Clinical trial NCT03131154
Conditions: Non-infectious Anterior Uveitis
Keywords: reproxalap
Sponsor: Aldeyra Therapeutics, Inc.
Start date: 2017-04-26; Completion date: 2019-04-26
Enrollment: 123 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A Phase 3, randomized, double-masked, vehicle-controlled trial to evaluate the safety and efficacy of ADX-102 ophthalmic solution in Subjects with non-infectious anterior-uveitis.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: ADX-102 Ophthalmic Solution (0.5%) intervention 2: Vehicle of ADX-102 Ophthalmic Solution
Intervention descriptions: intervention 1: ADX-102 Ophthalmic Solution (0.5%) administered for approximately four weeks. intervention 2: Vehicle of ADX-102 Ophthalmic Solution administered for approximately four weeks.

Protocol documents:
SAP_002.pdf: 













































































Prot_000.pdf: 


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Protocol ADX-102-UV-005 
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Investigator Statement 
 
Protocol Number:  ADX-102-UV-005 
 
Protocol Title:   
A Phase 3 Randomized, Double-Masked, Vehicle-Controlled Trial to Evaluate the Safety and 
Efficacy of ADX-102 Ophthalmic Solution in Subjects with Non-infectious Anterior Uveitis  
 
I understand that all information concerning ADX-102 in connection with this study and not 
previously published is confidential. This confidential information includes the Investigator’s 
Brochure, Clinical Study Protocol, Case Report Form, clinical methodology, and basic scientific 
data. 
 
I will not initiate this study without approval from the Institutional Review Board/Ethics 
Committee and I understand that any changes in the protocol must be approved in writing by 
Aldeyra Therapeutics, Inc., and the Institutional Review Board/Ethics Committee before they 
can be implemented, except when necessary to eliminate immediate hazards to the subjects. 
 
I will use only the informed consent form approved by Aldeyra Therapeutics and by my 
Institutional Review Board (IRB) and will fulfill all responsibilities for submitting pertinent 
information to the IRB responsible for this study.  
 
By my signature below, I attest that I have read, understand, and agree to abide by all the 
conditions, instructions, and restrictions contained in Protocol Number ADX-102-UV-005, and 
will conduct the trial in accordance with Good Clinical Practice (GCP) and applicable regulatory 
requirements.   
 
Site Name 
 
 
Site Address  
 
 
 
Investigator’s Printed Name 
 
 
Investigator’s Signature  
 
Date 


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1 
Synopsis 
Name of Sponsor Company:  
Aldeyra Therapeutics, Inc. 
Drug Under Study:  
ADX-102  
Title of Protocol: A Phase 3 Randomized, Double-Masked, Vehicle-Controlled Trial to Evaluate the Safety and 
Efficacy of ADX-102 Ophthalmic Solution in Subjects with Non-infectious Anterior Uveitis 
Protocol Number: 
ADX-102-UV-005 
Phase: 3 
Indication: Anterior Uveitis  
Primary Objective:  To evaluate the efficacy of ADX-102 Ophthalmic Solution on anterior chamber cell count 
(ACC), in subjects with non-infectious anterior uveitis. 
 
Secondary Objectives:  To evaluate the safety and efficacy of ADX-102 Ophthalmic Solution on the signs and 
symptoms of anterior uveitis in subjects with non-infectious anterior uveitis. 
Study Endpoints 
 
Signs and symptoms of anterior uveitis which include anterior chamber cell count, anterior chamber 
flare, limbal injection, hypopyon, peripheral anterior synechiae, keratic precipitates, posterior synechiae, 
ocular pain, lacrimation, photophobia, blurry vision and visual acuity  
 
Incidence of adverse events (AEs), changes in clinical laboratory values and changes in intraocular 
pressure (IOP) values 
 
Self-reported visual function with the National Eye Institute Visual Function Questionnaire (VFQ-25) 
Study Design:  
This is a randomized, double-masked, vehicle-controlled Phase 3 clinical trial in which approximately 120 
subjects with endogenous non-infectious anterior uveitis will be randomized (1:1) to receive either: 
Group 1 
ADX-102 Ophthalmic Solution (0.5%)  
Group 2 
Vehicle of ADX-102 Ophthalmic Solution 
Randomization will be stratified based on baseline ACC score. The dosing schedule is summarized in Table 1. 
Subjects will be followed for up to five (5) weeks and monitored for safety and efficacy at seven (7) scheduled 
visits.  Efficacy will be assessed by standard ophthalmic examination procedures and response to treatment will 
be graded according to established uveitis scales. 
Each subject’s study participation will consist of the following visits: Screening/Randomization (Day 1; Visit 1), 
Day 4 +/- 1 day (Visit 2), Week 1 (Day 8 +/- 1 day; Visit 3), Week 2 (Day 15 +/- 2 days; Visit 4), Week 3 (Day 
22 +/- 2 days; Visit 5), Week 4 (Day 29 +/- 3 days; Visit 6/EOT/ET) and Week 5 telephone follow-up (Day 36 
+/- 3 days; Visit 7/End of Study [EOS]). The total time in the study is approximately 5 weeks. 
At the Screening/Randomization Visit, subjects will provide written informed consent and then study eligibility 
will be assessed. Eligible subjects will be randomized, dispensed study drug and instructed on dosing as well as 
on completing the subject dosing diary.  Subjects will be randomly assigned treatment as described above.  
Treatment Period: Subjects will be instructed to administer study drug and to return to the clinic for Weeks 1 
through 4.  
Rescue therapy will be available to all subjects that do not demonstrate a clinical response based on predefined 
rescue criteria.  Rescued subjects will complete the Week 4 / End of Treatment/Early Termination (EOT/ET) 
visit. 


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Rescue Therapy 
  
 
 
 
 
 
 
 
 
 
 
 
Once it is determined that rescue therapy is needed the subject should be considered an Early Termination and the 
Week 4 (Visit 6) assessments should be completed. 
Concomitant Medications 
 
 
Subject Population: Subjects with endogenous non-infectious anterior uveitis 
Number of Subjects:  Approximately 120 subjects (male 
and female)  
Number of Centers:  Approximately 45 centers in 
the United States 
Test Product and Doses:  
 
ADX-102 Ophthalmic Solution (0.5%) 
 
Vehicle of ADX-102 Ophthalmic Solution 
Route of Administration:    
Topical ocular solution 
Criteria for Inclusion: 
All subjects entered into this trial must meet the following criteria: 
1. Subject is willing and able to comply with the protocol requirements, has gone through the consent 
process and has signed an approved informed consent form.    
2. Male or female subjects aged ≥ 18 years and ≤ 85 years. 
3. Subjects with acute endogenous non-infectious anterior uveitis with onset of symptoms within the 
previous 2 weeks.*  Subjects experiencing a bilateral episode of anterior uveitis may be eligible for 
study in both eyes. Evaluations for selective infectious etiologies, including but not limited to Syphilis, 
Tuberculosis (if indicated), Herpes Simplex, Herpes Zoster, CMV, Lyme Disease or other suspected 
infectious etiology, must be performed during the screening period or within 3 months of randomization. 
4. Presence of 6-50 anterior chamber cells within one field of view as measured with a slit lamp 
microscope (Grade 1+ to Grade 3+, Appendix 1) in the study eye(s). 
5. Subjects must have pachymetry corrected IOP <21 mmHg at baseline and non-glaucomatous cups in the 
opinion of the investigator with non-glaucomatous visual fields if available, and may only administer a 
maximum of 1 topical medication to control IOP in the study eye. 
6. Best corrected visual acuity (BCVA) better than or equal to 35 letters in the study eye and 65 letters in 
the non-study eye using ETDRS testing.  Note: this criteria is also applicable for a subject with bilateral 
uveitis. 
7. Females of childbearing potential must be using or willing to use a medically acceptable method (as 
defined by the Investigator) of birth control.  Women not of childbearing potential are defined as women 
who are either surgically sterile or postmenopausal.  Postmenopausal women are defined as women with 
cessation of menstruation for 12 consecutive months prior to signing of the informed consent form.   


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*A history of prior flare-ups or subsequent flare-ups in the non-study eye should not affect eligibility, provided 
that the subject is deemed capable of administering separate treatments to each eye. For example, if an enrolled 
subject experiences a flare-up in the non-study eye, the subject should remain in the study, and the non-study eye 
should receive the standard of care treatment. Likewise, if a potential subject was already receiving standard of 
care treatment in the non-study eye prior to enrollment, the second eye is eligible for the study and the non-study 
eye will continue to receive the standard of care. 
 
Criteria for Exclusion:  
Subjects will be excluded from this trial if they meet any of the following criteria: 
1. Have severe/serious ocular pathology in the study eye(s) which may preclude study completion, in 
the judgement of the Investigator. 
2. Any medical condition or clinical laboratory test which in the judgment of the Investigator makes 
the subject unsuitable for the study. 
3. Currently or within past 5 years, have a history of malignancy other than successfully treated 
squamous or basal cell carcinoma of the skin or successfully treated in situ cervical cancer. 
4. Active intermediate or posterior uveitis in the study eye(s). Note: a subject with isolated macular 
edema without evidence of active intermediate or posterior uveitis is eligible for enrolment.  
5. Known or observed mild to severe (1-4+) fibrinoid reaction. 
6. Previous anterior uveitis episode in the study eye ≤ 4 weeks prior to Visit 1. 
7. Cataract and intraocular lens (IOL) implantation surgery or corneal transplantation surgery in the 
study eye(s) within the past 3 months prior to Visit 1, or subjects who may require penetrating 
intraocular surgery in the study eye(s) during the study. 
 
Subjects who are 3 months past uncomplicated cataract and IOL implantation surgery and 
have shown documented complete clearing of inflammation post-surgery in the study 
eye(s) are eligible. 
 
Any other penetrating intraocular surgery in the study eye(s) within 3 months prior to Visit 
1 are eligible, assuming documented complete clearing of inflammation post-surgery in the 
study eye(s). 
8. Oral corticosteroid within the past 14 days prior to Visit 1. 
9. Topical ocular corticosteroid treatment in the study eye within the past 14 days prior to Visit 1 
(Maximum of 3 doses of topical ocular steroid in the study eye in the 7 days prior to Visit 1 is 
permitted). 
10. Intravitreal corticosteroid treatment in the study eye within the past 4 months prior to Visit 1. 
11. Sub-Tenon corticosteroid treatment in the study eye within the past 3 months prior to Visit 1. 
 
 
 
 
 
14. Prescribed nonsteroidal anti-inflammatory agents or immunosuppressive agents, unless the dose has 
been stable for the last 6 weeks prior to Visit 1 and no change in dosing is anticipated for the 
duration of the study. 
15. Systemic immunomodulatory agents (e.g. azathioprine, methotrexate, mycophenolate mofetil), 
unless the dose has been stable for the last 6 weeks prior to Visit 1 and no change in dosing is 
anticipated for the duration of the study. 
16. Pregnant or lactating female, or female of childbearing potential and using inadequate birth control 
methods. 
17. Have participated in another investigational device or drug study within 30 days prior to Visit 1. 
18. Participation in a prior ADX-102 study. 
Subjects with test results which do not meet the above inclusion/exclusion criteria may have the underlying test 
repeated once if it is thought to represent a laboratory error; a reversible, clinically insignificant intermittent 
condition; or is not consistent with the subject’s historical values.  If inclusion/exclusion criteria are not met after 
the repeat test, the subject should be considered a screen failure and should not be enrolled in the study. 
 
Criteria for Evaluation: 
 


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Efficacy: 
Anterior chamber cell count 
Anterior chamber flare 
Limbal injection 
Hypopyon 
Peripheral anterior synechiae 
Keratic precipitates 
Posterior synechiae 
Ocular pain 
Photophobia 
Lacrimation 
Blurry Vision 
Visual acuity  
Safety:  
Adverse events  
Changes in clinical laboratory values 
Changes in corrected IOP 
Statistical Analysis: 
 
Efficacy 
The primary efficacy analysis will be time to treatment success, where such time is defined as when a cell count 
of 0 is achieved and maintained to Week 4 without being rescued at any time prior to Week 4 will be analyzed 
using the method of Kaplan and Meier.  Between group comparisons will be made using the log rank test. 
 
Sample Size Rationale 
 
 
 
 
 
 
Safety 
Adverse events will be summarized, and event rates will be presented by treatment arm. Any other information 
collected (such as severity or relationship to study drug) will be listed as appropriate.  Any statistical tests 
performed to explore the data will be used only to highlight any interesting comparisons that may warrant further 
consideration. 
 
DSMB 
An independent data safety monitoring board (DSMB) will be established. They will review all available safety 
data after approximately 25 subjects have completed the study visit 7. The assessment of safety will be 
determined from ophthalmologic endpoints including slit lamp examinations, ocular scores, visual acuity and 
IOP, vital sign measurements, physical examinations, hematology and chemistry laboratory testing, use of 
concomitant medications, and review of adverse events (AEs).  Based on the safety data provided, the DSMB will 
determine if it is acceptable to continue the study or modify the study design as appropriate. Additional DSMB 
reviews will occur throughout the trial approximately every 6 months or as deemed necessary by the DSMB or 
Sponsor to ensure subject safety and well-being. Study enrollment and dosing will continue while the DSMB 
evaluates data.  A DSMB charter will be prepared.  The charter will contain the required information for the 
formation, activities and conduct of the DSMB. 
 
 


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Table 1. 
Dosing Schedule for Eye Drop Regimens 
 
Group 1 
Group 2 
Week 
ADX-102 
Vehicle 
1 
8x/Day 
8x/Day 
2 
6x/Day 
6x/Day 
3 
4x/Day 
4x/Day 
4 
4x/Day 
4x/Day 
5 
None 
None 
 
 


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Table 2. 
Schedule of Visits and Assessments 
 
Visit 1 
(Screening) 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
(EOT/ET) 
Visit 7 
(EOS)
Test/Procedure 
Day 1 
Day 4 
Day 4 
(± 1 day) 
Week 1 
Day 8 
(± 1 day) 
Week 2 
Day 15  
(± 2 days) 
Week 3 
Day 22 
(± 2 days) 
Week 4 
Day 29 
(± 3 days) 
Week 5a 
Day 36 
(± 3 days) 
Informed Consent 
✓ 
 
 
 
 
 
 
Eligibility Criteria 
✓ 
 
 
 
 
 
 
Medical History 
✓ 
 
 
 
 
 
 
Concomitant 
Medications 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Demographics 
✓ 
 
 
 
 
 
 
Ocular scores; 
ocular pain, blurry 
vision, photophobia, 
tearing scoresb, c 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
 
✓ 
 
 
 
 
✓ 
 
Uveitis 
Questionnaire 
✓ 
 
 
 
 
 
 
Height and weight 
✓ 
 
 
 
 
 
 
Vital Signs 
✓ 
 
 
 
 
✓ 
 
Uveitis-specific 
laboratory tests and 
Chest X-Rayd 
✓ 
 
 
 
 
 
 
Safety laboratory 
testse 
✓ 
 
 
 
 
✓ 
 
Urine pregnancy 
testf 
✓ 
 
 
 
 
✓ 
 
Best Corrected 
Visual Acuity 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
Intraocular 
pressureg 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
Slit lamp exam 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
Fundus exam 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
Corneal pachymetry 
✓ 
 
 
 
 
 
 
Subject Dosing 
Diary Dispensing 
✓ 
 
✓ 
✓ 
✓ 
 
 
Adverse events 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
EOT/ET = end of treatment/early termination; EOS = end of study; VFQ-25 = Visual Function Questionnaire 
a 
The Week 5/EOS visit will consist of a follow up phone call to collect Adverse Events and Concomitant 
Medications.  
b 
 
 
 
c 
Ocular pain, lacrimation, photophobia, and blurry vision will be measured by the subject completing a Visual 
Analog Scale (VAS). 
d 
During Screening only, the following 3 uveitis-specific diagnostic tests will be obtained in all subjects 
experiencing their first episode of anterior uveitis, or in subjects experiencing a repeat episode where prior tests 
of this nature have not been previously performed: 
1) HLA-B27 
2) Chest X-ray 


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3) Treponemal antibody test(s) including one or more of the following: 
a. 
FTA-ABS (Fluorescent treponemal antibody absorption) 
b. TP-PA (T. pallidum particle agglutination assay) 
c. 
MHA-TP (Micro-hemagglutination assay) 
d. Laboratory specific automated Immunoassay (IA) 
A non-treponemal antibody test such as RPR (Rapid Plasma Reagin) alone is not sufficient. 
If the study subject was tested prior to the screening visit, there needs to be evidence that these tests were 
performed: 
1) HLA-B27 at any time in the past 
2) Chest X-ray within the previous 6 months unless new onset pulmonary symptoms are documented 
3) Treponemal antibody test(s) within the previous 6 months unless intervening new onset symptoms of any 
STD, or STD exposure are documented 
Additional testing such as for RPR, ACE, ANCA, quantiferon and ANA may be performed at the discretion of 
the investigator.  
e  
Safety laboratory tests are hematology including: “hemoglobin, hematocrit, red blood cell (RBC) count, RBC 
morphology, white blood cell (WBC) count with differential, mean corpuscular volume (MCV), mean 
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and absolute platelet 
count” and chemistry including: “albumin, alkaline phosphatase, alanine aminotransferase (ALT; SGPT), 
aspartate aminotransferase (AST; SGOT), bilirubin (total and direct), blood urea nitrogen (BUN), calcium, 
carbon dioxide (CO2), chloride, creatinine, creatinine phosphokinase (CPK), glucose, phosphate, potassium, 
sodium, total protein, and uric acid.”   
f 
Required for women of child-bearing potential; must be negative for the subject to be randomized. 
g 
Once a subject has enrolled in the study, the same tonometry method should be used for that subject throughout 
the duration of the study.  IOP corrected for pachymetry (Ehlers N, Bramsen T, Sperling S. Applanation 
tonometry and central corneal thickness. Acta Ophthalmol. 1975;53:34-43).  Appendix 2. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2 
Table of Contents 
1 
Synopsis .........................................................................................................................3 
2 
Table of Contents .........................................................................................................10 
3 
List of Abbreviations and Definition of Terms............................................................13 
4 
Introduction ..................................................................................................................15 
4.1 
Non-infectious Anterior Uveitis ..................................................................................15 
4.1.1 
Current Treatments of Non-infectious Anterior Uveitis ..............................................15 
4.2 
Inflammation & Aldehyde Toxicity .............................................................................15 
4.3 
Clinical Studies of ADX-102 .......................................................................................16 
4.3.1 
Phase 1 Study ...............................................................................................................16 
4.3.2 
Phase 2 Clinical Trial of ADX-102 in Allergic Conjunctivitis Patients ......................17 
4.3.3 
Phase 2 Clinical Trial of ADX-102 in Non-infectious Anterior Uveitis .....................17 
4.4 
Minimization of Risk ...................................................................................................17 
4.5 
Potential Benefit ...........................................................................................................18 
4.6 
Dose Rationale .............................................................................................................18 
4.7 
Conduct of the Study ...................................................................................................19 
5 
Trial Objectives and Purpose .......................................................................................20 
5.1 
Objectives ....................................................................................................................20 
5.1.1 
Primary Objective ........................................................................................................20 
5.1.2 
Secondary Objectives ...................................................................................................20 
5.2 
Study Endpoints ...........................................................................................................20 
5.3 
Overall Study Design and Plan: Description ...............................................................20 
5.3.1 
Treatment Arms ...........................................................................................................20 
5.4 
Assessments by Study Visit .........................................................................................21 
5.4.1 
Screening Visit/Visit 1 .................................................................................................21 
5.4.2 
Visit 2/Day 4 (Day 4 +/- 1 Day) ..................................................................................22 
5.4.3 
Visits 3 through 5 .........................................................................................................22 
5.4.4 
Visit 6/End of Treatment (EOT) or Early Termination (ET) Visit ..............................23 
5.4.5 
Visit 7/End of Study (EOS) Visit.................................................................................24 
6 
Selection and Withdrawal of Subjects .........................................................................24 
6.1 
Inclusion Criteria .........................................................................................................24 
6.2 
Exclusion Criteria ........................................................................................................25 
6.3 
Protocol Exceptions and Deviations ............................................................................26 
6.4 
Subject Withdrawal Criteria ........................................................................................26 
7 
Treatment of Subjects ..................................................................................................27 
7.1 
Subject Numbering ......................................................................................................27 
7.2 
Description of Study Drug ...........................................................................................27 
7.3 
Concomitant Medications ............................................................................................28 
7.3.1 
Rescue Therapy ............................................................................................................28 
7.4 
Prohibited Medications ................................................................................................29 
7.5 
Treatment Compliance .................................................................................................29 
7.6 
Randomization and Masking .......................................................................................29 


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7.7 
Unmasking Procedures ................................................................................................29 
7.7.1 
Emergency Unmasking of Treatment Assignment ......................................................29 
7.7.2 
Unmasking for Regulatory Authorities ........................................................................30 
8 
Study Drug Materials and Management ......................................................................30 
8.1 
Study Drug ...................................................................................................................30 
8.2 
Study Drug Packaging and Labeling ...........................................................................30 
8.3 
Study Drug Storage ......................................................................................................31 
8.4 
Study Drug Preparation................................................................................................31 
8.5 
Administration .............................................................................................................31 
8.6 
Study Drug Accountability ..........................................................................................31 
9 
Treatment Assessments ................................................................................................32 
9.1 
Efficacy and Safety Parameters ...................................................................................32 
9.1.1 
Medical History and Concomitant Medications ..........................................................32 
9.1.2 
Demographics ..............................................................................................................32 
9.1.3 
Height, Weight and Vital Signs ...................................................................................32 
9.1.4 
Clinical Laboratory ......................................................................................................33 
9.1.5 
Visual Functioning Questionnaire – 25 (VFQ-25) ......................................................34 
9.1.6 
Ocular Scores ...............................................................................................................34 
9.1.7 
Visual Acuity ...............................................................................................................35 
9.1.8 
IOP Measurements .......................................................................................................35 
9.1.9 
Slit Lamp Exam ...........................................................................................................35 
9.1.10 
Fundus Exam ...............................................................................................................35 
9.1.11 
Corneal Pachymetry .....................................................................................................35 
9.1.12 
Dosing Instructions ......................................................................................................36 
9.2 
Adverse Events and Serious Adverse Events ..............................................................36 
9.2.1 
Adverse Events ............................................................................................................36 
9.2.2 
Treatment Emergent Adverse Events (TEAE) ............................................................38 
9.2.3 
Serious Adverse Events ...............................................................................................38 
9.2.4 
Unexpected Adverse Event ..........................................................................................39 
9.3 
Reporting Serious Adverse Events ..............................................................................39 
9.4 
Follow-up of Adverse Events ......................................................................................40 
9.5 
Reporting Safety Information to the IRB .....................................................................40 
9.6 
Pregnancies ..................................................................................................................41 
10 
Statistics .......................................................................................................................41 
10.1 
Sample Size ..................................................................................................................41 
10.2 
Randomization .............................................................................................................42 
10.3 
Data Safety Monitoring Board (DSMB) ......................................................................42 
10.4 
Analysis........................................................................................................................42 
10.5 
Analysis Populations ....................................................................................................42 
10.6 
Accountability and Background Characteristics ..........................................................43 
10.6.1 
Enrollment and Disposition .........................................................................................43 
10.6.2 
Subject Characteristics .................................................................................................43 
10.6.3 
Treatment Compliance .................................................................................................44 
10.7 
Efficacy Analyses ........................................................................................................44 
10.8 
Safety Analyses ............................................................................................................44 
10.8.1 
Adverse Events ............................................................................................................45 


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11 
Direct Access to Source Data/Documents ...................................................................45 
11.1 
Study Monitoring .........................................................................................................45 
11.2 
Data Collection ............................................................................................................46 
11.3 
Audits and Inspections .................................................................................................46 
12 
Quality Control and Quality Assurance .......................................................................46 
13 
Ethics............................................................................................................................47 
13.1 
Ethics Review ..............................................................................................................48 
13.1.1 
IRB Opinion .................................................................................................................48 
13.2 
Written Informed Consent ...........................................................................................48 
13.3 
Amendments to the Protocol ........................................................................................49 
13.4 
Discontinuation of the Study .......................................................................................49 
13.5 
Study Drug Supply, Storage and Tracking ..................................................................49 
13.6 
Confidentiality .............................................................................................................50 
13.7 
Publication Policy ........................................................................................................50 
14 
Retention of Records ....................................................................................................50 
15 
References ....................................................................................................................51 
 
List of Tables 
Table 1. 
Dosing Schedule for Eye Drop Regimens .....................................................................7 
Table 2. 
Schedule of Visits and Assessments ..............................................................................8 
 
List of Figures 
Figure 1.  0.5% 14C-ADX-102 Distribution to the Anterior Eye Cup Following Topical Ocular 
Application of 40 µL in Cynomolgus Macaques .........................................................19 
 
List of Appendices 
Appendix 1. 
Anterior Uveitis Grading Scales ............................................................................52 
Appendix 2. 
Correction Table for Adjusting IOP Based on Central Corneal Thickness ...........53 
 
 
 


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3 
List of Abbreviations and Definition of Terms 
The following abbreviations and specialist terms are used in this study protocol. 
(w/v %) 
Weight/volume Concentration 
βHCG  
Beta human chorionic gonadotropin 
ACE 
Angiotensin-converting enzyme 
AE(s) 
Adverse event(s) 
ALT 
Alanine aminotransferase 
ANA 
Antinuclear antibodies 
ANCA 
Antineutrophil Cytoplasmic Antibodies 
AP 
Alkaline phosphatase 
AST 
Aspartate aminotransferase 
BCVA 
Best-corrected Visual Acuity 
BID 
Twice a day 
BP 
Blood pressure 
bpm 
Beats per minute 
CBC 
Complete blood count 
CDROM 
Compact disc read-only optical memory 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
Contract research organization 
CS 
Clinically significant 
DBP 
Diastolic blood pressure 
DSMB 
Data Safety Monitoring Board 
EOS 
End of study 
EOT 
End of treatment 
ET 
Early termination 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FDA 
Food and Drug Administration 
FTA-ABS 
Fluorescent Treponemal Antibody-absorption 
GCP 
Good Clinical Practice 
HEENT 
Head, eyes, ears, nose, and throat 
HLA-B27 
Human leukocyte antigen subtypes B*2701-2759 
HR 
Heart rate 
IB 
Investigator’s Brochure 
IBD 
Irritable bowel disease 
ICH 
International Conference on Harmonization 


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IOL 
Intraocular Lens 
IOP 
Intraocular pressure 
IWRS 
Interactive Web Response System 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
MHA-TP 
Micro-hemagglutination assay 
mL 
milliliter 
mmHg 
millimeters of mercury 
NCS 
Not clinically significant 
PI 
Principal Investigator 
PRN 
As needed 
QD 
Once a day 
qHS 
At bedtime 
QID 
Four times a day 
RPR 
Rapid Plasma Reagin 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SBECD 
Sulfobutylether-beta-cyclodextrin 
SBP 
Systolic blood pressure 
SD 
Standard deviation 
STD 
Sexually Transmitted Disease 
TEAE 
Treatment emergent adverse events 
TID 
Three times a day 
TP-PA 
T. pallidum particle agglutination assay 
VAS 
Visual Analog Scale 
 
 
WBC 
White blood cells 
WOCBP 
Women of child-bearing potential 
EX 
example abbreviation 
 
 


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4 
Introduction 
4.1 
Non-infectious Anterior Uveitis 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
4.1.1 
Current Treatments of Non-infectious Anterior Uveitis 
 
 
 
 
 
 
    
4.2 
Inflammation & Aldehyde Toxicity 
 
 
 
 
 


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4.3 
Clinical Studies of ADX-102 
 
 
 
 
 


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4.3.2 
Phase 2 Clinical Trial of ADX-102 in Allergic Conjunctivitis Patients 
 
 
 
 
 
 
 
 
 
 
 
4.3.3 
Phase 2 Clinical Trial of ADX-102 in Non-infectious Anterior Uveitis 
 
 
 
 
 
 
 
 
 
  
 
 
 
4.4 
Minimization of Risk 
 
 
   
 


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4.5 
Potential Benefit 
 
 
 
 
 
 
 
   
4.6 
Dose Rationale 
 
 
 
 
 
 
 
 
 
 
 
 


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Figure 1. 0.5% 14C-ADX-102 Distribution to the Anterior Eye Cup Following Topical 
Ocular Application of 40 µL in Cynomolgus Macaques 
 
 
 
 
 
4.7 
Conduct of the Study 
This study will be conducted according to the protocol and in compliance with current principles 
of Good Clinical Practices (GCP) and International Conference on Harmonization (ICH). Further 
information on the ethical conduct of the study is provided in Section 13. 
 
 


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5 
Trial Objectives and Purpose 
5.1 
Objectives 
5.1.1 
Primary Objective 
To evaluate the efficacy of ADX-102 ophthalmic solution on anterior chamber cell count in 
subjects with non-infectious anterior uveitis. 
5.1.2 
Secondary Objectives 
To evaluate the safety and efficacy of ADX-102 ophthalmic solution on the signs and symptoms 
of anterior uveitis in subjects with non-infectious anterior uveitis. 
5.2 
Study Endpoints 
• 
Signs and symptoms of anterior uveitis which include anterior chamber cell count, 
anterior chamber flare, limbal injection, hypopyon, peripheral anterior synechiae, keratic 
precipitates, posterior synechiae, ocular pain, lacrimation, photophobia, blurry vision and 
visual acuity  
• 
Incidence of AEs, changes in clinical laboratory values and changes in IOP values 
• 
Self-reported visual function with the National Eye Institute VFQ-25 
5.3 
Overall Study Design and Plan: Description 
This is a randomized, double-masked, vehicle-controlled Phase 3 clinical trial in which 
approximately 120 subjects with endogenous non-infectious anterior uveitis will be randomized 
(1:1) to receive either: 
 
Group 1 
ADX-102 ophthalmic solution (0.5%)  
Group 2 
Vehicle of ADX-102 ophthalmic solution 
 
Randomization will be stratified based on baseline ACC score. The dosing schedule is 
summarized in Table 1. 
5.3.1 
Treatment Arms 
Subjects will be randomized to one of 2 treatment arms to receive ADX-102 ophthalmic solution 
or vehicle of ADX-102 ophthalmic solution in a 1:1 ratio. 


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5.4 
Assessments by Study Visit 
5.4.1 
Screening Visit/Visit 1 
The following procedures and assessments are to be performed during the Screening Visit / 
Visit 1: 
 
• 
Explain the purpose of the study to prospective subject and obtain written informed 
consent. 
• 
Review inclusion/exclusion criteria (See Sections 6.1 and 6.2). 
• 
Obtain ocular scores on the Visual Analog Scale (VAS); ocular pain, blurry vision, 
photophobia, tearing scores (Section 9.1.6). 
• 
  
   
• 
Document medical history and collect demographic information (See Sections 9.1.1 and 
9.1.2).  
• 
Complete uveitis questionnaire. 
• 
Record concomitant medications (ocular and non-ocular) that the subject is taking in the 
30 days prior to consent. 
• 
Collect height, weight, and vital signs. (See Sections 9.1.3). 
• 
Collect blood and urine samples for clinical laboratory tests (hematology and chemistry; 
see Section 9.1.4). The laboratory tests will include a urine βHCG for women of 
childbearing potential (WOCBP). Any woman with a positive pregnancy test will be 
ineligible for the study.  
o During Screening only, the following 3 uveitis-specific diagnostic tests will be 
obtained in all subjects experiencing their first episode of anterior uveitis, or in 
subjects experiencing a repeat episode where prior tests of this nature have not been 
previously performed: 
1) HLA-B27 
2) Chest X-ray 
3) Treponemal antibody test(s) including one or more of the following: 
a. FTA-ABS (Fluorescent treponemal antibody absorption) 
b. TP-PA (T. pallidum particle agglutination assay) 
c. MHA-TP (Micro-hemagglutination assay) 
d. Laboratory specific automated Immunoassay (IA) 
A non-treponemal antibody test such as RPR (Rapid Plasma Reagin) alone is not 
sufficient. 
If the study subject was tested prior to the screening visit, there needs to be evidence 
that these tests were performed: 
1) HLA-B27 at any time in the past 


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2) Chest X-ray within the previous 6 months unless new onset pulmonary 
symptoms are documented 
3) Treponemal antibody test(s) within the previous 6 months unless intervening 
new onset symptoms of any STD, or STD exposure are documented 
Additional testing such as for RPR, ACE, ANCA, quantiferon and ANA may be 
performed at the discretion of the investigator.  
• 
Complete visual acuity examination (Section 9.1.7). 
• 
Assess IOP (Section 9.1.8). 
• 
Perform slit lamp examination (Section 9.1.9). 
• 
Perform fundus exam (Section 9.1.10). 
• 
Perform corneal pachymetry (Section 9.1.11). 
• 
Once deemed eligible by the investigator, randomize subject through Interactive Web 
Response System (IWRS). Note: A subject may be rescreened only once. 
• 
Review study requirements and instructions on dosing and completing subject dosing 
diary. 
• 
Dispense study drug as assigned. 
• 
Dispense subject dosing diary. 
• 
Confirm day and time of Visit 2 (Day 4). 
• 
Assess for AEs 
5.4.2 
Visit 2/Day 4 (Day 4 +/- 1 Day) 
The following procedures and assessments are to be performed during the Visit 2 / Day4: 
 
• 
Assess for AEs and use of concomitant medications. 
• 
Obtain ocular scores; ocular pain, blurry vision, photophobia, tearing scores (Section 
9.1.6). 
• 
Complete visual acuity examination (Section 9.1.7). 
• 
Assess IOP (Section 9.1.8). 
• 
Perform slit lamp examination (Section 9.1.9). 
• 
Perform fundus exam (Section 9.1.10). 
• 
Confirm day and time of Visit 3. 
5.4.3 
Visits 3 through 5 
Visit 3 through 5, occur Week 1 (Day 8 +/- 1 day), Week 2 (Day 15+/- 2 days), and Week 3 
(Day 22 +/- 2 days). 
 
The following procedures and assessments are to be performed during the Visit 3 through 5: 


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• 
Collect subject dosing diary and review for dosing compliance. Remind subjects of 
requirements and instructions on dosing and completing subject dosing diary.   
• 
Collect all used and unused study drug. 
• 
Obtain ocular scores; ocular pain, blurry vision, photophobia, tearing scores 
(Section 9.1.6)  
• 
Assess for AEs and use of concomitant medications. 
• 
Complete visual acuity examination (Section 9.1.7). 
• 
Assess IOP (Section 9.1.8). 
• 
Perform slit lamp examination (Section 9.1.9). 
• 
Perform fundus exam (Section 9.1.10). 
• 
Dispense a new subject dosing diary. 
• 
Dispense study drug as assigned. 
• 
Confirm day and time of next visit. 
5.4.4 
Visit 6/End of Treatment (EOT) or Early Termination (ET) Visit 
Visit 6/EOT is to occur at Week 4 (Day 29 +/- 3 days). Subjects that terminate the study early for 
any reason should undergo the Visit 6 assessments as an ET visit. 
 
Once it is determined that rescue therapy is needed the subject should be considered an ET and 
the below assessments should be completed. 
 
The following procedures and assessments are to be performed during the Visit 6/EOT/ET: 
 
• 
Collect dosing diary and review for completion and dosing compliance. 
• 
Collect all used and unused study drug. 
• 
Obtain ocular scores; ocular pain, blurry vision, photophobia, tearing scores (Section 
9.1.6). 
• 
Have subject complete VFQ-25 (Section 9.1.5). 
• 
Assess for AEs and use of concomitant medications. 
• 
Collect Vital Signs (Section 9.1.3). 
• 
Collect blood samples for clinical laboratory tests (hematology and chemistry; see 
Section 9.1.4).  
• 
Complete visual acuity examination (Section 9.1.7). 
• 
Assess IOP (Section 9.1.8). 
• 
Perform slit lamp examination (Section 9.1.9). 
• 
Perform fundus exam (Section 9.1.10). 


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• 
For WOCBP a urine pregnancy test will be performed. 
• 
Confirm day and time for End of Study telephone call. 
5.4.5 
Visit 7/End of Study (EOS) Visit 
Visit 7/EOS is to occur at Week 5 (Day 36 +/- 3 days). 
 
The following will be collected via a follow up telephone call: 
 
• 
Assess for AEs and use of concomitant medications. 
• 
Remind subjects to report any new SAEs/AEs for up to 30 days after the last dose. 
6 
Selection and Withdrawal of Subjects 
6.1 
Inclusion Criteria 
All subjects entered into this trial must meet the following criteria: 
 
1. Subject is willing and able to comply with the protocol requirements, has gone through 
the consent process and has signed an approved informed consent form.    
2. Male or female subjects aged ≥ 18 years and ≤ 85 years. 
3. Subjects with acute endogenous non-infectious anterior uveitis with onset of symptoms 
within the previous 2 weeks.*  Subjects experiencing a bilateral episode of anterior 
uveitis may be eligible for study in both eyes. Evaluations for selective infectious 
etiologies, including but not limited to Syphilis, Tuberculosis (if indicated), Herpes 
Simplex, Herpes Zoster, CMV, Lyme Disease or other suspected infectious etiology, 
must be performed during the screening period or within 3 months of randomization.   
4. Presence of 6-50 anterior chamber cells within one field of view as measured with a slit 
lamp microscope (Grade 1+ to Grade 3+, Appendix 1) in the study eye(s). 
5. Subjects must have pachymetry corrected IOP <21 mmHg at baseline and non-
glaucomatous cups in the opinion of the investigator with non-glaucomatous visual fields 
if available, and may only administer a maximum of 1 topical medication to control IOP 
in the study eye.     
6. Best corrected visual acuity (BCVA) better than or equal to 35 letters in the study eye and 
65 letters in the non-study eye using ETDRS testing.  Note: this criteria is also applicable 
for a subject with bilateral uveitis. 
7. Females of childbearing potential must be using or willing to use a medically acceptable 
method (as defined by the Investigator) of birth control.  Women not of childbearing 
potential are defined as women who are either surgically sterile or postmenopausal.  


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Postmenopausal women are defined as women with cessation of menstruation for 12 
consecutive months prior to signing of the informed consent form.   
 
*A history of prior flare-ups or subsequent flare-ups in the non-study eye should not affect 
eligibility, provided that the subject is deemed capable of administering separate treatments to 
each eye. For example, if an enrolled subject experiences a flare-up in the non-study eye, the 
subject should remain in the study, and the non-study eye should receive the standard of care 
treatment. Likewise, if a potential subject was already receiving standard of care treatment in 
the non-study eye prior to enrollment, the second eye is eligible for the study and the non-study 
eye will continue to receive the standard of care. 
6.2 
Exclusion Criteria 
Subjects will be excluded from this trial if they meet any of the following criteria: 
 
1. Have severe/serious ocular pathology in the study eye(s) which may preclude study 
completion, in the judgement of the Investigator. 
2. Any medical condition or clinical laboratory test which in the judgment of the 
Investigator makes the subject unsuitable for the study. 
3. Currently or within past 5 years, have a history of malignancy other than successfully 
treated squamous or basal cell carcinoma of the skin or successfully treated in situ 
cervical cancer. 
4. Active intermediate or posterior uveitis in the study eye(s). Note: a subject with isolated 
macular edema without evidence of active intermediate or posterior uveitis is eligible for 
enrolment.  
5. Known or observed mild to severe (1-4+) fibrinoid reaction. 
6. Previous anterior uveitis episode in the study eye ≤ 4 weeks prior to Visit 1. 
7. Cataract and intraocular lens (IOL) implantation surgery or corneal transplantation in the 
study eye(s) within the past 3 months prior to Visit 1, or subjects who may require 
penetrating intraocular surgery in the study eye(s) during the study. 
 Subjects who are 3 months past uncomplicated cataract and IOL implantation 
surgery and have shown documented complete clearing of inflammation post-
surgery in the study eye(s) are eligible. 
 
Any other penetrating intraocular surgery in the study eye(s) within 3 months 
prior to Visit 1 are eligible, assuming documented complete clearing of 
inflammation post-surgery in the study eye(s). 
8. Oral corticosteroid within the past 14 days prior to Visit 1. 


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9. Topical ocular corticosteroid treatment in the study eye within the past 14 days prior to 
Visit 1 (Maximum of 3 doses of topical ocular steroid in the study eye in the 7 days prior 
to Visit 1 is permitted). 
10.  Intravitreal corticosteroid treatment in the study eye within the past 4 months prior to 
Visit 1. 
11.  Sub-Tenon corticosteroid treatment in the study eye within the past 3 months prior to 
Visit 1. 
 
 
14.  Prescribed nonsteroidal anti-inflammatory agents or immunosuppressive agents, unless 
the dose has been stable for the last 6 weeks prior to Visit 1 and no change in dosing is 
anticipated for the duration of the study. 
15.  Systemic immunomodulatory agents (e.g. azathioprine, methotrexate, mycophenolate 
mofetil), unless the dose has been stable for the last 6 weeks prior to Visit 1 and no 
change in dosing is anticipated for the duration of the study. 
16.  Pregnant or lactating female, or female of childbearing potential and using inadequate 
birth control methods. 
17.  Have participated in another investigational device or drug study within 30 days prior to 
Visit 1. 
18.  Participation in a prior ADX-102 study. 
Subjects with test results which do not meet the above inclusion/exclusion criteria may have the 
underlying test repeated once if it is thought to represent a laboratory error; a reversible, 
clinically insignificant intermittent condition; or is not consistent with the subject’s historical 
values.  If inclusion/exclusion criteria are not met after the repeat test, the subject should be 
considered a screen failure and should not be enrolled in the study. 
6.3 
Protocol Exceptions and Deviations 
Exceptions to the above eligibility criteria will not be granted. It is expected that subjects will 
meet all eligibility criteria.  Departures from the protocol should be avoided, unless required for 
the safety of the subject.  Protocol deviations will be documented by the study monitor and will 
be included in the final clinical study report. Protocol deviations should be submitted to the 
Institutional Review Board (IRB), in accordance with the site’s IRB requirements. 
6.4 
Subject Withdrawal Criteria 
Subjects may voluntarily withdraw from the study, or be removed from the study at the 
discretion of the Investigator or Sponsor, at any time.  The Investigator may withdraw a subject 


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at any time if it is determined that continuing in the study would result in a significant safety risk 
to the subject.  
 
If such withdrawal occurs, or if the subject fails to return for visits, the Investigator should 
determine the primary reason for a subject’s premature withdrawal from the study and record the 
reason in the subject’s study records. 
 
Premature withdrawal may occur for any of the following reasons: 
 
• 
Rescue therapy  
• 
Non-compliance with the protocol requirements 
• 
Death 
• 
Adverse event (AE)  
• 
Subject request 
• 
Investigator request 
• 
Sponsor request 
 
For subjects who are lost to follow-up (i.e., those subjects whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the Investigator should 
show “due diligence” by documenting in the source documents all steps taken to contact the 
subject, e.g., dates of telephone calls, registered letters, etc. 
All subjects prematurely discontinuing from the trial (prior to Visit 6), regardless of cause, 
should be seen as soon as possible for Visit 6/EOT/ET assessments (Section 5.4.4).   
 
Subjects who are withdrawn from the study for any reason will not be replaced. 
7 
Treatment of Subjects 
7.1 
Subject Numbering 
Each subject will be assigned a unique subject number.  If a subject fails to be randomized, the 
reason for not being randomized should be documented in the source documents and case report 
forms (CRFs). The subject will be considered a screen failure. 
7.2 
Description of Study Drug 
For study purposes ADX-102 and vehicle of ADX-102 ophthalmic solution are both referred to 
as study drug. 


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7.3 
Concomitant Medications 
All medications that are taken by the subject in the 30 days prior to consent must be recorded 
during the Screening (Visit 1).  Any changes in dosage or new medications added as a result of 
intercurrent illness must be recorded in the CRFs.  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
7.3.1 
Rescue Therapy 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Once it is determined that rescue therapy is needed the subject should be considered an Early 
Termination and the Week 4 (Visit 6) assessments should be completed. 
7.4 
Prohibited Medications 
Use of the following medications is prohibited for the duration of a subject’s participation in the 
study from Screening (Visit 1) through Week 4 (Visit 6/EOT/ET):  
 
• 
Any investigational treatment other than ADX-102 
• 
Any medication part of exclusion criteria (See Section 6.2) 
7.5 
Treatment Compliance 
Study drug will be taken by the subject at home throughout the study.  Subjects will be dispensed 
study drug at Visit 1, Visit 3, Visit 4 and Visit 5. Information on the time and date of each dose 
will be recorded by the subject in the dosing diary.  Subjects will be instructed to return all used 
and unused study drug and the dosing diary to the clinic at Visits 3 through 6. 
7.6 
Randomization and Masking 
Subjects will be randomized through a central randomization process by IWRS during 
Screening/Visit 1.  A randomization number will be assigned for dosing. 
ADX-102 and/or vehicle of ADX-102 ophthalmic solution will be provided in subject packs 
masked to the subject, Investigator and study staff. 
7.7 
Unmasking Procedures 
7.7.1 
Emergency Unmasking of Treatment Assignment 
Emergency unmasking should only be performed when necessary in order to treat the subject.  
There is no known antidote to ADX-102, so symptomatic and supportive management of any 
suspected and treatment related adverse event, if necessary, is clinically indicated. 
 
Unmasking will result in the subject being discontinued from the study, irrespective of whether 
the Investigator ultimately agrees with the event being related to study drug (ADX-102).  Most 


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often, study drug discontinuation and knowledge of the possible treatment assignments are 
sufficient to treat a study subject who presents with an emergency condition. The Investigator 
will have the ability to break the mask for any subject through the centralized randomization 
system (IWRS). However, the Investigator should make every effort to contact the Sponsor’s 
medical monitor or their designee to discuss the subject’s emergency situation and the need to 
unmask prior to unmasking any subject, but must contact the Sponsor or designee within one 
working day after the unmasking occurs. The mask may be broken in the case of a pregnancy 
should the subject desire this information. Any subject for whom the mask is broken is to be 
discontinued from future study treatment.  The date, time and reason for breaking the mask are to 
be recorded in the subject’s source documents. 
7.7.2 
Unmasking for Regulatory Authorities 
In cases where unmasking is required for the purposes of reporting expedited safety events to 
country specific regulatory agencies or IRBs, the unmasking will be performed by an authorized 
member of the team.  A masked version of any documents to be submitted to the authorities will 
be shared as appropriate with study staff and site personnel. Only the authorized person(s) within 
the Pharmacovigilance and Regulatory Affairs will have access to the unmasked version of any 
documents. The procedures for requesting and obtaining unmasked information and for 
maintaining the integrity of the data and clinical trial are outlined in safety management plan.   
8 
Study Drug Materials and Management 
8.1 
Study Drug 
 
 
 
 
 
 
 
 
More information on ADX-102 can be found in the Investigator’s Brochure. 
8.2 
Study Drug Packaging and Labeling 
 
   


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8.3 
Study Drug Storage 
 
 
 
 
8.4 
Study Drug Preparation 
No preparation will be required. 
8.5 
Administration 
Study drug will be self-administered by the subject (or care giver).  Subjects will begin with one 
drop in the study eye 8 times per day and then taper weekly and as described in Table 1. 
8.6 
Study Drug Accountability 
Under supervision of the Investigator, the study pharmacist or designee will be responsible for 
drug accountability. The pharmacist or designee will keep an accurate inventory of test article(s) 
and dispensing using a drug dispensing log. The pharmacist or designee must keep study drug 
inventory available for inspection by the Sponsor, an agent for the Sponsor, and regulatory 
authorities.  
 


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Subjects will be required to return all used and unused study drug to the pharmacist or designee. 
If any unused material is remaining at the site at study completion, the pharmacy will be 
instructed how to dispose of or return the material to the Sponsor after the Sponsor’s 
representative has performed accountability. The Sponsor’s representative will complete 
authorization forms for disposal or return with the responsible pharmacist or designee. Copies of 
these forms should be included with the returned material. The original form should be 
maintained in the pharmacy within the site study files. 
9 
Treatment Assessments 
9.1 
Efficacy and Safety Parameters 
Standardization of data capture is provided in detail in the remainder of this section.  
Assessments should be performed as indicated. 
9.1.1 
Medical History and Concomitant Medications 
 
 
 
 
  
 
Concomitant medications used in the 30 days prior to consent to treat any medical conditions 
will be recorded on the CRF. 
 
A standard uveitis questionnaire will be completed at Screening (Visit 1). 
9.1.2 
Demographics 
During Screening (Visit 1), age, gender, race and ethnicity will be recorded on the CRF.   
9.1.3 
Height, Weight and Vital Signs 
Height and weight will be measured at Screening (Visit 1). 
 
Vital signs, measured after at least 5 minutes of rest, will include seated systolic blood pressure 
(SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory rate (RR), and body 
temperature and will be obtained at Screening (Visit 1) and Week 4 (Visit 6-EOT/ET). All vital 


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sign measurements will be performed by appropriately qualified and authorized study personnel, 
using appropriate equipment.  
 
Blood pressure (BP) will be measured after at least 5 minutes of rest by using an automated or 
manual sphygmomanometer. The same method should be used for an individual subject 
throughout the study. The results will be recorded in millimeters of mercury (mmHg). HR will 
be measured in the radial artery in the dominant arm for 30 seconds and will be recorded as beats 
per minute (bpm). RR will be measured and recorded in breaths per minute. Body temperature 
(oral measurement) will be measured using a digital thermometer. 
9.1.4 
Clinical Laboratory 
Samples of blood and urine will be collected for clinical laboratory tests.  Tests will be 
conducted as designated below: 
9.1.4.1 
Clinical Laboratory Tests Conducted 
Clinical laboratory evaluations will include: 
 
At Screening (Visit 1) and Week 4 (Visit 6-EOT/ET) - Hematology: hemoglobin, hematocrit, 
red blood cell (RBC) count, RBC morphology, white blood cell (WBC) count with differential, 
mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular 
hemoglobin concentration (MCHC), and absolute platelet count. 
 
At Screening (Visit 1) and Week 4 (Visit 6-EOT/ET) - Serum Chemistry Profile: albumin, 
alkaline phosphatase, alanine aminotransferase (ALT; SGPT), aspartate aminotransferase (AST; 
SGOT), bilirubin (total and direct), blood urea nitrogen (BUN), calcium, carbon dioxide (CO2), 
chloride, creatinine, creatinine phosphokinase (CPK), glucose, phosphate, potassium, sodium, 
total protein, and uric acid.  
 
At Screening (Visit 1) and Week 4 (Visit 6-EOT/ET) - For WOCBP a urine pregnancy test will 
be performed and must be negative for subjects to be enrolled. 
9.1.4.2 
Abnormal and Clinically Significant Results 
The Investigator must categorize all abnormal hematology and chemistry laboratory values as 
either clinically significant (CS) or not clinically significant (NCS). Clinical significance is 
defined as any variation in laboratory parameters, which has medical consequences that result in 
an alteration in the subject’s medical care. In case of CS laboratory results, the Investigator will 


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continue to monitor the subject with additional laboratory assessments until (1) values have 
reached normal range and/or baseline levels, or (2) the Investigator has judged that the abnormal 
values are not related to the administration of study drug or other protocol-specific procedures. 
9.1.5 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
9.1.6 
Ocular Scores 
Ocular pain, blurred vision, photophobia and tearing will each be measured using a visual 
analogue scale (VAS). The VAS is a continuous 100 mm line and subjects will be asked to 
indicate their level of agreement to a statement (0 = no symptoms, 100 = worst possible 
symptoms) by placing a single vertical on the scale. The subject’s completed VAS will become 
the source document and the response, measured in mm from the left, will be transcribed into the 
CRF. 
 
The VAS will be administered at Screening, Day 4, Week 1, Week 2, Week 3 and Week 4. 


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9.1.7 
Visual Acuity 
Visual acuity will be measured with spectacle or pinhole correction at each visit. The subject will 
be asked to read a standardized eye chart (ETDRS).  Detailed instructions on Visual Acuity 
Testing are provided in the Study Manual.  Subjects should be encouraged to make an effort to 
read as many letters as possible on the chart. Distance visual acuity only will be measured. The 
right eye should be tested first. Visual acuity will be measured at Screening, Day 4, Week 1, 
Week 2, Week 3 and Week 4. 
9.1.8 
IOP Measurements 
IOP measurements will be taken using an accepted tonometry method, which includes pneumatic 
tonometry, Tono-Pen applanation tonometry or Goldmann applanation tomnometry – depending 
on the preferred method at each site.  Once a subject has enrolled in the study, the same 
tonometry method will be used for that subject throughout the duration of the study. IOP will be 
measured at Screening, Day 4, Week 1, Week 2, Week 3 and Week 4. 
9.1.9 
Slit Lamp Exam 
External examination and biomicroscopy will be performed using a slit lamp.  Magnification will 
be consistent with standard clinical practice. The clinician will examine and grade the eyelid and 
then examine the conjunctiva, cornea and anterior chamber of the eye with the aid of a slit lamp.  
Fluorescein dye will be instilled into the ocular cul-de-sac to facilitate this examination.  The 
subject will be seated during the examination.  See Appendix 1 for grading scales. ACC grade 
will be determined and for Grade 1+ and lower only, a numerical cell count will be obtained. Slit 
lamp examination will be completed at Screening, Day 4, Week 1, Week 2, Week 3 and 
Week 4. 
9.1.10 
Fundus Exam 
A dilated funduscopic exam will be performed to evaluate the vitreous, retina, choroid and optic 
nerve.  Fundus findings will be noted, described and graded as normal or abnormal. Qualitative 
descriptions will be provided for any abnormal findings. A fundus examination will be 
completed at Screening, Day 4, Week 1, Week 2, Week 3 and Week 4. 
9.1.11 
Corneal Pachymetry 
Central corneal thickness will be measured by applanation ultrasound pachymetry. For each 
measurement the highest and lowest of five consecutive readings will be discarded, and the 
average of the remaining three will be recorded. In cases where a pachymeter is used that 


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calculates an average central corneal thickness from five or more measurements with a single 
touch to the eye, this average measurement may be used for the purposes of calculating the 
pachymetry corrected IOP. Corneal pachymetry will be completed at Screening. 
9.1.12 
Dosing Instructions 
All subjects will receive written dosing instructions about how to properly administer their eye 
drops along with a printed dosing diary in which to document each dose. At Visit 1, the staff will 
review these materials with the subject and confirm that the subject understands the instructions 
on how to dose and how to complete the diary. Subjects will be instructed to bring the dosing 
diary with them to Visit 3 through Visit 6 to be reviewed by the site staff. The site staff will 
ensure compliance and review/ remind the subject on instructions as needed. 
 
Missed Doses:  If subjects forget to take a dose at the scheduled time, they should take that dose 
as soon as they remember and record the time of dosing in the dosing diary. 
 
Exceptions: Subjects should not take a “make-up” dose within one hour of another scheduled 
dose. Instead they should take the next scheduled dose and note the missed dose on the dosing 
diary. 
9.2 
Adverse Events and Serious Adverse Events 
9.2.1 
Adverse Events 
Adverse Event 
 
An AE is any untoward medical occurrence in a patient or clinical investigation patient 
administered a study drug, which does not necessarily have a causal relationship with this 
treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of the study drug 
whether or not it is considered related to the study drug. AEs will be collected from the time the 
subject signs the informed consent form through 30 days after the last study drug administration. 
 
Abnormal laboratory and other abnormal investigational findings (i.e., physical exam) should not 
be reported as AEs unless they are associated with clinical signs and symptoms, lead to treatment 
discontinuation or are otherwise considered clinically relevant by the investigator.  In cases of 
surgical or diagnostic procedures, the condition/illness leading to such a procedure is considered 
as the AE rather than the procedure itself.  In case of a fatality, the cause of death is considered 
as the AE, and the death is considered as its outcome. 


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Events Not to Be Considered as Adverse Events 
 
Pre-existing medical conditions/signs/symptoms present before the screening period that do not 
worsen in severity or frequency during the study are defined as baseline medical conditions, and 
are not to be considered AEs. 
 
All AEs must be recorded in the site’s study records and the AE CRF with the following 
information: 
 
1. 
Relationship to Study Drug:  The Investigator must assess whether they consider an AE 
to be drug-related. In assessing this relationship, the Investigator must use information 
about the drug as outlined in the Investigator’s Brochure (IB), the subject’s pre-existent 
medical conditions/concurrent medication, and chronology of the event relative to drug 
administration.  
 
The following definitions will be used: 
 
• 
Definitely or possibly related applies to those AEs that, after careful medical 
consideration at the time they are evaluated, are considered by the Investigator (or 
other qualified physician) to have at least a possible relationship to study drug. 
 
• 
Unlikely or not related applies to those AEs that, after careful medical 
consideration at the time they are evaluated, are considered by the Investigator (or 
other qualified physician) to have no relationship, or an unlikely possibility of a 
relationship, to study drug. 
 
2. 
Event Severity:  The Investigator will be asked to use their medical judgment to assess 
the severity of the AE. 
 
The following are guidelines to be used by the Investigator to judge the event severity of an AE: 
 
 
 
 
 
 
 
• 
Life Threatening 
 


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3.  
Duration: Start and end dates and times, or if continuing. 
4. 
Frequency: whether the event is a single episode, recurrent or continuous. 
5. 
Action taken. 
6. 
Whether it constitutes a SAE, per definition below. 
7. 
Outcome: resolved, resolved/ with sequelae, continuing, death, or unknown (only for 
subjects that are lost to follow-up). 
 
The Investigator (or designee) should attempt to establish a diagnosis of the AE based on signs, 
symptoms and/or other clinical information.  In such cases, the diagnosis, and not the individual 
signs/symptoms or laboratory abnormalities, should be documented in the subject’s source 
documentation and the CRF unless the etiology of the event is unknown.   An assessment should 
be made at each visit (or more frequently if necessary) of any changes in severity, the suspected 
relationship to study drug, the interventions required to treat it and the outcome. 
9.2.2 
Treatment Emergent Adverse Events (TEAE) 
A TEAE will be an AE that occurred during the study after the first dose of study drug or that 
was present prior to dosing and exacerbates after the first dose of study drug. 
9.2.3 
Serious Adverse Events 
An SAE is any AE that results in any of the following outcomes: 
 
• 
Death: This includes death unrelated to the study drug (e.g. car accident).  If a subject 
dies during the study and an autopsy is performed, autopsy results will become part of the 
subject’s study chart and a copy should be sent to the Sponsor. 
• 
Life-threatening experience. Life-threatening means that the patient was at immediate 
risk of death from the reaction as it occurred (i.e., it does not include a reaction which 
hypothetically might have caused death had it occurred in a more severe form). 
• 
Required or prolonged inpatient hospitalization: Exceptions will be hospitalizations for a) 
elective or preplanned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since the start of study drug or b) treatment 
on an emergency outpatient basis for an event not fulfilling any of the definitions of a 
SAE and not resulting in hospital admission  
• 
Persistent or significant disability/incapacity 
• 
Congenital anomaly 
• 
Important medical events that may not result in death, be immediately life threatening, or 
require hospitalization may be considered a SAE when, based upon medical judgment, 


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they may jeopardize the patient and may require intervention to prevent one of the 
outcomes listed above. 
9.2.4 
Unexpected Adverse Event 
An unexpected adverse event is defined as an AE, the nature or severity of which is not 
consistent with the information in the Investigator’s Brochure for ADX-102. 
9.3 
Reporting Serious Adverse Events 
The Investigator is responsible for reporting all SAEs, regardless of causality, to the Sponsor or 
their designated representative by phone or fax (or email) within 24 hours of learning of the 
occurrence.  The reporting timeframe starts when the subject signs the informed consent form 
through 30 days after the last study drug administration. At a minimum, a description of the 
event and the Investigator’s judgment of causality must be provided at the time of the initial 
report. These preliminary reports will be followed by detailed descriptions that will include 
copies of hospital case reports, autopsy reports, and other documents when requested and 
applicable. 
 
Complications or progression of an initial SAE must be reported as a follow-up SAE Report to 
the original SAE, regardless of when the follow-up information is received by the Investigator.  
A follow-up SAE Report must be submitted within 24 hours of the Investigator receiving the 
follow up information.  An SAE that is considered completely unrelated to a previously reported 
one should be reported separately as a new SAE. 
 
In the event of a SAE, the investigator must immediately notify the appropriate contact in the 
Study Manual.  
 
The procedures for reporting SAEs are as follows: 
 
• 
Complete the “Serious Adverse Event Report Form”.  The Investigator may contact 
Pharmacovigilance via the telephone hotline for assistance with SAE reporting. 
• 
Fax or email the SAE Form to the attention of Pharmacovigilance within 24 hours of the 
Investigator’s knowledge of the event.  
 
The original copy of the SAE Report Form and the fax confirmation sheet (or email) must be 
kept with the source documentation at the study site. 
 


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Follow-up information should be communicated the same way, using a new SAE Report Form 
stating that it is a follow-up to the previously reported SAE and giving the date of the original 
report. The follow-up information should describe whether the event has resolved or continues, if 
and how it was treated, and whether the subject continued or withdrew from study participation.  
 
If the SAE was not previously documented in the Investigator’s Brochure and is thought to be 
related to study drug, the Sponsor or their designee may urgently require further information 
from the Investigator for regulatory authority reporting. The Sponsor may need to issue an 
Investigator Notification to inform all investigators involved in any study with the same drug that 
this SAE has been reported. 
 
The Investigator and study personnel should institute any supplemental investigations of SAEs 
based on their clinical judgment of likely causative factors. This may include clinical laboratory 
tests not specified in the protocol, histopathologic examinations, or consultations with specialists. 
The Sponsor or their designee may also request the Investigator to conduct supplemental 
assessments. 
 
The Investigator should notify Pharmacovigilance of any SAE occurring after a subject has 
withdrawn from the study when such a SAE occurs within 30 days of the last dose of study drug 
and may reasonably be related to the study drug. 
9.4 
Follow-up of Adverse Events 
All AEs will be followed until clinical database lock (or stabilization/resolution if it occurs 
before database lock).  All SAEs will undergo active follow-up until resolved or the event 
becomes chronic or stable.  Follow up data for SAEs obtained after clinical database lock will be 
incorporated into the safety database. 
9.5 
Reporting Safety Information to the IRB 
The Investigator is responsible for following all local regulations for the reporting of safety 
information, including the reporting of SAEs to the IRB. 
 
The Investigator must promptly report to his or her IRB all unanticipated problems involving 
risks to subjects.  This includes death from any cause and all serious adverse events reasonably 
or possibly associated with the use of study drug.  It is recommended that all SAEs occurring at a 
site, regardless of causality, be reported to the site’s IRB in accordance with the IRB 
requirements. 


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ADX-102 has been filed under an IND application with the US FDA.  An SAE may require 
safety reports to be filed to regulatory agencies if the SAE is related to the study drug and is 
unexpected based upon the current Investigator’s Brochure.  In this case, the Investigator will 
receive a copy of the safety report as submitted to the regulatory agencies.  The Investigator is 
responsible for submitting the safety report (initial and follow up) or other safety information 
(e.g., revised Investigator’s Brochure) to the IRB in accordance with the IRB requirements and 
maintain a copy in their files. 
9.6 
Pregnancies 
To ensure subject safety, each pregnancy in a subject on study drug must be reported to 
Pharmacovigilance within 24 hours of learning of its occurrence.  Subjects who become pregnant 
will be withdrawn from the study.  The pregnancy should be followed up to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or absence 
of any birth defects, congenital abnormalities, or maternal and/or newborn complications.  
 
Pregnancy should be recorded on a subject’s source documents and a Pregnancy Notification and 
Outcome Form and reported by the Investigator to Pharmacovigilance using the same procedure 
for reporting SAEs detailed in Section 9.3. A pregnancy, by itself, is not a SAE.   Pregnancy 
follow-up should also be recorded and should include an assessment of the possible relationship 
to the study drug of any pregnancy outcome. Any pregnancy-related SAE (e.g. spontaneous 
abortion) or any other SAE experienced during pregnancy must be recorded on a separate SAE 
Report Form and reported per SAE reporting procedures in Section 9.3. 
10 
Statistics 
10.1 
Sample Size 
  
 
 
 
 
 
 


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10.2 
Randomization 
This is a multicenter, randomized, double masked, parallel group study.   
 
  
 
Subjects are eligible for enrolment with ACC Grade 1+ to 3+ disease. However, if ≥ 60 study 
subjects are noted to have Grade 1+ ACC severity further enrolment of ACC Grade 1+ severity 
will be halted as the study population is designed to represent a range of NAU subjects and not 
predominantly Grade 1+ disease.  
 
Group 1 
ADX-102 ophthalmic solution (0.5%)  
Group 2 
Vehicle of ADX-102 ophthalmic solution 
10.3 
Data Safety Monitoring Board (DSMB) 
An independent data safety monitoring board (DSMB) will be established. They will review all 
available safety data after approximately 25 subjects have completed the study visit 7. The 
assessment of safety will be determined from ophthalmologic endpoints including slit lamp 
examinations, ocular scores, visual acuity and IOP, vital sign measurements, physical 
examinations, hematology and chemistry laboratory testing, use of concomitant medications, and 
review of adverse events (AEs).  Based on the safety data provided, the DSMB will determine if 
it is acceptable to continue the study or modify the study design as appropriate. Additional 
DSMB reviews will occur throughout the trial approximately every 6 months or as deemed 
necessary by the DSMB or Sponsor to ensure subject safety and well-being. Study enrollment 
and dosing will continue while the DSMB evaluates data.  A DSMB charter will be prepared.  
The charter will contain the required information for the formation, activities and conduct of the 
DSMB. 
10.4 
Analysis 
For purposes of analysis the baseline value is defined as the last non-missing value obtained 
prior to initiation of study drug, nominally the Screening Visit. 
10.5 
Analysis Populations 
The statistical analysis will be based on the analysis populations as defined below 
 


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Safety population 
The safety population consists of all randomized subjects who receive at 
least one dose of study drug, regardless of whether or not they undergo 
any study assessments.  Subjects in this population will be analyzed 
according to the treatment which they received.  All safety analyses will 
be based on this population 
ITT population 
The intent-to-treat population (ITT) is the population of all subjects who 
are randomized into a treatment group.  Subjects in this population will 
be analyzed according to the treatment group to which they were 
randomized. This population will be used for analyses of efficacy and 
pre-study/baseline characteristics. 
PP population 
The per protocol (PP) population is the subset of ITT subjects who meet 
all inclusion and exclusion criteria, remain on study medication, comply 
with treatment instructions, and do not have any significant protocol 
deviations or violations. Rescued subjects will not be excluded from PP 
solely on the basis of having been rescued and withdrawal of study 
medication and withdrawal from the study.  Significant protocol 
violations prior to being rescued may exclude a rescued subject from the 
PP.  Subjects in this population will be analyzed according to the 
treatment they receive. 
10.6 
Accountability and Background Characteristics 
10.6.1 
Enrollment and Disposition 
The number of subjects enrolled will be presented by treatment group.  The primary reasons for 
discontinuation will be summarized by treatment and based on the ITT population.  The number 
and percentage of subjects with protocol deviations leading to exclusion from the PP population 
will be presented by reason for exclusion, stratified by treatment.  All deviations and rescued 
subjects will be listed. 
10.6.2 
Subject Characteristics 
Subject characteristics will be obtained at the Screening/Visit 1 prior to randomization and will 
be summarized by treatment group and overall.  Summaries will include descriptive statistics for 
continuous measures (sample size, mean, standard deviation, median, minimum, maximum) and 
for categorical measures (sample size, frequency and percentages). 
 
Subject characteristics will be summarized on all study populations. 


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10.6.3 
Treatment Compliance 
Treatment compliance will be assessed in terms of the actual dose.  Treatment compliance will 
be used to characterize the subjects and determine clinical evaluability for some analyses.  
Treatment compliance will be summarized within each treatment group by means of descriptive 
statistics (n, mean, SD, median, minimum and maximum). 
10.7 
Efficacy Analyses 
All of the efficacy analyses will be performed on the ITT population.  The PP population will be 
used as supportive analyses. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.8 
Safety Analyses 
Values for all safety variables will be listed by subject and time point. 
 
Where appropriate, safety variables will be summarized by using descriptive statistics, separated 
by treatment arm, and time of assessment. Descriptive statistics for quantitative variables will 


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include: n, mean, median, minimum, maximum, and standard deviation. Descriptive statistics for 
qualitative variables will include frequency counts and percentages. 
10.8.1 
Adverse Events 
AEs will be coded by the Medical Dictionary for Regulatory Activities (MedDRA) preferred 
terms, and all summary tables for AEs will be organized by these categories. Frequency counts 
and percentages will be presented for subjects with AEs within each system organ class and 
preferred term, separated by treatment arm.  Both subjects ever experiencing an event as well as 
total events will be presented.  Descriptive statistics will also be presented for AE relationship 
and AE severity. If multiple intensities are reported for a given AE for a subject, the most severe 
intensity will be counted.  
 
SAEs and TEAEs that resulted in termination of the study drug and withdrawal from the study 
will be presented. 
11 
Direct Access to Source Data/Documents 
11.1 
Study Monitoring 
The investigator will allow the Sponsor or a designee to: 
 
• 
Inspect the site, the facilities, and the material used for the study; 
• 
Meet all members of the team involved in the study; 
• 
Consult all the documents relevant to the study; 
• 
Check that the CRFs have been correctly completed; 
• 
Have direct access to source documents for comparison of data therein with the data in 
the CRFs; 
• 
Check that AEs have been documented; and 
• 
Verify that the study is carried out in compliance with the protocol. 
 
This study will be monitored at regular intervals, by agreement of the Investigator.  
All information dealt with during these visits will be treated as strictly confidential. 
 
The Investigator will provide the sponsor with the following: 
• 
Progress reports at regular intervals 
• 
Adequately completed CRFs 


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11.2 
Data Collection 
For each subject, CRF and corresponding source records will be maintained at each clinical site.  
Case report forms should be completed in a timely manner, and every effort should be made to 
have forms completed and current in anticipation of a visit by the Sponsor’s monitor.  Upon 
study completion, the monitor will arrange for a final review of the study files, after which the 
file should be secured by storage for the appropriate period as specified in Section 14. 
11.3 
Audits and Inspections 
The Investigator may be informed that an audit will be carried out, at the request of the Sponsor, 
before, during, or after the study. 
 
The Investigator will be informed that the Regulatory Agencies may also carry out an inspection. 
In this case, the Investigator must inform the sponsor as soon as he receives the notification of 
inspection. 
 
The Investigator must allow the representatives of the Regulatory Agencies and persons 
responsible for the audit to: 
 
• 
Inspect the site, facilities, and material used for the study; 
• 
Meet all members of his team involved in the study; 
• 
Have direct access to study data and source documents; and 
• 
Consult all the documents relevant to the study. 
12 
Quality Control and Quality Assurance 
The Investigator or the appointed persons agree to complete the subject's CRF. Only the 
Investigator or appointed persons in his/her team may fill out or correct the CRFs.  
 
The Sponsor or their designee will review the CRFs entered by investigational site staff for 
completeness and accuracy and instruct the investigational site staff to make any required 
corrections or additions.  Queries will be sent to the investigational site and designated 
investigational site staff will be required to respond to the query and edit data as necessary.   
 
All corrections and alterations of data on the CRFs must be made by the Investigator or by the 
appointed persons as instructed in the CRF guidelines. If corrections or alterations are required 
of paper source documents, corrections may be made in the following manner: strike through the 
datum to be corrected using a single line so that the original remains legible; correction fluid 


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must never be used. The correction should be written to the side or above the original entry and 
must be initialed and dated by the Investigator or designee. 
 
It is the responsibility of the monitor to make certain that all data are completed on the CRFs. 
At the end of each study period, the Investigator must sign and date the CRF to attest to the: 
 
• 
Authenticity of the data collected in the CRF, and 
• 
Coherence between the data in the CRF and those in the source documents. 
 
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system.  
Adverse events will be coded using the Medical dictionary for regulatory activities (MedDRA) 
terminology. 
 
Randomization codes and study drug dispensation will be tracked using a centralized 
randomization process.  The system will be supplied by a vendor managing the database.   
 
After the above actions have been completed and the database has been declared to be complete 
and accurate, it will be locked for data analysis.  Any changes to the database after that time can 
only be made with the approval of Aldeyra Therapeutics, Inc. 
 
The Investigator will enter all subjects screened for study participation and the reason why 
individual subjects did not enter the study into the CRF. The Investigator must submit to the 
Sponsor or its representatives a completed CRF for each subject who receives any study drug. 
 
If computerized medical files are used, and if the computer system allows, no change made in the 
medical files by the Investigator should obscure the original information. The record must clearly 
indicate that a change was made and clearly provide a means to locate and read the prior 
information. The Investigator will save data at regular intervals. 
 
The Investigator must guarantee the integrity of the study data in the medical files by 
implementing security measures to prevent unauthorized access to the data and to the computer 
system. 
13 
Ethics 
This clinical study was designed and shall be implemented and reported in accordance with the 
ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 


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regulations (US Code of Federal Regulations Title 21), and with the ethical principles laid down 
in the Declaration of Helsinki. 
13.1 
Ethics Review 
13.1.1 
IRB Opinion 
Before initiation of the study, the Investigator must obtain approval or favorable opinion of the 
study, informed consent, privacy authorization, and any advertisement for subject recruitment 
from a properly constituted IRB before study start.  A signed and dated statement that the 
protocol and informed consent and advertisement (as applicable) have been approved by the IRB 
must be given to Aldeyra Therapeutics, Inc. or its designated representative(s) before study 
initiation.  Prior to study start, the Investigator is required to sign the Investigator statement page 
confirming his/her agreement to conduct the study in accordance with these documents and all of 
the instructions and procedures found in this protocol. 
 
The Investigator is responsible for obtaining continued review of the study at intervals not 
exceeding one year or otherwise specified by the IRB.  The Investigator must supply Aldeyra or 
its designated representative(s) with written documentation of continued review of the clinical 
study. 
 
The Investigator must promptly inform their IRB of all SAEs or other safety information 
reported from Sponsor or its designated representatives. 
13.2 
Written Informed Consent 
Subjects will be informed of the nature of the study, its aim, its possible risks and restrictions, its 
duration and the fee, if any, they will receive. The protocol will be explained during a meeting 
prior to the study and each subject must be informed that participation in the study is voluntary 
and that he/she may withdraw from the study at any time. At this meeting, the informed consent 
form will be given to each subject. The subject should read the form and obtain answers to any 
questions prior to signing and dating the informed consent form. The process of obtaining 
informed consent should be documented in the subject source documents.  Each Investigator 
must retain the original signed and dated informed consent form.  A copy of the signed and dated 
informed consent form will be given to the subject.  No subject can enter the study, or have study 
specific assessments performed before his/her informed consent has been obtained. 
 
Aldeyra Therapeutics, Inc. or its designated representative(s) will provide to Investigators in a 
separate document a proposed informed consent form that complies with the ICH GCP guideline 


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and regulatory requirements and is considered appropriate for this study.  Any changes to the 
proposed consent form suggested by the Investigator must be agreed to by Aldeyra or its 
designated representative(s) before submission to the IRB, and a copy of the approved version 
must be provided to Aldeyra or its designated representative(s) after IRB approval. 
13.3 
Amendments to the Protocol 
To alter the protocol, amendments must be written by Aldeyra Therapeutics, Inc., and approvals 
must be received from all parties that approved the original protocol (IRB, and if applicable, the 
local regulatory authorities) before implementation.  However, in cases where an amendment is 
required for subject safety, an amendment may be implemented prior to IRB approval.  
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any subject included in this 
study, even if this action represents a deviation from the protocol.   
 
Aldeyra may make administrative changes (i.e., changes that do not significantly affect subject 
safety, the study’s scope or scientific quality) without a formal protocol amendment. 
13.4 
Discontinuation of the Study 
Aldeyra Therapeutics, Inc. reserves the right to discontinue this study under the conditions 
specified in the clinical trial agreement. 
13.5 
Study Drug Supply, Storage and Tracking 
 
 
 
 
 
 
 
 
 
 
 
  
 


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The pharmacist or designee will keep an accurate accounting of all study drug dispensed, 
destroyed or returned.  Monitoring of drug accountability will be performed by the monitor 
during site visits and at the completion of the trial. 
13.6 
Confidentiality 
All study findings and documents will be regarded as confidential.  The Investigator and other 
study personnel must not disclose such information without prior written approval from Aldeyra 
Therapeutics, Inc. Subject confidentiality will be strictly maintained to the extent possible under 
the law.  Subject names must not be disclosed.  Subjects will be identified on the CRFs and other 
documents submitted to Aldeyra, or its designated representative, by their initials and/or assigned 
subject number.  Documents that identify the subject (e.g., the signed informed consent form) 
should not be submitted to Aldeyra or its designated representative, and must be maintained in 
confidence by the Investigator. 
13.7 
Publication Policy 
As is customary for multicenter trials, publication by individual study sites or 
Investigator/Institution will not be allowed without the explicit written permission of the 
Sponsor.  The Sponsor will determine authorship of the principal study manuscript(s) in 
conjunction with the Investigators, in abiding with current guidelines and requirements of 
medical journals. For such manuscript(s), masthead roles for Investigators will be determined 
based on subject enrollment and scientific contributions to the Study.   
14 
Retention of Records 
Essential documents, as listed below, must be retained by the Investigator for as long as required 
by national and international regulations.  The Sponsor will notify the 
Investigator(s)/institution(s) when the study-related records are no longer required.  The 
Investigator agrees to adhere to the document retention procedures by signing the protocol.   
 
Essential documents include: 
 
• 
IRB approvals for the study protocol and all amendments 
• 
All source documents and laboratory records 
• 
CRF copies (electronic copies on a CDROM) 
• 
Subjects' informed consent forms (with study number and title of trial) 
• 
FDA form 1572 
• 
Any other pertinent study document 
 


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15 
References 
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Aldeyra Therapeutics, Inc. 
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Final: V4.0 20Jun2018 
 
52 of 53 
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Aldeyra Therapeutics, Inc. 
Protocol ADX-102-UV-005 
Final: V4.0 20Jun2018 
 
53 of 53 
Proprietary and Confidential 
Appendix 2. Correction Table for Adjusting IOP Based on Central Corneal Thickness