Clinical trial NCT02595398
Conditions: Uveitis Uveitis, Posterior Uveitis, Anterior Uveitis, Intermediate Panuveitis
Keywords: Uveitis UME Posterior Uveitis Anterior Uveitis Intermediate Uveitis Panuveitis Non-infectious Uveitis Triamcinolone Choroid Choroidal Injection Suprachoroidal Microneedle Microinjection Triamcinolone acetonide
Sponsor: Clearside Biomedical, Inc.
Start date: 2015-11-17; Completion date: 2018-01-18
Enrollment: 160 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study is designed to evaluate the safety and efficacy of suprachoroidally administered triamcinolone acetonide, CLS-TA, in subjects with macular edema associated with non-infectious uveitis.

Detailed description:
This is a Phase 3, randomized, masked, sham-controlled, multicenter study to assess the safety and efficacy of 4 mg of CLS-TA administered via suprachoroidal injection compared to a sham injection procedure in the treatment of subjects with macular edema associated with non-infectious uveitis.

Qualified subjects will be randomized to receive two suprachoroidal injections of CLS-TA administered to the study eye or two sham injection procedures administered to the study eye approximately 12 weeks apart (Visit 2 and Visit 5). Follow-up visits will be conducted monthly up to 24 weeks (Visit 8).

Arms: arm 1: Suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA arm 2: Matching suprachoroidal syringe with sham procedure
Interventions: intervention 1: 4mg CLS-TA Suprachoriodal Injection intervention 2: Sham Procedure
Intervention descriptions: intervention 1: CLS-TA, 40 mg/mL (4 mg in 100 µL), administered as a single injection at 2 timepoints intervention 2: Sham procedure administered at 2 timepoints

Protocol documents:
Prot_SAP_000.pdf: 
Compound Name: 
CLS-TA, triamcinolone acetonide injectable suspension 
Protocol Number: 
CLS1001-301 
IND Number: 
115683 
NCT Number:  
NCT02595398 
Protocol Title 
PEACHTREE: A Phase 3, Randomized, Masked, 
Controlled Clinical Trial to Study the Safety and Efficacy 
of Triamcinolone Acetonide Injectable Suspension (CLS-
TA) for the Treatment of Subjects with Macular Edema 
associated with Non-Infectious Uveitis 
Sponsor: 
Clearside Biomedical, Inc. 
900 North Point Parkway, Suite 200 
Alpharetta, GA 30005 
Issue Date: 
Protocol Amendment 1 Date: 
Protocol Amendment 2 Date: 
Protocol Amendment 3 Date: 
25 August 2015 
24 November 2015 
22 July 2016 
12 April 2017 
 


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Clinical Protocol CLS1001-301 
Project: 
Compound Number/Name: 
Protocol Number: 
IND Number:  
Phase: 
Protocol Title: 
Sponsor: 
Medical Monitor: 
Original Protocol Issue Date: 
Amendment #3 Issue Date: 
Amendment #2 Issue Date: 
Amendment #1 Issue Date:
1001 
CLS-TA, triamcinolone acetonide injectable suspension 
CLS1001-301 
115683 
3 
PEACHTREE: A Phase 3, RandomizEd, MAsked, 
Controlled Clinical Trial to Study the Safety and Efficacy 
of Triamcinolone Acetonide Injectable Suspension (CLS-
TA) for tHe TReatment of Subjects with Macular Edema 
associated with Non-Infectious UvEitis 
Clearside Biomedical, Inc. 
900 North Point Parkway, Suite 200 
Alpharetta, GA  30005 
Chiltern, Inc.  
David Hoelscher, MD 
Senior Medical Officer 
David.Hoelscher@chiltern.com 
Direct:    +1 423 990 0288 
Mobile:   +1 512 694 8829 
Fax:        +1 423 968 3567 
 25AUG2015 
12APR2017 
22JUL2016 
 
24NOV2015 
________________________________________________ 
___12 April 2017______ 
Jennifer Kissner, Ph.D. 
 
 
 
 
 
 
 
 
 
 
 
Date 
Vice President, Clinical Development 
Clearside Biomedical, Inc. 
CONFIDENTIAL 
This protocol contains confidential information about a product provided by Clearside Biomedical, Inc.  
This information is provided for the exclusive use of the Investigators participating in this study.  Any 
and all confidential information contained herein may not be disclosed to any other person or party 
without the prior written consent of Clearside Biomedical, Inc.  


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Clinical Protocol CLS1001-301 
Investigator Signature Page 
I agree: 
•
To assume responsibility for the proper conduct of the study at this site.
•
To conduct the study in compliance with this protocol, any future amendments, and with 
any other study conduct procedures provided by the Sponsor, Clearside Biomedical, Inc.
(Clearside).
•
Not to implement any deviations from or changes to the protocol without agreement from 
the Sponsor and prior review and written approval from the Institutional Review Board /
Ethics Committee (IRB/IEC), except where necessary to eliminate an immediate hazard to 
the subjects, or for administrative aspects of the study (where permitted by all applicable 
regulatory requirements).
•
That I am thoroughly familiar with the appropriate use of the investigational drug(s), as 
described in this protocol and any other information provided by the Sponsor including, 
but not limited to the following: the current investigator’s brochure or equivalent 
document provided by Clearside and approved product label, if applicable.
•
That I am aware of, and will comply with, “good clinical practices” (GCP) and all 
applicable regulatory requirements.
•
To ensure that all persons assisting me with the study are adequately informed about the 
investigational drug(s) and of their study-related duties and functions as described in the 
protocol.
•
To periodic on-site monitoring of the case report forms (CRFs) and source documents by 
Clearside or designee and to on-site inspection of CRFs and source documents by 
appropriate regulatory authorities, including but not limited to the US Food and Drug 
Administration (FDA), local governing regulatory bodies, and IRB/IEC inspectors.
•
That I have been informed that certain regulatory authorities require the Sponsor to obtain 
and supply details about the investigator’s ownership interest in the Sponsor or study 
drug, and more generally about his/her financial ties with the Sponsor.  Clearside will use 
and disclose the information solely for the purpose of complying with regulatory 
requirements. 
Hence I: 
•
Agree to supply Clearside with any information regarding ownership interest and
financial ties (including those of my spouse and dependent children);
•
Agree to promptly update this information if any relevant changes occur during the
course of the study and for 1 year following completion of the study; and
•
Agree that Clearside may disclose this information about such ownership interests and
financial ties to regulatory authorities.
Investigator Name (Print) 
Investigator Signature 
Date 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................................8 
1. 
INTRODUCTION ........................................................................................................9 
1.1. 
Disease Background .....................................................................................................9 
1.2. 
Scientific Rationale .......................................................................................................9 
1.3. 
Description of Investigational Product .......................................................................10 
1.4. 
Summary of Clinical Experience and Justification for Route of 
Administration and Dose Selection ............................................................................11 
1.5. 
GCP Compliance ........................................................................................................11 
1.6. 
Population to be Studied .............................................................................................12 
2. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................13 
2.1. 
Primary Objective .......................................................................................................13 
2.2. 
Secondary Objective ...................................................................................................13 
2.3. 
Additional Objectives .................................................................................................13 
3. 
TRIAL DESIGN .........................................................................................................14 
3.1. 
Endpoints ....................................................................................................................14 
3.1.1. 
Primary Endpoint ........................................................................................................14 
3.1.2. 
Secondary Endpoint ....................................................................................................14 
3.1.3. 
Additional Endpoints ..................................................................................................14 
3.1.4. 
Safety Endpoints .........................................................................................................14 
3.2. 
Description of Study and Duration of Participation ...................................................14 
3.2.1. 
Description of Trial Design ........................................................................................14 
3.2.2. 
Trial Treatments ..........................................................................................................15 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................16 
4.1. 
Inclusion Criteria ........................................................................................................16 
4.2. 
Exclusion Criteria .......................................................................................................16 
4.2.1. 
Ophthalmic Exclusion Criteria ...................................................................................16 
4.2.2. 
General Exclusion Criteria .........................................................................................17 
4.3. 
Subject Discontinuation/Withdrawal from Clinical Study .........................................18 
4.3.1. 
Discontinuation of the Clinical Study.........................................................................18 
5. 
PROCEDURES ..........................................................................................................19 
5.1. 
Visit Description .........................................................................................................19 
5.1.1. 
General Procedures .....................................................................................................19 


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5.1.2. 
Re-screening Procedures ............................................................................................19 
5.1.3. 
Visit 1 – Screening (Day -14 to -1) ............................................................................19 
5.1.4. 
Visit 2 – Randomization/Treatment (Day 0) ..............................................................20 
5.1.5. 
Visit 3 – Week 4 Post Randomization Follow-Up (Day 28 ±5) .................................22 
5.1.6. 
Visit 4 – Week 8 Post Randomization Follow-up Visit (Day 56 ±5) .........................22 
5.1.7. 
Visit 5 – Week 12 – TREATMENT VISIT 2 (Day 84 ±5) ........................................22 
5.1.8. 
Visit 6 – Week 16 Post Randomization Follow-up Visit (Day 112 ±5) .....................24 
5.1.9. 
Visit 7 – Week 20 Post Randomization Follow-up Visit (Day 140 ±5) .....................24 
5.1.10. 
Visit 8 – Week 24 End of Study Visit (Day 168 ±5) or Early Termination 
Visit .............................................................................................................................24 
5.1.11. 
Unscheduled Visit .......................................................................................................25 
6. 
TREATMENT OF SUBJECTS ..................................................................................26 
6.1. 
Treatments to be Administered ...................................................................................26 
6.1.1. 
Study Eye Determination ............................................................................................27 
6.1.2. 
Treatment of the Fellow Eye (Non-Study Eye) ..........................................................27 
6.2. 
Concomitant Medications ...........................................................................................27 
6.2.1. 
Prohibited Medications ...............................................................................................27 
6.2.2. 
Additional Treatment ..................................................................................................28 
6.3. 
Treatment Compliance ................................................................................................28 
6.4. 
Drug Accountability ...................................................................................................28 
6.5. 
Masking / Unmasking .................................................................................................29 
7. 
ASSESSMENTS OF EFFICACY ..............................................................................31 
7.1. 
Best Corrected Visual Acuity (BCVA) ......................................................................31 
7.2. 
Central Subfield Thickness as Measured by SD-OCT ...............................................31 
7.3. 
Visual Function Questionnaire (VFQ-25) ..................................................................31 
7.4. 
EQ-5D .........................................................................................................................31 
7.5. 
Pharmacokinetics Assessments ..................................................................................31 
8. 
ASSESSMENTS OF SAFETY ..................................................................................32 
8.1. 
Intraocular Pressure ....................................................................................................32 
8.2. 
Slit-Lamp Biomicroscopy ...........................................................................................32 
8.2.1 
Cataract Lens Grading ................................................................................................32 
8.2.2 
Anterior Chamber Cells ..............................................................................................32 
8.2.3 
Anterior Chamber Flare ..............................................................................................33 


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8.3. 
Dilated Ophthalmoscopy ............................................................................................33 
8.3.1 
Vitreous Haze .............................................................................................................33 
8.4. 
Fluorescein Angiography ............................................................................................34 
8.5. 
Fundus Photography ...................................................................................................34 
8.6. 
Review of Systems .....................................................................................................34 
8.7. 
Clinical laboratory tests ..............................................................................................34 
8.8. 
Vital signs ...................................................................................................................35 
8.9. 
Evaluation of Adverse Events ....................................................................................35 
8.9.1. 
Definitions ..................................................................................................................36 
8.9.2. 
Adverse Event Reporting Procedures .........................................................................38 
8.9.3. 
Prompt Reporting of SAEs to the Sponsor .................................................................38 
8.9.4. 
Pregnancy Reporting ..................................................................................................39 
8.9.5. 
Transmission of SAE Reports and Pregnancy Forms .................................................39 
8.9.6. 
Regulatory Reporting Requirements for SAEs ...........................................................39 
8.9.7. 
Follow-up of AEs and SAEs .......................................................................................40 
9. 
STATISTICAL CONSIDERATIONS .......................................................................41 
9.1. 
Randomization ............................................................................................................41 
9.2. 
Determination of Sample Size and Level of Significance ..........................................41 
9.3. 
Subject Disposition, Demographic and Baseline Characteristics ...............................41 
9.4. 
Analysis Populations ..................................................................................................41 
9.5. 
Analysis Methods .......................................................................................................42 
9.5.1. 
Primary Efficacy Analysis ..........................................................................................42 
9.5.2. 
Secondary Efficacy Analysis ......................................................................................42 
9.5.3. 
Subgroup Analysis ......................................................................................................43 
9.5.4. 
Pharmacokinetic Analysis ..........................................................................................43 
9.5.5. 
Safety Analysis ...........................................................................................................43 
9.5.6. 
Interim Analysis ..........................................................................................................44 
9.5.7. 
Extent of Exposure .....................................................................................................45 
9.5.8. 
Procedure for Accounting for Missing, Unused, or Spurious Data ............................45 
9.5.9. 
Multiplicity .................................................................................................................45 
9.5.10. 
Procedure for Reporting Deviations from the Statistical Analysis Plan .....................45 
10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................46 
10.1. 
Investigator Training ..................................................................................................46 


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10.2. 
Monitoring ..................................................................................................................46 
10.3. 
Audits ..........................................................................................................................46 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................47 
12. 
ETHICS ......................................................................................................................48 
12.1. 
Institutional Review Board/Ethics Committee ...........................................................48 
12.2. 
Unanticipated Problems and Notification to Sponsor and IRB/IEC ..........................48 
12.3. 
Informed Consent Requirements ................................................................................49 
13. 
DATA HANDLING AND RECORD KEEPING ......................................................50 
13.1. 
Data Quality Control and Reporting ...........................................................................50 
13.1.1. 
Source Documents ......................................................................................................50 
13.1.2. 
Case Report Forms .....................................................................................................50 
13.1.3. 
Subject Tracking .........................................................................................................50 
13.1.4. 
Study Files ..................................................................................................................50 
13.2. 
Archiving of Data .......................................................................................................51 
13.3. 
Records Retention .......................................................................................................51 
14. 
FINANCING AND INSURANCE .............................................................................52 
14.1. 
Finance ........................................................................................................................52 
14.2. 
Insurance .....................................................................................................................52 
15. 
PUBLICATION POLICY ..........................................................................................53 
16. 
REFERENCES ...........................................................................................................54 
17. 
APPENDICES ............................................................................................................55 
APPENDIX A. TIME AND EVENTS SCHEDULE..................................................................56 
APPENDIX B. SUMMARY OF CHANGES FOR AMENDMENTS .......................................58 
 


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LIST OF TABLES 
Table 1: 
Anterior Chamber Cell Grading Scale ........................................................................33 
Table 2: 
Anterior Chamber Flare Grading Scale ......................................................................33 
Table 3: 
Scale for Determining Degree of Vitreous Haze ........................................................34 
Table 4: 
Clinical Laboratory Analytes to be Tested .................................................................35 
Table 5: 
Causality Definitions ..................................................................................................38 
 
LIST OF FIGURES 
Figure 1: 
Study Overview ..........................................................................................................15 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE  
Adverse Event 
BCVA 
Best Corrected Visual Acuity 
CRF 
Case Report Form 
CST 
Central Subfield Thickness 
EDC 
Electronic Data Capture 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
EQ-5D 
European Quality of Life 5-Dimensions 
FA 
Fluorescein Angiography 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Institutional Ethics Committee 
IOP 
Intraocular Pressure 
IRB 
Institutional Review Board 
IND 
Investigational New Drug  
IRT 
Interactive Response Technology 
ITT 
Intent-to-Treat 
IVT 
Intravitreal 
MedDRA 
Medical Dictionary for Regulatory Activities 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
OCT 
Optical Coherence Tomography 
PK 
Pharmacokinetics 
PP 
Per Protocol 
SAE 
Serious Adverse Event 
SCS 
Suprachoroidal Space 
SD-OCT 
Spectral-Domain Optical Coherence Tomography 
TA 
Triamcinolone Acetonide 
TEAEs 
Treatment Emergent Adverse Events 
VEGF 
Vascular Endothelial Growth Factor 
VFQ 
Visual Function Questionnaire 


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1. 
INTRODUCTION 
1.1. 
Disease Background  
Clearside is developing drugs to treat unmet or underserved blinding eye diseases. Part of this 
drug development strategy involves a novel approach using suprachoroidal administration to 
deliver drugs in high bioavailability via this local treatment paradigm to precisely access specific 
areas of the eye. Clearside’s developmental efforts have focused on uveitis where there is need 
for a locally administered medically beneficial therapy, which has the potential to provide a more 
encompassing and differentiating efficacious and safe treatment for patients. Based upon results 
from preclinical data in animal models of uveitis and from early clinical data in uveitis patients, 
the suprachoroidal approach for the treatment of uveitis is being developed to fulfill this unmet 
need.  
Uveitis is a general term used to describe a set of ocular inflammatory diseases. The whole eye 
can be affected in uveitis or the inflammation may dominate in specific locations of the eye. 
Uveitis is therefore classified by anatomic location within the eye as being anterior-, 
intermediate-, posterior- or pan-uveitis (Nussenblatt 1985) according to the primary site of 
inflammation. Each of these categories, however, encompasses a number of conditions that can 
be characterized further along other dimensions. Uveitis can be described by temporal features 
based on the onset (sudden or insidious), the duration (limited or persistent) and the course 
(acute, recurrent or chronic); and according to its etiology, in terms of being infectious or 
noninfectious, with the latter subgroup comprising entities that are either autoimmune, traumatic, 
idiopathic, or masquerade conditions (neoplastic or drug-induced disorders mimicking uveitis).  
Uveitis is the fifth most common cause of visual loss in the developed world (Goldstein 2009; 
Wood 2011; Miserocchi 2013). Significant vision loss can occur in up to 35% of children and 
adults, and uveitis accounts for 5% - 20% of legal blindness in both the United States and 
Europe, and perhaps as much as 25% of blindness in the developing world (Rothova 1996; 
Bodaghi 2001). 
There are a number of causes associated with this vision loss including cataract formation or 
progression, chorioretinal scarring, retinal detachment, and secondary glaucoma, but the 
dominant cause of vision loss within uveitis comes from chronic macular edema accounting for 
about one third of visual impairment or blindness (Wood, 2011; Dick, 1994; Karim, 2013). 
Approximately 30% of all uveitis patients and up to 60% of intermediate- and pan-uveitis 
patients experience macular edema (Lardenoye, 2006). 
Macular edema, the major cause of visual loss in uveitis, is defined as abnormal thickening of the 
macula associated with the accumulation of fluid in the outer plexiform and the inner nuclear 
layers of the retina, and occasionally the intracellular spaces as a result of the breakdown of the 
blood-retinal barrier (Dick, 1994; Cho, 2009).   
1.2. 
Scientific Rationale  
Uveitis is commonly treated with corticosteroids and other immunomodulatory agents; such 
treatments are either systemic or local. Systemic treatments are most commonly intravenous or 
oral whereas local treatments are either topical drops, intra-ocular or peri-ocular injections or 
implants. If the uveitis dominantly affects the anterior segment, topical steroid drops may be 


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effective therapy. In almost all other cases, steroids for initial treatment are given orally while 
non-steroidal immunosuppressive treatments are administered intravenously. Depending on the 
specific kind of uveitis both steroid and other immunosuppressive therapy may be used at the 
same time. Higher oral steroid doses, 60-80 mg/day, used for initial treatment are then tapered to 
a maintenance dose of <10 mg/day for management of ongoing uveitis. Based both on the 
specific differential diagnosis and on investigator preference, treatments in clinical practice tend 
to vary, although guidelines for the use of both steroids and other immunosuppressive agents are 
available (Jabs, 2000). 
The challenge with systemic, frequently oral, corticosteroid treatments for ophthalmic 
inflammatory conditions is that these treatments are often associated with adverse events (AEs) 
such as peptic ulcerations, osteoporosis, necrosis of the hip, weight gain, muscle weakness, 
hyperglycemia, and systemic hypertension. All currently used modes of steroid administration 
for ophthalmic conditions, including local administrations, are associated with increases in 
intraocular pressure that could result in glaucoma, progression of glaucoma, and to both the 
formation and the progression of cataracts (Karim, 2013).  
Topical corticosteroids given as eye drops for anterior uveitis, have not shown that they are 
capable of reducing complications of uveitis such as macular edema in a consistent manner. 
Since macular edema is the leading cause of sight threatening blindness in uveitis, methods other 
than topical drops are usually used when macular edema, or other local complications persist in 
uveitis. Intravitreal injections of corticosteroids, or implantation of sustained corticosteroid 
delivery devices in or proximal to the vitreous can be used to administer therapeutic agents so 
that they are available to the posterior segment, provide local therapy, and reduce macular edema 
and other local uveitic complications (Ghate, 2007).  While the intravitreal route of 
administration enables availability of the drug to the posterior segment, the procedure leads to 
significant exposure of the administered corticosteroid to anterior segment ocular structures. 
Similar issues plague periocular corticosteroid administration. Cataract formation, elevated 
intraocular pressure that can lead to glaucoma and worsening of pre-existing glaucoma are 
common adverse effects of periocular and intraocular administration of corticosteroid treatments. 
The potential advantages of using suprachoroidal administration to precisely provide local 
corticosteroid therapy to the affected tissues of the eye are that it can result in robust efficacy 
based upon data from animal models and from Phase 1/2 clinical data and it has the potential for 
reducing the amount of drug dosed because of the high bioavailability of drug in the retina and 
choroid. Further, the unique distribution of drug following suprachoroidal administration 
confining it to the posterior segment and sparing anterior segment portions of the eye, along with 
the extremely low systemic steroid exposure to other organs in the body can provide 
differentiating efficacy along with the potential for improved safety.   
1.3. 
Description of Investigational Product 
CLS-TA, triamcinolone acetonide injectable suspension (CLS-TA), is a sterile, preservative-free, 
aqueous suspension formulated for administration into the eye.  The drug product is terminally 
sterilized and is intended for single use.  CLS-TA is supplied as a 40 mg/mL sterile suspension in 
a 2 mL/13 mm TopLyo® single use vial with a rubber stopper and an aluminum seal.   
CLS-TA must be stored under ambient temperature conditions at ca. 20° - 25° C (68° - 77° F); 
do not freeze. CLS-TA should be protected from light by storing in the carton provided. 


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CLS-TA will be administered as a single injection of 4 mg in 100 microliters (µL). 
Additional information regarding CLS-TA is available in the Investigator’s Brochure. 
1.4. 
Summary of Clinical Experience and Justification for Route of 
Administration and Dose Selection 
TA has been safely and effectively used in human ocular therapeutics to treat ocular conditions 
involving inflammation for over 50 years. The initial recommended dose of the TA formulation 
(Triesence®) approved by the FDA for ocular indications is 4 mg in 100 µL.  
Clearside is developing CLS-TA, a proprietary TA formulation, for the treatment of non-
infectious uveitis by administration to the SCS. This therapy for uveitis is part of Clearside’s 
paradigm of developing drug treatments for unmet or underserved blinding eye diseases where 
the pathologies dominantly originate or manifest in the choroid and the retina.  
The dose of CLS-TA, administered as a single suprachoroidal injection, will be 4 mg in 100 µL. 
Clearside has one completed and one ongoing clinical study of up to 4 mg TA administered 
suprachoroidally to subjects with non-infectious uveitis.  
The completed clinical study, CLS1001-101, was a Phase 1/2, open-label, safety and tolerability 
study in subjects with intermediate-, posterior-, or pan- non-infectious uveitis. Each subject 
received a single suprachoroidal injection of 4 mg in 100 µL TA (Triesence). Nine (9) of the 11 
subject subjects in the safety analysis set (82%) completed the 26-week study. All subjects had at 
least one AE, with a total of 37 AEs reported. One serious event (unrelated pulmonary emboli; 
SAE) occurred. No deaths were reported. 
Approximately half of the reported AEs were ocular events. No significant increases in IOP were 
reported. Nine ocular AEs, in four subjects, were considered possibly related to TA. The most 
commonly reported AE, eye pain, was reported in 5 subjects. There were no serious adverse 
events (SAEs) reported as related to the study drug. No systemic AEs were reported as related to 
study drug. 
The ongoing clinical study, CLS1001-201, is a Phase 2, randomized, masked safety and efficacy 
study in subjects with macular edema associated with non-infectious uveitis. Each subject will 
receive a single suprachoroidal injection of CLS-TA, 4 mg in 100 µL or 0.8 mg in 100 µL. As of 
31JUL2015, 11 subjects have been enrolled into this study and 5 have completed the study. As of 
this date, fourteen AEs have been reported; 8 of the AEs in 4 subjects are ocular in nature and 
none have been reported as serious.  
Additional information regarding clinical experience with TA administered to the SCS, is 
available in the Investigator’s Brochure. 
1.5. 
GCP Compliance 
This clinical trial will be conducted in accordance with the principles of the Declaration of 
Helsinki, and in compliance with the International Conference on Harmonization (ICH) E6 Good 
Clinical Practice (GCP) guidelines and other applicable regulatory requirements. The 
Investigator and all clinical study staff will conduct the clinical study in compliance with the 
protocol. The Investigator will ensure that all personnel involved in the conduct of the study are 


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qualified to perform their assigned responsibilities through relevant education, training and 
experience. 
1.6. 
Population to be Studied 
The study population includes approximately 150 adult subjects to be enrolled at approximately 
60 study sites. To participate in the study, subjects must be 18 years or older with macular 
edema associated with non-infectious uveitis of any etiology, and from among those with 
anterior-, intermediate-, posterior- or pan-uveitis. The expected duration of participation in the 
study is up to 27 weeks. The complete inclusion and exclusion criteria are presented below in 
Section 4. 


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2. 
TRIAL OBJECTIVES AND PURPOSE 
The purpose of this study is to evaluate the safety and efficacy of suprachoroidally administered 
CLS-TA, triamcinolone acetonide injectable suspension, for the treatment of macular edema 
associated with non-infectious uveitis.  
2.1. 
Primary Objective 
The primary objective of the study is to demonstrate the efficacy of CLS-TA as shown by the 
change from baseline in BCVA in subjects with macular edema associated with non-infectious 
uveitis 
2.2. 
Secondary Objective 
• To determine mean change from baseline in central subfield thickness 
2.3. 
Additional Objectives 
• To determine systemic exposure to triamcinolone acetonide following suprachoroidal 
injection of CLS-TA 
• To determine the change from baseline with respect to subject-reported outcomes 
 


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3. 
TRIAL DESIGN 
3.1. 
Endpoints 
3.1.1. 
Primary Endpoint 
The primary endpoint is the proportion of subjects with a change from baseline of ≥ 15 letters in 
ETDRS BCVA at Visit 8 (24 weeks), subsequent to suprachoroidal injections of CLS-TA or 
sham injection procedures, in subjects with macular edema associated with non-infectious 
uveitis. 
3.1.2. 
Secondary Endpoint 
• Mean change from baseline in CST as measured by SD-OCT at 24 weeks (Visit 8)   
3.1.3. 
Additional Endpoints 
• Triamcinolone acetonide blood concentrations prior to each dose (Visit 2 and 5), 4 
weeks following the first dose (Visit 3) and at 24 weeks (Visit 8) 
• Change from baseline in subject reported outcomes as measured by the Visual 
Function Questionnaire, VFQ-25 and the EQ-5D questionnaire at Visit 8 (24 weeks)   
3.1.4. 
Safety Endpoints 
• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events 
(SAEs), grouped by organ system, relatedness to study treatment and severity  
• Percentage of subjects whose IOP increases are > 10 mmHg from their own baseline 
measurement at each follow-up visit (except Visit 2 & 5 [post-dose])  
• Percentage of subjects whose IOP increases to a reading > 30 mmHg at each follow-
up visit (except Visit 2 & 5 [post-dose]) 
• Percentage of subjects who require 1 or more additional IOP lowering medications at 
any follow-up visit (except Visit 2 & 5 [post-dose]) 
3.2. 
Description of Study and Duration of Participation 
3.2.1. 
Description of Trial Design 
This is a Phase 3, randomized, masked, sham-controlled, multicenter study to assess the safety 
and efficacy of 4 mg of CLS-TA administered via suprachoroidal injection compared to a sham 
injection procedure in the treatment of subjects with macular edema associated with non-
infectious uveitis.   
The study design includes 8 clinic visits over a maximum of 27 weeks.  Subject eligibility will be 
established at Visit 1 during the screening process (Day -14 to -1).  Eligible subjects will return 
to the clinic for Visit 2, Randomization (Day 0).  Qualified subjects will be randomized to 
receive two unilateral suprachoroidal injections of CLS-TA administered to the study eye or two 
unilateral sham injection procedures administered to the study eye, approximately 12 weeks 
apart (Visit 2 and Visit 5).  Follow-up visits will be conducted monthly up to 24 weeks (Visit 8). 


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Subjects will have a final evaluation conducted 24 weeks (Visit 8) following initial 
randomization. Approximately 25% of the subjects will be included in a pharmacokinetic 
evaluation for the study. Figure 1 below depicts the study overview: 
Figure 1: 
Study Overview 
3.2.2. 
Trial Treatments 
Subjects will be randomized at Visit 2 to Active or Control arms in a 3:2 ratio. 
Subjects randomized to the Active arm will receive unilateral suprachoroidal injections of 4 mg 
(100 µL of 40 mg/mL) CLS-TA at Day 0 (Visit 2) and Week 12 (Visit 5).   
Subjects randomized to the Control arm will receive unilateral sham injection procedures in 
which no drug or vehicle will be administered, at Day 0 (Visit 2) and Week 12 (Visit 5). The 
sham injection procedure will mimic the active injection in order to maintain the subject’s 
masking.   


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4. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1. 
Inclusion Criteria 
Subjects are eligible for participation in this study if s/he meets all of the following criteria: 
1. A diagnosis of non-infectious uveitis of any etiology and from among those with anterior-, 
intermediate-, posterior- or pan-uveitis 
2. Macular edema associated with non-infectious uveitis defined by: 
• A retinal thickness of  ≥ 300 microns in the central subfield, with fluid as measured 
by SD-OCT (using the Heidelberg SPECTRALIS® or Zeiss CirrusTM) and confirmed 
by the Central Reading Center 
3. ETDRS BCVA score of  ≥ 5 letters read (20/800 Snellen equivalent) and ≤ 70 letters read 
(20/40 Snellen equivalent) in the study eye 
4. Understands the language of the informed consent; willing and able to provide written 
informed consent prior to any study procedures; willing to comply with the instructions and 
attend all scheduled study visits 
5. At least 18 years of age 
4.2. 
Exclusion Criteria 
4.2.1. 
Ophthalmic Exclusion Criteria 
Subjects are ineligible for participation in this study if s/he meets any of the following criteria: 
1. Has significant media opacity in the study eye precluding evaluation of the retina and 
vitreous  
2. Has macular edema with etiology other than uveitis 
3. Any active ocular disease or infection in the study eye other than uveitis 
4. Intraocular pressure > 22 mmHg or uncontrolled glaucoma (open angle or angle closure) 
in the study eye at Visit 1; subjects are not excluded if IOP is ≤ 22 mmHg in the study 
eye with no more than 2 IOP lowering medications  
5. History of any vitreoretinal surgery (examples include but are not limited to scleral 
buckle, retrieval of a dropped nucleus or intraocular lens) in the study eye; prior 
photocoagulation and IVT injections are acceptable; prior cataract extraction, Yttrium-
Aluminum-Garnet laser capsulotomy, and pars plana vitrectomy is allowed, but must 
have been performed at least 3 months prior to Visit 2 
6. Has had cyclodestructive procedures or filtration surgeries in the study eye in the 3 
months prior to Visit 2 
7. Has high myopia in the study eye defined as a spherical equivalent > -6 diopters or an 
axial length ≥ 26 mm  
8. Has had photocoagulation or cryotherapy in the study eye within the 6 months prior to 
Visit 2  


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9. Has had any intravitreal injection of anti-VEGF treatment (bevacizumab, aflibercept, 
pegaptanib or ranibizumab) in the study eye in the 30 days prior to Visit 2  
10. In the study eye, any topical ocular corticosteroid in the 10 days prior to Visit 2; 
intraocular and periocular corticosteroid injection in the 2 months prior to Visit 2; an 
OZURDEX implant in the 6 months prior to Visit 2; RETISERT or ILUVIEN implant in 
the 3 years prior to Visit 2 
4.2.2. 
General Exclusion Criteria  
Subjects are not eligible for participation in this study if s/he meets any of the following criteria: 
11. Female subjects who are pregnant, lactating or planning a pregnancy. Females of 
childbearing potential must agree to submit to a pregnancy test at screening and agree to 
use an acceptable method of contraception throughout participation in the study.  
Acceptable methods of contraception include double barrier methods (condom with 
spermicide or diaphragm with spermicide), hormonal methods (oral contraceptives, 
implantable, transdermal, or injectable contraceptives), or an intrauterine contraceptive 
device with a documented failure rate of less than 1% per year.  Abstinence may be 
considered an acceptable method of contraception at the discretion of the Investigator, 
but the subject must agree to use one of the acceptable birth control methods if she 
becomes sexually active. 
12. Any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude 
participation in the study (e.g., unstable medical status including uncontrolled elevated 
blood pressure, cardiovascular disease, and glycemic control) or put the subject at risk 
due to study treatment or procedures 
13. Likely need for hospitalization or surgery within the study period, including planned 
elective surgery or hospitalization that cannot be deferred 
14. Hypersensitivity to any component of the CLS-TA, fluorescein or to topical anesthetics 
15. Is currently enrolled in an investigational drug or device study or has used an 
investigational drug or device within 30 days of Visit 2 
16. Has used acetazolamide (Diamox®) 1 week prior to Visit 2 
17. Has taken systemic corticosteroids at doses greater than 20 mg per day for oral 
prednisone (or equivalent for other corticosteroids) in the 2 weeks prior to Visit 2; 
subjects on 20 mg or less per day can be enrolled if no increase in dosing is anticipated 
for the duration of the study; decreases and termination of dose are allowable during the 
study 
18. Is currently using prescribed nonsteroidal anti-inflammatory drugs (excluding over-the-
counter use) unless the dose has been stable for at least 2 weeks prior to Visit 2, and no 
increase in dosing is anticipated for the study duration; decreases and termination of dose 
are allowable during the study 
19. Is currently using prescribed immunomodulatory therapies, unless the dose has been 
stable for at least 2 weeks prior to Visit 2, and no increase in dosing is anticipated for the 
study duration; decreases and termination of dose are allowable during the study 


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20. Has taken any fingolimod or any other drug in the 6 weeks prior to Visit 2, where the 
drug is known to induce macular edema 
4.3. 
Subject Discontinuation/Withdrawal from Clinical Study 
Subjects may withdraw from the study at any time and for any reason without obligation.  
Subjects may be removed from the study at the Investigator’s discretion.  Subjects who 
discontinue for any reason will not be replaced and their subject numbers will not be reassigned 
or re-used. 
If a subject withdraws from the study or if the Investigator removes a subject from the study, the 
Investigator should make every attempt to complete all Visit 8 assessments (Section 5.1.10.).  If 
an SAE is unresolved at the time of the subject’s final study visit, investigator should make every 
attempt to follow up until the SAE is resolved or stabilized, the subject is lost to follow-up, or 
there is some other resolution of the event.  If at any time during the study a subject is considered 
at immediate risk for a vision-threatening event due to study participation, the subject should be 
treated as soon as necessary, with the investigator determining appropriate care or additional 
therapy (Section 6.2.2.).  Subjects should not be discontinued from the study due to additional 
therapy or due to an AE unless the Investigator determines it to be in the subject’s best interest. 
4.3.1. 
Discontinuation of the Clinical Study 
The study or parts of the study may be discontinued by the Sponsor or at the recommendation of 
an Investigator after consultation with Sponsor, at any time.  This may be based on a significant 
number of AEs of a similar nature that warrant such action or at the request of the Sponsor. 
If the clinical study is prematurely terminated or suspended, the Sponsor will inform the 
Investigators and the regulatory authorities of the termination/suspension and the reason(s) for 
the termination/suspension.  The Investigator should promptly notify the IEC/IRB of the 
termination or suspension and of the reasons. 
 
 
4.3.2. 
Discontinuation of a Clinical Study Site 
The Sponsor reserves the right to close the investigational site, or terminate the study in its 
entirety at any time, for reasonable cause. Reasons for the closure of any investigational site or 
termination of a study may include: 
• Failure of the Investigator to accrue subjects into the study at an acceptable rate 
• Failure of the Investigator to comply with applicable regulations and GCPs 
• Submission of knowingly false information from the research facility to the sponsor, 
FDA, or other regulatory authorities 
• Insufficient adherence to protocol requirements and procedures 
If the study is prematurely discontinued, all study data must be returned to the Sponsor.  
Additionally, the site must conduct final disposition of all unused study drugs in accordance with 
Sponsor procedures.  Study termination and follow-up will be performed in compliance with the 
conditions set forth in regulatory guidelines. 


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5. 
PROCEDURES 
5.1. 
Visit Description 
5.1.1. 
General Procedures 
The study will consist of up to 8 study visits over a maximum of 27 weeks.  Subjects are 
expected to attend all study visits. All ocular assessments at Visit 1 and Visit 8 will be performed 
on both eyes. IOP will be collected in both eyes at all visits. All other ocular assessments at all 
other visits (Visits 2-7) will be performed on the study eye only.  Subjects will be screened for 
entry (Visit 1) and then return to the clinic within 14 days to be randomized/treated (Visit 2).  At 
randomization, subjects will receive either a single, unilateral, suprachoroidal injection of 4 
mg/100 µL CLS-TA or a single, unilateral sham injection procedure in the study eye. Subjects 
will be assessed post injection for safety.  Additional safety follow-up visits will occur monthly 
for 24 weeks. Subjects will receive a second injection of either 4 mg/100 µL CLS-TA or a sham 
injection procedure at Visit 5 (Week 12) based on their original randomization at Visit 2. The 
final study visit will occur at Visit 8 (Week 24).  
5.1.2. 
Re-screening Procedures  
 
A subject who is first designated as a screen failure prior to being randomized may be rescreened 
up to 2 additional times, for a total of three screenings, upon Sponsor approval. Subjects who are 
re-screened are required to sign a new consent form. 
5.1.3. 
Visit 1 – Screening (Day -14 to -1) 
At Visit 1, subjects will be screened for eligibility.  Before any study-specific assessments are 
performed, written informed consent will be obtained for each subject.  During Visit 1, the 
following procedures will be performed: 
1. Obtain written informed consent 
2. Assign subject number 
3. Collect demographics, medical and ocular history   
4. Review current and prior concomitant medications  
5. Measure resting heart rate and blood pressure  
6. Collect blood and urine for central lab tests prior to FA, including serum pregnancy test 
on females of childbearing potential 
7. Perform ophthalmic assessments on both eyes:  
a. ETDRS BCVA  
b. Slit-lamp biomicroscopy, including dilated lens grading   
c. IOP  
d. Dilated indirect ophthalmoscopy 
e. Fundus photography  


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f. SD-OCT 
g. FA   
8. Perform a review of systems 
9. Verify subject eligibility based on Inclusion/Exclusion requirements 
10. Determine study eye based upon eye specific eligibility criteria 
11. Schedule subject to return for Visit 2, Randomization/Treatment   
 
NOTE:  All images (SD-OCT, fundus photographs and FA) should be uploaded to the 
Central Reading Center. It will take approximately 2 business days for the Central 
Reading Center to confirm eligibility and the Central Laboratory report to arrive.  Allow 
sufficient time between Visit 1 and Visit 2 in order to confirm eligibility through the 
Central Reading Center and Central Laboratory reports.  
5.1.4. 
Visit 2 – Randomization/Treatment (Day 0) 
Visit 2 must occur within 14 days of Visit 1 (Screening) and may only occur once a subject 
qualifies for randomization, which includes central lab results being received and reviewed and 
confirmation of qualification by the Central Reading Center.   
Once eligibility is confirmed, subjects will be randomized via the IRT to receive a single, 
unilateral, suprachoroidal injection of CLS-TA (4 mg/100 µL) or a single, unilateral sham 
injection procedure.  Once randomized, subjects will receive an additional single, unilateral 
suprachoroidal injection of CLS-TA (4 mg/100 µL) or a single, unilateral sham injection 
procedure approximately 12 weeks later (Visit 5).  Subjects will remain in the same treatment 
arm for the duration of participation in the study.  
The following procedures will be performed: 
5.1.4.1. 
Pre-Injection Procedures  
The following must be performed prior to the injection (the same day as the injection): 
1. Assess for AEs 
2. Review changes to concomitant medications 
3. Review central lab results for any clinically significant abnormalities that would exclude 
the subject from entry 
4. Review the results received from the Central Reading Center to confirm that subject 
qualifies based on CST 
5. Review eligibility based on Inclusion/Exclusion criteria 
6. Measure resting heart rate and blood pressure  
7. Perform ophthalmic assessments on the study eye only, unless otherwise designated:  
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading   


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c. IOP (both eyes) 
d. Dilated ophthalmoscopy 
e. SD-OCT and upload images to the Central Reading Center 
8. Administer VFQ-25 and EQ-5D 
9. Collect a blood sample from those subjects participating in the PK procedure; blood must 
be collected PRIOR to dosing 
10. Log onto the IRT system and randomize subject   
5.1.4.2. 
Injection Procedure and Immediate Post-Injection Assessments 
Injection should be performed the same day as the pre-injection procedures.  For details on the 
injection procedure, please see the Manual of Procedures. The injecting physician and supporting 
study staff who are present during the injection are unmasked on a per subject basis. Unmasked 
personnel should not perform assessments for that subject at Visits 3,4,6,7 and 8. Unmasked 
personnel may also perform pre- and post-injection assessments, except BCVA, at Treatment 
visits (Visits 2 and 5) if masked staff are not available. 
1. Confirm study eye 
2. Retrieve study drug kit number assigned by IRT 
3. Prepare eye for injection per the investigator’s standard practice    
4. The UNMASKED injecting investigator should administer suprachoroidal injection of 
CLS-TA or perform the sham injection procedure to the study eye; see Manual of 
Procedures for detailed instructions 
5. Immediately following the injection, assess study eye by indirect ophthalmoscopy 
5.1.4.3. 
Post-Injection Procedures 
The following assessments must occur following the injection: 
1. Assess for AEs 
2. Review changes to concomitant medications 
3. Perform ophthalmic assessments on the study eye only:  
a. Perform slit-lamp biomicroscopy  
b. Perform  indirect ophthalmoscopy 
c. Evaluate IOP 10 - 30 minutes post injection 
• If IOP remains elevated, subject must remain on site until IOP is under 
control per investigator judgment 
• If IOP is < 30 mmHg, the subject may leave the clinic 
4. Schedule subject to return for next visit 
 


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5.1.5. 
Visit 3 – Week 4 Post Randomization Follow-Up (Day 28 ±5) 
Visit 3 will occur approximately 4 weeks post randomization. The visit should be 28 ±5 days 
from Visit 2. The following Visit 3 procedures will be performed by masked study staff: 
1. Assess for AEs 
2. Review changes to concomitant medications  
3. Perform ophthalmic assessments on the study eye only, unless otherwise designated:  
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading   
c. IOP (both eyes) 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the Central Reading Center 
4. Collect a blood sample from those subjects participating in the PK procedure 
5. Schedule subject to return for next visit 
5.1.6. 
Visit 4 – Week 8 Post Randomization Follow-up Visit (Day 56 ±5) 
Visit 4 will occur approximately 8 weeks post randomization. The visit should be 56 ± 5 days 
from Visit 2. The following Visit 4 procedures will be performed by masked study staff: 
1. Assess for AEs 
2. Review changes to concomitant medications  
3. Perform ophthalmic assessments on study eye only, unless otherwise designated:  
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading   
c. IOP (both eyes) 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the Central Reading Center 
4. Schedule subject to return for next visit 
5.1.7. 
Visit 5 – Week 12 – TREATMENT VISIT 2 (Day 84 ±5) 
Visit 5 will occur approximately 12 weeks post randomization.  At Visit 5, subjects will receive 
their second, single, unilateral study drug treatment.  The randomization arm initially assigned to 
a subject will remain the same throughout the study. The treatment must be administered by an 
UNMASKED injecting physician only.   
5.1.7.1. 
Pre-Injection Procedures  
The following must be performed prior to the injection (the same day as the injection): 
1. Assess for AEs 


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2. Review changes to concomitant medications 
3. Measure resting heart rate and blood pressure  
4. Confirm study eye 
5. Perform ophthalmic assessments on the study eye only, unless otherwise designated:  
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading   
c. IOP (both eyes) 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the Central Reading Center 
6. Collect a blood sample from those subjects participating in the PK procedure; blood draw 
must be collected PRIOR to dosing 
5.1.7.2. 
Injection Procedure and Immediate Post-Injection Assessments 
For details on the injection procedure, please see the Manual of Procedures. The Visit 5 injection 
procedure should be identical to the Visit 2 injection procedure. 
1. Confirm study eye 
2. Retrieve study drug kit number assigned by IRT  
3. Prepare eye for injection per the investigator’s standard practice  
4. The UNMASKED injecting investigator should administer a suprachoroidal injection of 
CLS-TA or perform the sham injection procedure in the study eye; see Manual of 
Procedures for detailed instructions 
5. Immediately following the injection, assess study eye by indirect ophthalmoscopy 
5.1.7.3. 
Post-Injection Procedures 
The following assessments must occur following the injection: 
1. Assess for AEs 
2. Review changes to concomitant medications 
3. Perform ophthalmic assessments on the study eye only:  
a. Perform slit-lamp biomicroscopy  
b. Perform  indirect ophthalmoscopy 
c. Evaluate IOP 10 - 30 minutes post injection 
• If IOP remains elevated, subject must remain on site until IOP is under 
control per investigator judgment 
• If IOP is < 30 mmHg, the subject may leave the clinic 
4. Schedule subject to return for next visit 


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5.1.8. 
Visit 6 – Week 16 Post Randomization Follow-up Visit (Day 112 ±5) 
Visit 6 will occur approximately 16 weeks post randomization. The visit should be 112 ± 5 
days from Visit 2. The following Visit 6 procedures will be performed by masked study staff: 
1. Assess for AEs 
2. Review changes to concomitant medications  
3. Perform ophthalmic assessments on study eye only, unless otherwise designated:  
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading   
c. IOP (both eyes) 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the Central Reading Center 
4. Schedule subject to return for next visit 
5.1.9. 
Visit 7 – Week 20 Post Randomization Follow-up Visit (Day 140 ±5) 
Visit 7 will occur approximately 20 weeks post randomization. The visit should be 140 ± 5 
days from Visit 2. The following Visit 7 procedures will be performed by masked study staff: 
1. Assess for AEs 
2. Review changes to concomitant medications  
3. Perform ophthalmic assessments on study eye only, unless otherwise designated: 
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading   
c. IOP (both eyes) 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the Central Reading Center 
4. Schedule subject to return for next visit 
5.1.10. 
Visit 8 – Week 24 End of Study Visit (Day 168 ±5) or Early Termination Visit 
Visit 8 will occur approximately 24 weeks post randomization. The visit should be 168 ± 5 days 
from Visit 2 or at the time of early termination. The following Visit 8 procedures will be 
performed by masked study staff: 
1. Assess for AEs 
2. Review changes to concomitant medications  
3. Measure resting heart rate and blood pressure  
4. Collect blood and urine for central lab tests prior to FA (including serum pregnancy test 
on females of childbearing potential) 


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5. Collect a blood sample from those subjects participating in the PK procedure 
6. Perform a review of systems 
7. Administer VFQ-25 & EQ-5D 
8. Perform ophthalmic assessments on both eyes:  
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading   
c. IOP  
d. Dilated indirect ophthalmoscopy 
e. Fundus photography and upload images to the Central Reading Center   
f. SD-OCT and upload images to the Central Reading Center  
g. FA and upload images to the Central Reading Center  
5.1.11. 
Unscheduled Visit 
To ensure subject safety during the trial, any subject who requires additional follow-up during 
the study for any reason should see the Investigator, even if such a visit does not fall within a 
scheduled study visit. The masked investigator/staff should complete assessments for an 
unscheduled visit whenever possible. 
Any visit that occurs between the regularly scheduled visits must be documented in the 
Unscheduled Visit pages of the Electronic Case Report Form (eCRF). If the patient is 
discontinuing at the Unscheduled Visit, the procedures for Visit 8 (Week 24) should be 
completed as described in Section 4.3 and captured on the Visit 8 eCRFs, not on the eCRFs for 
an Unscheduled Visit. 


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6. 
TREATMENT OF SUBJECTS 
6.1. 
Treatments to be Administered 
Treatment will consist of two unilateral suprachoroidal injections of 4 mg of CLS-TA in 100 µL, 
or two sham injection procedures, administered 12 weeks apart, according to the randomization 
assignment.  
Subjects will be randomized to either of the following groups:  
1. Active: 4 mg CLS-TA, triamcinolone acetonide injectable suspension, 40 mg/mL in         
100 µL 
2. Control: sham injection procedure 
Approximately 150 subjects will be randomized in a 3:2 ratio where approximately 90 subjects 
will be randomized to the Active arm and approximately 60 subjects will be randomized to the 
Control arm. The CLS-TA injections, or sham injection procedures, occur at Visit 2 (Day 0) and 
at Visit 5 (Day 84 ± 5).   
The study drug kits will be supplied to the site.  Each subject will be randomized to a study arm 
and be assigned a study drug kit at both Visit 2 (Day 0) and again at Visit 5 (Week 12).  Each kit 
will be identical (either two active kits or two sham kits). Each kit will contain the following 
components: 
Active Kit: 
• Vial of CLS-TA (40 mg/mL) 
• Clearside microinjector 
• Vial access device (for drug transfer)  
• 900 µm needle 
• 1100 µm needle 
Sham Kit: 
• Vial of CLS-TA (40 mg/mL) 
• Clearside microinjector 
• Vial access device (for drug transfer) 
• Sham hub 
All study drug injections may only be performed by trained Investigators.  Training will be 
documented by the Sponsor in writing.  Training documentation will be maintained at the site as 
well as with the Sponsor.    
 
Detailed instructions on the study drug injection procedure can be found in the Manual of 
Procedures. 


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6.1.1. 
Study Eye Determination 
The study eye will be the eye receiving the CLS-TA injection or the sham injection procedure 
depending upon the group to which the subject is randomized. The determination of the study 
eye will be based on Visit 1 (screening) information only. 
If both eyes meet study criteria, then the eye, in the Investigator’s opinion, with the better chance 
of achieving an improvement in BCVA should be used as the study eye. If both eyes qualify for 
the study, and appear similar in their chance of improvement, the right eye should be designated 
as the study eye. The eye that is not designated as the study eye will be denoted as the fellow 
eye. 
6.1.2. 
Treatment of the Fellow Eye (Non-Study Eye) 
Subjects may have bilateral disease, but only one study eye may be enrolled.  
Ocular therapy for the fellow eye is not subject to the requirements of this protocol. Systemic 
therapy for diseases of the fellow eye is subject to the list of prohibited medications below. Local 
medications are permitted for the fellow eye during the course of this trial. Medications used in 
the fellow eye will be recorded in the subject’s medical chart and the case report form (CRF).   
6.2. 
Concomitant Medications 
6.2.1. 
Prohibited Medications 
The list of prohibited medications provided below is not intended to be comprehensive, but 
rather to help guide the Investigator’s medical judgment. In cases where a subject presents with a 
medication not included on the following list, or should there be any question on the part of the 
Investigator, Investigators are encouraged to confer with the Medical Monitor for any 
clarification. 
Use of the following medications are prohibited at any time during the study: 
• Increases to topical ophthalmic NSAIDs in the study eye  
• Any corticosteroid implant (ie, Ozurdex®, Iluvien® or Retisert®) in the study eye 
• Topical, periocular or intravitreal corticosteroids in the study eye  
• Increases in dose of systemic prednisone or other equivalent steroid (eg, dexamethasone), 
including, but not limited to, the following routes: oral, intravenous, intramuscular, in 
sufficient doses and/or for sufficient time such that the Investigator has concerns about 
additional ocular exposure to steroids in terms of safety and/or efficacy 
• Anti-angiogenic drugs (anti-VEGF) in the study eye or systemically (including 
pegaptanib sodium, bevacizumab, ranibizumab, aflibercept) 
• Increases to dose of systemic immunosuppressant drugs 
• Fingolimod or any other drug known to induce ME 
• Acetazolamide (Diamox®) 
• Any investigational drug or device 


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In cases where there is anticipated need for the above listed medications during the study or if a 
subject presents to the Investigator having initiated treatment during the study with one of these 
medications or classes of medications, it is the responsibility of the Investigator to notify the 
Sponsor immediately. If additional therapy is necessary to treat uveitis in the study eye and 
normal standard of care requires these medications, they will be recorded in the subject’s case 
report form and should follow the guidelines presented for rescue criteria. Subjects will not be 
discontinued from the study due to initiation/change in a prohibited medication. 
6.2.2. 
Additional Treatment 
If at any time during the study a subject is considered at immediate risk for a vision-threatening 
event, the Investigator should immediately follow best medical practice in the Investigator’s 
judgment for treating the subject. All additional therapy will be recorded in the subject’s medical 
chart and the CRF.  
Rescue Criteria 
Beginning at Week 4 (Visit 3), if any of the following criteria are met in the study eye, 
the use of a treatment should be introduced. The therapy implemented is left to the 
discretion of the Investigator.   
• A decrease of 10 or more ETDRS BCVA letters read from baseline (Day 0) 
• An increase in CST of  ≥100 microns or 20%, whichever is lower, from baseline 
(Day 0) based on the CST measurement at the clinical site 
• A ≥ 1.5-step increase from baseline (Day 0) in the level of inflammation (eg, 
anterior chamber cells or vitreous haze) or an increase from 3+ to 4+  
• In the investigator’s medical judgement, the uveitic complications in the study 
eye have not improved and the condition needs to be addressed 
6.3. 
Treatment Compliance 
Study drug will only be administered by trained study investigators (principal investigator or 
sub-investigator) in the office at Visit 2 and at Visit 5. The injecting physician will be unmasked 
per patient.  No study drug will be dispensed to subjects; therefore, subject treatment compliance 
is not applicable.   
The date and time of the injection will be recorded in the subject’s medical chart and the CRF.  
All needles used and the needle length used for injection will also be recorded. All study drug 
kits (and all the components of each of the kits, such as the vial, the microinjector, etc.) will 
remain under the control of the study site staff at all times. Following injection, used 
microinjectors should be disposed of properly but used vials of study drug should be capped and 
maintained in the original box until accountability has been completed by the unmasked monitor. 
6.4. 
Drug Accountability 
Accountability of study drug kits will be conducted by an unmasked member of the site and 
verified by an unmasked monitor.  Accountability will be ascertained by performing 
reconciliation between the number of study drug cartons (kits and their components) sent to the 


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site, and the number used and unused at the time of reconciliation. Unmasked site staff will be 
queried about any discrepancies. 
Study drug shipment records will be verified and accountability performed by comparing the 
shipment inventory sheet to the actual quantity of drug and microinjectors received at the site.  In 
addition, receipt of study drug cartons will be confirmed via the IRT.  Accurate records of receipt 
and disposition of the study drug and microinjectors (eg, dates, quantity, subject number, kits 
used, kits unused, etc.) must be maintained by the unmasked investigator or his/her designee. 
Study drug will be stored ambient at 20 – 25o C (68 – 77o F) and this area should have limited, 
controlled access with temperature monitoring.  
At the end of the study and after an unmasked monitor has verified study drug kit accountability, 
all study drug (used and unused vials) and unused microinjector components are to be returned to 
the Sponsor (or designee) or destroyed at the site and documented per the site’s standard process. 
Any used microinjectors and vials of study drug involved in a product complaint must be 
maintained and returned to an unmasked person at the Sponsor (or designee).  All study drug and 
microinjector accounting procedures must be completed before the study is considered complete. 
6.5. 
Masking / Unmasking  
Subject randomization assignment will be protected using a masked allocation schedule created 
by a clinical allocation schedule system. Emergency unmasking of subjects by authorized 
clinical site personnel will occur via IRT according to procedures outlined in the Manual of 
Operations provided to the sites by the Sponsor. The Investigator should not unmask the 
subject’s randomization assignment without the Sponsor’s approval unless immediately required 
in response to a serious adverse event.  If the Sponsor was not notified prior to the unmasking 
event, the Investigator must immediately contact the Sponsor informing them as to the specific 
details of the occurrence. The Sponsor personnel involved in the collection, interpretation, 
analysis, review, or any decisions stemming from the study data will remain masked as to subject 
status for the duration of the study unless otherwise warranted. 
To maintain masking and minimize bias by the Investigator, sub-Investigator, all designated 
readers and graders, the subject, the Sponsor and monitors involved in reporting, obtaining 
and/or reviewing the clinical evaluations for a particular subject will not be aware of the specific 
randomization assignment for that subject. Only study staff who are designated by the 
Investigator to prepare and administer study drug and conduct test article accountability may 
know the randomization assignment. Both the masked or unmasked Investigator and staff may 
participate in evaluations conducted during the screening visit. The unmasked Investigator may 
participate in pre- and post-injection ophthalmic exams, except BCVA, at treatment visits (Visit 
2 and 5). Otherwise unmasked personnel will not be involved in a subject’s evaluations or 
assessments. Designee(s) will not discuss the test article with other site personnel or the Sponsor 
monitors and will instruct patients to not discuss the study drug or appearance of the packaging 
with the Investigator, sub-Investigator(s) or any other study staff while the study is ongoing. This 
level of masking will be maintained throughout the conduct of the study. 
The external packaging for the test article and sham control will be identical.  
The PK vendor analyzing samples will be unmasked to subject randomization codes and 
demographics in order to evaluate exposure levels. During the conduct of the study, Sponsor 


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staff working directly on the study will not have access to individually identifiable PK analysis 
data. 
If masking is compromised, any masked personnel who become unmasked will not conduct any 
further masked clinical evaluations with the subject whose treatment has been unmasked. The 
investigational site will notify the IRB and Sponsor/designee; follow-up training will be 
required. 


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7. 
ASSESSMENTS OF EFFICACY 
 
7.1. 
Best Corrected Visual Acuity (BCVA)   
Best Corrected Visual Acuity (BCVA) will be measured using ETDRS electronic visual acuity 
(eVA). BCVA will be recorded as total letter score in each eye following refraction. Visual 
acuity testing should precede any examination requiring contact with the eye.  
In order to provide standardization and well-controlled assessments of BCVA during the study, 
all BCVA assessments must be performed by trained staff who are certified on the study 
procedure using certified VA equipment/lanes. 
If eVA cannot be performed for any reason, BCVA will be measured using a standard ETDRS 
wall chart. If Roman letters are not familiar to the subject, Tumbling E charts may be used. 
7.2. 
Central Subfield Thickness as Measured by SD-OCT  
Retinal thickness and disease characterization will be assessed via spectral domain optical 
coherence tomography (SD-OCT) (Heidelberg SPECTRALIS® or Zeiss CirrusTM).  The SD-OCT 
instrument and technician must be certified prior to screening any subjects. The technician is 
encouraged to use the same certified photography equipment throughout the subject’s study 
participation.   All photos should be taken by the same photographer, whenever possible, on each 
subject per research site. Images will be sent to a central reading facility for analysis and 
interpretation in a masked fashion. 
7.3. 
Visual Function Questionnaire (VFQ-25)  
The VFQ-25 [25] consists of a base set of twenty-five vision-targeted questions representing 
eleven vision-related constructs, plus an additional single-item general health rating question. 
The VFQ-25 takes approximately 10 minutes on average to administer in the interviewer format. 
A trained technician will administer this questionnaire to the subject.  
7.4. 
EQ-5D 
EQ-5D is a standardized measure of health status developed to provide a simple, generic 
measure of health for clinical and economic appraisal. EQ-5D is designed for self-completion by 
respondents. It is cognitively undemanding, taking only a few minutes to complete. Instructions 
to respondents are included in the questionnaire. Subjects unable to read may have the EQ-5D 
read to them. 
7.5. 
Pharmacokinetics Assessments  
Approximately 25% of subjects will be enrolled in the pharmacokinetic portion of the study from 
select sites. Blood samples for measurement of CLS-TA plasma concentrations will be collected 
from those subjects who consent at participating sites, by venipuncture by qualified study 
personnel. A single blood sample will be obtained from each subject at the following time points: 
Day 0 (pre-dose), Week 4 visit (any time during visit), Week 12 visit (pre-dose) and Week 24 
visit (any time during visit). Blood samples will be processed and shipped to a central lab as 
outlined in the manual of procedures for the study.  


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8. 
ASSESSMENTS OF SAFETY 
8.1. 
Intraocular Pressure  
Intraocular pressure (IOP) will be measured by applanation tonometery and results will be 
recorded in mmHg. Where available, Goldmann applanation tonometry should be used at all 
visits. Tonopens may be used for post-injection pressure checks and in cases where no 
Goldmann is available. A single measurement will be made at approximately the same time of 
day. The technician is encouraged to use the same tonometry method for all pre-injection and 
non-injection measurements throughout the subject’s study participation. Tonometers must be 
calibrated for accuracy before the first subject screening at that site and according to the 
manufacturer specifications during the study, until the last subject has exited the study at that 
site. 
 
8.2. 
Slit-Lamp Biomicroscopy  
Slit-lamp biomicroscopy, including magnification, will be performed consistent with standard 
clinical practice. This procedure should be conducted in the same manner for all subjects and 
will include an assessment of each of the following as normal or abnormal: eyelids, cornea, 
anterior chamber, iris and lens. All abnormal findings will be described.  
 
8.2.1 Cataract Lens Grading 
If an abnormal finding of cataract is noted for the lens during the slit-lamp exam, the cataract 
should be assessed for nuclear opalescence, cortical opacity and posterior subcapsular opacity. 
Graders must verify training on the grading procedure provided in the Manual of Procedures. 
 
8.2.2 Anterior Chamber Cells 
Anterior chamber cells will be assessed clinically using a field size of 1 mm slit beam and using 
a standardized grading scale ranging from 0 to 4+, as defined in Table 1 (SUN 2005).  
 


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Table 1: 
Anterior Chamber Cell Grading Scale 
Score 
Cells in Field 
0 
<1 
0.5+ 
1-5 
1+ 
6-15 
2+ 
16-25 
3+ 
26-50 
4+ 
>50 
 
8.2.3 Anterior Chamber Flare 
Anterior chamber flare will be assessed clinically via slit lamp using a standardized scale ranging 
from 0 to 4, as defined in Table 2 (SUN 2005).  
Table 2: 
Anterior Chamber Flare Grading Scale 
Score 
Description 
0 
None 
1+ 
Faint 
2+ 
Moderate (iris and lens details clear) 
3+ 
Marked (iris and lens details hazy) 
4+ 
Intense (fibrin or plastic aqueous) 
 
8.3. 
Dilated Ophthalmoscopy  
A dilated fundus examination will include an assessment of each of the following as normal or 
abnormal: vitreous, retina, macula, choroid and optic nerve. All abnormal findings will be 
described.  
 
8.3.1 Vitreous Haze 
Vitreous haze will be assessed clinically via indirect ophthalmoscopy using a standardized 
photographic scale ranging from 0 to 4, as defined in Table 3 (Nussenblatt 1985 as modified in 
Lowder 2011).  


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Table 3: 
Scale for Determining Degree of Vitreous Haze 
Score 
Description 
0 
no inflammation 
+0.5 
trace inflammation (slight blurring of the optic disc margins and/or loss 
of the nerve fiber layer reflex) 
+1 
mild blurring of the retinal vessels and optic nerve 
+1.5 
optic nerve head and posterior retina view obscuration greater than +1 but 
less than +2 
+2 
moderate blurring of the optic nerve head 
+3 
marked blurring of the optic nerve head 
+4 
optic nerve head not visible 
 
8.4. 
Fluorescein Angiography 
Fluorescein angiography (FA) images will be performed to examine the circulation of the retina. 
Study personnel who perform FA will be trained and certified by the central reading center prior 
to screening any subjects. Images will be sent to a central reading facility.  
8.5. 
Fundus Photography 
Fundus photographs will be collected to assess the disease and anatomical characteristics of the 
retina. Study personnel who perform FA will be trained and certified by the central reading 
center prior to screening any subjects. Images will be sent to a central reading facility.  
8.6. 
Review of Systems 
A review of body systems will include an assessment of each of the following as normal or 
abnormal: skin, cardiovascular, respiratory, neurological and musculoskeletal systems. All 
abnormal findings will be described. This exam may be performed by any medical doctor or 
legally qualified personnel per local laws/regulations. 
8.7. 
Clinical laboratory tests  
Non-fasting blood and urine samples will be collected during the study. Samples will be sent to a 
central lab for analysis. Analytes to be evaluated are listed in Table 4. 


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Table 4: 
Clinical Laboratory Analytes to be Tested 
 
 
8.8. 
Vital signs  
Resting heart rate and resting blood pressure (systolic and diastolic, preferably on the same arm 
each time) will be measured at Visits 1, 2, 5 and 8.  
 
8.9. 
Evaluation of Adverse Events   
Adverse events will be monitored continuously during the study beginning at the time of the 
subject’s signing of the informed consent. Subjects will be instructed to report all AEs during the 
study. Subjects will be assessed for the occurrence of AEs at each visit. Thus, AEs may be 
reported by the subject, discovered by the study staff questioning or detected through study 
assessments. All AEs (serious and non-serious) must be recorded on the source documents and 
AE CRFs, regardless of the assumed causal relationship with the test article. The following 
information about each AE will be collected: severity, onset and resolution dates, frequency, 
seriousness, relationship to study treatment, action taken and outcome. 
Chemistry (serum) 
Alanine amino transferase; serum albumin;  alkaline 
phosphatase; aspartate amino transferase; bilirubin, direct  
and total; total serum calcium; total carbon dioxide; serum 
chloride; total creatine kinase; serum creatinine; gamma 
glutamyl transaminase; glucose; lactate dehydrogenase; 
serum potassium; total serum protein; serum sodium; total 
cholesterol; triglycerides; urea 
Hematology  
CBC including: hemoglobin (Hgb), platelet count (PLT), 
red blood cell (RBC), white blood cell (WBC) and 
hematocrit (Hct); WBC differentials of: basophils; 
eosinophils, lymphocytes, monocytes and total neutrophils 
Urinalysis (Macro) 
Bilirubin; blood; glucose; ketone; protein; specific gravity;  
pH 
Pregnancy (serum)a  
aWomen of childbearing potential at 
screening and study exit only 
β-human chorionic gonadotropin (βHCG) 


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8.9.1. 
Definitions 
An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in 
humans and does not have to have a causal relationship with study treatment.   
An AE can therefore be any unfavorable and unintended sign (that could include a clinically 
significant abnormal laboratory finding), symptom, or disease temporally associated with the use 
of a medicinal product, whether or not considered related to the medicinal product.  
Whenever possible, the Investigator should group signs or symptoms that constitute a single 
diagnosis under a single AE term (eg, “cough, rhinitis and sneezing” might be grouped together 
as “upper respiratory tract infection”). 
An AE may include: 
• Any sign, medical diagnosis or symptom 
• Any new undesirable medical occurrence or unfavorable or unintended change of a pre-
existing condition that occurs during or after test article administration.  
NOTE:  
o The disease under study (ie, non-infectious uveitis) or sign or symptom associated 
with the disease are not considered adverse events unless more severe than 
expected for the subject’s condition 
o Symptoms associated with disease, which are consistent with the subject's usual 
clinical course are not considered adverse events, unless the subject experiences 
worsening of symptoms more severe than expected or unless the symptom(s) 
meet the criteria for an SAE 
• Clinically significant (as determined by the Investigator) laboratory abnormalities, 
ophthalmic assessments or vital signs (eg, requiring discontinuation of test article, 
specific treatment or a change in subject management). If possible, abnormal laboratory 
results or changes in vital signs that meet the definition of an AE should be reported as a 
clinical diagnosis rather than the abnormal laboratory value (eg, “hypertension” rather 
than “blood pressure increased”) 
All baseline conditions and AEs identified during the clinical study from the time the subject 
signs the informed consent, through the subject’s last day of study participation, will be 
documented on the appropriate CRF. Special considerations include:  
• Baseline conditions are not considered adverse events unless the condition worsens 
following study drug administration  
• Elective procedures or routinely scheduled treatments are not considered AEs; however, 
an untoward medical event occurring during the pre-scheduled elective procedure should 
be recorded as an AE 
• Changes in pre-existing medical conditions, including changes in severity, frequency or 
character, during the protocol-defined reporting period should be recorded as AEs 


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•
Overdose of either study drug or concurrent medication without any signs or symptoms is
not considered adverse events
•
Death itself is not considered an AE; it is instead the outcome of an AE
•
Pregnancy is not considered an AE. Reports of pregnancy will be reported to the Sponsor
in accordance with Section 8.9.4
A treatment-emergent AE (TEAE) is any AE temporally associated with the use of the study 
drug, whether or not considered causally related to the study drug that occurs after the subject 
receives the first dose of study drug. 
A serious adverse event (SAE) includes any event, if in the view of either the Investigator or 
the Sponsor, results in any of the following outcomes. 
•
Death
•
Life-threatening (ie, if in the view of the Investigator or Sponsor, the event’s occurrence
places the subject at immediate risk of death); it does not include an AE that, had it
occurred in a more severe form, might have caused death
•
In-patient hospitalization or prolongation of existing hospitalization
o
“In-patient” hospitalization means the subject has been formally admitted to a
hospital for medical reasons.  This may or may not be overnight.  It does not
include presentation at a casualty or emergency room.
•
A persistent or significant incapacity or substantial disruption of the ability to conduct
normal life functions
•
A congenital anomaly in the offspring of a subject who received study drug
•
Important medical events that may not result in death, be life-threatening or require
hospitalization may be considered an SAE when, based upon appropriate medical
judgment, they may jeopardize the subject and may require medical or surgical
intervention to prevent one of the outcomes listed in this definition
o
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.
The intensity of each AE will be graded using National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) v 4.03. The criteria can be accessed at: 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. 
The term “severe” is a measure of intensity. A severe AE is not necessarily a serious AE. 
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each AE based on this general guideline: 


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Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
Grade 2 
Moderate; minimal, local or noninvasive intervention 
indicated; limiting age-appropriate instrumental activities of 
daily living (ADL) 
Grade 3 
Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of the 
hospitalization indicated; disabling; limiting self-care ADL 
Grade 4 
Life threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE 
Causality is the relationship of an AE to study drug and will be assessed by the investigator as 
follows in Table 5:  
Table 5: 
Causality Definitions 
Causality 
Definition 
Related 
There is a reasonable causal association with 
administration of the study drug; the event is confirmed 
by stopping and/or restarting the drug or is not explained 
by any other reasonable hypothesis 
Not related 
There is no causal or temporal relationship to the study 
drug; related to other etiologies such as concomitant 
medications or conditions 
8.9.2. 
Adverse Event Reporting Procedures 
The Investigator will assess subjects for the occurrence of AEs at all scheduled and unscheduled 
visits. The occurrence of AEs should be sought by non-direct questioning of the subject at each 
visit. At each study visit, study personnel should ask the following question: “Have you had any 
problems since your last visit?" Adverse events may also be detected when they are volunteered 
by the subject during and between visits or through study assessments. All AEs (serious or non-
serious) reported by the subject will be reviewed by a qualified physician participating as an 
investigator in the study and must be recorded on the source documentation and AE CRF 
provided. 
8.9.3. 
Prompt Reporting of SAEs to the Sponsor 
An adverse event that is serious must be reported on an SAE form to the Sponsor immediately, 
but no later than 24 hours after the investigator becomes aware of the event.  


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Prompt reporting of a SAE requires: 
•
Completion and transmission of SAE information to the Sponsor within 24 hours of the
investigator’s knowledge of the event.  The SAE information should be completed as
thoroughly as possible before transmittal to the Sponsor.  It is very important that the
investigator provide his/her assessment of causality to study treatment at the time of
initial reporting of the SAE.
•
Prompt reporting of additional information for previously reported SAEs should follow
the same reporting timeframe as initial reports.
If an ongoing SAE changes in intensity or the relationship to study drug, a follow-up SAE report 
should be sent to the Sponsor within 24 hours after the clinical site becomes aware of the change 
in status. 
8.9.4. 
Pregnancy Reporting 
Pregnancy alone is not an AE. However, any report of pregnancy during a female subject’s 
participation in the study must be promptly reported to the Sponsor as soon as the Investigator is 
notified, using a Pregnancy Report Form. 
The Sponsor should be notified of any updates on the status of the pregnancy as soon as the 
information becomes available and the site will complete the Pregnancy Follow-up Form. 
8.9.5. 
Transmission of SAE Reports and Pregnancy Forms 
SAE reporting information and pregnancy reporting information should be transmitted to the 
Sponsor via email or fax as provided below.  
Chiltern, Inc. 
GlobalSAEInbox@chiltern.com 
Toll free fax US:  
888-726-8416
Toll free fax India: 
91-2266-459-811
Please refer to the study reference binder for complete contact information. Contact the Medical 
Monitor with any questions regarding a potential SAE. 
8.9.6. 
Regulatory Reporting Requirements for SAEs 
The Sponsor will determine which SAEs qualify for expedited reporting. Reports of those SAEs 
that qualify for expedited reporting will be unmasked for the individual subject and submitted to 
regulatory agencies in accordance with applicable local regulation. Expedited reports will also be 
distributed to Investigators without revealing the treatment assignment and will be submitted to 
IRB/IEC in accordance with institutional guidelines and local regulation. 


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8.9.7. 
Follow-up of AEs and SAEs 
All AEs and SAEs reported during study conduct must be followed until resolution, until the 
condition stabilizes, until the event is otherwise explained, or the subject is lost to follow-up.  
Subjects will be followed for any treatment-related SAEs reported at the end of participation 
until the condition stabilizes, the event is otherwise explained, the subject is lost to follow-up or 
the subject withdraws consent.   
NOTE: “Resolution” means the subject has returned to baseline state of health or the 
Investigator does not expect any further improvement in the subject’s condition or does not 
expect worsening of the AE. 
For a non-serious AE that is first identified on the last scheduled contact, the event must be 
recorded on the AE CRF with the current status noted, but no further follow-up needs to be 
performed. 
Post-Study SAEs:  Investigators are not obligated to actively seek SAE information in former 
study participants, however, any new SAE reported by the subject to the Investigator that occurs 
after the last scheduled contact and is determined by the Investigator to be associated with the 
use of study drug, should be reported to the Sponsor. The Investigator should follow related 
SAEs identified after the last scheduled contact until the event has resolved or stabilized or the 
subject is lost to follow-up.  


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9. 
STATISTICAL CONSIDERATIONS 
A detailed statistical analysis plan will be prepared for this study.  The plan will contain a 
discussion of the statistical methods, a description of the computational algorithms and data 
handling conventions, and specifications for the data summaries and listings.  It will be finalized 
before database lock.  
9.1. 
Randomization 
There will be approximately 150 subjects randomized at a 3:2 ratio to the two treatment arms. 
Assignment of subjects to treatment arms will be performed via IRT. 
9.2. 
Determination of Sample Size and Level of Significance 
The sample size of approximately 150 subjects at approximately 50 centers was based on clinical 
considerations appropriate for a randomized Phase 3 study.  
With a total sample size of 150 subjects in a 3:2 randomization this study will have 90% power 
to detect a difference between treatments if the actual proportion of subjects  showing 
improvement of 15 letters or more is 0.60 for the treated group and 0.34 in the sham group. 
Power analyses were conducted based on an assumption of the proportion of subjects gaining 15 
or more letters in the CLS-TA treated arm to be 0.6 while those in the untreated (sham) arm 
gaining 15 or more letters to be 0.13. Calculations for power based on lower confidence limit 
used the observed result for the treated group and subtracted the lower confidence interval for the 
difference (0.2636) from that difference to estimate the sham result (0.3364). 
Power analysis assumes that the parameter estimates are based on population values not sample 
results.  An observed sample result is expected to overestimate population differences 50% of the 
time.  By using a lower confidence interval estimate can be used to mitigate the risk that the 
sample estimate was larger than the population value.  In this case, a lower 90% one sided 
confidence interval the difference in proportions was used to calculate an offset from the 
observed result that would be the lowest likely population estimate. The offset was added to the 
estimate for the control group to create conservative estimates. The conservative power 
calculations were performed based on the conservative estimates. 
9.3. 
Subject Disposition, Demographic and Baseline Characteristics 
Subject disposition, demographic, and baseline characteristics will be summarized descriptively 
by treatment group and overall. 
9.4. 
Analysis Populations 
 
9.4.1 
Safety Population 
Safety population will include all randomized subjects who are administered at least one dose of 
the study drug. All safety analyses will be based on safety population. 
9.4.2 
Intent-to-Treat Population 


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Intent-to-treat (ITT) population includes all randomized subjects who have received at least one 
study treatment. Subjects will be analyzed as originally allocated after randomization. ITT 
population will be used for efficacy analyses.   
9.4.3 
Per Protocol Population 
Per-protocol (PP) population will include all subjects in the ITT population who do not have 
significant protocol deviations and who complete the 24 week visit. The rules for determining 
exclusions from the PP population will be finalized after a clinical review of the data and queries 
have been resolved but before unmasking treatment assignments. 
9.4.4 
Pharmacokinetic Population 
Pharmacokinetic population will include all subjects in the pharmacokinetic portion of the study 
that provided blood samples for triamcinolone acetonide concentration analysis. 
9.5. 
Analysis Methods 
Efficacy and safety endpoints are provided in Section 3.1.  
9.5.1. 
Primary Efficacy Analysis 
The primary endpoint is the proportion of subjects with a change from baseline of ≥ 15 letters in 
ETDRS BCVA at Visit 8 (24 weeks), subsequent to suprachoroidal injections of CLS-TA or 
sham injection procedures, in subjects with macular edema associated with non-infectious 
uveitis. 
A Cochran-Mantel-Haenszel test will be used to test differences in the proportion of subjects in 
the two groups who show 15 or more letters improvement in BCVA at the week 24 visit after 
adjusting for center effects. 
The formal hypothesis is: 
H0: All ORsite=1  H1: ORsite ≠1 
Where ORsite is the odds ratio adjusting for site 
Missing data imputed by LOCF in the ITT population will be used for the primary efficacy 
analysis. Observed data in the PP population will be used for sensitivity analysis. See Section 
9.5.8 for a description of the imputations for missing data. 
9.5.2. 
Secondary Efficacy Analysis 
9.5.2.1. 
Secondary Efficacy Endpoint 
•
Mean change from baseline in CST as measured by SD-OCT at 24 weeks (Visit 8)
9.5.2.2. 
Additional Endpoints 
•
Triamcinolone acetonide blood concentrations prior to each dose (Visit 2 and 5), 4
weeks following the first dose (Visit 3) and at 24 weeks (Visit 8)
•
Change from baseline in subject reported outcomes as measured by the Visual
Function Questionnaire (VFQ-25) and EQ-5D questionnaire at 24 weeks


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9.5.3. 
Subgroup Analysis 
No subgroup analyses are planned. 
9.5.4. 
Pharmacokinetic Analysis 
Standard population PK parameters will be calculated from plasma CLS-TA concentrations. To 
characterize the population PK of CLS-TA, PK parameters will be related to treatment arm. 
Samples from approximately 20 subjects in the Active arm will be available for analysis. 
Analysis will be conducted according to the nonlinear mixed-effects approach and will provide 
estimates of population characteristics (intrinsic and extrinsic factors) that define the population 
distribution of the PK parameters. 
9.5.5. 
Safety Analysis  
9.5.5.1. 
Safety Endpoints 
• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events 
(SAEs), grouped by organ system, relatedness to study medication, and severity  
• Percentage of subjects whose IOP increases are > 10 mmHg from their own baseline 
measurement at each follow-up visit (except Visit 2 & 5 [post-dose])  
• Percentage of subjects whose IOP increases to a reading > 30 mmHg at each follow-up 
visit (except Visit 2 & 5 [post-dose]) 
• Percentage of subjects who require 1 or more additional IOP lowering medications at any 
follow-up visit (except Visit 2 & 5 [post-dose]) 
9.5.5.2. 
Intraocular Pressure 
The observed and change from baseline in IOP will be summarized descriptively at each visit.  
Descriptive statistics include n, mean, median, minimum and maximum values.   
9.5.5.3. 
Cataract Lens Grading 
The distribution of responses (n, %) will be tabulated for each category of response. 
9.5.5.4. 
Slit-Lamp Biomicroscopy  
The distribution of responses (n, %) will be tabulated for each category of response. 
9.5.5.5. 
Dilated Indirect Ophthalmoscopy 
The distribution of responses (n, %) will be tabulated for each category of response. 
9.5.5.6. 
Fluorescein Angiography 
FA will primarily be used to support SD-OCT analysis. In the event that grading occurs, the 
distribution of responses (n, %) will be tabulated for each category of response. 


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9.5.5.7. 
Fundus Photographs 
Fundus photography will primarily be used to support SD-OCT analysis. In the event that 
grading occurs, the distribution of responses (n, %) will be tabulated for each category of 
response. 
9.5.5.8. 
Clinical Laboratory Assessments and Urine Pregnancy Tests 
The observations for each analyte will be summarized descriptively or tabulated categorically.  
Descriptive statistics include n, mean, median, minimum and maximum values. 
9.5.5.9. 
Review of Systems 
The proportion of subjects with abnormal body systems will be listed. 
9.5.5.10. Vital Signs 
The observations and change from baseline in vital signs will be summarized descriptively at 
each visit.  Descriptive statistics include n, mean, median, minimum and maximum values.   
9.5.5.11. Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding 
dictionary.  TEAEs will be defined as any event occurring post treatment (injection) or, if pre-
existing, worsening after Day 1.   
The incidence of TEAEs will be summarized by MedDRA system organ class and preferred 
term.  If the subject reports the same AE more than once, then that subject will only be counted 
once for the summary of that AE, using the most severe intensity and closest relationship to 
study treatment. 
TEAEs will be summarized as follows: 
• All TEAEs 
• All TEAEs by intensity 
• ALL TEAEs related to study drug 
• Treatment-emergent SAEs 
• TEAEs that lead to premature discontinuation of study drug   
• If few AE are reported, AEs will only be provided in a listing 
9.5.5.12. Prior and Concomitant Medications 
Prior and concomitant medications taken from 30 days (3 years for significant ophthalmic 
medications) prior to Visit 1 (Screening) through the duration of the subjects’ participation in the 
study will be summarized.   
9.5.6. 
Interim Analysis 
There is no interim analysis planned for this study.   


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9.5.7. 
Extent of Exposure 
The extent of exposure (i.e., whether a subject received the injection and whether it was a 
complete or partial injection) will be listed. 
9.5.8. 
Procedure for Accounting for Missing, Unused, or Spurious Data 
Any missing, unused, or spurious data will be noted in the final clinical report. 
Last Observation Carried Forward (LOCF) will be used if visits are missed in the ITT 
population.  No imputation for missed visits will be used in the PP population.  This provides an 
indication of the sensitivity of the data to missing observations.   
Likewise, LOCF will be used if a subject requires rescue medication. All data points will be set 
to missing following a subject’s receipt of a rescue medication; the last recorded data prior to the 
rescue will be carried forward to all subsequent visits for ITT. No imputation for rescue 
mediations will be used in the PP population.  
No imputation is planned for the safety data set.  
9.5.9. 
Multiplicity 
Since there is only one primary endpoint, no multiplicity adjustments are required for the 
primary analysis. 
9.5.10. 
Procedure for Reporting Deviations from the Statistical Analysis Plan 
The statistical analysis plan will be completed prior to breaking treatment code. 
Any deviations from the statistical analysis plan will be described and a justification given in the 
final clinical study report. 


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10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The Investigator will permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s) by providing direct access of 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 CRF such as medical history).  In addition, the Investigator will 
permit members of the sponsor company to witness and record (video and/or audio) subject 
injections if the subject agrees in writing by providing informed consent and appropriate HIPAA 
authorization.  
10.1. 
Investigator Training 
The injecting physicians will be trained by the Sponsor on study drug injection and training will 
be documented.  Only trained Investigators may administer study drug.  Investigators and key 
support staff will be trained by the Sponsor regarding all aspects of this protocol.  In addition, 
sites will be trained to perform imaging (SD-OCT, FA and fundus photos) per the protocol so 
that the data may be uploaded to a Central Reading Center.  Only trained and certified visual 
acuity technicians may measure BCVA on study subjects using certified exam lanes.   
It is the responsibility of the Investigator to train ancillary study staff if needed. 
10.2. 
Monitoring 
This study will be monitored in accordance with GCP and regulatory guidelines.  By signing this 
protocol, the investigator agrees to periodic, on-site monitoring of all appropriate study 
documentation. 
The progress of the study will be monitored by periodic on-site visits and frequent 
communications between the Sponsor (or designee) and the Investigator (either by phone, fax, 
email, or post). 
During these contacts, the monitor will: check and assess the progress of the study; review study 
data collected; conduct source document verification; identify any issues and address their 
resolution. 
The objectives of monitoring procedures are to verify that data are authentic, accurate, and 
complete; that the safety and rights of subjects are being protected; and that the study is 
conducted in accordance with the currently approved protocol (and any amendments), GCP, and 
all applicable regulatory requirements. 
10.3. 
Audits 
At its discretion, the Sponsor may conduct a quality assurance audit of this study.  If such an 
audit occurs, the Investigator agrees to allow the auditor direct access to all relevant documents 
and to schedule his/her time and the time of his/her staff to permit meetings with the auditor to 
discuss findings and any relevant issues. 
In addition, regulatory agencies may conduct a regulatory inspection of this study.  If such an 
inspection occurs, the investigator agrees to allow the inspector direct access to all relevant 
documents and to schedule his/her time and the time of his/her staff to permit meetings with the 
auditor to discuss findings and any relevant issues. 


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11. 
QUALITY CONTROL AND QUALITY ASSURANCE 
The progress of the study will be monitored by onsite, written, e-mail, and telephone 
communications between personnel at the study center and the Sponsor.  The Investigator will 
allow Sponsor monitors, or designee(s) to inspect all CRFs, subject records (source documents), 
signed informed consent forms, records of study medication receipt, storage, and disposition, and 
regulatory files related to the study. 
At the time of database lock, the clinical database will be audited in order to ensure accuracy of 
the data, as well as to provide an estimated error rate for the final, locked database.  The audit 
will involve a comparison of CRF values with values from data listings generated from the 
clinical database.  Values identified as critical safety and efficacy variables will be confirmed for 
100% of the subjects.  In addition, a random sample of subjects will be selected for which all 
data values, excluding comment fields, will be checked.  The number of subjects whose data will 
be randomly reviewed will be determined in order to provide sufficient accuracy for the 
estimated error rate of the clinical database.  


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12. 
ETHICS 
12.1. 
Institutional Review Board/Ethics Committee 
This protocol, the informed consent document, relevant supporting information, and all types of 
subject recruitment or advertisement information must be approved by the appropriate IRB/IEC 
before the study is initiated.  Any amendments to the protocol must also be approved, where 
necessary, by the IRB/IEC prior to implementing changes in the study.  Documentation of these 
approvals must be provided to the sponsor prior to the initiation of the amendment.  The 
IRB/IEC used must comply with current GCP and guidelines. 
The investigator’s responsibilities regarding the IRB/IEC are as follows:  
• Obtain IRB/IEC approval of the protocol, informed consent, and any advertisements to 
recruit subjects prior to their use 
• Obtain IRB/IEC approval for any protocol amendments and informed consent revisions 
before implementing the changes 
• Provide the IRB/IEC with any required information before and during the study.   
• Submit progress reports to the IRB/IEC, as required, during the conduct of the study; 
request re-review and approval of the study, as needed; provide copies of all IRB/IEC re-
approvals and relevant communication to the sponsor 
• Notify the IRB/IEC within 10 days of all serious and unexpected AEs related to the study 
medications that are reported to you by the sponsor.  The investigator is responsible for 
updating the IRB/IEC on the progress of the study and of any changes made to the 
protocol as deemed appropriate, but (in any case) at least once a year.  The investigator 
must also keep the IRB/IEC informed of any AEs, according to the IRB/IEC policy. 
12.2. 
Unanticipated Problems and Notification to Sponsor and IRB/IEC 
The Investigator will be responsible for notifying the Sponsor within 24 hours of awareness and 
the IRB/IEC within 10 days of all unanticipated problems involving risk to subjects or others.   
The regulations state that for studies conducted under 21 CFR part 312, investigators must report 
all "unanticipated problems" to the IRB [§§ 312.66, 312.53(c)(1)(vii), and 56.108(b)(1)]. 
As noted in FDA’s Guidance on Adverse Event Reporting to IRBs – Improving Human Subject 
Protection (Jan 2009), the following AEs should be considered as unanticipated problems that 
must be reported to the IRB.  
• A single occurrence of a serious, unexpected event that is uncommon and strongly 
associated with drug exposure (such as angioedema, agranulocytosis, hepatic injury, 
or Stevens-Johnson syndrome) 
• A single occurrence, or more often a small number of occurrences, of a serious, 
unexpected event that is not commonly associated with drug exposure, but 
uncommon in the study population (eg, tendon rupture, progressive multifocal 
leukoencephalopathy) 


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•
Multiple occurrences of an AE that, based on an aggregate analysis, is determined to 
be an unanticipated problem.  There should be a determination that the series of AEs 
represents a signal that the AEs were not just isolated occurrences and involve risk to 
human subjects (e.g., a comparison of rates across treatment groups reveals higher 
rate in the drug treatment arm versus a control).
•
An AE that is described or addressed in the investigator’s brochure, protocol, or 
informed consent documents, but occurs at a specificity or severity that is inconsistent 
with prior observations.  For example, if transaminase elevation is listed in the 
investigator’s brochure and hepatic necrosis is observed in study subjects, hepatic 
necrosis would be considered an unanticipated problem involving risk to human 
subjects.
•
A serious AE that is described or addressed in the investigator’s brochure, protocol, or 
informed consent documents, but for which the rate of occurrence in the study 
represents a clinically significant increase in the expected rate of occurrence
•
Any other AE or safety finding (e.g., based on animal or epidemiologic data) that 
would cause the sponsor to modify the investigator’s brochure, study protocol, or 
informed consent documents, or would prompt other action by the IRB to ensure the 
protection of human subjects 
12.3. 
Informed Consent Requirements 
The Investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation, in layman’s terms, regarding the nature of 
the study, along with the aims, methods, objectives, and any potential risks.  The informed 
consent document must be appropriately signed and dated by the subject or the subject’s legally 
authorized representative and the person obtaining the consent (if required by the IRB/IEC) prior 
to conducting/obtaining any study-related assessments, including the discontinuation of any 
medications prohibited for the study. 
If the informed consent document is amended during the study, the investigator must follow all 
applicable regulatory requirements pertaining to approval of the amended informed consent by 
the IRB/IEC and use of the amended form (including for ongoing subjects).  
The informed consent document shall also contain the subject's authorization for the use and 
disclosure of his/her protected health information (PHI) in connection with the study.  The 
authorization shall include at a minimum a clear description of the following:  the duration of the 
authorization, the subject's right of access to the PHI (or any suspension thereof during the 
course of the study), type of information to be used/disclosed in the study, the names or classes 
of parties that may use or disclose the PHI, the purpose of the use/disclosure of PHI, the extent of 
the subject's right to revoke the authorization, the extent to which participation in the study is 
conditioned on signing the authorization, and the potential for re-disclosure of PHI. 
Each informed consent will contain contact information with a phone number the subject should 
contact if they have medical concerns 24 hours a day. 
The original and any amended signed and dated informed consents must be retained at the study 
site. A copy must be given to the subject or subject’s legally authorized representative(s). 


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13. 
DATA HANDLING AND RECORD KEEPING 
Study data will be processed and managed for clinical data management according to ICH 
Guidelines and US Food and Drug Administration regulations for the handling and analysis of 
data for clinical trials. Clinical study data will be captured in CRFs by study personnel at the 
clinical sites.  CRFs will be monitored on a routine basis, with comparisons made to the various 
source documents maintained at the study sites.   
13.1. 
Data Quality Control and Reporting 
13.1.1. 
Source Documents 
Source documents consist of, but are not limited to, in-patient hospital charts, clinic notes, out-
patient records, original test results, laboratory data, worksheets, drug accountability records, 
consent forms, etc.  Source documents must be available for review and inspection during on-site 
monitoring of the study by the Sponsor, their designees, IRB, and/or regulatory authorities. 
It is required that the author of an entry in the source documents be identifiable. Direct access to 
source documentation must be allowed for the purpose of verifying that the data recorded on the 
eCRF are consistent with the original source data. 
13.1.2. 
Case Report Forms 
Source documentation for data collected in this study will be maintained at the investigative site.  
In cases where no source will be used, it will be noted in the investigator files.  Subject CRF data 
will be collected by EDC.  The EDC system will be Part 11 compliant and will have documented 
audit trail for all changes made to the CRF.  Data in the EDC system will be periodically 
monitored for accuracy. 
The investigator or designee must record all required subject data using the previously specified 
data collection method defined by Clearside.  The investigator must sign and date a declaration 
on the CRF attesting to his/her responsibility for the quality of all data recorded and that the data 
represents a complete and accurate record of each subject's participation in the study. 
ECRF data will be provided to the investigator at the end of the study and will need to be 
retained by the investigator.   
13.1.3. 
Subject Tracking 
A site drug accountability log, subject drug accountability logs, a subject identification log (to be 
retained by the Investigator only), and a subject screening/enrollment log may be used to track 
subject participation in the study.  In addition, subject randomization assignments will be tracked 
in an electronic IWRS system.   
13.1.4. 
Study Files 
Each investigational center will maintain a special study file.  This file is subject to monitoring 
and inspection as described under Section 10.2 and Section 10.3 of this protocol.  This file may 
contain, but is not limited to, the following: 
• Protocol and protocol amendments 


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•
Safety reports that were submitted to regulatory authorities
•
Investigator’s Brochure
•
IRB/IEC approvals
•
IRB/IEC approved informed consent and authorization form
•
IRB/IEC (or privacy board) waiver of authorization (if applicable)
•
Investigational center notice of privacy practices (if applicable)
•
IRB/IEC correspondence
•
IRB/IEC membership list
•
Study Communications/Correspondence 
(letters, memos, meeting notes, faxes, and
printed emails)
•
Signed Form FDA 1572 with corresponding curriculum vitae of Principal Investigator
and listed Sub-Investigator(s)
•
Site signature log
•
Delegation of authority log
•
Drug accountability records (receipt, dispensing, return or destruction)
•
Laboratory normal ranges and certification
•
Laboratory director’s curriculum vitae
•
SAE Reports (as applicable)
•
Subject identification log
•
Informed consent log
•
Investigator(s) financial disclosure statement
13.2. 
Archiving of Data 
The clinical database will be archived at Clearside and at the contract research organization 
responsible for data management for an agreed upon timeframe, if applicable.  
13.3. 
Records Retention 
The participating clinical center will retain all records related to the study in accordance with 
local and ICH GCP guidelines. 


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14. 
FINANCING AND INSURANCE 
14.1. 
Finance 
This study is supported by Clearside Biomedical, Inc. 
14.2. 
Insurance 
Documentation of product liability insurance is on file at Clearside Biomedical, Inc. and is 
available upon request.  


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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 the Sponsor. 


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16. 
REFERENCES 
Bodaghi B, Cassoux N, Bertrand W, et al. Chronic severe uveitis: etiology and visual outcome in 
927 patients from a single center. Medicine. 2001;80:263-270. 
Cho H, Madu A. Etiology and treatment of the inflammatory causes of cystoid macular edema. J 
Inflamm Res. 2009;2:37-43. 
Dick AD. The treatment of chronic uveitic macular edema. Br J Ophthalmol. 1994;78:1-2. 
Ghate D, Brooks W, McCarey BE, Edelhauser HF. Pharmacokinetics of intraocular drug 
delivery by periocular injections using ocular fluorophotometry. Invest Ophthalmol Vis Sci. 
2007;48:2230-7. 
Goldstein DA, Pyatetsky D, Tessler HH.  Classification, symptoms, and signs of uveitis.  
Duane’s Ophthalmology on DVD-ROM Ed 2009a:chap 32. 
Jabs DA, Rosenbaum JT,  Foster CS, et al. Guidelines for the use of immunosuppressive drugs in 
patients with ocular inflammatory disorders: recommendations of an expert panel. Am J 
Ophthalmol. 2000;130:492-513. 
Karim R, Sykakis E, Lightman S, Fraser-Bell S. Interventions for the treatment of uveitic 
macular edema: a systematic review and meta-analysis. Clin Opthalmol. 2013;7:1109-1144. 
Lardenoye C, Kooji B, Rothova A. Impact of macular edema on visual acuity in uveitis. 
Ophthalmology 2006;113:1446-1449. 
Lowder C, Belfort R, Lightman S, et al. Dexamethasone Intravitreal Implant for Noninfectious 
Intermediate or Posterior Uveitis. Arch Ophthalmol. 2011;129(5):545-553. 
Miserocchi E, Fogliato G, Modorati G and Bandello F. Review on the worldwide epidemiology 
of uveitis. Eur J Ophthalmol. 2013;23:705-717. 
Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory 
activity in intermediate and posterior uveitis. Ophthalmology. 1985;92(4):467– 471. 
Rothova A, Suttorp-van Schulten SA, Treffers WF and Kijlstra A. Causes and frequency of 
blindness in patients with intraocular inflammatory disease. Br J Ophalmol. 1996;80:332-336. 
SUN Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results 
from the first international workshop. Am J Ophthalmol 2005;150:509-516. 
Triesence [Package Insert]. Fort Worth, Texas: Alcon Laboratories, Inc., 2007. 
Wood B. An overview of uveitis and its management. US Pharmacist 2011. 


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17. 
APPENDICES 
 
 
 
 
 


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APPENDIX A. TIME AND EVENTS SCHEDULE 
Visit # 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit Type 
Screening 
Randomization 
/Treatment #1 
Follow-Up 
Treatment #2 
Follow-Up 
End Of 
Study 
Visit Window 
Day  
-14 to -1 
Day 0 
Month 1 
Week 4 
Day 28 ± 5 
Month 2 
Week 8 
Day 56 ± 5 
Month 3 
Week 12 
Day 84 ± 5 
Month 4 
Week 16 
Day 112  
± 5 
Month 5 
Week 20 
Day 140  
± 5 
Month 6 
Week 24 
Day 168  
± 5 
Assessments 
 
Pre-dose 
Post-dose 
 
 
Pre-dose 
Post-dose 
 
 
 
Informed Consent 
√ 
 
 
 
 
 
 
 
 
 
Assign Subject Number 
√ 
 
 
 
 
 
 
 
 
 
Demographics, Medical & Ocular Hx 
√ 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
√ 
√ 
 
 
 
 
 
 
 
 
Assess AEs 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Con Med Review 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Resting HR & BP 
√ 
√ 
 
 
 
√ 
 
 
 
√ 
Central Lab Tests1 
√ 
 
 
 
 
 
 
 
 
√ 
Review of Systems 
√ 
 
 
 
 
 
 
 
 
√ 
BCVA4 
√ 
√ 
 
√ 
√ 
√ 
 
√ 
√ 
√ 
Slit lamp Biomicroscopy2, 4 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
IOP5 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Dilated Indirect Ophthalmoscopy4 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
SD-OCT4 
√ 
√ 
 
√ 
√ 
√ 
 
√ 
√ 
√ 


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Visit # 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit Type 
Screening 
Randomization 
/Treatment #1 
Follow-Up 
Treatment #2 
Follow-Up 
End Of 
Study 
Visit Window 
Day  
-14 to -1 
Day 0 
Month 1 
Week 4 
Day 28 ± 5 
Month 2 
Week 8 
Day 56 ± 5 
Month 3 
Week 12 
Day 84 ± 5 
Month 4 
Week 16 
Day 112  
± 5 
Month 5 
Week 20 
Day 140  
± 5 
Month 6 
Week 24 
Day 168  
± 5 
Assessments 
 
Pre-dose 
Post-dose 
 
 
Pre-dose 
Post-dose 
 
 
 
VFQ-25 & EQ-5D 
 
√ 
 
 
 
 
 
 
 
√ 
PK Blood Draw (optional)  
 
√ 
 
√ 
 
√ 
 
 
 
√ 
Select Study Eye/Confirm Study Eye 
√ 
 
 
 
 
√ 
 
 
 
 
Fluorescein Angiogram4 
√ 
 
 
 
 
 
 
 
 
√ 
Fundus Photos4 
√ 
 
 
 
 
 
 
 
 
√ 
IWRS/Randomize 
 
√ 
 
 
 
√ 
 
 
 
 
Study Drug Treatment3 
 
 
 
 
 
 
 
 
 
1. Central lab test samples should be collected prior to FA being performed; central labs include a serum pregnancy test for females of child bearing potential 
2. Any finding of cataract should be graded  
3. Injection should be administered the same day as the pre-injection assessments at Visit 2 and at Visit 5 
4. Completed for both eyes at Visit 1 and Visit 8; study eye only for all other visits 
5. IOP collected for both eyes, except post-injection when data is collected for study eye only 
 
 
INJECT3 
INJECT3 


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APPENDIX B. SUMMARY OF CHANGES FOR AMENDMENTS 


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Amendment 1 
 
 
 
 
Section Changed 
Initial Protocol  
(Changed From) 
Modified Protocol  
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
List of Abbreviations 
 
EQ-5D: European Quality of Life 5-
Dimensions 
 
To Add an abbreviation and 
its associated definition 
None 
Section 4.2.1. Ophthalmic 
Exclusion Criteria  
#5. History of any vitreoretinal 
surgery (scleral buckle, pars plana 
vitrectomy, retrieval of a dropped 
nucleus or intraocular lens, etc.; 
prior photocoagulation and IVT 
injections are acceptable) 
 
#5. History of any vitreoretinal 
surgery (examples include but are 
not limited to scleral buckle, pars 
plana vitrectomy, retrieval of a 
dropped nucleus or intraocular lens; 
prior photocoagulation and IVT 
injections are acceptable) 
 
To clarify that the surgeries 
provided are a partial list of 
potential excluded surgeries 
None 
Section 4.2.2. General 
Exclusion Criteria 
#20. Has taken any 
interferon/fingolimod or any other 
drug in the 6 weeks prior to Visit 2, 
where the drug is known to induce 
macular edema 
 
#20. Has taken any fingolimod or 
any other drug in the 6 weeks prior 
to Visit 2, where the drug is known 
to induce macular edema 
 
Interferon has been 
removed from this criteria 
as it is not known to induce 
macular edema 
None 
Section 5.1.7. Visit 5 – 
Week 12 – TREATMENT 
VISIT 2 
The randomization code and kit 
number initially assigned to a 
subject will remain the same 
throughout the study. 
The randomization arm initially 
assigned to a subject will remain the 
same throughout the study. 
To clarify that a new kit 
number will be assigned at 
Visit 5 
None 
Section 5.1.7.2. Injection 
Procedure and Immediate 
Post-Injection Assessments  
 
 
 
Retrieve study drug kit number 
assigned by IRT AT VISIT 2 
 
Retrieve study drug kit number 
assigned by IRT 
To clarify that a new kit 
number will be assigned at 
Visit 5 
None 


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Amendment 1 
 
 
 
 
Section Changed 
Initial Protocol  
(Changed From) 
Modified Protocol  
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 6.2.1. Prohibited 
Medications 
 
Interferon / fingolimod or any other 
drug known to induce ME 
 
Fingolimod or any other drug known 
to induce ME 
 
Interferon has been 
removed from this list as it 
is not known to induce 
macular edema 
 
 
Section 6.2.2. Additional 
Treatment 
 
In the investigator’s medical 
judgement, the uveitic complications 
in the study eye have not improved 
and the condition needs to be 
addressed 
 
To clarify that additional 
therapy may be 
implemented, at the 
Investigator’s discretion, for 
those subjects whose uveitis 
symptoms are not 
improving 
Investigator’s discretion 
may be used to treat 
subjects who are not 
improving. 
Section 6.5. 
Masking/Unmasking 
 
 
 
 
 
 
 
If masking is compromised, any 
personnel unmasked will not 
conduct any further masked clinical 
evaluations with the unmasked 
subject. 
Both the masked or unmasked 
Investigator and staff may 
participate in evaluations conducted 
during the screening visit. 
 
If masking is compromised, any 
masked personnel who become 
unmasked will not conduct any 
further masked clinical evaluations 
with the subject whose treatment has 
been unmasked. 
 
To clarify which 
staff/investigators may 
conduct evaluations during 
the screening visit 
 
 
To clarify who is eligible to 
conduct clinical evaluations 
following an unmasking 
event 
None 
 
 
 
 
 
None 
Section 8.2.2. Cataract 
Lens Grading 
 
 
 
Graders must verify training on the 
grading procedure. 
Graders must verify training on the 
grading procedure provided in the 
Manual of Procedures. 
 
To clarify where the 
cataract grading procedure 
is located 
None 


CLS1001-301 Clinical Protocol 
 
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Version 4.0 
12 April 2017 
Page 61 of 65 
CONFIDENTIAL 
Amendment 1 
 
 
 
 
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Initial Protocol  
(Changed From) 
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Impact on Subjects 
(Risk/Benefit) 
Section 8.7. Clinical 
Laboratory Tests; Table 4 
Urinalysis: Bilirubin; blood; 
glucose; ketone; protein; specific 
gravity; urobilinogen and pH 
 
Urinalysis: Bilirubin; blood; 
glucose; ketone; protein; specific 
gravity; pH 
To remove urobilinogen 
from the analytes to be 
tested; bilirubin is a 
satisfactory measure of 
potential clinical problems 
 
None 
Throughout protocol 
Miscellaneous typographical and 
formatting errors  
 
 
To correct typographical 
and formatting errors  
None 
Amendment 2 
 
 
 
 
Section Changed 
 
 
Previous Protocol  
(Changed From) 
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(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Throughout protocol 
 
Miscellaneous typographical and 
formatting errors  
 
To correct typographical 
and formatting errors  
None 
 
 


CLS1001-301 Clinical Protocol 
 
Clearside Biomedical, Inc. 
Version 4.0 
12 April 2017 
Page 62 of 65 
CONFIDENTIAL 
Amendment 2 
 
 
 
 
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Impact on Subjects 
(Risk/Benefit) 
Section 4.2.1 Ophthalmic 
Exclusion Criteria, 
Criterion # 5 
History of any vitreoretinal surgery 
(examples include but are not 
limited to scleral buckle, pars plana 
vitrectomy, retrieval of a dropped 
nucleus or intraocular lens; prior 
photocoagulation and IVT 
injections are acceptable) in the 
study eye; prior cataract extraction 
or Yttrium-Aluminum-Garnet laser 
capsulotomy is allowed, but must 
have been performed at least 3 
months prior to Visit 2 
History of any vitreoretinal surgery 
(examples include but are not 
limited to scleral buckle, retrieval of 
a dropped nucleus or intraocular 
lens; (prior photocoagulation and 
IVT injections are acceptable) in the 
study eye; prior cataract extraction, 
Yttrium-Aluminum-Garnet laser 
capsulotomy, and pars plana 
vitrectomy is allowed, but must have 
been performed at least 3 months 
prior to Visit 2 
To include pars plana 
vitrectomy as an allowed 
vitreoretinal surgery if 
conducted at least 3 months 
prior to subject 
randomization.  3 months is 
sufficient to allow healing; 
altered clearance from the 
vitreous is not a concern 
with this method of 
delivery.  
None 
Amendment 3 
 
 
 
 
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Title page 
1220 Old Alpharetta Rd., Suite 300 
Alpharetta, GA  30005 
900 North Point Parkway, Suite 200 
Alpharetta, GA  30005 
Clearside Biomedical, Inc. 
Address change 
None 
Section 1.6. Population to 
be Studied  
The study population includes 
approximately 150 adult subjects to 
be enrolled at approximately 50 
study sites. 
The study population includes 
approximately 150 adult subjects to 
be enrolled at approximately 60 
study sites. 
To update the number of 
clinical sites participating 
on the study 
None 
 
 


CLS1001-301 Clinical Protocol 
 
Clearside Biomedical, Inc. 
Version 4.0 
12 April 2017 
Page 63 of 65 
CONFIDENTIAL 
Amendment 3 
 
 
 
 
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Previous Protocol  
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Modified Protocol  
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Impact on Subjects 
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Section 4.2.1 Ophthalmic 
Exclusion Criteria, 
Criterion # 17, 18, & 19 
unless the dose has been stable for 
at least 2 weeks prior to Visit 2, and 
no change in dosing is anticipated 
for the study duration 
unless the dose has been stable for at 
least 2 weeks prior to Visit 2, and no 
increase in dosing is anticipated for 
the study duration; decreases and 
termination of dose are allowable 
during the study 
To clarify that decreases in 
doses of systemic 
corticosteroid, 
immunomodulatory and 
NSAID therapy are allowed 
during the study 
None 
Section 5. Procedures & 
Appendix A 
All ocular assessments at Visit 1 
and Visit 8 will be performed on 
both eyes. Ocular assessments at all 
other visits (Visits 2-7) will be 
performed on the study eye only.   
Perform ophthalmic assessments on 
the study eye only:  
1. ETDRS BCVA 
2. Slit-lamp biomicroscopy  
3. IOP  
4. Dilated ophthalmoscopy 
5. SD-OCT and upload 
images to the Central 
Reading Center 
 
All ocular assessments at Visit 1 and 
Visit 8 will be performed on both 
eyes. IOP will be collected in both 
eyes at all visits. All other ocular 
assessments at all other visits (Visits 
2-7) will be performed on the study 
eye only.   
Perform ophthalmic assessments on 
the study eye only, unless otherwise 
designated:  
6. ETDRS BCVA 
7. Slit-lamp biomicroscopy  
8. IOP (both eyes) 
9. Dilated ophthalmoscopy 
10. SD-OCT and upload 
images to the Central 
Reading Center 
To collect IOP data on the 
fellow eye at all visits for 
comparison to the study eye 
IOP 
None 


CLS1001-301 Clinical Protocol 
 
Clearside Biomedical, Inc. 
Version 4.0 
12 April 2017 
Page 64 of 65 
CONFIDENTIAL 
Amendment 3 
 
 
 
 
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Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 5. Procedures 
Slit-lamp biomicroscopy 
Slit-lamp biomicroscopy, including 
dilated lens grading 
To clarify that dilated lens 
grading is to be conducted 
when a finding of cataract is 
noted during the slit lamp 
exam, consistent with the 
Time and Events Schedule 
(Appendix A) 
None 
Section 6.2.1. Prohibited 
Medications 
Use of the following medications 
are prohibited at any time during 
the study: 
• 
Changes to topical 
ophthalmic NSAIDs in the 
study eye  
• 
Anti-angiogenic drugs 
(anti-VEGF) in the study 
eye or systemically 
(including pegaptanib 
sodium, bevacizumab, 
ranibizumab) 
Use of the following medications are 
prohibited at any time during the 
study: 
• 
Increases to topical 
ophthalmic NSAIDs in the 
study eye  
• 
Anti-angiogenic drugs 
(anti-VEGF) in the study 
eye or systemically 
(including pegaptanib 
sodium, bevacizumab, 
ranibizumab, aflibercept) 
To prohibit only increases 
in topical ophthalmic 
NSAIDs 
 
 
 
 
To clarify that aflibercept is 
an additional example of an 
anti-VEGF medication 
None 
 
 
 
 
 
 
None 
 


CLS1001-301 Clinical Protocol 
 
Clearside Biomedical, Inc. 
Version 4.0 
12 April 2017 
Page 65 of 65 
CONFIDENTIAL 
Amendment 3 
 
 
 
 
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Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 8.1. IOP 
Measurement 
Intraocular pressure (IOP) will be 
measured by applanation 
tonometery (Goldmann or 
Tonopen) and results will be 
recorded in mmHg. A single 
measurement will be made at 
approximately the same time of 
day. The technician is encouraged 
to use the same tonometry method 
throughout the subject’s study 
participation. Tonometers must be 
calibrated for accuracy before the 
first subject screening at that site 
and according to the manufacturer 
specifications during the study, 
until the last subject has exited the 
study at that site. 
 
Intraocular pressure (IOP) will be 
measured by applanation tonometery 
and results will be recorded in 
mmHg. Where available, Goldmann 
applanation tonometry should be 
used at all visits. Tonopens may be 
used for post-injection pressure 
checks and in cases where no 
Goldmann is available. A single 
measurement will be made at 
approximately the same time of day. 
The technician is encouraged to use 
the same tonometry method for all 
pre-injection and non-injection 
measurements throughout the 
subject’s study participation. 
Tonometers must be calibrated for 
accuracy before the first subject 
screening at that site and according 
to the manufacturer specifications 
during the study, until the last 
subject has exited the study at that 
site. 
To collect higher quality 
IOP measurements by 
requiring that the more 
accurate applanation 
equipment is used at all 
visits 
None