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
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 38
Healthy volunteers: no

Brief summary:
This open-label study is designed to evaluate the safety of suprachoroidally administered triamcinolone acetone injectable suspension, CLS-TA, in patients with non-infectious uveitis with and without macular edema.

Detailed description:
This is a Phase 3, open-label multicenter study to assess the safety of 4 mg of CLS-TA administered via suprachoroidal injection in the treatment of patients diagnosed with noninfectious uveitis with and without macular edema.

Qualified patients will be enrolled and receive two suprachoroidal injections of CLS-TA 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

Interventions: intervention 1: 4 mg CLS-TA Suprachoriodal Injection
Intervention descriptions: intervention 1: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints

Protocol document:
Prot_SAP_000.pdf: 
Compound Name: 
CLS-TA, triamcinolone acetonide injectable suspension 
Protocol Number: 
CLS1001-302 
IND Number: 
115683 
NCT Number:  
NCT03097315 
Protocol Title 
AZALEA: Open-label Safety Study of Suprachoroidal 
Triamcinolone Acetonide Injectable Suspension in Patients 
with Non-Infectious Uveitis 
Sponsor: 
Clearside Biomedical, Inc. 
900 North Point Parkway, Suite 200 
Alpharetta, GA 30005 
Issue Date: 
Protocol Amendment 1 Date: 
16 January 2017 
27 April 2017 
 


CLS 1001-302 Clinical Protocol 
CLS-T A (triamcinolone acetonide) Injectable Suspension 
Clearside Biomedical, Inc. 
Project: 
Compound Number/Name: 
Protocol Number: 
Phase: 
IND Number: 
Protocol Title: 
Sponsor: 
Medical Monitor: 
Original Protocol Issue Date: 
Amendment #1 Issue Date: 
CLEARS I DE 
Clinical Protocol CLSlOOl-302 
1001 
CLS-T A, triamcinolone acetonide injectable suspension 
CLS 1001-302 
3 
115683 
AZALEA: Open-label Safety Study of Suprachoroidal 
Triamcinolone Acetonide Injectable Suspension in Patients 
with Non-Infectious Uveitis 
Clearside Biomedical, Inc. 
900 North Point Parkway, Suite 200 
Alpharetta, GA 30005, USA 
Peter Nicholas, MD, PhD 
16JAN2017 
27 APR 2017 
CONFIDENTIAL 
'11-1/fR. 020r1 
Date 
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. 
27 April 2017 
Page 1of58 
CONFIDENTIAL 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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INVESTIGATOR’S AGREEMENT 
 
I have received and read the Investigator’s Brochure for CLS-TA. I have read the CLS1001-302 
protocol and agree to conduct the study as outlined. I agree to maintain the confidentiality of all 
information received or developed in connection with this protocol.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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PROCEDURES IN CASE OF EMERGENCY 
 
Table 1: 
Emergency Contact Information 
Role in Study 
Name 
Telephone number 
Medical Monitor 
(24-Hour emergency contact) 
Peter Nicholas, MD, PhD 
919.259.9521 
Sponsor Clinical Lead 
Ellie Smith 
678.448.4717 
Principal Investigator 
The Coordinating Principal Investigator will be appointed by the 
Sponsor before the end of the study.  As part of his or her 
responsibilities, the Coordinating Principal Investigator will 
review the final Clinical Study Report and will sign the report to 
confirm that it accurately describes the conduct and results of the 
study. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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2. 
SYNOPSIS 
Name of Sponsor/Company: 
Clearside Biomedical, Inc. 
Name of Investigational Product: 
CLS-TA (triamcinolone acetonide) injectable suspension 
Name of Active Ingredient: triamcinolone acetonide 
Title of Study: AZALEA: Open-label Safety Study of Suprachoroidal Triamcinolone Acetonide 
Injectable Suspension in Patients with Non-Infectious Uveitis 
Study center(s): Multi-center 
Protocol Number: CLS1001-302 
Studied period: 6 Month Duration 
Estimated date first subject enrolled: 1Q2017 
Estimated date last subject completed: 2Q2018 
Phase of development:  
Phase 3 
Objectives:  
Primary: To evaluate the safety of suprachoroidally administered CLS-TA in subjects with non-
infectious uveitis. 
Secondary: 
• 
To assess changes to signs and complications of uveitis  
• 
To collect use information on the suprachoroidal injection procedure 
• 
To determine systemic exposure to triamcinolone acetonide following suprachoroidal injection 
Number of subjects (planned): Approximately 35 
Diagnosis and main criteria for inclusion:  
Patients diagnosed with non-infectious uveitis for which the administration of local corticosteroid 
therapy would be a viable treatment option 
Investigational product, dosage and mode of administration:  
CLS-TA, injectable suspension, 4.0 mg in 100 µL administered via suprachoroidal injection 
Criteria for evaluation: 
The primary endpoint is the incidence of treatment-emergent adverse events and serious adverse 
events, grouped by organ system, relatedness to study medication, and severity  
Statistical methods: 
All data collected in the study database will be presented in the listings. Listings will include change 
from baseline. Baseline is Visit 2 (Day 0).  
The safety population will include all subjects who are administered at least one dose of CLS-TA 
(4 mg/100 µL).  All analyses will be based on safety population.   
Descriptive statistics are displayed to provide an overview of the study results.  Descriptive statistics 
include n, mean, median, minimum, and maximum values.  The distribution of responses (n, %) will 
be tabulated for each category of response. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
2. 
SYNOPSIS ...................................................................................................................4 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .................5 
4. 
LIST OF ABBREVIATIONS.....................................................................................10 
5. 
INTRODUCTION ......................................................................................................11 
5.1. 
Disease Background ...................................................................................................11 
5.2. 
Scientific Rationale .....................................................................................................11 
5.3. 
Description of Investigational Product .......................................................................12 
5.4. 
Summary of Clinical Experience and Justification of Dose Selection .......................12 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................14 
6.1. 
Primary Objective .......................................................................................................14 
6.2. 
Secondary Objective ...................................................................................................14 
7. 
INVESTIGATIONAL PLAN .....................................................................................15 
7.1. 
Overall Study Design ..................................................................................................15 
7.2. 
Endpoints ....................................................................................................................15 
7.2.1. 
Primary Endpoint ........................................................................................................15 
7.2.2. 
Safety Endpoints .........................................................................................................15 
7.2.3. 
Additional Endpoints ..................................................................................................15 
7.3. 
Number of Subjects ....................................................................................................16 
7.4. 
Treatment Assignment ................................................................................................16 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................17 
8.1. 
Inclusion Criteria ........................................................................................................17 
8.2. 
Exclusion Criteria .......................................................................................................17 
8.2.1. 
Ophthalmic Exclusion Criteria ...................................................................................17 
8.2.2. 
General Exclusion Criteria .........................................................................................18 
8.3. 
Subject Withdrawal Criteria .......................................................................................18 
8.4. 
Visit Procedure Descriptions ......................................................................................19 
8.4.1. 
General Procedures .....................................................................................................19 
8.4.2. 
Re-screening Procedures ............................................................................................19 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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8.4.3. 
Visit 1 – Screening (Day -30 to 0) ..............................................................................19 
8.4.4. 
Visit 2 –Treatment (Day 0) .........................................................................................20 
8.4.5. 
Follow-Up: Visit 3 – Week 4 (Day 28 ±5) .................................................................21 
8.4.6. 
Follow-Up: Visit 4 – Week 8 (Day 56 ±5) .................................................................22 
8.4.7. 
Visit 5 – Week 12 – Treatment #2 (Day 84 ±5) .........................................................22 
8.4.8. 
Follow-Up: Visit 6 – Week 16 (Day 112 ± 5) & Visit 7 – Week 20 (Day 140 
±5) ...............................................................................................................................23 
8.4.9. 
Visit 8 – Week 24 End of Study (Day 168 ± 5) or Early Termination .......................24 
8.4.10. 
Unscheduled Visit .......................................................................................................24 
9. 
TREATMENT OF SUBJECTS ..................................................................................25 
9.1. 
Treatments to be Administered ...................................................................................25 
9.2. 
Study Eye Determination ............................................................................................25 
9.3. 
Treatment of the Fellow Eye ......................................................................................25 
9.4. 
Additional Treatment ..................................................................................................25 
9.4.1. 
Rescue Criteria ............................................................................................................25 
9.5. 
Concomitant Medications ...........................................................................................26 
9.6. 
Treatment Compliance ................................................................................................26 
9.7. 
Randomization and Masking ......................................................................................26 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................27 
10.1. 
Study Drug ..................................................................................................................27 
10.2. 
Study Drug Packaging and Labeling ..........................................................................27 
10.3. 
Study Drug Storage .....................................................................................................27 
10.4. 
Study Drug Preparation ..............................................................................................27 
10.5. 
Administration ............................................................................................................27 
10.6. 
Study Drug Accountability .........................................................................................27 
10.7. 
Study Drug Handling and Disposal ............................................................................28 
11. 
ASSESSMENTS OF EFFICACY ..............................................................................29 
11.1. 
Best Corrected Visual Acuity .....................................................................................29 
11.2. 
Central Subfield Thickness as Measured by Spectral Domain Optical 
Coherence Tomography ..............................................................................................29 
11.3.  
Pharmacokinetics Assessments ..................................................................................29 
12. 
ASSESSMENTS OF SAFETY ..................................................................................30 
12.1. 
Safety Parameters .......................................................................................................30 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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12.1.1. 
Intraocular Pressure ....................................................................................................30 
12.1.2. 
Slit-Lamp Biomicroscopy ...........................................................................................30 
12.1.3. 
Cataract Lens Grading ................................................................................................30 
12.1.4. 
Anterior Chamber Cells ..............................................................................................30 
12.1.5. 
Anterior Chamber Flare ..............................................................................................31 
12.1.6. 
Indirect Ophthalmoscopy ............................................................................................31 
12.1.7. 
Fluorescein Angiography ............................................................................................32 
12.1.8. 
Fundus Photography ...................................................................................................32 
12.1.9. 
Resting Heart Rate and Blood Pressure ......................................................................32 
12.1.10. 
Pregnancy Test ............................................................................................................32 
12.1.11. 
Central Laboratory Tests ............................................................................................32 
12.1.12. 
Review of Body Systems ............................................................................................33 
12.2. 
Adverse and Serious Adverse Events .........................................................................33 
12.2.1. 
Definition of Adverse Events .....................................................................................33 
12.2.2. 
Relationship to Study Drug ........................................................................................33 
12.2.3. 
Recording Adverse Event ...........................................................................................34 
12.2.4. 
Intensity ......................................................................................................................34 
12.2.5. 
Reporting Adverse Events ..........................................................................................35 
12.2.6. 
Follow-up of AEs and SAEs .......................................................................................35 
13. 
STATISTICAL CONSIDERATIONS .......................................................................37 
13.1. 
Determination of Sample Size and Level of Significance ..........................................37 
13.2. 
Subject Disposition, Demographic and Baseline Characteristics ...............................37 
13.3. 
Analysis Populations ..................................................................................................37 
13.3.1. 
Safety Population ........................................................................................................37 
13.3.2. 
Pharmacokinetic Population .......................................................................................37 
13.4. 
Analysis Methods .......................................................................................................37 
13.4.1. 
Primary Safety Analysis .............................................................................................37 
13.4.2. 
Secondary Safety Analysis .........................................................................................38 
13.4.3. 
Pharmacokinetic Analysis ..........................................................................................39 
13.4.4. 
Procedure for Accounting for Missing, Unused or Spurious Data .............................39 
14. 
DIRECT ACCESS TO SOURCE DOCUMENTS .....................................................40 
14.1. 
Study Monitoring ........................................................................................................40 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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14.2. 
Audits and Inspections ................................................................................................40 
14.3. 
Institutional Review Boards/Independent Ethics Committees ...................................41 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................42 
16. 
ETHICS ......................................................................................................................43 
16.1. 
Ethical Review ............................................................................................................43 
16.2. 
Ethical Conduct of the Study ......................................................................................43 
16.3. 
Written Informed Consent ..........................................................................................43 
17. 
DATA HANDLING AND RECORDKEEPING .......................................................44 
17.1. 
Inspection of Records .................................................................................................44 
17.2. 
Retention of Records ..................................................................................................44 
18. 
PUBLICATION POLICY ..........................................................................................45 
19. 
REFERENCES ...........................................................................................................46 
20. 
APPENDICES ............................................................................................................47 
APPENDIX A. TIME AND EVENTS SCHEDULE..................................................................48 
APPENDIX B:  SUMMARY OF CHANGES ............................................................................50 
 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................3 
Table 2: 
Abbreviations and Specialist Terms ...........................................................................10 
Table 3: 
Anterior Chamber Cell Grading Scale ........................................................................31 
Table 4: 
Anterior Chamber Flare Grading Scale ......................................................................31 
Table 5: 
Scale for Determining Degree of Vitreous Haze ........................................................32 
 
LIST OF FIGURES 
Figure 1: 
Anatomy of the Eye ....................................................................................................12 
Figure 2: 
Study Schedule ...........................................................................................................16 
 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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4. 
LIST OF ABBREVIATIONS  
The following abbreviations and specialist terms are used in this study protocol. 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse event 
BCVA 
Best corrected visual acuity 
CRC 
Central reading center 
CRF 
Case report form 
CST 
Central subfield thickness 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
FA 
Fluorescein angiography/angiogram 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug  
IOP 
Intraocular pressure 
IRB 
Institutional Review Board 
IVT 
Intravitreal 
ME 
Macular edema 
MedDRA 
Medical Dictionary for Regulatory Activities 
OCT 
Optical coherence tomography 
PK 
Pharmacokinetics 
RVO 
Retinal vein occlusion 
SAE 
Serious adverse event 
SC 
Suprachoroidal 
SCS 
Suprachoroidal space 
SD-OCT 
Spectral-domain optical coherence tomography 
TA 
Triamcinolone acetonide 
TEAEs 
Treatment-emergent adverse events 
US 
United States 
VEGF 
Vascular endothelial growth factor 
VA 
Visual acuity 
 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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5. 
INTRODUCTION 
Clearside Biomedical is developing a proprietary formulation of triamcinolone acetonide (CLS 
TA) to treat non-infectious uveitis. This multicenter, open-label study is designed to evaluate the 
safety of suprachoroidally injected CLS-TA in subjects with non-infectious uveitis. 
Suprachoroidal (SC) injection is a novel drug delivery approach that employs Clearside’s 
proprietary suprachoroidal space (SCS™) microinjector and allows drugs to be precisely 
administered to the SCS via a minimally invasive injection procedure. This injection has been 
shown in animal models to allow distribution of drug candidates dominantly to the posterior 
segment ocular tissues while limiting exposure to anterior structures in the eye, thereby 
providing the potential for improved efficacy and safety. The purpose of this study is to expand 
the safety database of suprachoroidally injected CLS-TA in patients with non-infectious uveitis. 
5.1. 
Disease Background  
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 (US) 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 (ME), 
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 ME (Lardenoye, 2006). 
5.2. 
Scientific Rationale  
Clearside is developing CLS-TA, a proprietary TA formulation, for the treatment of non-
infectious uveitis administered by SC injection. 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.  
Uveitis is commonly treated with corticosteroids and other immunomodulatory agents; such 
treatments are either systemic or local. 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 (IOP) that could result in glaucoma, 
progression of glaucoma, and to both the formation and the progression of cataracts (Karim, 
2013).  
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 and Phase 2 clinical data. Further, the 
unique distribution of drug following suprachoroidal administration confining it to the posterior 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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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.   
5.3. 
Description of Investigational Product 
CLS-TA, triamcinolone acetonide injectable suspension, is a preservative-free, terminally 
sterilized, aqueous suspension, formulated for administration into the eye. It will be administered 
as a single SC injection of 4 mg in 100 µL. The suprachoroidal space (SCS) is the region of the 
eye between the sclera and the choroid (Figure 1). 
Figure 1: 
Anatomy of the Eye 
  
 
Additional information regarding CLS-TA, triamcinolone acetonide injectable suspension, is 
available in the Clinical Investigator’s Brochure.  
5.4. 
Summary of Clinical Experience and Justification of Dose Selection 
Triamcinolone acetonide (TA) has been used safely and effectively in human ocular therapeutics 
to treat conditions involving inflammation for over 50 years. The initial recommended dose of 
the TA formulation approved by the US Food and Drug Administration for ocular indications is 
4 mg in 100 μL (TRIESENCE Prescribing Information, 2007). The dose of CLS-TA 
administered as a single suprachoroidal injection will be similar (4 mg in 100 μL). TRIESENCE 
and CLS-TA contain the same active and inactive ingredients at approximately the same 
concentrations. Both formulations are aqueous suspensions that have been terminally sterilized 
and designed for ophthalmic use.  
Clearside has completed 2 clinical trials in patients with non-infectious uveitis and one clinical 
trial in patients with retinal vein occlusion (RVO). 
The completed clinical study, CLS1001-101 (NCT01789320), was a Phase 1/2, open-label, 
safety and tolerability study in subjects with intermediate, posterior, or pan non-infectious uveitis 
(Goldstein 2016). Each subject received a single SC injection of 4 mg in 100 µL TA 
(TRIESENCE®). Nine of the 11 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 adverse 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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event (unrelated pulmonary emboli; SAE) occurred. No deaths were reported. No significant 
increases in IOP were reported. The most commonly reported AE, eye pain, was reported in 5 
subjects. All subjects in the per-protocol (n=8) analysis set showed improvements in BCVA in 
this study. 
The completed clinical study, CLS1001-201 (NCT02255032), was a Phase 2, randomized, 
masked safety and efficacy study in subjects with ME associated with non-infectious uveitis. 
Twenty-two subjects were assigned to receive a single SC injection of CLS-TA, either 4 mg in 
100 µL or 0.8 mg in 100 µL in a 4:1 randomization. Subjects in the 4.0 mg treatment group were 
observed to have a mean reduction in central subfield thickness (CST) of 164 microns (p=0.002) 
when measured from Baseline at 2 months. One SAE (unrelated atrial fibrillation) occurred. No 
subjects discontinued due to an AE, and there were no Investigator-reported increases in IOP at 
follow-up visits. 
The completed clinical study, CLS1003-201 (CT02303184), was a Phase 2, randomized, masked 
safety and efficacy study in subjects with ME following RVO. Forty-six subjects were randomly 
assigned 1:1 to either SC injection of CLS-TA administered in conjunction with an intravitreal 
(IVT) injection of aflibercept (ACTIVE), or an IVT injection of aflibercept alone (CONTROL). 
Subjects were observed to have a mean reduction in CST of 445 µm in the ACTIVE group and 
342 µm in the CONTROL group when measured from Baseline at 3 months. Mean 
improvements in best corrected visual acuity (BCVA) were 16, 20 and 19 letters in the ACTIVE 
group and 11, 12 and 11 letters in the CONTROL group at Months 1, 2 and 3 respectively. Sixty 
percent fewer additional intravitreal aflibercept injections (p=0.013) were required in the 
ACTIVE group receiving the combination of suprachoroidal CLS-TA and intravitreal aflibercept 
compared to subjects in the CONTROL arm. No subjects discontinued due to an AE and no 
SAEs were reported. Two subjects in the active group reported 2 events each of ocular 
hypertension and IOP increase.  All events were mild or moderate in intensity and considered to 
be related to study drug. 
Safety profiles have been similar in all three studies with eye pain being the most commonly 
reported AE. Additional information regarding clinical experience with TA administered to the 
SCS is available in the Investigator’s Brochure. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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6. 
TRIAL OBJECTIVES AND PURPOSE 
The purpose of this open-label study is to evaluate the safety of suprachoroidally administered 
CLS-TA for the treatment of non-infectious uveitis.  
6.1. 
Primary Objective 
The primary objective of this study is to evaluate the safety of suprachoroidally administered 
CLS-TA in subjects with non-infectious uveitis.  
6.2. 
Secondary Objective 
The secondary objectives of the study are: 
• To assess changes to signs and complications of uveitis 
• To collect use information on the suprachoroidal injection procedure 
• To determine systemic exposure to triamcinolone acetonide after suprachoroidal injection 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is a Phase 3, open-label, multi-center study to assess the safety of 4 mg of CLS-TA 
administered via suprachoroidal injection for the treatment of subjects with non-infectious 
uveitis.   
The study design includes 8 clinic visits over a maximum of 29 weeks.  Subject eligibility will be 
established at Visit 1 during the screening process (Day -30 to 0).  Eligible subjects will return to 
the clinic for Visit 2 (Day 0).  Visit 1 and Visit 2 can occur on the same day. Qualified subjects 
will receive two unilateral suprachoroidal injections of CLS-TA administered to the study eye, 
approximately 12 weeks apart (Visit 2 and Visit 5).  Follow up visits will be conducted every 4 
weeks up to 24 weeks (Visit 8).  Subjects will have a final evaluation conducted 24 weeks (Visit 
8) following Treatment #1 (Day 0).  All subjects will be included in pharmacokinetic evaluations 
at Visits 2, 3, 5 and 8. 
Subjects will be assessed via study procedures outlined in the time and events schedule.   
7.2. 
Endpoints 
7.2.1. 
Primary Endpoint 
The primary endpoint is the incidence of treatment-emergent adverse events (TEAEs) and SAEs, 
grouped by organ system, relatedness to study medication, and severity.  
7.2.2. 
Safety Endpoints 
• Percentage of subjects whose IOP increases are >5 and > 10 mmHg from their own 
baseline measurement at each follow-up visit (except Visits 2 & 5 [post-dose])  
• Percentage of subjects whose IOP increases to a reading > 30 mmHg at each follow-
up visit (except Visits 2 & 5 [post-dose]) 
• Percentage of subjects who require 1 or more additional IOP lowering medications at 
any follow-up visit (except Visits 2 & 5 [post-dose]) 
• Percentage of subjects who experience an 11 – 20 mm, 21-30 mm, >30 mm rise in 
IOP 30 min post injection 
• Mean change in lens grading based on standardized cataract grading system 
assessment  
7.2.3. 
Additional Endpoints 
• User evaluation and information pertaining to the use of the microinjector during the 
injection procedure  
• Triamcinolone acetonide blood concentrations prior to each dose (Visits 2 and 5), 4 
weeks following the first dose (Visit 3) and at 24 weeks (Visit 8) 
• Percentage change in anterior chamber cells and flare, and vitreous haze 
• Mean change from baseline in Early Treatment of Diabetic Retinopathy Study 
(ETDRS) BCVA 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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• Mean change from baseline in CST  
• Percentage of subjects with <300 micron CST 
• Percentage of subjects with a decrease in systemic concomitant uveitis medications  
• Percentage of subjects in whom any additional therapy was initiated to manage 
uveitis  
7.3. 
Number of Subjects 
Approximately 35 subjects with non-infectious uveitis will be enrolled into the study. 
7.4. 
Treatment Assignment  
After Screening (Day -30 to Day 0) and Baseline assessments on Day 0, subjects will be 
assigned to the study treatment that consists of two unilateral suprachoroidal injections of 4 mg 
(100 µL of 40 mg/mL) CLS-TA administered to the study eye, approximately 12 weeks apart 
(Visit 2 and Visit 5).   
 
 
Figure 2: 
Study Schedule  
 
CLS-TA=Triamcinolone Acetonide Injectable Suspension 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Inclusion Criteria 
Individuals 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 for which the administration of local 
corticosteroid therapy would be a viable treatment option; either anterior-, intermediate-, 
posterior- or pan-uveitis are acceptable; both active and inactive uveitis are acceptable 
2. ETDRS BCVA score of ≥ 5 letters read in the study eye 
3. 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 
4. At least 18 years of age 
8.2. 
Exclusion Criteria 
8.2.1. 
Ophthalmic Exclusion Criteria 
An individual is 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. Any active ocular disease or infection in the study eye other than uveitis 
3. 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  
4. Has a history of severe glaucoma as defined by optic nerve damage (cup/disc ratio of      
≥ 0.9 or any notching of optic nerve to the rim)  
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 ,filtration surgeries, or laser trabeculoplasty 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  
9. Has had any IVT injection of anti-vascular endothelial growth factor 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 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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Ozurdex® implant in the 6 months prior to Visit 2; Retisert®or Iluvien® implant in the 3 
years prior to Visit 2 
8.2.2. 
General Exclusion Criteria  
Individuals 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 (eg. 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 OR was ever enrolled in a 
previous clinical study of CLS-TA 
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; 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; 
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; decreases and termination of dose are 
allowable during the study 
8.3. 
Subject Withdrawal Criteria 
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 withdraw prematurely from the study will be asked to complete study assessments 
at the Early Termination Visit. If an SAE is unresolved at the time of the subject’s final study 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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visit, the 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.  
8.4. 
Visit Procedure Descriptions 
8.4.1. 
General Procedures 
The study will consist of up to 8 study visits over a maximum of 29 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 collected on the study eye only.   
Subjects will be screened for entry at Visit 1 (Days -30 to 0) and the study eye will be identified.  
Each eligible subject will return to the clinic within 30 days to be treated at Visit 2 (Day 0). Visit 
1 and Visit 2 can occur on the same day. After baseline assessments on Day 0, subjects will 
receive an active SC dose of CLS-TA in the study eye. Subjects will be assessed after injection 
for safety. 
Additional safety follow-up visits will occur every 4 weeks for 24 weeks.  Subjects will receive a 
second SC injection of CLS-TA at Visit 5 (Week 12).  The final study visit will occur at Visit 8 
(Week 24).  
8.4.2. 
Re-screening Procedures  
Subjects may be re-screened if the reason for their initial screening failure has changed. A 
subject who is designated as a screen failure before being randomly assigned at Visit 2 (Day 0) 
may be re-screened up to 2 additional times, for a total of 3 screenings, upon Sponsor approval.  
Subjects who are re-screened are required to sign a new consent form. Screening assessments 
must be repeated if timings for the assessments fall outside of the specified study windows.  
8.4.3. 
Visit 1 – Screening (Day -30 to 0) 
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 by study staff: 
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 fluorescein angiography (FA) 
7. Collect serum or urine for local pregnancy test on females of childbearing potential 
8. Perform ophthalmic assessments on both eyes:  
a. ETDRS BCVA  


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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b. Slit-lamp biomicroscopy, including dilated lens grading  
c. IOP (Goldmann applanation tonometry) 
d. Dilated indirect ophthalmoscopy 
e. Fundus photography and upload images to the Central Reading Center (CRC) 
f. SD-OCT and upload images to the CRC 
g. FA and upload images to the CRC 
9. Perform a review of systems 
10. Verify subject eligibility based on Inclusion/Exclusion requirements 
11. Determine study eye based upon eye specific eligibility criteria (see Section 9.2) 
12. Schedule subject to return for Visit 2, Treatment, or continue on to Visit 2 procedures   
8.4.4. 
Visit 2 –Treatment (Day 0) 
Visit 2 may occur on the same day as Visit 1 (Screening) but must occur within 30 days of Visit 
1 (Screening). The following procedures will be performed by study staff: 
8.4.4.1. 
Pre-Injection Procedures  
The following must be performed prior to the injection of CLS-TA (the same day as the 
injection). If Visit 1 and Visit 2 are performed on the same day, the pre-injection procedures in 
Visit 2 can be waived: 
1. Assess for AEs 
2. Review changes to concomitant medications 
3. Review lab results for any clinically significant abnormalities that would exclude the 
subject from entry 
4. Measure resting heart rate and blood pressure  
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 (Goldmann applanation tonometry), both eyes 
d. Dilated ophthalmoscopy 
e. SD-OCT and upload images to the CRC 
6. Collect a blood sample for PK analysis; blood must be collected PRIOR to dosing 
8.4.4.2. 
Injection Procedure and Immediate Post-Injection Assessments 
For details on the injection procedure, please see the Investigator Site File.  
1. Confirm study eye 
2. Retrieve study drug kit number  


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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3. Prepare eye for injection per the investigator’s standard practice    
4. The injecting investigator should administer suprachoroidal injection of CLS-TA 
procedure to the study eye; see Manual of Procedures for detailed instructions 
5. Immediately following the injection, assess study eye by indirect ophthalmoscopy 
8.4.4.3. 
Post-Injection Procedures 
The following assessments must occur following the injection of CLS-TA: 
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 approximately 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. Document injection procedure use information 
5. Schedule subject to return for next visit 
8.4.5. 
Follow-Up: Visit 3 – Week 4 (Day 28 ±5) 
Visit 3 should be 42 ±5 days from Visit 2.  The following procedures will be performed by study 
staff at Visit 3: 
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 (Goldmann applanation tonometry), both eyes 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the CRC 
4. Collect a blood sample for PK analysis 
5. Schedule subject to return for next visit 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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8.4.6. 
Follow-Up: Visit 4 – Week 8 (Day 56 ±5) 
Visit 4 should be 56 ±5 days from Visit 2. The following procedures will be performed by study 
staff at Visit 4: 
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 (Goldmann applanation tonometry), both eyes 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the CRC 
4. Schedule subject to return for next visit 
8.4.7. 
Visit 5 – Week 12 – Treatment #2 (Day 84 ±5) 
At Visit 5, subjects will receive their second, unilateral, suprachoroidal injection of CLS-TA. 
The following Visit 5 procedures will be performed by study staff: 
8.4.7.1. 
Pre-Injection Procedures  
The following must be performed prior to the injection of CLS-TA (the same day as the 
injection): 
1. Assess for AEs 
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 (Goldmann applanation tonometry), both eyes 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the CRC 
7. Collect a blood sample for PK analysis; blood must be collected PRIOR to dosing 
8.4.7.2. 
Injection Procedure and Immediate Post-Injection Assessments 
For details on the injection procedure, please see the Investigator Site File.  The Visit 5 injection 
procedure should be identical to the Visit 2 injection procedure. 
1. Confirm study eye 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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2. Retrieve study drug kit number  
3. Prepare eye for injection per the investigator’s standard practice  
4. The injecting investigator should administer a suprachoroidal injection of CLS-TA in the 
study eye 
5. Immediately following the injection, assess study eye by indirect ophthalmoscopy 
8.4.7.3. 
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 approximately 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. Document injection procedure use information 
5. Schedule subject to return for next visit 
8.4.8. 
Follow-Up: Visit 6 – Week 16 (Day 112 ± 5) & Visit 7 – Week 20 (Day 140 ±5) 
Visit 6 should be 112 ± 5 days from Visit 2. Visit 7 should be 140 ±5 from Visit 2.  The 
following procedures will be performed by 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 (Goldmann applanation tonometry), both eyes 
d. Dilated indirect ophthalmoscopy 
e. SD-OCT and upload images to the CRC 
4. Schedule subject to return for next visit 


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8.4.9. 
Visit 8 – Week 24 End of Study (Day 168 ± 5) or Early Termination  
Visit 8 should be 168 ± 5 days from Visit 2 or at the time of early termination.  The following 
Visit 8 procedures will be performed by 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) 
5. Collect a blood sample for PK analysis 
6. Perform a review of systems 
7. Perform ophthalmic assessments on both eyes, unless otherwise designated:  
a. ETDRS BCVA 
b. Slit-lamp biomicroscopy, including dilated lens grading  
c. IOP (Goldmann applanation tonometry), both eyes 
d. Dilated indirect ophthalmoscopy 
e. Fundus photography and upload images to the CRC 
f. SD-OCT and upload images to the CRC 
g. FA and upload images to the CRC 
8.4.10. 
Unscheduled Visit 
To ensure subject safety during the study, any subject who requires additional follow-up or 
treatment for any reason at any time during the study that does not fall on a scheduled study visit 
should have that visit recorded as an Unscheduled Visit.  


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9. 
TREATMENT OF SUBJECTS 
9.1. 
Treatments to be Administered 
Treatment will consist of two unilateral suprachoroidal injections of 4 mg of CLS-TA in 100 µL, 
administered 12 weeks apart.  
Approximately 35 subjects will be enrolled.  The CLS-TA injections will occur at Visit 2 
(Day 0) and at Visit 5 (Day 84 ± 5).   
All SC 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 SC injection procedure can be found in the Investigative Site File. 
 
9.2. 
Study Eye Determination 
The study eye will be the eye receiving the SC CLS-TA injection.  The determination of the 
study eye will be based on Screening/Baseline information and will be determined prior to 
injection. 
If both eyes meet study criteria, then 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. 
9.3. 
Treatment of the Fellow Eye  
Subjects may have bilateral disease, but only one eye will be designated the study eye and 
treated.  
Local medications are permitted for the fellow eye during the course of this trial. The choice of 
local 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.  Medications used for therapy of the fellow eye will be recorded in the subject’s medical 
chart and the case report form (CRF).   
9.4. 
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. 
9.4.1. 
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 may 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) 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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• 
An increase in CST of ≥ 100 µm 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 flare, or vitreous haze) or an increase from 3+ to 4+  
• 
A decrease of 10 or more ETDRS BCVA letters read from the best ETDRS BCVA data 
observed during the study, along with an increase in other signs or complications 
associated with the patient’s uveitis 
• 
In the investigator’s medical judgement, the uveitic complications in the study eye have 
not improved and the condition needs to be addressed 
9.5. 
Concomitant 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: 
• Any corticosteroid implant (ie, Ozurdex®, Iluvien® or Retisert™) in the study eye 
• Topical, periocular or IVT corticosteroids in the study eye  
• Anti-angiogenic drugs (anti-VEGF) in the study eye or systemically (including 
pegaptanib sodium, bevacizumab, ranibizumab) 
• Any investigational drug or device 
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. 
9.6. 
Treatment Compliance 
Study drug will only be administered by trained study investigators (Principal Investigator or 
Sub-Investigator) in the office at Visit 2 and Visit 5.  No study drug will be dispensed to 
subjects; subject treatment compliance is not applicable.   
9.7. 
Randomization and Masking 
This study is neither randomized nor is the study treatment masked. Investigators, study staff, 
subjects and the sponsor will be aware of the investigational treatment provided to the subject. 


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10. STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. Study Drug 
CLS-TA, triamcinolone acetonide injectable suspension, 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. 
Additional information regarding CLS-TA is available in the Investigator’s Brochure. 
10.2. Study Drug Packaging and Labeling 
The study drug kits for SC injection of CLS-TA will be supplied to each site by the Sponsor (or 
designee) and will be labeled for “Investigational Use only”. 
10.3. Study Drug Storage 
CLS-TA will be stored at ambient temperatures between 15°C and 25°C (59°F-77°F) in an area 
with limited, controlled access and temperature monitoring; do not freeze. CLS-TA should be 
protected from light by storing in the carton provided. 
10.4. Study Drug Preparation 
Shake the vial of CLS-TA vigorously for 10 seconds to ensure a uniform suspension before 
withdrawing the product from the vial.  
10.5. Administration 
CLS-TA will be administered as a single SC injection of 4 mg in 100 µL. 
All CLS-TA 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 CLS-TA injection procedure can be found in the Investigative Site 
File. 
The date and time of the injection will be recorded in the subject’s medical chart and the CRF. 
All needles used, the needle length used for injection and procedure use information will also be 
recorded. 
10.6. Study Drug Accountability 
Accountability of study drug kits will be conducted by either designated study staff and/or the 
study monitor. Accountability will be ascertained by performing reconciliation between the 
number of study drug cartons (kits and components) sent to the site and the number used and 
unused at the time of reconciliation.   
Study drug shipment records will be verified and accountability performed by comparing the 
shipment inventory sheet to the actual quantity of drug and injectors received at the site. 
Accurate records of receipt and disposition of the study drug and injectors (eg, dates, quantity, 


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subject number, kits used, and kits unused) must be maintained by the Investigator or his/her 
designee.  
10.7. Study Drug Handling and Disposal 
At the end of the study and after study drug kit accountability has been verified, all study drug 
(used and unused vials) and unused microinjector components will be returned to the Sponsor (or 
designee) or destroyed at the site and documented according to the site’s standard process. Any 
used injectors and vials of study drug involved in a product complaint must be maintained and 
return to the Sponsor (or designee). All study drug and injector accounting procedures must be 
completed before the study is considered complete. 
 


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11. 
ASSESSMENTS OF EFFICACY 
For additional information on an assessment, see the Investigative Site File. 
11.1. Best Corrected Visual Acuity  
BCVA will be evaluated by ETDRS using electronic visual acuity or standardized lighting and 
lanes. The method of visual acuity assessment should remain consistent throughout a subject’s 
study participation. The results will be reported as the number of letters read 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. 
11.2. Central Subfield Thickness as Measured by Spectral Domain Optical 
Coherence Tomography 
Retinal thickness and disease characterization will be assessed via spectral domain – optical 
coherence tomography (SD-OCT). The SD-OCT instrument and technician must be certified 
before screening any subjects. The technician is encouraged to use the same certified equipment 
throughout the subject’s study participation. All images should be taken by the same technician, 
whenever possible, on each subject per research site. De-identified images will be uploaded to 
the CRC. 
11.3. Pharmacokinetics Assessments 
Blood samples for measurement of CLS-TA plasma concentrations will be collected by 
venipuncture by qualified study personnel. A single blood sample will be obtained from each 
subject at the following time points: Day 0 (Visit 2) pre-dose, Week 4 (Visit 3) any time during 
visit, Week 12 (Visit 5) pre-dose and Week 24 (Visit 8) 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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12. 
ASSESSMENTS OF SAFETY 
For additional information on an assessment, see the Investigative Site File. 
12.1. 
Safety Parameters 
12.1.1. 
Intraocular Pressure  
Intraocular pressure will be measured by applanation tonometery and results will be recorded in 
mmHg.  Goldmann applanation tonometry should be used at all visits. Tonopens may be used for 
post-injection pressure checks. 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. 
12.1.2. 
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.  
12.1.3. 
Cataract Lens Grading 
If an abnormal finding of cataract is noted during the slit-lamp exam, the cataract should be 
graded for nuclear opalescence, cortical opacity and posterior subcapsular opacity.  Graders 
must verify training on the grading procedures. 
12.1.4. 
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 3 (SUN, 2005).  
 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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Table 3: 
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 
12.1.5. 
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 4 (SUN, 2005).  
Table 4: 
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) 
 
12.1.6. 
Indirect Ophthalmoscopy  
Indirect ophthalmoscopy should be performed according to the Investigator’s standard 
procedure. This procedure should be the same for all subjects observed at the Investigator’s site. 
The fundus will be examined thoroughly and the following variables will be assessed as normal 
or abnormal (including but not limited to): vitreous, retina, choroid, and optic nerve/disc, 
appearance of vessels, absence of neovascularization.   
12.1.6.1. 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 5 (Nussenblatt 1985 as modified in 
Lowder 2011).  


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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Table 5: 
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 
 
12.1.7. 
Fluorescein Angiography 
Fluorescein angiography will be performed for anatomic assessments and will include the area of 
fluorescein leakage, area of capillary nonperfusion, the presence of retinal vascular and optic 
nerve head staining, and retinal pigment epithelium abnormalities. Digital equipment will be 
registered and photographers certified for the imaging procedures. De-identified images will be 
uploaded to the CRC.  
12.1.8. 
Fundus Photography 
Color fundus photographs will be obtained. It is recommended that when both fundus 
photographs and FA are conducted in the same visit, the fundus photographs should be taken 
first. All photographs should be taken by the same photographer, whenever possible, on all 
subjects per research site. Digital equipment will be registered and photographers certified for 
the imaging procedures. De-identified images will be uploaded to the CRC. 
12.1.9. 
Resting Heart Rate and Blood Pressure 
Resting heart rate and resting blood pressure (systolic and diastolic, preferably on the same 
group each time) will be measured at Visits 1, 2, 5 and 8 after the subject has rested for about 5 
minutes. 
12.1.10. 
Pregnancy Test 
Pregnancy tests will be performed on all females of childbearing potential. Urine or serum 
pregnancy tests may be performed locally. 
12.1.11. 
Central Laboratory Tests 
Non-fasting clinical laboratory tests will be performed at Visits 1 and 8. These laboratory tests 
include serum chemistry, hematology, and urinalysis and are to evaluate any underlying disease 
condition. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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12.1.12. 
Review of Body 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. 
12.2. Adverse and Serious Adverse Events 
12.2.1. 
Definition of Adverse Events 
12.2.1.1. Adverse Event  
An AE is the development of an undesirable medical condition or the deterioration of a pre-
existing medical condition after or during exposure to a pharmaceutical product, whether or not 
considered causally related to the product. In clinical studies, an AE can include an undesirable 
medical condition occurring at any time, including baseline or washout periods, even if no study 
treatment has been administered. 
All AEs that occur after any subject has signed consent, before treatment, during treatment, or 
during the study participation, whether or not they are related to the study, must be recorded on 
the forms provided. 
12.2.1.2. Serious Adverse Event 
An SAE is an AE occurring during any study phase (ie, baseline, treatment, washout, or follow-
up), and at any dose of the investigational product, comparator, or placebo, that fulfils one or 
more of the following: 
• 
Results in death 
• 
Is immediately life-threatening 
• 
Requires in-patient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability or incapacity 
• 
Results in a congenital abnormality or birth defect 
• 
Is an important medical event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above. 
All SAEs that occur after any subject has been enrolled, before treatment, during treatment, or 
during study participation, whether or not they are related to the study, must be recorded. 
12.2.2. 
Relationship to Study Drug 
An Investigator who is qualified in medicine must make the determination of relationship to the 
investigational product for each AE (Unrelated or Related). The Investigator should decide 
whether, in his or her medical judgment, there is a reasonable possibility that the event may have 
been caused by the investigational product. If no valid reason exists for suggesting a relationship, 
then the AE should be classified as “unrelated.” If there is any valid reason, even if 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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undetermined, for suspecting a possible cause-and-effect relationship between the investigational 
product and the occurrence of the AE, then the AE should be considered “related.” 
12.2.3. 
Recording Adverse Event 
Adverse events spontaneously reported by the subject and/or in response to an open question 
from the study personnel or revealed by observation will be recorded during the study at the 
investigational site. Clinically significant changes in laboratory values, blood pressure, and pulse 
need not be reported as AEs. However, abnormal values that constitute an SAE or lead to 
discontinuation of administration of study drug must be reported and recorded as an AE.  
Information about AEs will be collected from the signing of the consent form until the end of the 
study. Serious adverse event information will be collected from signing of the consent form until 
the end of study participation. The AE term should be reported in standard medical terminology 
when possible. For each AE, the Investigator will evaluate and report the onset (date and time), 
resolution (date and time), intensity, causality, action taken, seriousness outcome (if applicable), 
and whether or not it caused the subject to discontinue the study. 
12.2.4. 
Intensity 
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 an SAE. 
Grade refers to the intensity of the AE. The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of intensity for each AE based on this general guideline: 
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 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Section 12.2.1.2. An AE of severe intensity 
may or may not be considered serious. 
Should a pregnancy occur, it must be reported and recorded on the provided pregnancy form.  
Pregnancy in itself is not regarded as an AE unless there is a suspicion that an investigational 
product may have interfered with the effectiveness of a contraceptive medication. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or 
congenital abnormality) must be followed up and documented even if the subject was 
discontinued from the study. 
All reports of congenital abnormalities/birth defects are SAEs. Spontaneous miscarriages should 
also be reported and handled as SAEs. Elective abortions without complications should not be 
handled as AEs. 
12.2.5. 
Reporting Adverse Events 
All SAEs (related and unrelated) will be recorded from the signing of the consent form until the 
end of study participation. Any SAEs considered related to the investigational product and 
discovered by the Investigator at any time after the study should be reported. All SAEs must be 
reported to Clearside Biomedical, or its designee, within one business day of the first awareness 
of the event. The Investigator must complete, sign, and date the SAE pages, verify the accuracy 
of the information recorded on the SAE pages with the corresponding source documents, and 
send a copy by fax to Clearside Biomedical, or its designee.   
Additional follow-up information, if required or available, should be faxed to Clearside 
Biomedical, or its designee, within one business day of receipt. The information should be 
recorded on a follow-up SAE form and placed with the original SAE information and kept with 
the appropriate section of the CRF and/or study file. 
Clearside Biomedical is responsible for notifying the relevant regulatory authorities of certain 
events. It is the Principal Investigator’s responsibility to notify the Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) of all SAEs that occur at his or her site. Investigators 
will also be notified of all unexpected, serious, drug-related events (7/15-Day Safety Reports) 
that occur during the clinical study. Each site is responsible for notifying its IRB/IEC of these 
additional SAEs. 
12.2.6. 
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 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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SAEs identified after the last scheduled contact until the event has resolved or stabilized or the 
subject is lost to follow-up.  


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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13. 
STATISTICAL CONSIDERATIONS 
A detailed statistical analysis plan will be prepared for this study.  Even though the endpoints in 
this study will only be based on descriptive statistics, the plan will contain a discussion of the 
statistical methods, a description of any computational algorithms and data handling 
conventions, and specifications for the data summaries and listings.  It will be finalized before 
database lock. No inferential statistical analyses will be performed. All safety and efficacy 
endpoints will be summarized using descriptive statistics.  
Pharmacokinetic analyses to determine systemic levels of triamcinolone acetonide following 
suprachoroidal injection will be described in a separate detailed plan. 
13.1. 
Determination of Sample Size and Level of Significance 
Approximately 35 subjects will be enrolled in this open-label safety study. Because this is a 
safety study, it was not powered for hypothesis testing; statistical analyses were descriptive in 
nature. The study sample size was not based on statistical calculations or statistical assumptions. 
13.2. 
Subject Disposition, Demographic and Baseline Characteristics 
Subject disposition, demographic, and baseline characteristics will be summarized descriptively. 
13.3. 
Analysis Populations 
13.3.1. 
Safety Population 
The safety population will include all subjects who are administered at least one dose of CLS- 
TA.  All analyses will be based on the Safety Population. 
13.3.2. 
Pharmacokinetic Population 
The pharmacokinetic population will include all subjects who are administered at least one dose 
of CLS-TA. Analyses will be conducted on all samples collected during the study.  
13.4. 
Analysis Methods 
Safety and efficacy endpoints are provided in Section 7.12.  
13.4.1. 
Primary Safety Analysis 
The primary endpoint is the incidence of treatment-emergent adverse events (TEAEs) and SAEs, 
grouped by organ system, relatedness to study medication, and severity. 
The TEAEs and SAEs will be summarized by system organ class (SOC) and preferred term (PT) 
by presenting the number and percentage of subjects with each TEAE and SAE. The following 
AE summaries will be produced:  
• 
TEAEs by SOC and PT 
• 
SAEs by SOC and PT 
• 
Treatment-related TEAEs by SOC and PT 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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• 
Treatment-related SAEs by SOC and PT  
• 
TEAEs by SOC, PT, and maximum severity 
In the summary, subjects may be counted under multiple SOCs and PTs, but for each SOC and 
PT, subjects are only counted once. If a subject has the same AE on multiple occasions, the 
highest severity (severe, moderate, mild) recorded for the event will be presented and the highest 
drug relationship will be presented on the respective tables. Percentages are based on the number 
of subjects in the Safety population. 
All AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA). 
13.4.2. 
Secondary Safety Analysis 
Unless otherwise specified, all continuous variables will be summarized with descriptive 
statistics including: the number of observation (n), mean, standard deviation, median, minimum 
and maximum.  All categorical/qualitative data will be presented using the number of 
observations (n), the frequency count and percentages by visit. The listings will be provided 
using the safety population. In general, the subject listings will be sorted by the subject number 
and assessment date (and time, if applicable). 
13.4.2.1. Extent of Exposure 
The extent of exposure (the number of injections and whether it was a complete or partial 
injection) will be listed. 
13.4.2.2. Secondary Safety Endpoints 
• Percentage of subjects whose IOP increases are >5 and > 10 mmHg from their own 
baseline measurement at each follow-up visit (except Visits 2 & 5 [post-dose])  
• Percentage of subjects whose IOP increases to a reading > 30 mmHg at each follow-
up visit (except Visits 2 & 5 [post-dose]) 
• Percentage of subjects who require 1 or more additional IOP lowering medications at 
any follow-up visit (except Visits 2 & 5 [post-dose]) 
• Percentage of subjects who experience an 11 – 20 mm, 21-30 mm, >30 mm rise in 
IOP 30 min post injection 
• Mean change in lens grading based on standardized cataract grading system 
assessment  
13.4.2.3. Additional Endpoints 
• User evaluation and information pertaining to the use of the microinjector during the 
injection procedure  
• Triamcinolone acetonide blood concentrations prior to the each dose (Visits 2 and 5), 
4 weeks following the first dose (Visit 3) and at 24 weeks (Visit 8) 
• Percentage change in anterior chamber cells and flare and vitreous haze 
• Mean change from baseline in ETDRS BCVA  
• Mean change from baseline in CST  


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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• Percentage of subjects with <300 micron CST 
• Percentage of subjects with a decrease in systemic concomitant uveitis medications  
• Percentage of subjects in whom any additional therapy was initiated to manage 
uveitis  
13.4.2.4. Subgroup analysis 
No subgroup analyses are planned. 
13.4.3. 
Pharmacokinetic Analysis 
Standard population PK parameters will be calculated from plasma CLS-TA concentrations. 
Samples from approximately 35 subjects enrolled in the study will be available for analysis. 
Analyses will be conducted according to the nonlinear mixed-effects approach and will provide 
estimates of population characteristics (intrinsic and extrinsic factors) that describe the 
population distribution of the PK parameters. 
13.4.4. 
Procedure for Accounting for Missing, Unused or Spurious Data  
Any missing, unused, or spurious data will be noted in the final clinical study report. 
No imputation is planned for safety data. Methodology for handling missing or partial dates will 
be addressed in the Statistical Analysis Plan. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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14. 
DIRECT ACCESS TO SOURCE DOCUMENTS 
14.1. 
Study Monitoring  
Before an investigator can enter a subject into the study, a representative of Clearside 
Biomedical, Inc will visit the study site (unless waiver criteria are met) to: 
• Determine the adequacy of the facilities 
• Discuss with the Investigator(s) and other personnel their responsibilities with regard to 
protocol adherence and the responsibilities of Clearside Biomedical, Inc or its 
representatives. This will be documented in a Clinical Study Agreement between 
Clearside Biomedical, Inc and the Investigator. 
During the study, a monitor from Clearside Biomedical, Inc or its representative will have 
regular contacts with the study site to: 
• Provide information and support to the Investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the CRFs, and that investigational product accountability checks 
are being performed 
• Perform source data verification. This includes a comparison of the data in the CRFs with 
the subject’s medical records at the hospital or practice, and other records relevant to the 
study. This will require direct access to all original records for each subject (eg, clinic 
charts). 
• Record and report any protocol deviations not previously sent to Clearside Biomedical, 
Inc or designee. 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm any SAEs 
have been forwarded to Clearside Biomedical, Inc or designee and those SAEs that met 
criteria for reporting have been forwarded to the IRB/IEC. 
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or advice. 
14.2. 
Audits and Inspections 
Authorized representatives of Clearside Biomedical, a regulatory authority, an Independent 
Ethics Committee or an Institutional Review Board may visit the study site to perform audits or 
inspections, including source data verification. The purpose of a Clearside Biomedical audit or 
inspection is to systematically and independently examine all study-related activities and 
documents to determine whether these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, Good Clinical Practice guidelines of 
the International Conference on Harmonization, and any applicable regulatory requirements.  
The Investigator should contact Clearside Biomedical immediately if contacted by a regulatory 
agency about an inspection. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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14.3. 
Institutional Review Boards/Independent Ethics Committees 
The Principal Investigator must obtain IRB/IEC approval for the investigation. Initial IRB/IEC 
approval and all materials approved by the IRB/IEC for this study, including the subject consent 
form and recruitment materials, must be maintained by the Investigator and made available for 
inspection. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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15. 
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 site 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 drug receipt, storage, and disposition; and 
regulatory files related to the study. 
At the time of database lock, the clinical database will be audited 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 to provide sufficient accuracy for the estimated error rate of the 
clinical database.  


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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16. 
ETHICS 
16.1. 
Ethical Review 
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favorable opinion in writing by an IRB or IEC as appropriate. The 
Investigator must submit written approval to Clearside Biomedical, Inc, or designee, before he or 
she can enroll any subject into the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements. In addition, the IRB or IEC must approve all 
advertising used to recruit subjects for the study. The protocol must be re-approved by the IRB 
or IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB or IEC with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product. Clearside Biomedical, Inc will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
16.2. 
Ethical Conduct of the Study  
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with the International Council for Harmonisation 
Guideline for Good Clinical Practice, and applicable regulatory requirements. 
16.3. 
Written Informed Consent  
The Principal Investigator(s) at each site will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose, and possible risk and benefit of the study.  
Subjects must also be notified that they are free to discontinue from the study at any time. The 
subject should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed Informed Consent Form. A copy 
of the signed Informed Consent Form must be given to the subject.   


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
Clearside Biomedical Inc, and designees, will be allowed to conduct site visits to the 
investigation facilities for the purpose of monitoring any aspect of the study. The Investigator 
agrees to allow the monitor to inspect the drug storage area, study drug stocks, drug 
accountability records, subject charts and study source documents, and other records relative to 
study conduct. 
17.2. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 2 
years after the last marketing application approval, or if not approved, 2 years after the 
discontinuance of the test article for investigation or according to local regulation. If it becomes 
necessary for Clearside Biomedical, Inc or the Regulatory Authority to review any 
documentation relating to the study, the Investigator must permit access to such records. 
  


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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18. 
PUBLICATION POLICY 
The institutions and Investigators participating in this study shall have no right to publish or 
present the results of this study without the prior written consent of Clearside Biomedical, Inc. 


CLS-TA, triamcinolone acetonide injectable suspension                                                       Clearside Biomedical, Inc  
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19. 
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. 
Dick AD. The treatment of chronic uveitic macular edema. Br J Ophthalmol. 1994;78:1-2. 
Goldstein DA, Pyatetsky D, Tessler HH. Classification, symptoms, and signs of uveitis. Duane’s 
Ophthalmology on DVD-ROM Ed 2009a:chap 32. 
Goldstein DA, Do D, Noronha G et al. Suprachoroidal corticosteroid administration: a novel 
route for local treatment of noninfectious uveitis. Trans Vis Sci Tech. 2016;5(6):14, 
doi:10.1167/tvst.5.6.14. 
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 [Prescribing Information]. Fort Worth, Texas: Alcon Laboratories, Inc., 2007. 
Wood B. An overview of uveitis and its management. US Pharmacist 2011. 


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20. 
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 
Treatment #1 
Follow-Up 
Treatment #2 
Follow-Up 
End of 
Study 
Visit Window 
Day -30 to 0 
Day 0 
Week 4 
Day 28 ± 5 
Week 8 
Day 56 ± 5 
Week 12 
Day 84 ± 5 
Week 16 
Day 112 ± 5 
Week 20 
Day 140 ± 5 
Week 24 
Day 168 ± 5 
Assessments 
 
Pre-dose5 
Post-
dose 
 
 
Pre-dose 
Post-dose 
 
 
 
Informed Consent 
√ 
 
 
 
 
 
 
 
 
 
Assign Subject 
Number 
√ 
 
 
 
 
 
 
 
 
 
Demographics, 
Medical & Ocular 
History 
√ 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
√ 
√ 
 
 
 
 
 
 
 
 
Assess AEs 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Con Med Review 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Resting HR & BP 
√ 
√ 
 
 
 
√ 
 
 
 
√ 
Lab Tests1 
√ 
 
 
 
 
 
 
 
 
√ 
Review of Body 
Systems 
√ 
 
 
 
 
 
 
 
 
√ 
BCVA4 
√ 
√ 
 
√ 
√ 
√ 
 
√ 
√ 
√ 
Slit lamp 
Biomicroscopy2, 4 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
IOP6 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 


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Visit # 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit Type 
Screening 
Treatment #1 
Follow-Up 
Treatment #2 
Follow-Up 
End of 
Study 
Visit Window 
Day -30 to 0 
Day 0 
Week 4 
Day 28 ± 5 
Week 8 
Day 56 ± 5 
Week 12 
Day 84 ± 5 
Week 16 
Day 112 ± 5 
Week 20 
Day 140 ± 5 
Week 24 
Day 168 ± 5 
Assessments 
 
Pre-dose5 
Post-
dose 
 
 
Pre-dose 
Post-dose 
 
 
 
Dilated Indirect 
Ophthalmoscopy4 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
SD-OCT4 
√ 
√ 
 
√ 
√ 
√ 
 
√ 
√ 
√ 
PK Blood Draw  
 
√ 
 
√ 
 
√ 
 
 
 
√ 
Select Study 
Eye/Confirm Study 
Eye 
√ 
 
 
 
 
√ 
 
 
 
 
Fluorescein 
Angiogram4 
√ 
 
 
 
 
 
 
 
 
√ 
Fundus Photos4 
√ 
 
 
 
 
 
 
 
 
√ 
Study Drug 
Treatment3 
 
 
 
 
 
 
 
 
 
1. Central lab test samples should be collected prior to fluorescein angiogram being performed; local labs include a urine or 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 1/2 and at Visit 5 
4. Completed for both eyes at Visit 1 and Visit 8; study eye only for all other visits 
5. If Visit 1 and Visit 2 occur on the same day, the Screening procedures can replace the Pre-dose procedures of Visit 2  
6. IOP collected for both eyes, except post-injection when data are collected for study eye only 
 
 
INJECT3 
INJECT3 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 50 of 58 
CONFIDENTIAL 
APPENDIX B: 
SUMMARY OF CHANGES 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 51 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Throughout protocol 
 
 
Miscellaneous typographical 
and formatting errors as well as 
clarifications for readability 
 
To correct typographical and 
formatting errors and improve 
readability  
None 
Cover 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 
List of Abbreviations 
 
PK – Pharmacokinetics 
To include the term:  
pharmacokinetics (PK) 
None 
7.2.3. Additional Endpoints 
and 13.4.2.3. Additional 
Endpoints 
Percentage change in anterior 
chamber cells and vitreous haze 
Percentage change in anterior 
chamber cells and flare, and 
vitreous haze 
To include percentage change 
in flare as an additional 
endpoint 
None 
Section 8.2.1. Ophthalmic 
Exclusion Criteria #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 
To exclude subjects who have 
had vitreoretinal surgery except 
the allowed surgeries that are 
listed. 
None 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 52 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 8.2.1. Ophthalmic 
Exclusion Criteria #6 
Has had cyclodestructive 
procedures or filtration 
surgeries in the study eye in the 
3 months prior to Visit 2 
Has had cyclodestructive 
procedures, filtration surgeries, 
or laser trabeculoplasty in the 
study eye in the 3 months prior 
to Visit 2 
To exclude subjects who have 
had laser trabeculoplasty 
None 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 53 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 8.2.2. General 
Exclusion Criteria #17, 18, & 
19 
 
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; 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, 
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; decreases and 
termination of dose are 
allowable during the study 
To clarify that decreases or 
termination in doses of systemic 
corticosteroid, 
immunomodulatory and NSAID 
therapy are allowed during the 
study 
None 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 54 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 8.4. Visit Procedure 
Descriptions & Appendix A  
All ocular assessments at Visit 
1 and Visit 8 will be performed 
on both eyes. Data for ocular 
assessments at all other visits 
(Visits 2-7) will be collected on 
the study eye only. 
5. Perform ophthalmic 
assessments on the study eye 
only:  
a. 
ETDRS BCVA 
b. Slit-lamp biomicroscopy  
a. 
IOP (Goldmann 
applanation tonometry) 
c. 
Dilated ophthalmoscopy 
d. SD-OCT and upload 
images to the CRC 
 
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 collected on 
the study eye only. 
5. Perform ophthalmic 
assessments on the study eye 
only, unless otherwise 
designated:  
a. 
ETDRS BCVA 
b. Slit-lamp biomicroscopy  
a. 
IOP (Goldmann 
applanation tonometry, both 
eyes) 
c. 
Dilated ophthalmoscopy 
d. SD-OCT and upload 
images to the CRC 
To collect IOP data on the 
fellow eye at all visits for 
comparison to the study eye 
IOP 
Additional risk common to IOP 
collection procedure  
Section 8.4. Visit Procedure 
Descriptions 
Slit-lamp biomicroscopy 
Slit-lamp biomicroscopy, 
including dilated lens grading 
To be consistent with the Time 
and Events Schedule (Appendix 
A) 
None 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 55 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
9.4.1. Rescue Criteria 
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+ 
A ≥ 1.5-step increase from 
baseline (Day 0) in the level of 
inflammation (eg, anterior 
chamber cells or flare, or 
vitreous haze) or an increase 
from 3+ to 4+ 
To include anterior chamber 
flare as an example of a sign of 
inflammation  
None 
 
 
A decrease of 10 or more 
ETDRS BCVA letters read 
from the best ETDRS BCVA 
data observed during the study, 
along with an increase in other 
signs or complications 
associated with the patient’s 
uveitis 
To ensure that any subjects who 
experience a substantial 
decrease in BCVA, along with 
worsening of uveitis, receive 
appropriate treatment 
This additional criterion will 
ensure that study eyes are never 
undertreated 
13. Statistical Considerations 
 
Pharmacokinetic analyses to 
determine systemic levels of 
triamcinolone acetonide 
following suprachoroidal 
injection will be described in a 
separate detailed plan. 
To include an analysis of the 
pharmacokinetic data collected 
None 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 56 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 2. Synopsis and 
Section 6.2. Secondary 
Objectives 
 
 
 
 
 
The secondary objectives of the 
study are: 
• 
To assess changes to signs 
and complications of uveitis 
• 
To collect use information 
on the suprachoroidal injection 
procedure 
 
The secondary objectives of the 
study are: 
• 
To assess changes to signs 
and complications of uveitis 
• 
To collect use information 
on the suprachoroidal injection 
procedure 
• 
To determine systemic 
exposure to triamcinolone 
acetonide after suprachoroidal 
injection 
To include an objective for 
determining the systemic 
exposure to triamcinolone 
acetonide after suprachoroidal 
injection 
None 
Section 7.1 Overall Study 
Design, Section 7.2.3. 
Additional Endpoints, and 
Section 13.4.2.3. Additional 
Endpoints 
 
• 
Triamcinolone acetonide 
blood concentrations prior to 
the first dose (Visit 2), 4 weeks 
following the first dose (Visit 
3), 12 weeks following the first 
dose (and prior to the second 
dose, Visit 5) and at 12 weeks 
after the second dose (24 
weeks, Visit 8) 
To describe the timing of blood 
draws for collection of 
pharmacokinetic data from all 
subjects 
None 
Section 8.4. Visit Procedure 
Descriptions and Appendix A 
 
Collect a blood sample for PK 
analysis; for Visit 2 and 5; 
blood must be collected PRIOR 
to dosing 
To collect blood samples for 
pharmacokinetic data from all 
subjects 
There is an additional risk 
common to blood draw 
procedures 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 57 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
11.3. Pharmacokinetics 
Assessments 
 
Blood samples for measurement 
of CLS-TA plasma 
concentrations will be collected 
by venipuncture by qualified 
study personnel. A single blood 
sample will be obtained from 
each subject at the following 
time points: Day 0 (Visit 2) pre-
dose, Week 4 (Visit 3) any time 
during visit, Week 12 (Visit 5) 
pre-dose and Week 24 (Visit 8) 
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. 
To describe the collection of 
blood samples for 
pharmacokinetic analysis 
None 
13.3.2. Pharmacokinetics 
Population 
 
Pharmacokinetic population 
will include all subjects who are 
administered at least one dose 
of CLS-TA. Analysis will be 
conducted on all samples 
collected during the study. 
To describe the population to be 
included in pharmacokinetic 
analysis 
None 


CLS1001-302 Clinical Protocol 
 
Clearside Biomedical, Inc. 
27 April 2017 
Page 58 of 58 
CONFIDENTIAL 
Amendment 1 
Section Changed 
 
 
Initial Protocol 1.0 
(Changed From) 
Protocol version 2.0 
(Changed To) 
Reason for Change 
Impact on Subjects 
(Risk/Benefit) 
Section 13.4.3. 
Pharmacokinetics Analysis 
 
Standard population PK 
parameters will be calculated 
from plasma CLS-TA 
concentrations. Samples from 
approximately 35 subjects 
enrolled in the study will be 
available for analysis. Analyses 
will be conducted according to 
the nonlinear mixed-effects 
approach and will provide 
estimates of population 
characteristics (intrinsic and 
extrinsic factors) that describe 
the population distribution of 
the PK parameters. 
To describe the analysis of 
pharmacokinetic data  
None  
Section 12.1.9. Resting Heart 
Rate and Blood Pressure 
Resting heart rate and resting 
blood pressure (systolic and 
diastolic, preferably on the 
same group each time) will be 
measured at every visit after the 
subject has rested for about 5 
minutes. 
Resting heart rate and resting 
blood pressure (systolic and 
diastolic, preferably on the 
same group each time) will be 
measured at Visits 1, 2, 5 and 8 
after the subject has rested for 
about 5 minutes. 
To clarify that resting heart rate 
and resting blood pressure 
should be measured at specified 
visits 
None