Clinical trial NCT04222712
Conditions: Non-infectious Anterior Uveitis
Sponsor: Tarsier Pharma
Start date: 2020-02-01; Completion date: 2020-08-24
Enrollment: 16 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of this study is to evaluate the safety of TRS01 eye drops in participants with active non-infectious anterior uveitis

.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: TRS01 eye drops intervention 2: TRS01 eye drops
Intervention descriptions: intervention 1: Dosed four times a day (QID) intervention 2: Dosed four times a day (QID)

Protocol documents:
Prot_SAP_000.pdf: 
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  CONFIDENTIAL 
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Project: 
TRS01 
Compound Number / Name: 
TRS01 
Protocol Number: 
GADOT 20/20 
Protocol Title: 
A Phase I/IIa Randomized, Double-Masked, Dose-
Ranging Study to Evaluate the Safety and 
Tolerability of TRS01 Eye Drops in Subjects with 
Active Non-infectious Anterior Uveitis. 
Sponsor: 
Tarsius Pharma, Ltd. 
19 Yahalom St. 
Zichron Yaacov 
30900 Israel 
Medical Monitor: 
 
  
 
Tarsius Pharma, Ltd. 
Clinical Protocol GADOT 20/20 Trial 
NCT04222712


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Project: 
 
 
 
 
TRS01 
 
Compound Number / Name: 
 
TRS01 
 
Protocol Number: 
 
 
 
GADOT 20/20 
 
Protocol Title: 
A Phase I/IIa Randomized, Double-Masked, Dose-
Ranging Study to Evaluate the Safety and 
Tolerability of TRS01 Eye Drops in Subjects with 
Active Non-infectious Anterior Uveitis. 
Sponsor: 
 
 
 
 
Tarsius Pharma, Ltd. 
 
 
 
 
 
 
19 Yahalom St. 
 
 
 
 
 
 
Zichron Yaacov 
 
 
 
 
 
 
 
30900 Israel 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Contact for Serious   
 
 
 
Adverse Events: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator Name: 
 
___________________________________________ 
 
Investigator’s Signature: 
 
___________________________________________                                 ________________ 
 
 
 
 
 
 
 
 
 
 
Date  
 
 
 
 
Tarsius Pharma, Ltd. 
Clinical Protocol GADOT 20/20 Trial 
Investigator Signature Page 




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two sites. 
Study subjects will administer the randomly assigned treatment 4 times a 
day (QID) for 28 days. All study subjects will return for examination on 
Week 1, Week 2, Week 3, Week 4, Week 7 and Week 10.  
Clinical assessments will include the following:  
• Slit-lamp biomicroscopy 
• Dilated ophthalmoscopy 
• Intraocular pressure (IOP)  
• Best Corrected Visual Acuity (BCVA)   
• Macular optical coherence tomography (OCT) 
• Anterior Chamber SD-OCT (if available at the site) 
• Adverse events (AEs)  
• Subject-rated ocular pain assessment 
The Study Visit Schedule and assessments to be performed are described 
in Appendix 1. 
Rescue therapy will be offered if one or more of the following rescue 
criteria are met and a rescue therapy treatment plan is discussed with the 
Tarsius Medical Officer: 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Safety and 
Tolerability 
Outcomes 
Assessment of both systemic and ocular adverse events. AEs will be 
captured by verbatim term and coded using MedDRA. 
Relevant clinical findings will also be recorded in the electronic case report 
form (eCRF) related to the following: 
1. BCVA using ETDRS 
2. Slit-lamp biomicroscopy, specifically evaluation of intraocular 
anterior inflammation 
3. IOP measurement 
4. Dilated ophthalmoscopy 
5. Safety parameters of interest include a change from baseline to each 
visit in ocular signs such as corneal/conjunctival tolerability and IOP 
measurements. 
Exploratory 
Efficacy 
Measurements 
• Anterior chamber cell count by slit-lamp biomicroscopy and by 
anterior chamber SD-OCT in selected sites. 
• Anterior chamber flare assessed on slit-lamp biomicroscopy  
• Change in macular edema by macular OCT 
• Subject-rated ocular pain assessment  
Eligibility 
Criteria 
Inclusion Criteria 
Individuals of either gender or any race will be eligible for study 
participation if they are: 
1) 18 years of age or older 
2) Able to provide informed consent, follow instructions and 
complete all required study visits for the duration of the study. 
3) Diagnosed with active non-infectious anterior uveitis requiring 
an increase or initiation of topical steroids for management of 
ocular inflammation.  
An eligible subject must have: 
 
 
 
 
 
 
 
 
 
     
 


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5) Use adequate birth control by men and women, if of reproductive 
potential and sexually active. Adequate birth control is defined as 
agreement to consistently practice an effective and accepted 
method of contraception throughout the duration of the study and 
for 2 weeks after the last study visit. 
a) For females of childbearing potential, adequate birth control 
methods will be defined as hormonal contraceptives, 
intrauterine device or double barrier contraception, i.e., 
condom + diaphragm, condom or diaphragm + spermicidal 
gel or foam. 
b) For males, adequate birth control methods will be defined as 
double barrier contraception, i.e., condom + diaphragm, 
condom or diaphragm + spermicidal gel or foam. 
c) For postmenopausal females, menopause is defined as one 
year without menses; if in question, a follicle-stimulating 
hormone of >40 IU/L must be documented. Hysterectomy, 
bilateral oophorectomy, or bilateral tubal ligation must be 
documented, as applicable. 
Exclusion Criteria 
In order for a subject to be eligible they may not:  


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• Have any form of infectious uveitis. 
• Have active retinitis. 
• Have cancer or melanoma that is actively treated with 
immunotherapy. 
• Be pregnant or lactating. 
• Have been treated with intravitreal or periocular steroids in the study 
eye within 90 days of Visit 1 or for the duration of the study  
(including but not limited to Iluvien, Retisert, Ozurdex, etc.). 
• Have been treated with any intravitreal injection within 30 days 
prior Visit 1 or for the duration of the study. 
• Require treatment with any systemic steroids greater than 10 
mg/day.   
• Require topical ocular therapy with steroids more than twice a day 
(BID) in the study eye.  Note: up to 3 additional drops of topical 
steroids within 7 days prior to Visit 1 is permitted. 
• Be diagnosed with Fuchs Corneal Dystrophy. 
• Use any topical ophthalmic medications other than those allowed in 
the study. 
• Have any significant ocular disease in addition to the uveitis that 
may confound the trial results per the Investigator’s judgement. 
• In the opinion of the Investigator, have current clinically significant 
dry eye requiring therapy of greater than twice a day (BID) eye 
drops in the study eye. Use of PRN artificial tears up to twice a day 
is allowed and should not be dosed within 10 minutes of 
investigational product dosing. 
• Use any Cannabidiol products during the trial. 
• 
, narrow angle glaucoma, or glaucoma treated 
with more than two anti-glaucoma drugs in the study eye. Anti-
glaucoma eye drops should be dosed at least 30 minutes before the 
investigational product dosing. 
• Have poor posterior view due to dilation or media opacity that limits 
ability to do OCT, or photography.  
• Have any clinically significant systemic disease or condition (e.g. 
hematological diseases) that, in the Investigator's opinion, may 
confound the trial results, pose a safety risk to the subject or 
preclude the subject from adhering to the protocol or completing the 


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trial per protocol, or instilling eye drops. 
• Have had corneal refractive, laser or incisional surgery in the study 
eye within three months of Visit 1. 
• Have a known history of alcohol and/or drug abuse. 
• Have been exposed to an investigational drug or investigational 
medical device within 60 days prior to Visit 1. 
• Be an employee of the site that is directly involved in the 
management, administration, or support of this study or be an 
immediate family member of the same.  
 


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TABLE OF CONTENTS 
1 
Introduction ......................................................................................................................... 15 
1.1 
Description of Investigational Product ........................................................................... 16 
1.2 
GCP Compliance ............................................................................................................ 18 
1.3 
Study Population ............................................................................................................ 18 
1.3.1 
Determination of Study Eye .................................................................................... 18 
2 
Study Objectives.................................................................................................................. 19 
3 
Study Design ........................................................................................................................ 20 
3.1 
Safety Endpoints ............................................................................................................ 20 
3.2 
Exploratory Efficacy Endpoints ..................................................................................... 20 
3.3 
Description of the Study Design .................................................................................... 20 
3.3.1 
Investigational product kit ...................................................................................... 22 
3.3.2 
Treatments administered ......................................................................................... 23 
3.3.3 
Method to minimize bias ........................................................................................ 23 
4 
Selection of Study Population ............................................................................................ 24 
4.1 
Subject Inclusion Criteria ............................................................................................... 24 
4.2 
Subject Exclusion Criteria .............................................................................................. 25 
4.2.1 
Masking and Randomization Methodology ............................................................ 27 
4.3 
Informed Consent ........................................................................................................... 27 
5 
Study Assessments .............................................................................................................. 28 
5.1 
Timing of Study Assessments ........................................................................................ 28 
5.1.1 
Visit 1: Screening/Randomization:  Day 1 ............................................................. 28 
5.1.2 
Visit 2: Week 1/Day 7 (±2 days) Treatment Evaluation ......................................... 29 
5.1.3 
Visit 3: Week 2/Day 14 (±2 days) Treatment Evaluation ....................................... 29 
5.1.4 
Visit 4: Week 3/Day 21 (±2 days) Treatment Evaluation ....................................... 30 
5.1.5 
Visit 5: Week 4/ Day 28 (±2 days) Evaluation and End of Study Treatment ......... 31 
5.1.6 
Visit 6:  Week 7/Day 49 (± 3 days) Follow-up Period: .......................................... 31 
5.1.7 
Visit 7: Week 10/Day 70 (± 3 days) Follow-up Period .......................................... 31 
5.1.8 
Unscheduled Visits ................................................................................................. 32 
5.2 
Withdrawal Criteria / Early Termination ....................................................................... 32 
6 
Treatment of Subjects......................................................................................................... 33 
6.1 
Prior and Concomitant Therapy ..................................................................................... 33 


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6.2 
Permitted Medications.................................................................................................... 33 
6.3 
Rescue medication use ................................................................................................... 34 
6.4 
Medications Not Permitted............................................................................................. 35 
6.5 
Treatment Compliance ................................................................................................... 35 
7 
Safety and Efficacy Variables ............................................................................................ 36 
7.1 
Safety Variable ............................................................................................................... 36 
7.2 
Safety Variables ............................................................................................................. 36 
7.2.1 
Adverse Events ....................................................................................................... 37 
7.2.2 
Criteria for Rescue Therapy .................................................................................... 37 
7.2.3 
Other Safety Variables ............................................................................................ 38 
7.3 
Adverse Event Definitions ............................................................................................. 38 
7.4 
Procedures for AE Reporting by the Investigator .......................................................... 39 
7.5 
Serious Adverse Event Reporting by the Investigator ................................................... 40 
8 
Exploratory Efficacy ........................................................................................................... 42 
8.1 
Efficacy Variables .......................................................................................................... 42 
8.1.1 
Anterior Chamber Cells .......................................................................................... 42 
8.1.2 
Flare ........................................................................................................................ 42 
8.1.3 
Macular OCT .......................................................................................................... 43 
8.1.4 
Best Corrected Visual Acuity ................................................................................. 43 
8.1.5 
Subject-Rated Ocular Pain Assessment .................................................................. 43 
9 
Statistics ............................................................................................................................... 44 
9.1 
Statistical Methods ......................................................................................................... 44 
9.1.1 
Subject Disposition, Demographic and Background Characteristics ..................... 44 
9.1.2 
Analysis of Safety ................................................................................................... 44 
9.1.3 
Analysis of Efficacy ................................................................................................ 44 
9.2 
Sample Size Estimation .................................................................................................. 45 
9.3 
Level of Significance ..................................................................................................... 45 
9.4 
Procedure for Accounting for Missing, Unused, or Spurious Data ............................... 45 
9.5 
Procedure for Reporting Deviations from the Statistical Plan ....................................... 45 
9.6 
Subjects to be Included in the Analysis ......................................................................... 45 
10 Direct Access to Source Data/Documents ......................................................................... 46 
11 Quality control .................................................................................................................... 47 


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12 Ethics .................................................................................................................................... 48 
12.1 Independent Ethics Committee or Institutional Review Board ...................................... 48 
13 Amendments to the Protocol .............................................................................................. 49 
14 Data handling and recordkeeping ..................................................................................... 50 
14.1 Records Retention .......................................................................................................... 50 
15 Publication Policy................................................................................................................ 51 
16 Appendices ........................................................................................................................... 52 
17 References ............................................................................................................................ 53 
 
 
 
 


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LIST OF TABLES 
TABLE 1: TRS01 DOSING VOLUME AND DOSE DELIVERY ............................................................. 16 
TABLE 2: COMPOSITION OF TRS01 
AND  
 INVESTIGATIONAL PRODUCT ........................... 17 
TABLE 3: OCULAR SAFETY MEASURES .......................................................................................... 36 
 
 
LIST OF FIGURES 
Figure 1:  Study Schematic ........................................................................................................... 22 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation/Term 
Definition 
ACC 
Anterior Chamber Cells 
AE 
Adverse Event 
API 
Active Pharmaceutical Ingredient  
 
 
AR 
Adverse Reaction 
BCVA 
Best Corrected Visual Acuity 
BID 
Twice Daily 
C 
Degrees Celsius 
CRF 
Case Report Form 
eCRF 
Electronic Case Report Form 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
F 
Degrees Fahrenheit  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee  
IOP 
Intraocular Pressure 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IU/L 
International Units per Liter 
ITT 
Intent-to-Treat 
IWRS 
Interactive Web Response System 
LDPE 
Low-density polyethylene 
MedDRA 
Medical Dictionary for Regulatory Activities 
µg 
Microgram 
µL 
Microliter 
mmHg 
Millimeters of Mercury 
mg 
Milligram 
mL 
Milliliter 
OCT 
Optical Coherence Tomography 
OD 
Oculus Dexter (right eye) 
OS 
Oculus Sinister (left eye) 


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Abbreviation/Term 
Definition 
OTC 
Over the counter 
OU 
Oculus Uterque (both eyes) 
PP 
Polypropylene 
PP 
Per Protocol 
PRN 
As Needed 
QID 
Four times daily 
SAE 
Serious Adverse Event 
SAR 
Suspected Adverse Reaction 
SD-OCT 
Spectral-Domain Optical Coherence Tomography 
US 
United States of America 
VA 
Visual Acuity 
w/v 
Weight to Volume 
 
 


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1 
INTRODUCTION 
Uveitis refers to a broad spectrum of ocular inflammatory diseases which are associated with 
both systemic infectious and non-infectious conditions.  Non-infectious uveitis, a potentially 
blinding condition that is the fifth leading cause of visual loss in the developed world (third 
leading cause of preventable blindness), has been estimated to account for 10% of all visual 
impairment in the western world and 10–15% of cases of total blindness [Nussenblatt, 1990; 
Merida et al., 2015].  
The inflammation associated with uveitis affects the uvea of the eye (iris, ciliary body and 
choroid) and it is characterized by an inflammatory process that may be acute, recurrent, chronic 
or acute-on-chronic. Untreated, recurrent bouts of uveitis eventually lead to tissue destruction 
from direct inflammation or from complications such as cataract, glaucoma and macular edema. 
Clinically, uveitis manifestations include pain, blurry vision, conjunctival hyperemia, anterior 
chamber cells, anterior chamber flare, fibrin deposition and corneal endothelial inflammatory 
precipitates. 
Uveitis may affect either the anterior or the posterior segment or in the case of panuveitis, it 
affects the entire eye.  Anterior uveitis, which specifically refers to uveitis in the anterior 
segment of the eye, is the most common and accounts for approximately 80% of non-infectious 
uveitis cases in the United States [Thorne et al., 2016].   
The present clinical trial evaluates the treatment of non-infectious anterior uveitis with TRS01. 
Topical corticosteroids represent first line treatment for both non-infectious anterior uveitis and 
postoperative inflammation [Kim et al., 2019]. The side effects associated with steroid use 
significantly limit prolonged treatment. The most common adverse effects of ocular steroids are 
cataract and elevated intraocular pressure (IOP) which can lead to steroid related glaucoma. 
Given the limitations of steroid treatment, there is an unmet medical need for an effective anti-
inflammatory drug that does not have an IOP-elevating effect or cause the formation of cataracts. 
Tarsius Pharma, Ltd. has developed a novel therapeutic approach for local prevention and 
treatment of ophthalmic inflammatory diseases. 
 
 
 
 
  
 
 
 
 
TRS is the active drug substance of TRS01 which is an 
 drug product 
candidate developed for topical ocular administration (eye drops).  Pre-clinical studies have 
demonstrated the safety and tolerability of TRS01.   




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Double-masked doses will be assigned through the randomization program. The treatment 
schedule is shown in Figure 1:  Study Schematic. TRS01 will be administered no more 
frequently than four times daily (QID) per protocol. 
 
TABLE 2: COMPOSITION OF TRS01 
 AND 
 INVESTIGATIONAL PRODUCT 
Ingredient 
Ingredient name 
According to USP 
Function 
Concentration (%w/v) 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.2 
GCP COMPLIANCE 
The study will be conducted in accordance with the study protocol, Good Clinical Practice 
(GCP), International Conference on Harmonization (ICH) of technical requirements for 
registration of pharmaceuticals for human use guidelines. Compliance with these requirements is 
consistent with the ethical principles that have their origins in the Declaration of Helsinki 
(Declaration of Helsinki, 2013). 
1.3 
STUDY POPULATION  
The study population will consist of male and female subjects, aged 18 or older, with active non-
infectious anterior uveitis requiring treatment with corticosteroids. Up to 20 subjects that meet 
the selection criteria will be randomized to two treatment groups. 
 
1.3.1 Determination of Study Eye  
 
 
 
 
    
 
 
 


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2 
STUDY OBJECTIVES 
The primary objective of the study is to investigate the safety and tolerability of TRS01 
 
 (w/v) eye drops in subjects with active non-infectious anterior uveitis. 
The exploratory objective of the study is to evaluate the preliminary efficacy of TRS01
 
(w/v) eye drops in reducing inflammation is subjects with active non-infectious anterior 
uveitis.  
 
 


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3 
STUDY DESIGN 
This is a Phase I/IIa randomized, double-masked, dose-ranging study designed to evaluate 
the safety and tolerability of TRS01 eye drops 
 in subjects with active non-
infectious anterior uveitis.  
 
3.1 
SAFETY ENDPOINTS 
The primary safety parameter in this study is the incidence and severity of treatment-emergent 
and treatment-related adverse events (AEs), both systemic and ocular adverse events in subjects 
with inflammation due to active non-infectious anterior uveitis.   
1. BCVA 
2. Slit-lamp biomicroscopy 
3. IOP measurement 
4. Dilated ophthalmoscopy 
5. Safety parameters of interest include a change from baseline to each visit in ocular signs 
such as corneal/conjunctival tolerability and IOP measurements. 
All relevant clinical findings will be recorded in the electronic case report form (eCRF). 
3.2 
EXPLORATORY EFFICACY ENDPOINTS 
1. Anterior Chamber Cell count on slit-lamp biomicroscopy. Anterior chamber spectral-
domain optical coherence tomography (SD-OCT) will also be conducted at selected sites. 
2. Anterior chamber flare assessed on slit-lamp biomicroscopy  
3. Change in macular edema by macular OCT 
4. Subject-rated ocular pain assessment  
3.3 
DESCRIPTION OF THE STUDY DESIGN 
This is a Phase I/IIa randomized, double-masked,  dose-ranging study designed to evaluate 
the safety and tolerability of TRS01 eye drops 
 in subjects with active non-
infectious anterior uveitis.  
Potential study subjects will be required to sign an informed consent document and meet all 
inclusion/exclusion criteria. 
Eligible subjects will be randomized to treatment as follows:  
• 
 
 
 
Once it is determined that all eligibility criteria have been met subjects will be enrolled and 
treated with one of two concentrations of TRS01 in a 1:1 ratio. Approximately 20 eligible 
subjects will be enrolled at approximately two sites. 


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Study subjects will administer the randomly assigned treatment 4 times a day (QID) for 28 days. 
All study subjects will return for examination on Weeks 1, 2, 3 and 4 (Treatment Phase) with  
post-treatment evaluations (Follow-Up Phase) at Weeks 7 and Week 10.  Figure 1:  Study 
Schematic summarizes the study phases, anticipated visits and number of subjects at each phase 
and Appendix 1 summarizes the schedule of assessments from Screening through Week 10. 
Treatment assignments will be masked to Tarsius, study subjects, Investigators, and site staff. In 
order to prevent unmasking, all study medications during the Treatment Period will be supplied 
in identical packages. 
Randomization is employed as an unbiased method of assigning subjects to two groups in equal 
allocation (1:1 ratio).  
Visits: 
1. Visit 1/Day 1 – Screening/Randomization: Initial screening for eligibility and randomization 
to treatment.   Subjects who meet the qualification criteria with anterior chamber cells Grade 
 in the study eye will be randomized and will initiate 
dosing with IP. The subject’s first dose will occur after randomization under the observation 
of an unmasked staff member.   
1.1. 
 post first dose, AEs, if any, will be recorded. Subjects will be 
given one bottle of IP and instructed to dose at the remaining time points for that day 
(midday, afternoon, and evening if appropriate) and to begin dosing four times a day on 
the following day and onward. 
2. Visit 2/Week 1 – Evaluation 
. 
3. Visit 3/Week 2 – Evaluation 
. 
4. Visit 4/Week  3 – Evaluation 
. 
5. Visit 5/Week 4 – Conclusion of 28 days of dosing/treatment phase, 
. 
6. Visit 6/Week 7 – Evaluation 
7. Visit 7/Week 10 – Evaluation and study completion. 
Please note that both eyes cannot be part of the study – there should be a treated eye (study eye) 
and an untreated eye (non-study eye). 
A schematic of the study design is below in Figure 1:  Study Schematic. 
 
 
 
 
 




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3.3.2 Treatments administered 
Eligible subjects for GADOT 20/20 Trial will be randomized in a 1:1 ratio to receive 
 
 of TRS01
 or TRS01
 for the 28-day Treatment Period. All doses 
will be administered as eye drops in the inferior conjunctival fornix.  
Subjects will be asked by unmasked study personnel to dose with the drops prior to leaving the 
clinic on Day 1. Subjects will be advised to 
 and to 
dose approximately every four hours during the day (example: first dose - morning, second dose 
- midday, third dose - afternoon and fourth dose - evening). To increase assurance of IP delivery, 
subjects will be instructed to repeat a dose if they feel they did not effectively dispense adequate 
IP into their study eye. Every daily application of the drug will be recorded in the subject’s 
dosing diary. 
3.3.3 Method to minimize bias 
In order to prevent unmasking during the study, the two doses of TRS01 will be supplied in 
identical packages identified with kit numbers. 
 
 
 
  
The first dose will be administered under the supervision of an unmasked staff member and will 
serve as confirmation that the subject can adequately administer the IP. In the event that it 
becomes necessary to unmask a specific subject’s treatment assignment, the Principal 
Investigator will contact Tarsius Medical Officer or the back-up Medical Officer. Unmasking 
will be allowed for individual subjects after it is determined necessary by the Medical Officer 
and the Principal Investigator, thus leaving the masking of the remaining subjects intact. 
 
 




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contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel 
or foam. 
b. For males, adequate birth control methods will be defined as double barrier 
contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel 
or foam. 
c. For post-menopausal females, menopause is defined as one year without menses; 
if in question, a follicle-stimulating hormone of >40 IU/L must be documented. 
Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be 
documented, as applicable. 
4.2 
SUBJECT EXCLUSION CRITERIA 
In order for a subject to be eligible at Visit 1 (Screening and Randomization) they may not:  
1. Have any form of infectious uveitis. 
2. Have active retinitis. 
3. Have cancer or melanoma that is actively treated with immunotherapy. 
4. Be pregnant or lactating. 
5. Have been treated with intravitreal or periocular steroids in the study eye within 90 days 
prior to Visit 1 or for the duration of the study (including but not limited to Iluvien, 
Retisert, Ozurdex, etc.). 
6. Have been treated with any intravitreal injection within 30 days prior to Visit 1 or for the 
duration of the study. 
7. Require treatment with any systemic steroids greater than 10 mg/day.   
8. Require topical ocular therapy with steroids more than BID in the study eye.  Note: up to 
3 additional drops of topical steroids within 7 days prior to Visit 1 is permitted. 
9. Be diagnosed with Fuchs Corneal Dystrophy. 
10. Use any topical ophthalmic medications other than those allowed in the study. 
11. Have any significant ocular disease in addition to the uveitis that may confound the trial 
results per the Investigator’s judgement. 
12. In the opinion of the Investigator, have current clinically significant dry eye requiring 
therapy of greater than twice a day (BID) eye drops in the study eye. Use of PRN 
artificial tears up to twice a day is allowed and should not be dosed within 10 minutes of 
investigational product dosing. 
13. Use any Cannabidiol products during the trial. 
14. 
, narrow angle glaucoma or glaucoma treated with more than two 
anti-glaucoma drugs in the study eye. Anti-glaucoma eye drops should be dosed at least 
30 minutes before the investigational product dosing. 
15. Have poor posterior view due to dilation or media opacity that limits ability to do OCT, 


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or photography.  
16. Have any clinically significant systemic disease or condition (e.g. hematological 
diseases) that, in the Investigator's opinion, may confound the trial results, pose a safety 
risk to the subject or preclude the subject from adhering to the protocol or completing the 
trial per protocol, or instilling eye drops. 
17. Have had corneal refractive, laser or incisional surgery in the study eye within three 
months of the Visit 1. 
18. Have a known history of alcohol and/or drug abuse. 
19. Have been exposed to an investigational drug or investigational medical device within 60 
days prior to Visit 1. 
20. Be an employee of the site that is directly involved in the management, administration, or 
support of this study or be an immediate family member of the same. 
 
 
 


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4.2.1 Masking and Randomization Methodology 
Eligible subjects will be randomized in a 1:1 ratio to receive TRS01-
 or TRS01
 on Day 
1. 
Randomization will occur after subjects meet all eligibility requirements at Screening Day 
1/Visit 1. Each subject will be assigned a unique subject number.  
Each kit package 
 will contain a kit number that can be later correlated 
to the subject number and treatment assignment at the site. 
 
 
The randomization codes and all data sets will be stored in a secure area accessible only to 
delegated study personnel and only released on completion of the study and after the study 
database has been locked. 
In this study all parties are to be masked to the allocated treatment; sponsor, investigators, study 
staff  and subjects. At the site, there will be designated unmasked study staff that will train the 
subject on all study procedures related to IP administration. 
In emergency situations for reasons of subject safety (e.g. serious unexpected /unlisted drug 
related event; medical emergency; potentially life-threatening drug interaction) the masking code 
may need to be broken. In those cases, whenever possible, a request for unmasking should be 
discussed with the sponsor prior to unmasking. Detailed instruction on the method for breaking 
the mask will be provided during site training and noted in the Investigator study file. 
Following the first IP administration, if the subject perceives any AE that may be attributed to 
the IP, these should be reported to the unmasked site personnel.  
4.3 
INFORMED CONSENT  
Prior to undergoing any study-related activity, the Principal Investigator or his/her designee will 
discuss the purpose and pertinent details of the study with each potentially eligible subject. The 
explanation will be sufficiently detailed to allow the subject to make an informed decision to 
participate in the study. If the subject is willing to participate in the study, he/she will be 
requested to give written informed consent. A copy of the Informed Consent Form (ICF) will be 
signed by both the subject and the Principal Investigator or his/her designee. 
The signed and dated ICF will be retained with the study records, and a copy of the signed and 
dated ICF will be given to the subject.  
 
 


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5 
STUDY ASSESSMENTS 
5.1 
TIMING OF STUDY ASSESSMENTS 
All procedures will be performed according to the following schedule unless otherwise specified. 
See also the summary of assessments in Appendix 1 that outlines this schedule in tabular form. 
Note:  The same investigator in each site must assess and score anterior chamber cells and flare 
across all study visits for subjects. 
5.1.1 Visit 1: Screening/Randomization:  Day 1  
This visit should be scheduled to occur in the morning, if possible, to allow for QID dosing on Day 
1 for randomized subjects.  Ocular assessments are to be performed on both eyes, unless otherwise 
noted.  Perform the following assessments: 
• Signed and dated informed consent 
• Demographic information including iris color 
• Medical and Ophthalmic History  
• Inclusion/exclusion criteria 
• Concomitant Medications 
• Urine pregnancy test (if female of child-bearing potential) 
• Subject-Rated Ocular Pain Assessment – prior to other assessments 
• BCVA  
• Slit-lamp biomicroscopy  
• Intraocular pressure by Goldmann Applanation Tonometry  
• Dilated Ophthalmoscopy  
• Anterior Chamber SD-OCT (study eye only) in selected sites 
• Macular OCT (study eye only) 
• Randomization:  subjects that meet eligibility criteria should be randomized to one of 
the treatment groups through the Interactive Web Response System (IWRS). 
• Dispensation of IP and Dosing Diary: the subject will receive one bottle from the 
study kit and will be instructed to self-administer the first drop prior to leaving the 
clinic, under the supervision of the unmasked personnel. The subject will be 
instructed to record this first dose and all subsequent doses in the dosing diary. 
• 
 minutes post IP administration the subject will be assessed for 
AEs in both eyes. If any AEs are reported at Visit 1 that may be attributed to the 
IP, these should be handled by the unmasked personnel.  
• The subject will be instructed to take the bottle home and administer the IP up to 
three more times depending on the time of the visit, but approximately every 4 


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hours.  Following the day of this visit the subject will be instructed to begin using 
the drops four times a day and to continue for the duration of the treatment period. 
• Subjects should be reminded to continue on their previous medication regimen and 
that the dosing should remain stable throughout the IP treatment period (Note:  
changes to the dosing of cycloplegic medications during the study is permitted). 
The subjects should also be reminded to wait 10 minutes between dosing IP and 
their other medications.  
5.1.2 Visit 2: Week 1/Day 7 (±2 days) Treatment Evaluation 
This visit will occur no more than 9 days and no less than 5 days after Visit 1 and the following 
will be performed/assessed (in both eyes, unless otherwise noted):  
• Subject-Rated Ocular Pain Assessment – prior to any other assessments  
• Concomitant medication update 
• Occurrence of any AEs since the last visit 
• BCVA 
• Slit-lamp biomicroscopy  
• Intraocular pressure by Goldmann Applanation Tonometry  
• Dilated Ophthalmoscopy  
• Anterior Chamber SD-OCT (study eye only) in selected sites only 
• 
 
• Review of subject’s Dosing Diary by unmasked personnel 
• 
 
 
  
5.1.3 Visit 3: Week 2/Day 14 (±2 days) Treatment Evaluation 
Perform the following assessments. Ocular assessments are to be performed on both eyes, 
unless otherwise noted: 
• Subject-Rated Ocular Pain Assessment – prior to any other assessments 
• Occurrence of any AE’s since last visit 
• Concomitant medication update 
• BCVA 
• Slit-lamp biomicroscopy  
• Intraocular pressure by Goldmann Applanation Tonometry  
• Dilated Ophthalmoscopy 
 


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• Anterior Chamber SD-OCT (study eye only) in selected sites only 
• 
 
• Review subject’s Dosing Diary by unmasked personnel 
• 
 
 
  
5.1.4 Visit 4: Week 3/Day 21 (±2 days) Treatment Evaluation  
Perform the following assessments. Ocular assessments are to be performed on both eyes, 
unless otherwise noted: 
• Subject-Rated Ocular Pain Assessment – prior to any other assessments 
• Occurrence of any AE’s since last visit 
• Concomitant medication update 
• BCVA 
• Slit-lamp biomicroscopy  
• Intraocular pressure by Goldmann Applanation Tonometry  
• Dilated Ophthalmoscopy 
• Anterior Chamber OCT (study eye only) in selected sites only 
• 
 
• Review subject’s Dosing Diary by unmasked personnel 
• 
 
 
  
• 
 
 


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5.1.5 Visit 5: Week 4/ Day 28 (±2 days) Evaluation and End of Study Treatment  
Note:  
  Perform the following assessments. 
Ocular assessments are to be performed on both eyes, unless otherwise noted: 
• Subject-Rated Ocular Pain Assessment – prior to other assessments 
• Occurrence of any AE’s since last visit 
• Concomitant Medications 
• Urine pregnancy test (if female of child-bearing potential) 
• BCVA 
• Slit-lamp biomicroscopy  
• Intraocular pressure by Goldmann Applanation Tonometry  
• Dilated Ophthalmoscopy  
• Anterior Chamber SD-OCT (study eye only) in selected sites only 
• Macular OCT (study eye only)  
• 
 
• Review subject’s Dosing Diary by unmasked personnel 
5.1.6 Visit 6:  Week 7/Day 49 (± 3 days) Follow-up Period:  
Perform the following assessments. Ocular assessments are to be performed on both eyes, 
unless otherwise noted: 
• Subject-Rated Ocular Pain Assessment – prior to any other assessments  
• Concomitant medication update 
• Occurrence of any AEs since the last visit 
• BCVA 
• Slit-lamp biomicroscopy  
• Intraocular pressure by Goldmann Applanation Tonometry  
• Dilated Ophthalmoscopy  
• Anterior Chamber SD-OCT (study eye only) in selected sites only 
5.1.7 Visit 7: Week 10/Day 70 (± 3 days) Follow-up Period 
Perform the following assessments. Ocular assessments are to be performed on both eyes, 
unless otherwise noted: 


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• Subject-Rated Ocular Pain Assessment – prior to other assessments 
• Occurrence of any AE’s since last visit 
• Concomitant Medications 
• BCVA 
• Slit-lamp biomicroscopy  
• Intraocular pressure by Goldmann Applanation Tonometry  
• Dilated Ophthalmoscopy  
• Anterior Chamber SD-OCT (study eye only) in selected sites only 
• Macular OCT (study eye only)  
5.1.8 Unscheduled Visits 
If at any time during the study, outside of the above scheduled visits, the subject requests 
or the investigator determines the subject should be assessed for treatment of an AE, an 
unscheduled visit may occur. Adverse events and concomitant medications will be 
recorded and the following assessments should be performed on the study eye (and non-
study eye if applicable/necessary.): 
• BCVA 
• Slit-lamp biomicroscopy 
• IOP by Goldmann Applanation Tonometry 
• Dilated ophthalmoscopy, if indicated 
5.2 
WITHDRAWAL CRITERIA / EARLY TERMINATION 
Subjects have the right to withdraw from the study at any time, for any reason, without jeopardizing 
their medical care. Where possible, subjects will be followed for safety and encouraged to return 
for follow-up visits for any unresolved safety events. 
In addition, the Investigator or Tarsius’ Medical Officer can discontinue a subject from further 
study medication administration for other reasons related to the best interest of the subject. 
If a subject is discontinued from study and/or study medication administration at any point of the 
Treatment Period, he or she will be encouraged to remain in the study for follow up through Visit 
7 (Week 10).   
The reason a subject discontinued from the study is to be clearly described on the Study Exit 
electronic case report form (eCRF). 
Subjects who withdraw from the study will not be replaced. Subjects who withdraw from the study 
prior to Visit 7 (Week 10) will be asked to complete all procedures outlined in Visit 7 (Week 10). 


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Female subjects of child-bearing potential will also have a UPT performed at the early termination 
visit. Termination of the study may also occur as determined by the Sponsor, FDA, or  other 
regulatory authorities. 
6 
TREATMENT OF SUBJECTS 
6.1 
PRIOR AND CONCOMITANT THERAPY  
At the Screening visit, medications that were taken within the previous 30 days will be collected. 
At each study visit thereafter, subjects will be questioned concerning any new medications or 
changes in their current concomitant medications since their previous study visit. 
For all medications, the generic name, indication, route of administration, frequency, dose, start 
date and end date (if applicable) will be collected. 
6.2 
PERMITTED MEDICATIONS  
Subjects on therapy for their uveitis will not be asked to stop their usual medications, rather they 
will add TRS01 QID to their current regimen. Therapy considered necessary for the subject’s 
welfare that does not interfere with the evaluation of the study medication will be permitted to be 
given at the discretion of the Principal Investigator.   
The decision to administer a prohibited medication or treatment would be taken with the safety 
of the subject as the primary consideration. Whenever possible, the Tarsius Medical Director will 
be notified before any prohibited medications or treatments are administered. The Tarsius 
Medical Monitor should also be contacted if the permissibility of a specific medication or 
treatment is in question.   
Any subject placed on rescue therapy will discontinue use of the IP and continue study 
participation through Visit 7. 
 
 Subjects on rescue therapy due to lack of 
efficacy should not be withdrawn from the study, but rather followed through the end of the 
study. 
Rescued subjects experiencing an AE at the time of rescue will be followed through stabilization 
or resolution of the AE or the end of the study (whichever comes first).  
The following medications are also specifically permitted during the trial:   
• Glaucoma eye drops with the exclusion of Prostaglandins.  Note:  subjects may be treated 
with up to two glaucoma eye drops in the study eye. Anti-glaucoma eye drops should be 
 before the investigational product dosing. 
• Mydriatic agents 
• Use of PRN artificial tears up to twice a day 
• 
 
 


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The above medications, if used at the onset of the trial, must not be discontinued during the 
course of the trial and the dosing and regimen should remain stable through Visit 5 (end of 
IP treatment period).   
6.3 
RESCUE MEDICATION USE 
Rescue medications will be administered in cases detailed in section 7.2.2. Rescue therapy will 
be defined as any treatment (above the permitted dosages outlined in the eligibility criteria and in 
Section 6.2) that would have a therapeutic effect on inflammation in the anterior segment, other 
than the IP (e.g., systemic treatment with an immunosuppressant agent, ocular injection of 
steroids, or topical corticosteroids in the study eye), regardless of the purpose of administration 
and whether it was recorded as a rescue therapy on the eCRF.  
The addition or increase in systemic immunosuppressive therapy (e.g., methotrexate, 
cyclosporine, cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus, 
azathioprine, or adalimumab) or other therapy considered as a rescue therapy, would be 
administered based on the Investigator’s best judgment and only after discussion with Tarsius’ 
Medical Director. 
 
 


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6.4 
MEDICATIONS NOT PERMITTED 
Use of the following medications are not permitted either during the study or for the timeframes, 
frequency or dose levels defined here: 
1. Intravitreal or periocular steroids in the study eye within 90 days of Visit 1. 
2. Any intravitreal injection within 30 days of Visit 1. 
3. Topical ocular therapy with steroids more than BID in the study eye, throughout the 
IP treatment period. 
4. Treatment with systemic steroids >10mg/day, throughout the IP treatment period. 
5. Any topical ophthalmic medications (either eye) other than medications specifically 
allowed as part of the trial, throughout the IP treatment period.  Note: Use of PRN 
artificial tears up to twice a day (BID) is allowed and should not be dosed within 10 
minutes of investigational product dosing.  Further, changes in the dosing of 
cycloplegics as needed during the study is allowed. 
6. Other investigational drugs or or investigational medical device within 60 days prior 
to Visit 1. 
6.5 
TREATMENT COMPLIANCE 
In order to obtain reliable safety and efficacy data, it is critical that each subject comply with the 
dosing schedule specified in the protocol.  
Subjects will be instructed to record administration information from Day 1 and for the duration 
of the study in a dosing diary. 
 
 


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7 
SAFETY AND EFFICACY VARIABLES 
7.1 
SAFETY VARIABLE 
Incidence and severity of treatment-related AEs and SAEs, both systemic and ocular reported 
adverse events. 
7.2 
SAFETY VARIABLES 
Safety measures include AEs/SAEs and clinical assessments from the slit-lamp biomicroscopy 
findings, IOP, and dilated ophthalmoscopy findings. 
AEs and ocular safety measures to be collected in this study are listed in Table 3.  
TABLE 3: OCULAR SAFETY MEASURES  
Safety Measure 
Note 
Slit-lamp biomicroscopy: 
Lid hyperemia, lid edema, 
conjunctival hyperemia, 
chemosis, corneal edema, 
conjunctival discharge/exudate  
The status of each of these biomicroscopy parameters will be rated 
as 0 = None, 1 = Mild, 2 = Moderate, or 3 = Severe. For each 
abnormal record, the clinical significance (Clinically Significant or 
Not Clinically Significant) will also be determined. Slit-lamp 
biomicroscopy will be performed at all study visits.   
Intraocular pressure 
The IOP measurements will be performed by Goldmann 
applanation tonometry with a single measurement. IOP pressure 
recorded in mmHg (e.g., 18 mmHg). IOP measurements will be 
performed at all study visits,   
 Dilated Ophthalmoscopy: 
Vitreous haze, retina vessels, 
macula, optic nerve, cup/disc 
ratio.  
The status of the macula, vessels and optic nerve will be 
determined as Normal or Abnormal. The cup/disc ratio will be 
recorded with two decimal points (e.g., 0.80). Dilated 
ophthalmoscopy will be performed at all visits.  
BCVA 
The visual acuity test is used via a standardized ETDRS chart. 
 
These ocular safety measures will be summarized using descriptive statistics. For continuous 
ocular safety measures, changes from Baseline (Day 1/Visit 1) variables will also be summarized 
descriptively.  Safety parameters of interest include a change from baseline to each visit in ocular 
signs such as corneal/conjunctival tolerability, IOP measurements. 
 
 
 


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7.2.1 Adverse Events 
Adverse events will be collected for subjects following signing of the ICF through the end of the 
study. The information will include at least a description of the event, onset date, and resolution 
date, as well as seriousness, severity and relation to study medication (as determined by the 
Investigator), location (right eye [OD], left eye [OS], both eyes [OU] or other), action taken, and 
outcome. All AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) dictionary, current version. Ocular and non-ocular AEs will be summarized 
separately.   
Suspected adverse reactions (SARs), also known as adverse drug reactions or suspected adverse 
drug reactions, are AEs considered by the Investigator to be related to the study medication and 
included in the Investigator’s Brochure. 
An AE will be considered as an ocular AE if the Investigator selects ‘OD’, ‘OS’, or ‘OU’ for the 
AE eCRF field “Eye(s) affected”. 
Any AE that causesloss of vision of 15 or more letters (i.e., 3 lines) should be recorded as a 
serious adverse event (SAE). Examples include endophthalmitis, retinal vascular occlusion, 
retinal detachment involving the macula/fovea, etc. AEs that cause loss of 15 or more letters (i.e., 
3 lines) that are expected to resolve should not be recorded as an SAE.  Examples include 
corneal edema, corneal abrasion, cystoid macular edema or other conditions that are known to 
affect vision but expected to resolve and not results in a permanent impact on vision.  
7.2.2 Criteria for Rescue Therapy  
Rescue therapy will be offered if one or more of the following rescue criteria are met and a 
rescue therapy treatment plan is discussed with the Tarsius Medical Officer: 
• If visual acuity in the study eye decreases by >2 lines compared to baseline, which in the 
opinion of the investigator, is due to non-infectious anterior uveitis. 
• 
 
 
 
 
 
 
 
 
 
 
 
 
If rescue therapy is initiated, the subject will be instructed to discontinue IP.  The choice of 
rescue therapy will be at the discretion of the Investigator.  If rescue therapy is administered, the 
generic name, indication, route of administration, frequency, dose, start date, and stop date (if 
applicable) will be recorded on the eCRF. In addition, if other local therapy (i.e., periocular or 
intravitreal corticosteroids) is administered in the non-study eye, then the generic name, 


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indication, route of administration, frequency, dose, start date and end date (if applicable) would 
also be recorded on the eCRF. 
Any medication administered on Visit 5 (Day 28) after the subject has exited the study will not 
be considered as rescue therapy. 
 
If possible, during the visit where rescue therapy is initiated, Macular OCT should be performed 
for the study eye. 
 
7.2.3 Other Safety Variables 
Other safety measures are discussed in section 7.2 above.  
 
7.3 
ADVERSE EVENT DEFINITIONS 
 
Adverse Event (AE): Any untoward medical occurrence associated with the use of an 
investigational product in humans, whether or not considered drug related.  
 
Adverse Reaction (AR): any AE caused by a drug. Adverse reactions are a subset of all 
suspected adverse reactions where there is reason to conclude that the drug caused the event.  
 
Suspected Adverse Reaction (SAR):  
Any AE for which there is a reasonable possibility that the drug caused the AE. For the purposes 
of IND safety reporting, “reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the AE. A SAR implies a lesser degree of certainty about 
causality than adverse reaction, which means any AE caused by a drug.  
 
Unexpected: An AE or SAR is considered “unexpected” if it is not listed in the Investigator’s 
Brochure or is not listed at the specificity or severity that has been observed; or, if an 
Investigator’s Brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. 
  
Life-threatening: An AE or SAR is considered “life-threatening” if, in the view of either the 
Investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. 
 
A SERIOUS ADVERSE EVENT (SAE) is any AE or suspected adverse reaction occurring at 
any dose that:  
• Results in death.  
• Is life-threatening.  


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• Results in a persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions.  
• Requires inpatient hospitalization.  
• Prolongs inpatient hospitalization.  
• Is a congenital anomaly/birth defect.  
• Is a significant medical event (i.e., one that may jeopardize the subject or may require 
intervention to prevent one or more of the other outcomes listed above).  
 
A NON-SERIOUS ADVERSE EVENT is any AE that does not meet the definitions for SAEs 
as described above.  
 
Each AE will be classified as SERIOUS or NON-SERIOUS using the definitions provided 
above.  
 
The SEVERITY of each AE will be classified as MILD, MODERATE, or SEVERE.  
The Investigator will review each event and assess its RELATIONSHIP to use of 
investigational product (unrelated, probably, definitely). The AE will be assessed using the 
following definitions:  
 
Unrelated:  
• Event occurring before dosing.  
• Event easily explained by uveitis status. 
• Event or intercurrent illness due wholly to factors other than investigational product 
use.  
 
Probable:  
• Reasonable temporal relationship with investigational product use.  
• Likely to be known reaction to agent or chemical group, or predicted by known 
pharmacology.  
• Event cannot easily be explained by subject’s clinical state or other factors.  
 
Definite:  
• Distinct temporal relationship with investigational product use.  
• Known reaction to agent or chemical group, or predicted by known pharmacology.  
• Event cannot be explained by subject’s clinical state or other factors.  
 
7.4 
PROCEDURES FOR AE REPORTING BY THE INVESTIGATOR 
AEs will be monitored throughout the study and will be recorded on the CRF with the date and 
time of onset, date and time of resolution, severity, seriousness, causality (relationship to use of 
investigational product), treatment required, and the outcome.  
 
To elicit AEs, simple questions with minimal suggestions or implications should be used as the 
initial questions at all evaluation points during the trial. For example:  
• How have you felt since your last assessment?  


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• Have you had any health problems since your last assessment?  
 
The severity of each AE should be categorized as mild, moderate, or severe.  
 
The causality of use of investigational product in relation to the AE will be assessed by the 
Investigator after careful medical consideration and categorized as unrelated, probable, or 
definite.  
 
If an AE occurs, the Investigator will institute support and/or treat as deemed appropriate. If a 
non-SAE is unresolved at the time of the last day of the study, an effort will be made to follow 
up until the AE is resolved or stabilized, the subject is lost to follow-up, or there is some other 
resolution of the event.  
 
7.5 
SERIOUS ADVERSE EVENT REPORTING BY THE INVESTIGATOR 
Serious Adverse Event Reporting  
It is the responsibility of the Investigators or their designees to report any event of this nature to 
the sponsor or a designee within 24 hours of the event being brought to the Investigators’ or their 
staffs’ attention. It is also the responsibility of the Investigator to report all SAEs reported at their 
site to their Institutional Review Board (IRB), as required. The Investigator should make every 
attempt to follow all SAEs to resolution. 
 
The following information should be provided when an SAE is reported to the sponsor or 
designee:  
1. Protocol Number  
1. Site Number  
2. Subject Number  
3. Subject Demographic information, including:  
• Date of Birth  
• Sex  
• Race  
4. Investigational product start date  
5. Date of last dose of investigational product  
6. Date investigational product reinitiated (if investigational product interrupted)  
7. SAE information, including:  
• SAE term (diagnosis only; if known or serious signs/symptoms)  
• Description of SAE/narrative  
• Date/time of onset  
• Severity  
• Outcome  
• Date/time of resolution or death (if duration < 24 hours)  


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• Relationship to investigational product  
• Action taken with investigational product  
8. Criteria for classifying the event as serious, including whether the SAE:  
• Resulted in death.  
• Was life-threatening  
• Required inpatient hospitalization.  
• Prolonged inpatient hospitalization.  
• Resulted in a persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions.  
• Was a congenital anomaly/birth defect  
• Important medical events that may not result in death, were not life-threatening, or 
did not require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.  
 
9. Concomitant medications  
10. Relevant history  
11. Possible causes of SAE other than investigational product  
12. Copy of AE page from the CRF  
 
NOTE: If an SAE occurs in any study involving TRS01 that is unexpected and is determined to 
be related or possibly related to investigational product, all sites will be notified by the sponsor 
and each site should report it to its IRB. 
 
 
 
 


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8 
EXPLORATORY EFFICACY  
Measures of efficacy will be based on Investigator assessments of ACC and flare. At select sites, 
anterior chamber SD-OCT automated quantification of anterior chamber cells may also be used 
as a secondary measure of anterior chamber inflammation [Sharma et al., 2015].  
8.1 EFFICACY VARIABLES 
Efficacy of TRS01 will be assessed by evaluation of anterior chamber inflammation by 
Investigator assessment with slit-lamp biomicroscopy, and may also be assessed by anterior 
chamber SD-OCT automated quantification of anterior chamber cells at select sites. 
Slit-lamp biomicroscopy of both eyes will be used to examine eye structures at each study visit. 
At Day1/Visit 1 (Screening/Randomization), slit-lamp biomicroscopy will be performed prior to 
IP administration. Areas assessed will include lids/lashes, conjunctiva, cornea, anterior chamber 
cells and flare, iris, pupil, lens.   
8.1.1 Anterior Chamber Cells 
Note:  The same investigator in each site must assess and score anterior chamber cells and flare 
across all study visits for an individual subject. 
 
8.1.1.1 Slit-lamp biomicroscopy  
At each visit, slit-lamp biomicroscopy (halogen illumination system is required) will be 
performed by the Investigator on both eyes to assess ACC.  
The following scoring scale for anterior chamber cells will be used: 
 
  
  
  
  
 
8.1.1.2 Spectral- Domain Optical Coherence Tomography 
Anterior chamber SD-OCT imaging will be performed for the study eye on Visit 1/Day 1 after 
randomization (before first drop administration) and at each subsequent study visit, at select 
sites. 
 
 
 
 
 
8.1.2 Flare 
The level of flare in the anterior chamber will be assessed by the Investigator at each study visit 
for both eyes, using slit-lamp biomicroscopy and recorded according to the following scale: 
• 
 
 
 


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• 
 
 
  
 
 
8.1.3 Macular OCT 
Both the average center subfield thickness and the macular volume will be evaluated on site by 
the investigator.  Macular OCT will be performed for the study eye at Visit 1, Visit 5 and Visit 7 
at select sites.  Macular OCT should also be performed for the study eye at the visit where a 
subject is placed on rescue therapy. 
8.1.4 Best Corrected Visual Acuity  
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) charts 
either retro-illuminated or frontally illuminated at a distance of 4 meters. Visual acuity will be 
measured with spectacle or pinhole correction at all study visits. The BCVA score and Snellen 
equivalent will both be recorded. 
8.1.5 Subject-Rated Ocular Pain Assessment 
In the clinic, subjects will be handed a laminated card on which is printed the Subject-Rated 
Ocular Pain Assessment. Each subject will be asked to subjectively rate their pain at every visit  
based on this scale. This information will be provided to study personnel to enter into the 
subject’s source documentation.  
The grading scale for pain to be used will be as follows:  
• 0 = None: Absence of pain.  
• 1 = Minimal: Presence of mild sensation or discomfort (e.g., diffuse or focal foreign body 
sensation, mild transient burning or stinging, etc.)  
• 2 = Mild: Mild, tolerable aching of the eye.  
• 3 = Moderate: Moderate or more prolonged aching sufficient to have desire to use over 
the counter (OTC) analgesics (e.g. acetaminophen).  
• 4 = Moderately Severe: More prolonged aching requiring the use of an OTC analgesic  
other than acetaminophen.  
• 5 = Severe: Aching or throbbing pain that is not tolerable  (e.g. constant or nearly 
constant sharp stabbing pain, throbbing or aching, etc.) requiring prescription analgesics. 
 
 


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9 
STATISTICS 
9.1 
STATISTICAL METHODS 
Continuous measures (e.g., age) will be summarized descriptively by the mean, standard 
deviation, median, minimum and maximum values. Categorical measures will be 
summarized by the number and percent of subjects. The statistical analyses will be performed in 
accordance with the Statistical Analysis Plan. All study data will be listed by treatment, subject 
and visit (as applicable). 
 
9.1.1 Subject Disposition, Demographic and Background Characteristics 
 
Subject disposition, demographic characteristics, iris color, and background variables will be 
summarized by treatment group. 
 
9.1.2 Analysis of Safety 
Analysis of safety data will be presented for all subjects. AEs will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA, most current version add in version once 
finalized) and categorized by system organ class using preferred terms. Treatment emergent AEs 
will be listed by study group. Treatment related AEs will be tabulated by study group and will be 
reported by incidence (both number of events and number of subjects) with respect to their 
intensity and relationship to the IP. Ophthalmoscopy findings will be summarized descriptively. 
IOP measurements, VA, and slit-lamp biomicroscopy assessments will be summarized as safety 
outcomes. 
 
9.1.3 Analysis of Efficacy 
Efficacy measures will be ACC and flare.  
Both Investigator-rated ACC and flare data will be assessed as a change from baseline (Visit 
1/Day 1) Weeks 1 through 4 and a descriptive comparison of the two active treatment groups 
will be performed. 
If available, anterior chamber SD-OCT cell data will be assessed as a change from baseline 
(Visit 1/Day 1) on Weeks 1 through 4 and a descriptive comparison of the two active treatment 
groups will be performed.  
Changes in subject-rated ocular pain assessment on Weeks 1 through 4 will be evaluated via a 
descriptive comparison between the two active treatment groups. 
 


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9.2 
SAMPLE SIZE ESTIMATION 
This is a Phase I/IIa clinical study to evaluate the safety and tolerability of TRS01 with the 
sample size of up to 20 randomized subjects, across approximately 2 sites, as proposed by 
Tarsius. No formal sample size estimation was undertaken as this trial is exploratory in nature. 
 
 
9.3 
LEVEL OF SIGNIFICANCE 
Level of significance to be outlined in the Statistical Analysis Plan. 
 
9.4 
PROCEDURE FOR ACCOUNTING FOR MISSING, UNUSED, OR SPURIOUS DATA 
Any missing, unused, or spurious data will be noted in the final clinical study report. 
 
 
9.5 
PROCEDURE FOR REPORTING DEVIATIONS FROM THE STATISTICAL PLAN  
Any deviations from the statistical analysis plan will be described and a justification given in 
the final clinical study report. 
 
 
9.6 
SUBJECTS TO BE INCLUDED IN THE ANALYSIS 
Intent-to-Treat (ITT) Population: The ITT population will include all randomized subjects 
who took at least 1 dose of investigational product.  The Safety Population will include all 
randomized subjects. 
 
Per Protocol (PP) Population: The PP population is a subset of the ITT population, which will 
include those subjects who did not have significant protocol deviations.  The PP population will 
be defined and documented by the clinical study team and the biostatistician prior to database 
lock and unmasking of the subjects. 
 


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10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The Investigator will permit trial-related monitoring, audits, IRB review, and regulatory 
inspection(s) by providing direct access to source data and documents (such as tests performed as 
a requirement for participation in the study and other medical records required to confirm 
information contained in the case report form such as medical history) to the monitor. 


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11 QUALITY CONTROL 
The progress of the study will be monitored by on-site, written, e-mail, and telephone 
communications between personnel at the study center and the sponsor (or designated monitor). 
The Investigator will allow Tarsius Pharma, Ltd. monitors or designee to inspect all CRFs; 
subject records (source documents); signed informed consent forms; records of investigational 
product receipt, storage, and disposition; and regulatory files related to the study. 
 
 


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12 ETHICS 
12.1 
INDEPENDENT ETHICS COMMITTEE OR INSTITUTIONAL REVIEW BOARD 
The clinical study protocol, protocol amendments, ICF, and all other appropriate study-related 
documents will be reviewed and approved by an appropriate Independent Ethics Committee 
(IEC) according to local laws and regulations for study sites outside the United States (US), or 
Institutional Review Board (IRB) constituted in accordance with US Title 21 Code of Federal 
Regulations Part 56 for sites in the US. A copy of the letter indicating EC/IRB approval will be 
provided to Tarsius Pharma, Ltd. (Tarsius) prior to study initiation or implementation of each 
relevant protocol amendment.   
 
 
 


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13 AMENDMENTS TO THE PROTOCOL 
Amendments to the protocol shall be planned, documented, and signature authorized prior to 
implementation. 
If an amendment to the protocol is required, the amendment will be originated and documented 
by the Sponsor (or its representative). The written amendment must be reviewed and approved 
by the Sponsor and submitted to the IRB for approval. 
Amendments specifically involving change to trial design, risk to subject, increase of dosing or 
exposure, subject number increase, addition or removal of new tests or procedures, shall be 
reviewed and approved by the appropriate IRB. The amendment will be submitted formally to 
regulatory authorities by the Sponsor as applicable, after IRB approval and specifically when an 
increase of dosing or subject exposure and/or subject number has been proposed; or, when the 
addition or removal of an Investigator is necessitated. 
 
 


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14 DATA HANDLING AND RECORDKEEPING 
All procedures for the handling and analysis of data will be conducted using GCP and will meet 
ICH guidelines and US FDA regulations, for sites in the US, for the handling and analysis of 
data for clinical trials. Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation 
checks will be implemented and applied to the database. Query reports pertaining to data 
omissions and discrepancies will be forwarded to the clinical Investigator and monitor(s) for 
resolution. The study database will be updated in accordance with the resolved query reports. All 
changes to the study database will be documented.  
14.1 
RECORDS RETENTION  
The study center will retain all records related to the study in accordance with local and ICH 
GCP guidelines.  
 


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15 PUBLICATION POLICY 
The institution and Investigators participating in this trial shall have no right to publish or present the 
results of this study without the prior written consent of Tarsius Pharma. 
 
 
 
 
 


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16 APPENDICES 
Appendix 1: Schedule of Assessments 
  
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7/ 
ET1 
Assessment schedule: 
Treatment Period 
Follow-up Period 
  
Day 1 
Week 1 
Day 7 
±1 day 
Week 2 
Day 14 
±2 day 
Week 3 
Day 21 
±2 day 
Week 4 
Day 28 
±2  
day7 
Week 7 
Day 49 
±3 days 
Week 10 
Day 70 
±3 days 
Signed and dated 
Informed Consent 
x 
  
 
  
  
 
  
  
Medical & Ophthalmic 
History  
x 
  
 
  
  
 
  
  
Demographics including 
Iris color 
x 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
x 
  
 
  
  
 
  
  
Concomitant Medications 
x 
x 
x 
x 
x 
x 
x 
Urine pregnancy test 
x 
  
 
  
x 
 
 
Subject-rated Ocular Pain 
Assessment2 
x 
x 
x 
x 
x 
x 
x 
BCVA  
x 
x 
 x 
x 
x 
x 
x 
Slit-lamp biomicroscopy3 
x 
x 
x 
x 
x 
x 
x 
Intraocular pressure 
x 
x 
x  
x 
x 
x 
x 
Dilated ophthalmoscopy 
x 
x 
x 
x 
x 
x 
x 
Randomization 
x 
 
 
 
 
 
 
Anterior Chamber SD-
OCT4 
x  
x 
x 
x 
x 
x 
x 
Macular OCT4,5 
x 
 
 
 
x 
 
x 
Adverse events 
Assessment (AEs)6 
x 
x 
x 
x 
x 
x 
x 
 
 
  
  
 
 
 
 
  
  
  
  
 
 
 
  
 
1.Visit 7 is also the Early Termination visit; 2.The Subject-Rated Ocular Pain Assessment must be performed prior to any other assessments;       
3. The same investigator must assess and score anterior chamber cells and flare across all study visits for an individual subject.; 4.May be 
conducted at select sites, on study eye only; 5. Macular OCT should also be performed for the study eye at the visit where a subject is placed on 
rescue therapy.  6. At Visit 1, 40 min ± 10 min post first administration of investigational product.  7. 
  


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17 REFERENCES 
1. Kim T, et al. Safety and efficacy of twice daily administration of KPI-121 1% for ocular 
inflammation and pain following cataract surgery. Clin Ophthalmol. 2019; 13: 69–86. 
2. Mérida S, et al. Macrophages and Uveitis in Experimental Animal Models. Mediators of 
Inflammation. 2015; ID 671417. 
3. Nussenblatt RB.  The natural history of uveitis. International Ophthalmology. 1990; 14: 
303-308. 
4. Sharma S, et al. Automated Analysis of Anterior Chamber Inflammation by Spectral-
Domain Optical Coherence Tomography. Ophthalmology. 2015 Jul;122(7):1464-70. 
5. Thorne JE, Suhler E, Skup M, Tari S, Macaulay D, Chao J, Ganguli A. Prevalence of 
Noninfectious Uveitis in the United States: A Claims-Based Analysis. JAMA 
Ophthalmol. 2016; 1;134(11):1237-1245.