organ class and preferred term for 
treatment-related TEAEs; and by system organ class, preferred term, and 
study day of onset. Separate summaries will be performed for ocular and 
non-ocular AEs.  
 
Other safety endpoints including visual acuity, slit-lamp biomicroscopy, 
undilated fundoscopy, and intraocular pressure will be summarized by 
treatment group and visit using descriptive statistics. Changes or shifts 
from baseline will also be summarized where appropriate. For assessments 
performed by eye, study eye, and fellow eye will be summarized 
separately.  
10.4.8 Exploratory Pharmacodynamic (Efficacy) Measures 
 
 
 
 
  

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 38 of 67 
 
  
 
  
10.4.9 Interim Analyses 
 
11 COMPLIANCE WITH GOOD CLINICAL PRACTICES, 
ETHICAL CONSIDERATIONS, AND ADMINISTRATIVE 
ISSUES 
This study will be conducted in compliance with the protocol, Good Clinical Practices 
(GCPs), including the International Council on Harmonization (ICH) Guidelines, and in 
general, consistent with the Declaration of Helsinki.  In addition, all applicable local, 
state, and federal requirements relevant to the use of study drugs in the countries involved 
will be adhered to. 
11.1 Protection of Human Subjects 
11.1.1 Subject Informed Consent 
Informed consent/assent must take place before any study specific 
procedures are initiated.  Signed and dated written informed consent 
must be obtained from each subject and/or from the subject’s parent or 
legal guardian prior to enrollment into the study.  If the subject is under 
the legal age of consent, the consent form must be signed by a legal 
guardian or as required by state and/or local laws and regulations. 
All informed consent/assent forms must be approved for use by the 
sponsor and receive approval/favorable opinion from an IRB/IEC prior to 
their use.  If the consent form requires revision (e.g., due to a protocol 
amendment or significant new safety information), it is the investigator’s 
responsibility to ensure that the amended informed consent is reviewed 
and approved by Ora prior to submission to the governing IRB/IEC and 
that it is read, signed, and dated by all subjects subsequently enrolled in 
the study as well as those currently enrolled in the study. 
If informed consent is taken under special circumstances (oral informed 
consent), then the procedures to be followed must be determined by Ora 
and/or study Sponsor and provided in writing by Ora and/or study Sponsor 
prior to the consent process. 
11.1.2 Institutional Review Board (IRB) Approval 
This study is to be conducted in accordance with Institutional Review 
Board regulations (U.S. 21 CFR Part 56.103).  The investigator must 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 39 of 67 
 
obtain appropriate IRB approval before initiating the study and 
re-approval at least annually. 
Only an IRB/ERC approved version of the informed consent form will be 
used. 
11.2 Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that originated 
with the Declaration of Helsinki. 
11.3 Subject Confidentiality 
All personal study subject data collected and processed for the purposes of this study 
should be maintained by the investigator and his/her staff with adequate precautions 
as to ensure that the confidentiality of the data in accordance with local, state, and 
federal laws and regulations. 
Monitors, auditors, and other authorized representatives of Ora, the Sponsor, the 
IRB/IEC approving this study, the Food and Drug Administration (FDA), the 
Department of Health and Human Services (DHHS), other domestic government 
agencies, and other foreign regulatory agencies will be granted direct access to the 
study subject’s original medical and study records for verification of the data and/or 
clinical trial procedures.  Access to this information will be permitted to the 
aforementioned individuals to the extent permitted by law. 
A report of the results of this study may be published or sent to the appropriate health 
authorities in any country in which the study drug may ultimately be marketed, but 
the subject’s identity will not be disclosed in these documents. 
11.4 Documentation 
Source documents may include a subject’s medical records, hospital charts, clinic 
charts, the investigator’s study subject files, as well as the results of diagnostic tests 
such as X-rays, laboratory tests, and electrocardiographs (EKGs).  The investigator’s 
copy of the case report forms serves as the investigator’s record of a subject’s study-
related data. 
11.4.1 Retention of Documentation 
All study related correspondence, subject records, consent forms, record of 
the distribution and use of all study drug and copies of case report forms 
should be maintained on file for at least two years after the last approval of 
a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region; or until at least 
two years have elapsed since the formal discontinuation of clinical 
development of the study drug. These documents will be retained for a 
longer period if required by the applicable regulatory requirements or by 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 40 of 67 
 
an agreement with the sponsor.  It is the responsibility of the Sponsor to 
inform the investigator/institution as to when these documents no longer 
need to be retained. 
If the responsible investigator retires, relocates, or for other reasons 
withdraws from the responsibility of keeping study records, custody must 
be transferred to a person who will accept the responsibility.  The 
Sponsor must be notified in writing of the name and address of the new 
custodian. 
11.5 Labeling, Packaging, Storage, Accountability, and Return or 
Disposal of Study Drug 
11.5.1 Labeling/Packaging 
  
 
 
11.5.2 Storage of Study Drug 
 
 
 
  
11.5.3 Accountability of Study Drug 
 
 
 
  
 
 
 
 
 
  
11.5.4 Return or Disposal of Study Drug 
 
11.6 Recording of Data on Source Documents and Electronic Case 
Reports Forms (eCRFs) 
All subject data will be captured in the subject source documents which will be 
transcribed in the eCRFs. The investigator is responsible for ensuring that study data 
is completely and accurately recorded on each subject’s eCRF, source documents, 
and all study-related materials. All study data should also be attributable, legible, 
contemporaneous, and original. Recorded datum should only be corrected in a 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 41 of 67 
 
manner that does not obliterate, destroy, or render illegible the previous entry (e.g., by 
drawing a single line through the incorrect entry and writing the revision next to the 
corrected data). An individual who has corrected a data entry should make clear who 
made the correction and when, by adding to the correction his/her initials as well as 
the date of the correction.  
Data entry of all enrolled and randomized subjects will use software that conforms to 
21 CFR Part 11 requirements, and will be performed only by staff who have been 
trained on the system and have access to the system. Data will not be entered for 
screen failure subjects. An audit trail will be maintained within the electronic system 
to capture all changes made within the eCRF database. After the end of the study and 
database lock, compact discs (CDs) containing copies of all applicable subjects’ 
eCRFs will be provided to each Investigator Site to be maintained on file by the 
Investigator. 
11.7 Handling of Biological Specimens 
 
 
   
11.8 Publications 
 
  
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 42 of 67 
 
12 REFERENCES 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 43 of 67 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
Confidential 
Page 45 of 67 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 46 of 67 
 
Appendix 2:  Examination Procedures, Tests, Equipment, and 
Techniques 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 47 of 67 
 
Visual Acuity Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 48 of 67 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 49 of 67 
 
 
 
 
   
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 50 of 67 
 
Ora Calibra® Ocular Discomfort Scale  
 
   
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 51 of 67 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
 
 
 
  
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 53 of 67 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 54 of 67 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 55 of 67 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 56 of 67 
 
  
 
 
 
  
 
  
 
 
    
 
  
 
 
  
 
   
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 57 of 67 
 
  
 
 
 
 
 
 
 
  

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 59 of 67 
 
  
 
 
 
 
 
 
  
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 60 of 67 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 61 of 67 
 
 
 
 
 
  
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
 
 
 
 
 
 
  
 
  
 
  
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 63 of 67 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 64 of 67 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 65 of 67 
 
Appendix 3:  Amendment Summary of Changes  
Not applicable 
 
 
 
 
 
 
 
 
 
 
 

 
Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-DES-007 
 
Final V1.0 27Mar2017 
Confidential 
Page 66 of 67