Clinical trial NCT02748512
Conditions: Non-Infectious Uveitis
Sponsor: EyePoint Pharmaceuticals, Inc.
Start date: 2016-02-23; Completion date: 2017-08-17
Enrollment: 26 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial is a 12 month, Phase 3, multi-center, randomized, single-masked (subject), controlled study designed to evaluate the utilization and safety of the Mk II inserter and the safety of the FAI insert, in subjects with non-infectious uveitis affecting the posterior segment of the eye.

Detailed description:
This trial is a 12 month, Phase 3, multi-center, randomized, single-masked (subject), controlled study designed to evaluate the utilization and safety of the MK II inserter and the safety of the FAI insert, in subjects with non-infectious uveitis affecting the posterior segment of the eye.

Arms: arm 1: The test article is the Fluocinolone Acetonide Intravitreal (FAI) insert, which contains 0.18 mg FA and delivers FA into the vitreous humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day. The FAI insert will be administered to the study eye as an intravitreal injection through the pars plana. arm 2: The test article is the Fluocinolone Acetonide Intravitreal (FAI) insert, which contains 0.18 mg FA and delivers FA into the vitreous humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day. The FAI insert will be administered to the study eye as an intravitreal injection through the pars plana.
Interventions: intervention 1: FAI Insert administered using the Mk II inserter intervention 2: FAI Insert administered using the Mk I inserter
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
 
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Fluocinolone Acetonide Intravitreal Insert 
 
pSivida Corp. 
Protocol PSV-FAI-006 [Version 3.0; April 4, 2016] 
Confidential 
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PROTOCOL PSV-FAI-006 
 
 
A CONTROLLED, MULTI-CENTER STUDY OF THE UTILIZATION AND 
SAFETY OF THE MK II INSERTER AND THE SAFETY OF THE FAI INSERT 
IN SUBJECTS WITH NON-INFECTIOUS UVEITIS AFFECTING THE 
POSTERIOR SEGMENT OF THE EYE 
 
IND Number 113140 
 
Protocol Release Date: April 4, 2016 
 
Version 3.0 
 
pSivida Corp. 
480 Pleasant Street 
Watertown, MA 02472 USA 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document contains confidential information, which should not be copied, referred to, 
released or published without written approval from pSivida Corp.  Investigators are cautioned 
that the information given in this protocol might be subject to change and revision.  Any 
conclusion regarding efficacy and safety must be considered provisional. 
 


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PROTOCOL APPROVAL PAGE 
 
Protocol Title: A CONTROLLED, MULTI-CENTER STUDY OF THE UTILIZATION AND 
SAFETY OF THE MK II INSERTER AND THE SAFETY OF THE FAI INSERT IN 
SUBJECTS WITH NON-INFECTIOUS UVEITIS AFFECTING THE POSTERIOR SEGMENT 
OF THE EYE 
 
 
Protocol Number: PSV-FAI-006 
 
Version Number: 3.0 
 
Date: April 4, 2016 
 
This protocol has been reviewed and approved by pSivida Corp. 
 
__________________________ 
 
_____________________________ 
Flavio Leonin, MD 
 
 
 
 
     Date 
Senior Manager, Clinical Affairs 
 
__________________________ 
 
_____________________________ 
Gerard E. Riedel, PhD 
 
 
 
 
     Date 
Vice President, Regulatory Affairs 
 
__________________________ 
 
____________________________ 
Paul Ashton, PhD  
 
 
 
 
 
Date 
Chief Executive Officer 
 


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INVESTIGATOR’S AGREEMENT 
 
I have read the attached protocol, concur that it contains all information necessary to conduct the 
study, and agree to follow the study procedures as outlined in this protocol. 
 
I agree to comply with FDA regulations (21 CFR Parts 50, 54, 56 and 312) and ICH guidelines.  
I will not initiate the study until I have obtained written approval by the appropriate Institutional 
Review Board/Ethics Committee and have complied with all financial and administrative 
requirements of the governing body of the clinical institution.  I will obtain written informed 
consent from all study participants prior to performing any screening procedures. 
 
This protocol and related information is subject to the Confidentiality Agreement between 
myself and pSivida Corp. and as such must be held in confidence and not disclosed to any third 
party for a period of seven (7) years from the date of the Confidentiality Agreement, or until said 
information shall become a matter of public knowledge, or until a formal written agreement for 
that purpose has been entered into by the parties. 
 
 
_____________________________  
____________ 
 
Principal Investigator Signature  
 
Date 
 
_____________________________ 
Print Name 


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1. 
PERSONNEL CONTACT INFORMATION 
 
Role in Study 
Name 
Address and Telephone Number 
Sponsor 
pSivida Corp. 
480 Pleasant Street, Suite B300 
Watertown, MA 02472 USA 
Telephone: 1-617-926-5000 
Telefax:  
1-617-926-5050 
Medical Monitor 
PPD 
Steven Gross, MD 
3900 Paramount Parkway 
Morrisville, NC 27540 USA 
Telephone: 1-888-483-7729 
Drug Safety Physician 
PPD 
Steven Gross, MD 
3900 Paramount Parkway 
Morrisville, NC 27540 USA 
Telephone: 1-888-483-7729 
24-Hour Emergency Contact 
PPD Support Center 
Medical Support Center 
Telephone: 1-888-483-7729 
Telefax:  
1-888-529-3580 
Contract Research 
Organization (CRO) 
PPD 
Suzanne Pio 
Project Manager 
3900 Paramount Parkway 
Morrisville, NC 27540 USA 
Telephone: 1-919-428-5231 
 


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2. 
SYNOPSIS 
Name of Sponsor/Company: 
pSivida Corp. 
Name of the Investigational Product: 
Fluocinolone Acetonide Intravitreal (FAI) Insert,  
administered using either the Mk I inserter or the Mk II inserter 
Name of Active Ingredient: 
Fluocinolone Acetonide 
Title of Study: A controlled, multi-center study of the utilization and safety of the Mk II inserter and the 
safety of the FAI insert in subjects with non-infectious uveitis affecting the posterior segment of the eye. 
Studied Period (years): 1 year 
Phase of Development: 3 
Objectives: To evaluate the utilization and safety of the Mk II inserter and to evaluate the safety of the 
FAI insert in subjects with non-infectious uveitis affecting the posterior segment of the eye. 
Primary Objective: 
To assess the utilization and the safety of the Mk II inserter, and the safety of the FAI insert, from the 
day of treatment through 7 days following treatment. 
Secondary Objective: 
To assess the safety of the FAI insert during 12 months following treatment. 
Methodology: A 12 month, multi-center, randomized, controlled, single masked utilization and safety 
study.  
Number of Subjects (planned): One or both eyes in each subject will be designated as the study eye(s); 
the study will enroll approximately 30 eyes (20 Mk II inserter: 10 Mk I inserter) at approximately 3-10 
sites. 
Diagnosis and Main Criteria for Inclusion:  
Diagnosis: 
Unilateral or bilateral non-infectious uveitis affecting the posterior segment of the eye 
Inclusion Criteria: 
1. Male or non-pregnant female at least 18 years of age at time of consent 
2. At least one eye has a history of non-infectious uveitis affecting the posterior segment 
3. Subject has ability to understand and sign the Informed Consent Form 
4. Subject is willing and able to comply with study requirements 
Exclusion Criteria: 
1. Allergy to fluocinolone acetonide or any component of the FAI insert 
2. Ocular malignancy in either eye, including choroidal melanoma 
3. Uveitis with infectious etiology  
4. Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis 
(dendritic keratitis), vaccinia, and varicella  
5. Current mycobacterial infections of the eye or fungal diseases of ocular structures 
6. Subjects who yield, during screening, a confirmed positive test for human immune deficiency 
virus (HIV) or syphilis 
7. Systemic infection within 30 days prior to study Day 1 
8. Peripheral retinal detachment in area of insertion 


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9. Elevated intraocular pressure (IOP) > 21 mmHg, or chronic hypotony < 6 mmHg 
10. Concurrent therapy at screening with IOP-lowering pharmacologic agent in the study eye  
11. Current diagnosis of any form of glaucoma or ocular hypertension in study eye at Screening, 
unless study eye has been previously treated with an incisional surgery procedure that has 
resulted in stable IOP in the normal range (10-21 mmHg) 
12. Known history of clinically significant IOP elevation in response to steroid treatment in either 
eye, unless study eye has been previously treated with an incisional surgery procedure that has 
resulted in stable IOP in the normal range (10-21 mmHg) 
13. Ocular surgery or capsulotomy performed on the study eye within 30 days prior to study Day 1 
14. Intravitreal treatment of study eye: with FAI insert within 36 months prior to study Day 1;with 
Retisert within 30 months prior to study Day 1; with Ozurdex within 90 days prior to study Day 
1; or with Triesence or Trivaris within 30 days prior to study Day 1 
15. Peri-ocular or subtenon steroid treatment of study eye within 30 days prior to study Day 1 
16. Treatment with an investigational drug or device within 30 days prior to study Day 1, except the 
FAI insert within this protocol 
17. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to 
use an acceptable method of contraception as outlined in this protocol from at least 14 days 
prior to study Day 1 until the Month 12 Visit 
18. Any condition which, in the judgment of the Investigator, could make the subject inappropriate 
for entry into this study 
Treatment Assignment: 
All study subjects will receive the FAI insert in the designated study eye(s).  Eyes will be randomized 
(2:1) to receive the FAI insert by administration with either the Mk II inserter or the Mk I inserter, 
respectively.  Randomization will be stratified on the basis of the Investigator administering the FAI 
insert.  
Designation of Study Eye: 
For subjects with unilateral uveitis, the study eye will be the affected eye; for subjects with bilateral 
uveitis, the study eye(s) will be the eye(s) satisfying the inclusion/exclusion criteria.   
Treatment of Study Eye or Non-Study Eye:  
If a subject experiences an adverse event or persistence/worsening of uveitis in a study eye or a non-
study eye, the Investigator should administer appropriate treatment, consistent with the subject’s 
medical need and the Investigator’s standard care.  Subjects who experience an adverse event or 
persistence/worsening of uveitis will continue in the study. 
IOP Reduction Therapy: 
The treatment of elevated IOP must be instituted whenever the IOP is > 30 mmHg, or at a lower IOP 
level based on the Investigator’s discretion and in accordance with the Investigator’s standard of care.  
Treatment may include referral to another ophthalmologist.  If the elevated IOP does not respond to 
pharmacologic treatment, alternative treatment should be considered. 
Investigational Product (Test Article), Dosage and Mode of Administration: 
Test article therapy: Administration of test article on study Day 1, followed by standard care. 
The test article is the Fluocinolone Acetonide Intravitreal (FAI) insert, which contains 0.18 mg FA and 
delivers FA into the vitreous humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day.   The 
FAI insert will be administered to the study eye as an intravitreal injection through the pars plana, using 
either the Mk I inserter or the Mk II inserter. 
Study Procedures: 


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Screening (within 60 days prior to study Day 1): 
Informed consent, eligibility determination, medical history, ophthalmic history including history of 
non-infectious uveitis, demographics, vital signs, clinical labs, ophthalmic examination (includes 
BCVA, IOP, dilated ophthalmoscopy and anterior, posterior and intermediate slit lamp examination), 
visual field, concomitant medications and a pregnancy test, as appropriate. 
Treatment Day (Day 1): 
Eligibility confirmation, including meeting the eligibility criteria, vital signs, ophthalmic exam, 
pregnancy test. Following study number assignment, subjects will receive the FAI insert in the study 
eye.  Additional assessments on Day 1 will include concomitant medications, adverse events (AEs), 
post-insertion safety assessment and assessment of the inserter and its instructions for use. Additionally, 
subjects will be contacted on the next day to identify any complaint or adverse event. 
Follow-up Visits: 
Following Study Day 1, subjects will return on Study Day 7, Day 28, Month 3 and  
Month 12 (follow-up visits).  Evaluations will include: vital signs, ophthalmic exam, concomitant 
medications and AEs.  All subjects / subject eyes enrolled in the study will be followed for 12 months. 
Study Outcomes:  
The primary utilization and safety analyses of the inserters will be conducted at Day 7; safety analyses 
of the FAI insert will be conducted at Day 7 and Month 12. Analyses will be based on individual eyes. 
 
Evaluation of Mk II inserter and Mk I inserter:  
A. Utilization evaluation (based on individual eye): 
Utilization will be evaluated on Day 1, by the investigator who administers the FAI insert 
(Investigator) and by a trained observer (Observer). The Investigator will complete a 
questionnaire addressing specific aspects of the use of the inserter. The Observer will complete 
a questionnaire related to the observed procedure and the instructions for use. Elements to be 
assessed in the evaluations will include: 
a. Inserter operation and ease of use 
b. Instructions for use 
c. Differences between observed procedure and instructions for use 
B. Safety evaluation (based on individual eye): 
Safety will be evaluated over one period: Day 1- Day 7, and will include: 
a. Ocular adverse events, including: procedure-related adverse events, IOP increase/decrease, 
medications/procedures required to treat adverse events, clinically significant ocular 
changes 
 
Evaluation of the FAI insert: 
A. Safety evaluation 
Safety will be evaluated for two periods: through Day 7 and through Month 12.  Descriptive 
statistics will be used to present the results of all safety evaluations and will include: 
a. Ocular adverse events (base on individual eye), including: IOP increase/decrease, 
medications/procedures required to control elevated/low IOP, development or 
worsening of cataract, cataract-related procedures, clinically significant ocular changes 
b. Systemic adverse events 
 
 
 


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Statistical Methods: 
Utilization analyses:  
The primary endpoint of the study is the ease of intravitreal administration and will be based on 
individual eyes. The ease of intravitreal administration for each eye studied will be evaluated by the 
Investigator performing the procedure using either the Mk I or Mk II inserter, and will be reported as: 
• 
Very easy (VE) 
• 
Easy (E) 
• 
Routine (R) 
• 
Difficult (D) 
• 
Very difficult (VD) 
The trial will be deemed a success for the Mk II inserter if the following condition is met:  
The proportion of Mk II procedures scored as satisfactory (scored as either VE, E or R) is not lower 
than the corresponding proportion of satisfactory Mk I procedures. 
 
Sample size – With a sample size of 20 eyes in the Mk II inserter group, the 95%, two-sided confidence 
interval of satisfactory procedures in the Mk II inserter group will be no larger than 27.2% - 72.8% 
when the exact binomial method and a proportion of 10 satisfactory procedures out of 20 Mk II inserter 
procedures are employed. All other satisfactory procedure proportions for the Mk II inserter will result 
in two-sided, 95% confidence bounds that are narrower than that described above.  
 
With a sample size of 10 eyes in the Mk I inserter group, the 95%, a two-sided confidence interval of 
satisfactory procedures in the Mk I inserter group will be no larger than 18.7% - 81.3% when the exact 
binomial method and a proportion of 5 satisfactory procedures out of 10 Mk I inserter procedures are 
employed. All other satisfactory procedures proportions for the Mk I inserter will result in two-sided, 
95% confidence bounds that are narrower than that described above. 
 
The secondary utilization outcomes of the study will be analyzed descriptively, will be based on 
individual eyes and will include: 
• 
Clarity of the instructions for use, as assessed by the Investigator performing the procedure  
• 
Differences between observed procedure and instructions for use, as assessed by an Observer 
 
Safety Analyses:  
Safety will be analyzed descriptively and will include: 
• 
Procedure-related safety (based on individual eye):  
o procedure-related ocular adverse events (including IOP increase/decrease), 
medications/procedures required to treat adverse events, clinically significant ocular 
changes 
• 
FAI insert safety: 
o Ocular adverse events(based on individual eye): IOP increase/decrease, 
medications/procedures required to control elevated/low IOP, development or 
worsening of cataract, cataract-related procedures, clinically significant ocular changes  
o Systemic adverse events 


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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
PROTOCOL APPROVAL PAGE ...................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
1. 
PERSONNEL CONTACT INFORMATION ..............................................................4 
2. 
SYNOPSIS ...................................................................................................................5 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .................9 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................13 
5. 
INTRODUCTION ......................................................................................................14 
5.1. 
Uveitis .........................................................................................................................14 
5.2. 
Summary of Data for Intravitreal Fluocinolone Acetonide ........................................14 
5.3. 
Study Rationale ...........................................................................................................16 
5.4. 
Description of the FAI insert ......................................................................................17 
5.5. 
Description of the Mk I Inserter .................................................................................18 
5.6. 
Description of the Mk II Inserter ................................................................................18 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................19 
6.1. 
Primary Objective .......................................................................................................19 
6.2. 
Secondary Objective ...................................................................................................19 
7. 
INVESTIGATIONAL PLAN .....................................................................................19 
7.1. 
Overall Study Design ..................................................................................................19 
7.2. 
Number of Subjects ....................................................................................................19 
7.3. 
Control (Reference) ....................................................................................................19 
7.4. 
Test Article .................................................................................................................20 
7.5. 
Measures Taken to Minimize Bias .............................................................................20 
7.6. 
Number of Study Sites and Investigators ...................................................................20 
7.7. 
Study Duration ............................................................................................................20 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................23 
8.1. 
Subject Inclusion Criteria ...........................................................................................23 
8.2. 
Subject Exclusion Criteria ..........................................................................................23 
8.3. 
Subject Withdrawal Criteria .......................................................................................24 
9. 
STUDY PROCEDURES ............................................................................................24 


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9.1. 
Subject Informed Consent and Screening ...................................................................24 
9.2. 
Assignment of Subject/Eye Identification Number ....................................................24 
9.3. 
Screen Failures ............................................................................................................25 
9.4. 
Randomization ............................................................................................................25 
9.5. 
Study Schedule ...........................................................................................................25 
9.6. 
Screening, Day -60 to Day 0 .......................................................................................25 
9.7. 
Procedures on Day of Treatment (Day 1) ...................................................................26 
9.8. 
Criteria for FAI Insert Removal .................................................................................29 
9.9. 
Follow-up Visits .........................................................................................................29 
9.10. 
Unscheduled Follow-up Visits ...................................................................................30 
9.11. 
Treatment of Worsening/Recurrence of Uveitis .........................................................30 
9.12. 
Treatment of Elevated IOP .........................................................................................30 
9.13. 
Cataract Removal and Other Elective Ocular Surgery ...............................................30 
9.14. 
Concomitant Medications/Procedures ........................................................................30 
9.15. 
Description of Procedures ...........................................................................................31 
9.16. 
Laboratory Testing ......................................................................................................31 
9.17. 
Protocol Deviations ....................................................................................................31 
9.18. 
Study Termination or Suspension ...............................................................................32 
10. 
INVESTIGATIONAL MATERIALS ........................................................................32 
10.1. 
FAI Insert ....................................................................................................................32 
10.2. 
FAI Insert in Mk I Inserter..........................................................................................32 
10.3. 
FAI Insert in Mk II Inserter ........................................................................................33 
10.4. 
Investigational Product Storage ..................................................................................33 
10.5. 
Supply and Accountability of Investigational Materials ............................................33 
11. 
ASSESSMENT OF SAFETY .....................................................................................34 
11.1. 
Adverse and Serious Adverse Events .........................................................................34 
11.2. 
Adverse Event Assessment .........................................................................................36 
11.3. 
Recording of Adverse Events .....................................................................................37 
11.4. 
Adverse Event Reporting ............................................................................................38 
11.5. 
Expedited Safety Reporting ........................................................................................39 
12. 
REPORTING OF TECHNICAL COMPLAINTS......................................................40 
13. 
ASSESSMENT OF UTILIZATION AND SAFETY.................................................41 
13.1. 
Primary Utilization Endpoint ......................................................................................41 


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13.2. 
Secondary Utilization Endpoints ................................................................................41 
13.3. 
Safety ..........................................................................................................................41 
14. 
DATA ANALYSES ...................................................................................................41 
14.1. 
Sample Size ................................................................................................................41 
14.2. 
Study Populations .......................................................................................................42 
14.3. 
Analyses ......................................................................................................................42 
15. 
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS .........................44 
15.1. 
Quality Control and Quality Assurance ......................................................................44 
15.2. 
Institutional Review Boards / Ethics Committees ......................................................44 
15.3. 
Informed Consent Process ..........................................................................................45 
15.4. 
Source Documentation ................................................................................................45 
15.5. 
Electronic Case Report Forms ....................................................................................46 
15.6. 
Retention of Study Records ........................................................................................46 
15.7. 
Monitoring of the Study..............................................................................................46 
15.8. 
Discontinuation of the Study ......................................................................................47 
15.9. 
Policy for Publications ................................................................................................47 
16. 
ETHICS ......................................................................................................................48 
16.1. 
Ethics Review .............................................................................................................48 
16.2. 
Ethical Conduct of the Study ......................................................................................48 
16.3. 
Written Informed Consent ..........................................................................................48 
17. 
REFERENCES ...........................................................................................................49 
18. 
APPENDIX 1: MEASUREMENT OF BCVA BY ETDRS.......................................50 
18.1. 
Refraction Technique ..................................................................................................52 
18.2. 
4-Meter Test and 1-Meter Test ...................................................................................55 
19. 
APPENDIX 2: METHODS OF CLINICAL EVALUATION ...................................57 
19.1. 
Ophthalmoscopy and Grading of Vitreous Haze ........................................................57 
19.2. 
Anterior Chamber Cells Grading ................................................................................58 
19.3. 
Fundus Examination ...................................................................................................58 
19.4. 
Intraocular Pressure ....................................................................................................58 
19.5. 
Visual Field Measurement ..........................................................................................58 
20. 
APPENDIX 3: QUESTIONNAIRES .........................................................................59 
20.1. 
Mk I Questionnaires ...................................................................................................59 
20.2. 
Mk II Inserter Questionnaires .....................................................................................60 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................13 
Table 2: 
Schedule of Procedures and Assessments ..................................................................22 
 
 
LIST OF FIGURES 
Figure 1: 
FAI Insert ....................................................................................................................17 
Figure 2: 
Study Design ...............................................................................................................21 
 
 


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
AREDS 
Age Related Eye Disease Study 
BCVA 
Best Corrected Visual Acuity 
CFR 
Code of Federal Regulations  
CRF 
Case Report Form 
DME 
Diabetic Macular Edema 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
ExSR 
Expedited Safety Report 
FA 
Fluocinolone Acetonide 
FAI Insert 
Fluocinolone Acetonide Intravitreal Insert 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practices 
hpf 
High power field 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IOP 
Intraocular Pressure 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System 
NDA 
New Drug Application 
Observer 
A staff member in the study site who has been trained in the instructions for use for both 
inserters that are being evaluated in PSV-FAI-006 and who has been trained in completing the 
questionnaires described in Section 20 . 
PVA 
Polyvinyl Alcohol  
SAE 
Serious Adverse Event 
SOC 
System Organ Class 
SOP 
Standard Operational Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
VA 
Visual Acuity 


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5. 
INTRODUCTION 
pSivida Corp. is developing a drug product candidate to treat chronic non-infectious uveitis 
affecting the posterior segment of the eye.  This includes posterior uveitis, intermediate uveitis 
with or without anterior uveitis, and panuveitis. 
pSivida’s product candidate is an intravitreal insert that contains 0.18 mg of Fluocinolone 
Acetonide (FA) and releases FA into the vitreous humor for 36 months, at a nominal rate of 
approximately 0.2 μg FA/day.  In this protocol, this specific drug product candidate is abbreviated as 
“FAI insert” (for Fluocinolone Acetonide Intravitreal insert). 
The clinical trial described in this protocol will be conducted in compliance with the protocol, 
Good Clinical Practices (GCP) as well as all applicable regulatory requirements. 
5.1. 
Uveitis 
Uveitis is defined as inflammation of the uveal tract (iris, ciliary body, choroids) or adjacent 
structures.  The cause of inflammatory reaction of the inner eye can be infectious, traumatic, 
neoplastic or autoimmune.  According to the classification scheme recommended by the 
International Uveitis Study Group, the disease can be classified on the basis of anatomic 
locations: anterior, intermediate, posterior, or panuveitis. 
Uveitis has been estimated to be responsible for approximately 10% of blindness in the United 
States (Suttorp-Schulten 1996).  Generally, posterior uveitis occurs in all age groups and affects 
people of different ethnic origins.  The inflammation that affects the choroid and retina may be a 
primary intra-ocular process or may be an ocular manifestation of systemic disease.  Posterior 
uveitis accounts for most of the loss of vision in eyes with uveitis, due to any one or more of the 
following: cystoid macular edema, choroidal neovascularization, glaucoma, retinal detachment, 
subretinal fibrosis, cataract, or optic disk atrophy. 
A product that is relatively simple to administer and delivers corticosteroid locally for an 
extended period of time may offer significant benefits over existing local and systemic steroid 
therapies. 
5.2. 
Summary of Data for Intravitreal Fluocinolone Acetonide 
The FAI insert to be used in the present study contains the same drug product as Iluvien™, an 
intravitreal fluocinolone acetonide product candidate that is commercially available in the United 
States and Europe for the treatment of diabetic macular edema (DME) [Iluvien prescribing 
information (December 2014)]. 
Additionally, Retisert®, a larger FDA-approved intraocular product that requires surgical 
implantation, also contains the same active ingredient as the FAI insert.  Compared to the FAI 
insert, Retisert delivers approximately 3 times as much FA at rates approximately 3 times faster. 
Retisert has been approved by FDA for the treatment of chronic non-infectious uveitis affecting 
the posterior segment of the eye [Retisert prescribing information (June 2011)]. 


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5.2.1. 
Nonclinical Data 
Details of the nonclinical pharmacology, pharmacokinetics and toxicology data that support the 
clinical use of the FAI insert are presented in the Investigator’s Brochure (IB). 
5.2.2. 
Clinical Data 
There are two products related to the FAI insert (Retisert and Iluvien) for which there is 
considerable previous human experience that is relevant to the clinical evaluation of the FAI 
insert. Additionally, the FAI insert is currently being evaluated in PSV-FAI-001, a phase III 
clinical study in subjects with chronic non-infectious uveitis affecting the posterior segment of 
the eye. 
5.2.2.1. 
Previous Human Experience with Retisert 
Retisert is a sustained release intravitreal product indicated for the treatment of chronic non-
infectious uveitis affecting the posterior segment of the eye [Retisert Prescribing Information 
(June 2011)].  Retisert contains 0.59 mg FA and is surgically inserted into the affected eye 
through a pars plana incision.  Retisert is designed to release FA at a nominal initial rate of 0.6 
μg FA/day decreasing over the first month to a steady state between 0.3-0.4 μg FA/day over 
approximately 30 months.  Because Retisert and the FAI insert both utilize FA as the active 
ingredient, previous human experience with Retisert identifies potential FA-related safety issues 
that are relevant to the clinical studies proposed for the FAI insert.  Details of the clinical 
experience with Retisert are presented in the IB. 
5.2.2.2. 
Previous Human Experience with Iluvien 
Iluvien is an intravitreal product candidate that is administered by injection and is designed to 
provide long term delivery of FA.  Iluvien was invented by pSivida and licensed to Alimera 
Sciences, Inc. for certain ophthalmic indications, excluding uveitis.  Two Iluvien product 
candidates were evaluated in clinical trials; both contained 0.18 mg FA.  A “high dose” Iluvien 
insert was designed to provide a nominal initial release rate of 0.5 μg FA/day slowing to 0.2 μg 
FA/day.  A “low dose” Iluvien insert was designed to provide a constant nominal release rate of 
approximately 0.2 μg FA/day for 36 months.  Both inserts were administered by intravitreal 
injection.  The low dose Iluvien insert has been approved for the treatment of DME, both in 
Europe and in the US [Iluvien prescribing information (December 2014)]. 
The “low dose” Iluvien insert and the FAI insert contain the same drug product. Consequently, 
previous human experience with Iluvien is highly relevant to the clinical studies that evaluate the 
FAI insert.  
Pharmacokinetics 
The pharmacokinetics of FA release from high dose or low dose Iluvien inserts in human 
subjects with DME was assessed using plasma and aqueous humor sampling (Campochiaro 
2013).  This three year study demonstrated that Iluvien inserts release FA continuously within 
the eye for 36 months, and that FA is not measurable in the plasma at any time through 36 
months. 


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FA levels in the aqueous humor of subjects receiving a low dose Iluvien insert (the same drug 
product as the FAI insert) were initially 2 ng/mL (month 1), gradually decreasing to 0.5 ng/mL 
(month 36). 
Systemic FA levels were below the level of detection at all time points.  This observation is 
consistent with the low systemic bioavailability of FA associated with an intraocular route of 
administration and the low intraocular daily dose released by the Iluvien inserts. 
Additional details of the clinical experience with Iluvien are presented in the IB. 
5.2.2.3. 
Previous Human Experience with the FAI insert in uveitis subjects 
The FAI insert is currently being evaluated in two phase 3 trials (PSV-FAI-001 and PSV-FAI-
005)  in subjects with chronic non-infectious uveitis affecting the posterior segment. In both 
studies, subjects are randomized (2:1) to receive either an intravitreal administration of the FAI 
insert or sham injection, respectively. Following treatment, subjects are being followed for three 
years. As of August 1, 2015, PSV-FAI-001 has completed enrollment (N=129) and is following 
subjects, and PSV-FAI-005 is actively enrolling subjects.   
All study data are currently masked to treatment assignment.  As of August 1, 2015, a total of 42 
serious adverse events (SAEs) have been reported from both studies; none of these events was 
considered to be a suspected unexpected serious adverse reaction (SUSAR) that requires 
expedited safety reporting.  Eight of the 42 SAE reports were non-ocular events judged by the 
investigator to be unrelated to study treatment. The remaining 34 SAE reports involved ocular 
events, of which 17 events were reported in the non-study eye and judged by the investigator to 
be unrelated to study treatment. The remaining 17 ocular events were reported in the study eye: 9 
events were assessed by the investigator as not related to study treatment [sterile endophthalmitis 
(two events), uveitis (two events), macular edema (two events), cataract worsening, neovascular 
glaucoma, optic disc swelling], and 8 events were assessed by the investigator as possibly or 
probably related to study treatment [elevated IOP (three events), cataract (two events), hypotony 
(two events), and cystoid macular edema].  Additional information may be found in the IB.  
5.2.3. 
Current benefit-risk profile of the FAI insert 
Because the efficacy and safety of the FAI insert in uveitis subjects have not yet been fully 
evaluated, the current benefit-risk profile is based primarily upon previous human experience 
with Retisert and Iluvien, as well as the (masked) experience to date in PSV-FAI-001. Currently, 
all data are consistent with the expected benefit-risk profile of the FAI insert; subjects are 
expected to experience a significant decrease in the frequency of recurrence of uveitis, and are 
expected to most frequently experience an adverse event associated with cataract or elevated 
IOP.  
5.3. 
Study Rationale 
Based on information reported in the Iluvien phase 3 trials and in PSV-FAI-001, pSivida Corp. 
has modified the inserter used in intravitreal administration of the FAI insert. This modified 
inserter (the Mk II inserter) is expected to be easier to use than the Mk I inserter used in PSV-
FAI-001.  


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PSV-FAI-006 is designed to assess the utilization and safety of the Mk II inserter (compared to 
the Mk I inserter) and to also assess the safety of the FAI insert.  
5.4. 
Description of the FAI insert  
5.4.1. 
Drug Name 
Fluocinolone acetonide is the active ingredient in the FAI insert. 
Fluocinolone acetonide is a member of a class of fluorinated synthetic corticosteroids that 
includes dexamethasone, triamcinolone acetonide and fluocinolone acetonide. 
5.4.2. 
Drug Formulation 
FA is combined with one excipient, polyvinyl alcohol (PVA), to form a FA-PVA core (3.5 mm 
length x 0.34 mm diameter) that is contained within a polyimide tube.  The polyimide tube has a 
permeable PVA membrane at one end and an impermeable silicone adhesive plug on the other 
end.  Figure 1 shows the FAI insert adjacent to a grain of rice. 
Figure 1: 
FAI Insert 
 
5.4.3. 
Route of Administration 
The FAI insert is administered as an intravitreal injection through the pars plana.  For this study, 
the FAI insert will be provided in one of two sterile preloaded inserters: the Mk I inserter (25 
gauge needle) or the Mk II inserter (27 gauge needle). 
5.4.4. 
Dose and Duration  
The FAI insert is designed to release FA for a period of 36 months at a nominal rate of 
approximately 0.2 μg FA/day. 


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5.5. 
Description of the Mk I Inserter 
The Mk I inserter is a sterile, pre-loaded, modified syringe that uses a 25 gauge XX-thin wall 
needle to penetrate the conjunctiva and sclera; the needle is not retracted after intravitreal 
injection has been completed. The Mk I inserter has been used previously in clinical study PSV-
FAI-001. 
5.6. 
Description of the Mk II Inserter 
The Mk II inserter is a sterile, pre-loaded applicator that uses a 27 gauge standard wall needle to 
penetrate the conjunctiva and sclera; the needle is retracted during intravitreal injection. 


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6. 
TRIAL OBJECTIVES AND PURPOSE 
To evaluate the utilization and safety of the Mk II inserter and to evaluate the safety of the FAI 
insert in eyes with non-infectious uveitis affecting the posterior segment of the eye. 
6.1. 
Primary Objective 
To assess the utilization and the safety of the Mk II inserter, and the safety of the FAI insert, 
from the day of treatment through 7 days following treatment. 
6.2. 
Secondary Objective 
To assess the safety of the FAI insert over a period of 12 months following treatment. 
7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This trial is a 12 month, phase 3, multi-center, randomized, single-masked (subject), controlled 
study designed to evaluate the utilization and safety of the Mk II inserter and the safety of the 
FAI insert, in subjects with non-infectious uveitis affecting the posterior segment of the eye. 
As depicted in Figure 2, all subjects will receive the FAI insert on Day 1 of the study, 
administered using either an Mk I inserter or an Mk II inserter.  If both eyes in a subject with 
bilateral uveitis satisfy the study’s inclusion/exclusion criteria, both eyes may be enrolled in the 
study.  In this case, randomization of a subject’s second eye will occur independently and will 
occur no earlier than the study Day 7 visit for the subject’s first study eye.  Subjects will receive 
standard care in the study eye(s) and any non-study eye for 12 months following enrollment, in 
accord with medical need and the Investigator’s standard practice.  Eyes will be assessed 
according to the schedule presented in Table 2.  The primary utilization and safety analyses of 
the inserters will be conducted at Day 7; safety analyses of the FAI insert will be conducted at 
Day 7 and Month 12. 
7.2. 
Number of Subjects 
A total enrollment of approximately 30 eyes is planned for this study.  Enrollment of 
approximately 25 subjects is expected, and will continue until: 
• at least 20 and 10 study eyes each have been treated using the Mk II and Mk I inserters, 
respectively, and  
• at least 10 different investigators each have performed at least one administration 
procedure. 
7.3. 
Control (Reference) 
FAI insert administered with an Mk I inserter. 


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7.4. 
Test Article 
FAI insert administered with an Mk II inserter. 
7.5. 
Measures Taken to Minimize Bias 
At least 10 different investigators will administer the FAI insert, and randomization will be 
stratified by investigator. 
Each time a subject’s eye is enrolled in the study, one investigator will serve as the treating 
investigator (Investigator); another person will serve as the trained observer (Observer).  On 
study Day 1, the Investigator will administer the FAI insert, and the Observer will observe the 
procedure used by the Investigator to administer the FAI insert. The Investigator and the 
Observer will complete questionnaires related to the administration of the FAI insert on Day 1.  
The Investigator (or designee) will perform all subsequent study assessments.  Study personnel 
will not disclose to the subject which inserter was used for intravitreal administration of the FAI 
insert. 
7.6. 
Number of Study Sites and Investigators 
This study will be conducted in at least 3 study sites; intravitreal administrations will be 
performed by at least 10 Investigators.  Each study site must have at least one Investigator and 
one Observer; sites are permitted to have more than one Investigator and/or more than one 
Observer. 
7.7. 
Study Duration 
All subjects will be followed for 12 months after treatment. 


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Figure 2: 
Study Design 
ELIGIBILITY 
SCREENING
INFORMED 
CONSENT
Eligibility Confirmation,
Randomization: 
Treatment with FAI insert 
using Mk I or Mk II inserter
Day 7
Follow-up 
visits 
(D28, M3)
Month
12
PRIMARY 
UTILIZATION AND 
SAFETY ANALYSIS
SAFETY ANALYSIS
Eligibility
Screen 
Failure
Eligibility
Screen 
Success
Day 
1
 


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Table 2: 
Schedule of Procedures and Assessments 
Assessments 
Screening 
Day  
1 
Day  
7 
Day  
28 
Month 
3 
Month 
12 
Timing/Interval 
-60 to  
1 
±3D 
±14D 
±21D 
±28D 
Medical/Ophthalmic History 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
Vital Signsa 
X 
X 
X 
X 
X 
X 
Clinical Labsb  
X 
 
 
 
 
 
Ophthalmic Examinationc 
X 
X 
X 
X 
X 
X 
Visual Field 
X 
 
 
 
 
X 
Pregnancy Testd 
X 
X 
 
 
 
X 
Randomization 
 
X 
 
 
 
 
FAI Insert Administration 
 
X 
 
 
 
 
Post-Administration Assessmente 
 
X 
 
 
 
 
Questionnairef 
 
X 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Adverse Events (AEs) 
 
X 
X 
X 
X 
X 
 
a Includes systolic/diastolic blood pressure and pulse rate after subject is in the sitting position for at least 5 minutes.  Height and weight at screening visit only. 
b HIV and syphilis serology testing. 
c Ophthalmic examination includes: BCVA, IOP [recorded as the mean of three measurements], dilated indirect ophthalmoscopy, and anterior, posterior and 
intermediate slit lamp examinations. 
d Females of child-bearing potential only: urine test conducted only at Screening, Day 1 and Month 12. 
e Includes indirect opththalmoscopy to verify adequate central retinal artery perfusion, absence of any other complications, verification of insert placement;  
IOP [recorded as the mean of three measurements]; follow-up contact with the subject the day following Study Day 1 regarding the subject’s ocular condition, 
and any complaint and/or adverse event. 
f Following each administration of the FAI insert, the Investigator and the Observer will each complete a questionnaire related to the administration procedure. 


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8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Subject Inclusion Criteria 
1. Male or non-pregnant female at least 18 years of age at time of consent 
2. At least one eye has a history of non-infectious uveitis affecting the posterior segment 
3. Subject has ability to understand and sign the Informed Consent Form 
4. Subject is willing and able to comply with study requirements 
8.2. 
Subject Exclusion Criteria 
1. Allergy to fluocinolone acetonide or any component of the FAI insert 
2. Ocular malignancy in either eye, including choroidal melanoma 
3. Uveitis with infectious etiology  
4. Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex 
keratitis (dendritic keratitis), vaccinia, and varicella  
5. Current mycobacterial infections of the eye or fungal diseases of ocular structures 
6. Subjects who yield, during screening, a confirmed positive test for human immune 
deficiency virus (HIV) or syphilis 
7. Systemic infection within 30 days prior to study Day 1 
8. Peripheral retinal detachment in area of insertion 
9. Elevated intraocular pressure (IOP) > 21 mmHg, or chronic hypotony < 6 mmHg 
10. Concurrent therapy at Screening with IOP-lowering pharmacologic agent in the study eye  
11. Current diagnosis of any form of glaucoma or ocular hypertension in study eye at 
Screening, unless study eye has been previously treated with an incisional surgery 
procedure that has resulted in stable IOP in the normal range (10-21 mmHg) 
12. Known history of clinically significant IOP elevation in response to steroid treatment in 
either eye, unless study eye has been previously treated with an incisional surgery 
procedure that has resulted in stable IOP in the normal range (10-21 mmHg) 
13. Ocular surgery or capsulotomy performed on the study eye within 30 days prior to study 
Day 1 
14. Intravitreal treatment of study eye: with FAI insert within 36 months prior to study Day 
1; with Retisert within 30 months prior to study Day 1; with Ozurdex within 90 days 
prior to study Day 1; or with Triesence or Trivaris within 30 days prior to study Day 1 
15. Peri-ocular or subtenon steroid treatment of study eye within 30 days prior to study Day 1 
16. Treatment with an investigational drug or device within 30 days prior to study Day 1, 
except the FAI insert within this protocol 


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17. Pregnant or nursing females; females of childbearing potential who are unwilling or 
unable to use an acceptable method of contraception as outlined in this protocol from at 
least 14 days prior to study Day 1 until the Month 12 Visit 
18. Any condition which, in the judgment of the Investigator, could make the subject 
inappropriate for entry into this study 
8.3. 
Subject Withdrawal Criteria 
Subjects have the right to withdraw from the study at any time, for any reason, without 
jeopardizing their medical care.  The following are examples of criteria for considering 
withdrawal from this study: 
• Withdrawal of subject consent 
• Intercurrent illness (including death) that prevents continuation of regular follow-up 
visits 
All subjects will be followed for safety through the final visit unless the subject is withdrawn 
from the study. 
The Investigator, IRB/EC and pSivida Corp. also have the right to withdraw subjects from the 
study for the following reasons: when continuation may jeopardize the health of the subject, 
protocol violations, AEs or concurrent conditions, administrative or other reasons. 
Subjects who withdraw for any reason from the study following randomization and 
administration of study treatment will not be replaced. 
9. 
STUDY PROCEDURES 
9.1. 
Subject Informed Consent and Screening 
The Investigator will obtain written informed consent from each subject as a condition of 
enrollment in the study.  Informed consent will be obtained after providing the prospective study 
participant with an adequate explanation of the protocol procedures and prior to the subject’s 
participation in the study (including screening procedures). 
The content of the informed consent form (ICF) will conform to FDA regulations as defined in 
21 CFR Part 50, other necessary regulations, and must have current Institutional Review Board 
(IRB)/ Ethics Committee (EC) approval. 
The subject will sign the ICF before any study procedure is initiated.  The subject or guardian 
will sign and date one or two copies of the ICF in the presence of the Investigator or designee, in 
accordance with applicable local requirements.  A signed original copy will be retained with the 
subject records, and either a copy of the signed original or another signed original of the ICF will 
be given to the subject, in accordance with applicable local requirements. 
9.2. 
Assignment of Subject/Eye Identification Number 
Once a subject has provided written informed consent and it has been determined that the subject 
will undergo screening, a subject/eye identification number (ID number) will be assigned by the 


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study site.  The first 3 digits of the ID number will be the assigned site number, followed by a 3-
digit subject number in sequential order (i.e., 201001, etc.), followed by a 1-digit eye 
identification number:  the subject’s first eye (if eligible) to be randomized will be assigned the 
additional digit “1” (e.g., 201001-1); the subject’s second eye (if eligible) to be randomized will 
be assigned the additional digit “2” (e.g., 201001-2). 
The ID number and subject initials are to be recorded on all study documents and will link the 
documents to the subject’s name and medical record.  To maintain confidentiality, the subject’s 
name should not be recorded on any study document other than the ICF. 
9.3. 
Screen Failures 
Study sites will document all screen failures on the Subject Screening/Enrollment Log with the 
reason for the failure to be enrolled.  Subjects who fail to meet inclusion/exclusion criteria during 
the screening period or on study Day 1 may be rescreened. 
9.4. 
Randomization 
Following confirmation of eligibility at Day 1, eyes will be randomly assigned (2:1) to receive 
the FAI insert using either the Mk II inserter or the Mk I inserter, respectively. Randomization 
assignments will be administered through a central Interactive Web Response System (IWRS).  
Randomization will be stratified on the basis of the investigator administering the treatment. 
The randomization schedule will be prepared using a blocked randomization and will be 
generated by an independent statistician.  Only those subjects who have been enrolled in the 
study will have data recorded on the electronic case report forms (eCRF). 
9.5. 
Study Schedule 
See Table 2 for the schedule of visits and assessments.  The screening visit and Day 1 
(administration of study treatment) are to be within a 60-day period.  The windows for the 
follow-up visits are Day 7: +/- 3 days; Day 28: +/- 14 days; Month 3: +/- 21 days;  
Month 12: +/- 28 days.  
9.6. 
Screening, Day -60 to Day 0 
All study data will be collected for all subject eyes, at screening and subsequent study visits. 
After obtaining informed consent, the following assessments will be performed: 
• Demographic information, medical history and ophthalmic history including a history 
of the subject’s uveitis and its management over the previous 12 months 
• Height, weight and vital signs (includes systolic/diastolic blood pressure and pulse 
rate after subject is in the sitting position for at least 5 minutes) 
• HIV and syphilis serology testing 
• Ophthalmic exam, including: BCVA, IOP (recorded as the mean of three 
measurements), dilated indirect ophthalmoscopy and anterior, posterior and 
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• Visual field 
• Collect urine for urine pregnancy test (females of childbearing potential) 
• Concomitant medications 
• Verification that the subject satisfies all inclusion and exclusion criteria.  
Investigators should not continue screening any subject who does not meet the 
screening eligibility requirements 
When screening assessments have been completed, the Investigator should schedule the 
subject to return for the Day 1 visit. 
9.7. 
Procedures on Day of Treatment (Day 1) 
9.7.1. 
Designation of Study Eye and Randomization 
For subjects with unilateral uveitis, the study eye will be the affected eye. 
For subjects with bilateral uveitis, the study eye(s) will be the eye(s) meeting eligibility criteria. 
If both eyes satisfy eligibility criteria, both eyes may be enrolled in the study.  In a subject with 
both eyes eligible for enrollment, randomization of the subject’s second study eye may occur no 
sooner than the study Day 7 visit of that subject’s first study eye, and no later than the last day of 
the study Day 7 visit window of that subject’s first study eye. . 
If the subject’s eye meets the inclusion and exclusion criteria at Screening and Day 1, 
randomization will be performed via the IWRS.  Randomization will be stratified on the basis of 
the investigator administering treatment.   
Treatment assignments will be masked to study subjects. Any non-study eye may receive any 
standard treatment at the discretion of the Investigator. 
9.7.2. 
Data Collection Prior to Intravitreal Administration of FAI Insert  
• Vital signs (blood pressure and pulse rate after subject is in the sitting position for at 
least 5 minutes) 
• Ophthalmic exam , including: BCVA, IOP (recorded as the mean of three 
measurements), dilated indirect ophthalmoscopy and anterior, posterior and 
intermediate slit lamp examinations 
• Urine Pregnancy test 
• Concomitant medications 
• Verification that the subject/study eye satisfies all other inclusion and exclusion 
criteria 


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9.7.3. 
FAI Insert Administration Procedure 
9.7.3.1. 
Administration using the Mk I Inserter 
The intravitreal injection procedure should be carried out under aseptic conditions, which include 
use of sterile gloves, a sterile drape, a sterile caliper, and a sterile eyelid speculum (or 
equivalent).  Adequate anesthesia and a broad-spectrum microbicide should be given prior to the 
injection.  
1. Optimal placement of the FAI insert is inferior to the optic disc and posterior to the 
equator of the eye.  Measure 4 millimeters inferotemporal from the limbus with the aid of 
calipers for point of entry into the sclera.  
2. Using sterile procedure, open the sterile foil pouch containing the Mk I inserter. 
3. Remove the Mk I inserter from the sterile pouch by grasping the barrel of the inserter; do 
not grasp the plunger. 
4. Remove the black plunger stop from the plunger. 
5. Carefully remove the protective cap from the needle and inspect the needle tip to ensure 
it is not bent.  
6. Remove the trombone wire from the distal end of the needle.  Prior to injection, keep the 
inserter tip above the horizontal plane to ensure that the FAI insert does not fall out of the 
inserter.  
7. Gently displace the conjunctiva so that after withdrawing the needle, the conjunctival and 
scleral needle entry sites will not align.  Care should be taken to avoid contact between 
the needle and the lid margin or lashes. 
8. Insert the needle through the conjunctiva and sclera up to the positive stop of the inserter. 
a. If the Investigator is unable to insert the needle through the conjunctiva and sclera, 
please contact the monitor and sponsor immediately. 
9. Depress the plunger at the back of the inserter fully to deliver the FAI insert into the back 
of the eye. 
10. Remove the Mk I inserter from the eye and discard. 
11. Remove the lid speculum and perform indirect ophthalmoscopy to verify adequate central 
retinal artery perfusion, absence of any other complications, and to verify the placement 
of the insert. 
a. If the FAI insert is observed to be misplaced within the eye, please contact the 
monitor and sponsor immediately.  Administration of a second FAI insert within the 
study eye is not permitted in this protocol. 
12. Following the injection, monitor the subject for elevation in intraocular pressure and for 
endophthalmitis.  Determine IOP (recorded as a mean of three measurements) within 10 
to 30 minutes following the injection.  Prescribe a topical antibiotic for the subject to self-
administer 4 times per day for 3-5 days.  Instruct the subject to report without delay any 
symptoms suggestive of endophthalmitis. 


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13. Contact the subject on the next day to determine the subject’s ocular condition and to 
identify any complaint or adverse event. 
9.7.3.2. 
Administration using the Mk II Inserter 
The intravitreal injection procedure should be carried out under aseptic conditions, which include 
use of sterile gloves, a sterile drape, a sterile caliper, and a sterile eyelid speculum (or 
equivalent).  Adequate anesthesia and a broad-spectrum microbicide should be given prior to the 
injection.  
1. Optimal placement of the FAI insert is inferior to the optic disc and posterior to the 
equator of the eye.  Measure 4 millimeters inferotemporal from the limbus with the aid of 
calipers for point of entry into the sclera.  
2. Using sterile procedure, open the sterile foil pouch containing the Mk II inserter in its 
tray. 
3. Remove the sterile tray lid and then remove the Mk II inserter from the sterile tray. 
4. Carefully remove the protective cap from the needle and inspect the needle tip to ensure 
it is not bent.  
5. Visually check through the viewing window of the inserter to confirm that the amber-
colored FAI insert is present. 
6. Gently displace the conjunctiva so that after withdrawing the needle, the conjunctival and 
scleral needle entry sites will not align. Care should be taken to avoid contact between the 
needle and the lid margin or lashes.  
7. Insert the needle through the conjunctiva and sclera up to the hub of the inserter. 
a. If the Investigator is unable to insert the needle through the conjunctiva and sclera, 
please contact the monitor and sponsor immediately. 
8. Press the button on the top of the inserter and confirm that the spring-loaded slide retracts 
with an audible “click”. 
9. Depress the plunger at the back of the inserter fully to deliver the FAI  insert into the 
back of the eye. 
10. Remove the Mk II inserter from the eye and discard. 
11. Remove the lid speculum and perform indirect ophthalmoscopy to verify adequate central 
retinal artery perfusion, absence of any other complications, and to verify the placement 
of the insert. 
a. If the FAI insert is observed to be misplaced within the eye, please contact the 
monitor and sponsor immediately.  Administration of a second FAI insert within the 
study eye is not permitted in this protocol. 
12. Following the injection, monitor the subject for elevation in intraocular pressure and for 
endophthalmitis.  Determine IOP (recorded as a mean of three measurements) within 10 
to 30 minutes following the injection.  Prescribe a topical antibiotic for the subject to self-
administer 4 times per day for 3-5 days.  Instruct the subject to report without delay any 
symptoms suggestive of endophthalmitis. 


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13. Contact the subject on the next day to determine the subject’s ocular condition and to 
identify any complaint or adverse event. 
9.8. 
Criteria for FAI Insert Removal 
Investigators should consider removing the FAI insert if any of the following events occur: 
• Apparent intolerance to insert 
• Endophthalmitis 
• Partial extrusion or exposure of insert 
Based on prior human experience with the FAI insert and with Iluvien, the likelihood that insert 
removal will become necessary is very small. 
9.9. 
Follow-up Visits 
The subject will return to the study site on Day 7, Day 28, Month 3 and Month 12, for a total 
follow-up duration of 12 months.  Subjects may be seen more frequently if medically indicated.  
Table 2 provides descriptions of the procedures to be performed, as indicated, at the scheduled 
visits. 
All assessments will be made for both eyes of each subject.  Data from study eyes, and adverse 
event data from non-study eyes, will be entered in the study’s electronic case report forms 
(eCRFs). 
9.9.1. 
Visit on Day 7 (±3 Days) 
Assessments include: 
• Vital signs (systolic and diastolic blood pressure and pulse rate after subject is in the 
sitting position for at least 5 minutes) 
• Ophthalmic exam: BCVA, IOP (recorded as the mean of three measurements), dilated 
indirect ophthalmoscopy and anterior, posterior and intermediate slit lamp examinations 
• Concomitant medications 
• Adverse events 
9.9.2. 
Visits on Day 28 (±14 Days) and Month 3 (±21 Days) 
Assessments include: 
• Vital signs (systolic and diastolic blood pressure and pulse rate after subject is in the 
sitting position for at least 5 minutes) 
• Ophthalmic exam: BCVA, IOP (recorded as the mean of three measurements), dilated 
indirect ophthalmoscopy and anterior, posterior and intermediate slit lamp examinations 
• Concomitant medications 
• Adverse events 
 


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9.9.3. 
Visit at Month 12 (±28 Days) 
Assessments include:  
• Vital signs (systolic and diastolic blood pressure and pulse rate after subject is in the 
sitting position for at least 5 minutes)  
• Ophthalmic exam: BCVA, IOP (recorded as the mean of three measurements), dilated 
indirect ophthalmoscopy and anterior, posterior and intermediate slit lamp examinations 
• Visual Field 
• Pregnancy test (females of child bearing potential) 
• Concomitant medications 
• Adverse events  
9.10. 
Unscheduled Follow-up Visits 
Additional examinations may be conducted as necessary to ensure the safety and well-being of 
subjects during the study period.  Electronic case report forms (eCRFs) should be completed for 
each unscheduled visit or test that the subject completes. 
9.11. 
Treatment of Worsening/Recurrence of Uveitis 
In the event of a worsening/recurrence of uveitis in either eye, standard therapy will be 
administered, continued and ended in a manner that follows the Investigator’s standard practice.  
Subjects who experience a worsening/recurrence of uveitis will continue in the study. 
9.12. 
Treatment of Elevated IOP  
Pharmacologic treatment (eye drops) of elevated IOP must be instituted whenever IOP is  
> 30 mmHg, and may be instituted at lower IOP levels, at the discretion of the Investigator and 
in accordance with the Investigator’s standard of care.  Treatment may include referral to another 
ophthalmologist.  If IOP does not adequately respond to pharmacologic treatment, alternative 
treatment should be considered.  The Investigator should obtain information on the treatment 
administered by non-study ophthalmologists for inclusion in the study records. 
9.13. 
Cataract Removal and Other Elective Ocular Surgery 
Cataracts occurring in the study subjects during the study should be removed by extra-capsular 
extraction with phacoemulsification. Any other elective ocular surgery should be managed 
according to the Investigator’s standard practice. 
9.14. 
Concomitant Medications/Procedures 
At screening, information on prior and concomitant medications taken within the previous 30 
days (whether continuing or not) will be collected.  All prior and concomitant medications, 
including pre- and post-ocular procedure medications, will be listed in the subject’s medical 
record and on the concomitant medication eCRF page.  At each study visit, each subject should 


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be questioned concerning any new medications or changes in the subject’s current medications 
since the previous study visit. 
For all medications, the generic name, indication, route of administration, frequency, dose, start 
date and stop date (if applicable) will be collected. 
9.15. 
Description of Procedures 
Refer to Table 2 and the appendices (Section 18, Section 19 and Section 20) for details about the 
following procedures. 
9.15.1. 
Slit Lamp Examination 
Slit lamp examination should be performed using the Investigator’s standard procedure.  This 
procedure should be the same for all subjects examined at the site and use the same equipment.  
Observations should be made to indicate the absence or presence of findings for conjunctiva, 
cornea, iris, and anterior and posterior chambers.  All findings are to be documented in the 
source documentation and the appropriate eCRF. 
9.15.2. 
Dilated Indirect Ophthalmoscopy 
Dilated indirect ophthalmoscopy should be performed as part of each ophthalmic examination.  
This procedure should be the same for all subjects examined at the site and use the same 
equipment.  All findings are to be documented in the source documentation and the appropriate 
eCRF. 
9.15.3. 
Visual Acuity 
BCVA will be measured according to the standard procedure developed for ETDRS at 4 meters 
(or at 3 meters if the electronic ETDRS system is employed).  Corrected-distance VA is to be 
reported as number of letters read correctly by the subject.  The details of refraction and VA 
determination procedures are provided in Section 18. 
9.15.4. 
Intraocular Pressure 
IOP will be reported as an average of 3 measurements (preferably using Goldmann applanation 
tonometry), using the Investigator’s standard procedure. 
9.16. 
Laboratory Testing 
Clinical laboratory testing will include HIV and syphilis serology testing, and urine pregnancy 
tests (for females of childbearing potential). 
9.17. 
Protocol Deviations 
The Investigator will not deviate from the requirements from this protocol without prior approval 
from pSivida Corp. unless necessitated by a medical emergency (i.e., those that impact subject 
safety or the validity of the study).  All other significant changes to the protocol will be made by 
pSivida Corp. as a protocol amendment and approved by IRB/EC and the appropriate regulatory 
authority prior to implementation. 


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9.18. 
Study Termination or Suspension 
If the trial is prematurely terminated or suspended for any reason, the Investigator/institution 
should promptly inform the trial subjects, should assure appropriate therapy and follow-up for 
the subjects, and, where required by the applicable regulatory requirement(s), should inform the 
regulatory authority. 
In addition, if the Investigator terminates or suspends a trial without prior agreement of pSivida, 
the Investigator should inform the institution where applicable, and the Investigator/institution 
should promptly inform pSivida and the IRB/EC, and should provide pSivida and the IRB/EC a 
detailed written explanation of the termination or suspension. 
If pSivida terminates or suspends this trial, the Investigator should promptly inform the 
institution where applicable and the Investigator/institution should promptly inform the IRB/EC 
and provide the IRB/EC a detailed written explanation of the termination or suspension. 
If the IRB/EC terminates or suspends its approval/favorable opinion of this trial, the Investigator 
should inform the institution where applicable and the Investigator/institution should promptly 
notify pSivida and provide pSivida with a detailed written explanation of the termination or 
suspension. 
10. 
INVESTIGATIONAL MATERIALS 
10.1. 
FAI Insert 
The FAI insert is an injectable intravitreal sustained-release FA delivery system pre-loaded into 
an injection device.  Each insert contains a drug core of FA as the active ingredient within a 
cylindrical polyimide polymer tube 3.5 mm long with an external diameter of 0.37 mm.  One end 
of the tube is capped with an impermeable polymer (silicone adhesive); the other end is capped 
with a permeable polyvinyl alcohol membrane.  FA release occurs through the permeable end of 
the cylinder.  Each FAI insert contains 0.18 mg FA and delivers FA into the vitreous humor for 
36 months, as demonstrated in a clinical pharmacokinetics study of Iluvien (Campochiaro 2013).  In 
vitro data demonstrate that initial FA release occurs at a rate of approximately 0.2 μg FA/day, 
gradually decreasing over three years to a rate of approximately 0.1 μg FA/day.  The FAI insert 
is designed to be injected through the pars plana into the vitreous. 
10.2. 
FAI Insert in Mk I Inserter 
The FAI insert in the Mk I inserter will be supplied as an individual finished product in primary, 
secondary and tertiary packaging.  The primary packaging is the applicator, which includes a 25 
gauge needle that is attached to the applicator.  The FAI insert is pre-loaded in the applicator.  
The pre-loaded applicator is placed into the secondary packaging, a 2.5” x 15” foil chevron 
pouch and heat-sealed.  Lastly, the foil pouch is placed into a 3.5” x 18” Tyvek chevron pouch.  
The outer chevron pouch will be labeled as investigational drug in accordance with applicable 
regulations.  The assembled units are subsequently sterilized by gamma irradiation, resulting in a 
sterile, single-use product.  Each unit is placed in a SBS shelf carton for shipment. 


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10.3. 
FAI Insert in Mk II Inserter 
The FAI insert in the Mk II inserter will be supplied as an individual finished product in primary, 
secondary and tertiary packaging.  The primary packaging is the applicator, which includes a 27 
gauge needle that is attached to the applicator.  The FAI insert is pre-loaded in the applicator, 
which is then placed in a tray with cover.  This assembly is then placed into the secondary 
packaging, a 6” x 14.3” foil chevron pouch and heat-sealed.  Lastly, the foil pouch is placed into 
a 7.5” x 18” Tyvek chevron pouch.  The outer chevron pouch will be labeled as investigational 
drug in accordance with applicable regulations.  The assembled units are subsequently sterilized 
by gamma irradiation, resulting in a sterile, single-use product.  Each unit is placed in a SBS 
shelf carton for shipment. 
10.4. 
Investigational Product Storage 
Investigational product must be stored at controlled room temperature [15°-25ºC (59-77ºF)] in a 
secured location accessible only to study personnel. 
10.5. 
Supply and Accountability of Investigational Materials 
pSivida Corp. will supply the finished product units (Mk I inserter or Mk II inserter) for this 
study.  A log will be maintained at each study site, showing the subject/eye ID number for which 
each unit is dispensed, the date and who dispensed the unit.  Sufficient finished product units will 
be supplied to each investigative site to allow replacement, as necessary, of any damaged unit. 
The Investigator must maintain records of all shipments of study materials and account for all 
used and unused materials.  All unused and damaged study materials must be returned to pSivida 
Corp. or destroyed on site, with an accounting of all materials supplied, used, and returned, and 
an explanation for any discrepancies. 


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11. 
ASSESSMENT OF SAFETY 
11.1. 
Adverse and Serious Adverse Events 
The following are specific definitions of terms guided by the International Conference on 
Harmonization (ICH) Guidelines for Good Clinical Practice (GCP) and the U.S. Code of Federal 
Regulations (CFR) that apply to this section. 
11.1.1. 
Adverse Event 
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a 
pre-existing medical condition in a patient or clinical investigation subject administered an 
investigational (medicinal) product; an AE does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of investigational product, whether or not considered related to the investigational product. 
11.1.2. 
Serious Adverse Event 
A serious adverse event (SAE) is any untoward medical occurrence that: 
• Results in death  
• Is life-threatening 
(The term “life-threatening” refers to an event in which the subject was at risk of 
death at the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more intense.)  
• Requires in-patient hospitalization or prolongs existing hospitalization  
• Results in persistent or significant disability / incapacity  
• Is a congenital anomaly / birth defect  
• Is a medically important event or reaction 
(Medical and scientific judgment should be exercised in deciding whether other 
situations should be considered serious such as important medical events that might 
not be immediately life-threatening or result in death or hospitalization but might 
jeopardize the patient or might require intervention to prevent one of the other 
outcomes listed in the definition above.)  
The following hospitalizations are not considered SAEs: 
• A visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered “important medical event” or life threatening 
event) 
• Elective surgery, planned prior to signing consent 
• Admissions as per protocol for a planned medical/surgical procedure 


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• Routine health assessment requiring admission for baseline/trending of health status 
(e.g., routine colonoscopy) 
• Medical/surgical admission for purpose other than remedying ill health state and was 
planned prior to entry into the study.  Appropriate documentation is required in these 
cases 
• Admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (e.g., lack of housing, economic 
inadequacy, care-giver respite, family circumstances, administrative) 
11.1.3. 
Protocol-Defined Ocular Adverse Events  
The following ocular events must be reported as AEs during this trial:  
• decrease in visual acuity of ≥15 letters, compared to the most recent previous 
measurement of visual acuity 
• moderate or severe (grade 3 or 4) ocular findings compared to the last ophthalmic 
examination 
• worsening of > 2 steps in anterior chamber cell count or vitreous haze, compared to 
the last ophthalmic examination 
• increase in IOP of > 10 mmHg at two visits at least 1 week apart or an increase in 
IOP to > 25 mmHg 
11.1.4. 
Protocol-Defined Ocular Serious Adverse Events 
The following ocular events must be reported as SAEs during this trial: 
• An AE which causes a decrease in visual acuity of ≥ 30 letters, compared to the most 
recent previous measurement of visual acuity, lasting more than 1 hour 
• An AE which causes a decrease in visual acuity to light perception or worse, lasting 
more than 1 hour 
• An AE which requires surgical intervention (e.g., conventional surgery, vitreous tap 
or biopsy with intravitreal injection of anti-infectives, or laser or retinal cryopexy 
with gas) to prevent permanent loss of sight 
• An AE which is associated with severe intraocular inflammation (i.e., 4.0 anterior 
chamber cell score, 4+ flare or 4+ vitritis) 
• Two consecutive IOP measurements of 30 mmHg or higher taken at least 72 hours 
apart when a subject is already being treated with two glaucoma medications  
• An IOP < 6 mmHg requiring medical intervention 
• An AE which in the opinion of the Investigator requires medical or surgical 
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11.1.5. 
Laboratory Test Abnormalities 
All laboratory test values captured as part of the study should be recorded on the appropriate 
laboratory test results pages of the eCRF. 
In addition, the following laboratory abnormalities should also be captured on the non-serious 
AE CRF page (paper or electronic) or SAE paper CRF page as appropriate: 
• Any laboratory test result that is clinically significant or meets the definition of an 
SAE 
• Any laboratory abnormality that required the subject to receive specific corrective 
therapy 
It is expected that, wherever possible, the clinical rather than the laboratory term would be used 
by the reporting Investigator (e.g., anemia versus low hemoglobin value). 
11.1.5.1. Pregnancy 
Sexually active women of child bearing potential (WOCBP) must be encouraged to use an 
effective method of birth control during the course of the study, in a manner such that risk of 
failure is minimized. 
All WOCBP MUST have a negative urine pregnancy test within 48 hours prior to receiving the 
investigational product.  If the pregnancy test is positive, the subject must not receive the 
investigational product and must not be enrolled in the study. 
Pregnancy testing must also be performed on all WOCBP throughout the study as specified and 
the results of all pregnancy tests (positive or negative) recorded on the eCRF. 
Any female subject of child-bearing potential should be instructed to contact the Investigator 
immediately if the subject suspects that she may be pregnant (e.g., missed or late menstrual 
period) at any time during study participation. NOTE: Pregnancy is not classified as an adverse 
event in this trial. 
11.2. 
Adverse Event Assessment 
11.2.1. 
Relationship to Study Treatment 
The study treatment relationship to each AE should be determined by the Investigator using these 
explanations: 
Unrelated:  Evidence indicates no plausible direct relationship to the study medication, 
device or procedure, or there is a reasonable causal relationship between non-investigational 
product, concurrent disease, or circumstance and the AE. 
Possibly Related:  There is reasonable causal relationship between the investigational 
product, device or procedure and the AE suggests that the association of the event with the 
study medication, device, or procedure is unknown; however, the adverse event is not 
reasonably supported by other conditions. 
Probably Related:  Suggests that a reasonable temporal sequence of the event with 
medication administration, device usage or the index procedure exists and, based upon the 


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Investigator's clinical experience, the association of the event with study medication, device 
or procedure is likely.  
The Investigator will make the determination of relationship to the investigational product for 
each AE (Unrelated, Possibly Related or Probably 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, device or procedure.  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 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 as related. 
If the relationship between the AE/SAE and the investigational product is determined to be 
“possible” or “probable” the event will be considered to be related to the investigational product 
for the purposes of expedited regulatory reporting. 
11.2.2. 
Severity 
AE severity is defined as a qualitative assessment of the degree of intensity of an AE as 
determined by the Investigator or reported to him/her by the subject.  The assessment of severity 
is made irrespective of test article relationship or seriousness of the event and should be 
evaluated according of the following scale: 
Mild:  Awareness of event but easily tolerated.  Usually transient, requiring no special 
treatment, and does not interfere with the subject’s daily activities. 
Moderate:  Discomfort enough to cause some interference with usual activity.  Traditionally 
introduces a low level of inconvenience or concern to the subject and may interfere with 
daily activities, but are usually relieved by simple therapeutic measures. 
Severe:  Causes an interruption of the subject’s usual daily activity and traditionally requires 
systemic drug therapy or other treatment. 
11.3. 
Recording of Adverse Events 
Medical conditions or diseases present before a subject starts study treatment are only considered 
AEs if they worsen after the start of the study treatment. 
Adverse events can be spontaneously reported or elicited at each study visit through open-ended 
questioning, examination or evaluation of a subject.  In order to prevent reporting bias, subjects 
should not be questioned regarding the specific occurrence of one or more AEs. 
The Investigator will record all AEs of enrolled subjects in the appropriate eCRF.  If known, the 
diagnosis of the underlying illness or disorder should be recorded, rather than its individual 
symptoms. 
The following information should be captured for all AEs: onset and end date, severity, 
seriousness, relationship to investigational product, action taken, treatment required and 
outcome.  If treatment for the AE was administered, it should be recorded on the appropriate 
eCRF page. 


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Completion of supplemental eCRF pages may be requested for AEs and/or laboratory 
abnormalities that are reported / identified during the course of the study. 
The Investigator will take or organize all appropriate and necessary therapeutic measures 
required for resolution of the adverse event.  Any medication necessary for the treatment of an 
adverse event must be recorded on the concomitant medication eCRF.  If more than one distinct 
AE occurs, each event should be recorded separately. 
11.4. 
Adverse Event Reporting 
All subjects enrolled in the study will be evaluated for adverse events.  For the individual 
subjects, adverse events will be collected from Day 1 until study completion. 
All AEs will be evaluated from their onset until resolution, stabilization, last day of participation 
in the study of the patient or the last day of the study, whichever is first. 
Adverse events that continue after the subject’s discontinuation or completion of the study will 
be followed until their medical outcomes are determined or until no further change in the 
condition is expected.  The event and outcome will be reported in writing by the Investigator to 
the sponsor.  The Investigator shall supply the sponsor and IRB/EC with any additional 
requested information, notably for reported deaths of subjects. 
11.4.1. 
Reporting of Serious Adverse Event  
All SAEs that occur during the course of the study, including death, must be reported within 24 
hours following the site’s knowledge of the SAE and recorded on the Serious Adverse Event 
eCRF (or use a back-up paper form if the eCRF system is not functioning).  SAEs will also be 
reported to regulatory authorities and IRBs/ECs based on the applicable regulatory requirements.  
Minimal information to be provided includes: 
• Identification of the study 
• Identification of the initial reporter 
• Patient identification number  
• Event term 
• Date of onset of the event 
• Severity criteria of the event 
• Reporting criteria 
• Narrative description of the event 
• Outcome if known 
• Causal relationship to the investigational medication, device and procedure 
• Additional and follow-up information as requested by the medical monitor 
 


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11.4.2. 
Reporting of Pregnancy 
To ensure patient safety, each pregnancy in a female subject must be reported by the 
Investigator, within 24 hours of learning of its occurrence.  The pregnancy will also be reported 
to regulatory authorities and Ethics Committees based on the applicable regulatory requirements.  
The pregnancy should be followed up to determine outcome, including spontaneous or voluntary 
termination, details of the birth, and the presence or absence of any birth defects, congenital 
abnormalities, or maternal or newborn complications. 
Pregnancy should be recorded on the Pregnancy Report Form.  Pregnancy follow-up should be 
recorded on the same form and should include an assessment of the possible relationship to the 
study drug of any pregnancy outcome.  Any SAE experienced during pregnancy must be 
reported as appropriate. 
If any male subject's partner becomes or is found to be pregnant during the male subject's 
treatment with the investigational product, the Investigator must record and submit this 
information on a Pregnancy Report Form as described above. 
11.4.3. 
Other Safety Considerations 
Any significant changes noted during interim/final examinations, procedures or any other 
potential safety assessment should also be recorded on the appropriate AE or SAE eCRF. 
For additional information, Investigators should contact:  
PPD Medical Support Center 
Telephone: 
1-888-483-7729 
Telefax: 
 
1-888-529-3580 
11.5. 
Expedited Safety Reporting 
Adverse drug reactions (ADRs) that are suspected, serious, and unexpected are subject to 
expedited reporting.  Reports which add significant information on specificity or severity of a 
known, already documented serious ADR constitute unexpected events.  For example, an event 
more specific or more severe than described in the protocol under safety assessments would be 
considered "unexpected".  Specific examples would be (a) acute renal failure as a labeled ADR 
with a subsequent new report of interstitial nephritis and (b) hepatitis with a first report of 
fulminant hepatitis. 
The purpose of expedited reporting is to make regulators, investigators, and other appropriate 
people aware of new, important information about serious adverse product reactions.  Therefore, 
such reporting will generally involve events previously unobserved or undocumented.  
Accordingly, expedited reporting will ordinarily be inappropriate for adverse drug reactions that 
are serious but expected. 
In accordance with local regulations, pSivida will notify investigators of all SAEs that are 
suspected (probably or possibly related to the investigational product) and unexpected (i.e., not 
previously described in the Investigator’s Brochure). 
Investigators will be notified about these events through the use of an expedited safety report 
(ExSR). 


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Other important findings which may be reported by the sponsor as an ExSR include: increased 
frequency of a clinically significant expected SAE, an SAE considered associated with study 
procedures that could modify the conduct of the study, lack of efficacy that poses significant 
hazard to study subjects, clinically significant safety finding from a nonclinical (e.g., animal) 
study, important safety recommendations from a study data monitoring committee, or sponsor 
decision to end or temporarily halt a clinical study for safety reasons. 
Upon receiving an ExSR from pSivida, the Investigator must review and retain the ExSR with 
the Investigator’s Brochure.  Where required by local regulations or when there is a central 
IRB/EC for the study, the sponsor will submit the ExSR to the appropriate IRB/EC.  The 
Investigator and IRB/EC will determine if the informed consent requires revision.  The 
Investigator should also comply with the IRB/EC procedures for reporting any other safety 
information. 
12. 
REPORTING OF TECHNICAL COMPLAINTS 
Technical complaints include quality complaints reported in writing, electronically, or orally 
involving the use or attempted use of this product that identify any defects in the product (e.g., 
failure of the inserter to deliver the FAI insert), or dissatisfaction with any other characteristic(s) 
of the product (labeling, packaging, etc.). 
Any technical complaint should be reported within 24 hours by telefax (1-617-926-5050) to 
Marty Nazzaro at pSivida Corp. 
The complaint report should include the following information:  
• Product identification number 
• Investigator name, study site name, and contact number 
• Date the complaint occurred  
• Brief description of the complaint  
• Subject involved? (yes or no); if yes, were any AEs associated with the complaint? 
(yes or no), (If an AE is associated with the complaint, refer to Section 11.) 
 
The unit that is the subject of the complaint should be returned for analysis to: 
 
pSivida Corp.  
Attention: Marty Nazzaro or Gerard Riedel 
480 Pleasant Street, Suite B300 
Watertown, MA 02472 USA 
 
Any complaint about an investigational product must be reported regardless of whether the 
defect or deficiency had any effect on a subject or on study personnel. 


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13. 
ASSESSMENT OF UTILIZATION AND SAFETY 
13.1. 
Primary Utilization Endpoint 
The primary utilization endpoint is defined as the proportion of intravitreal insertion procedures 
that are assessed by the Investigator as satisfactory.  A satisfactory procedure is defined as one 
receiving a score from the Investigator as either Very Easy (VE), Easy (E), or Routine (R), 
according to the following categories: 
• Very Easy (VE) 
• Easy (E) 
• Routine (R) 
• Difficult (D) 
• Very Difficult (VD) 
Please refer to Section 20 for additional information. 
13.2. 
Secondary Utilization Endpoints 
Secondary endpoints include: 
• Clarity of the Instructions for Use, as assessed by the Investigator  
• Differences between observed procedure and instructions for use, as assessed by an 
Observer  
13.3. 
Safety  
Safety endpoints include:  
• Procedure-related adverse events, including: ocular adverse events (including IOP 
increase/decrease), clinically significant ocular changes, medications/procedures 
required to treat adverse events 
• All other adverse events, including: ocular adverse events, IOP increase/decrease,  
medications/procedures required to control elevated/low IOP; development or 
worsening of cataract; cataract-related procedures; clinically significant ocular 
changes, systemic adverse events, medications/procedures required to treat adverse 
events 
14. 
 DATA ANALYSES 
14.1. 
Sample Size 
With a sample size of 20 eyes in the Mk II inserter group, the 95%, two-sided confidence 
interval of the satisfactory procedures proportion will be no larger than 27.2% - 72.8% when the 
exact binomial method and a satisfactory procedures proportion of 10 out of 20 are employed. 


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All other satisfactory procedures proportions for the Mk II inserter will result in two-sided, 95% 
confidence bounds that are narrower than that described above.  
With a sample size of 10 eyes in the Mk II inserter group, the 95%, two-sided confidence 
interval of the satisfactory procedures proportion will be no larger than 18.7% - 81.3% when the 
exact binomial method and a satisfactory procedures proportion of 5 out of 10 are employed. All 
other satisfactory procedures proportions for the Mk I inserter will result in two-sided, 95% 
confidence bounds that are narrower than that described above.  
These confidence bounds, based on eye, are thought to adequately characterize the ease of use 
and other performance characteristics of the two inserters being studied. 
The study will continue until at least 20 Mk II and 10 Mk I inserter attempts have been 
randomized and performed, and at least 10 different investigators have attempted at least one 
administration procedure. 
14.2. 
Study Populations 
14.2.1. 
Intent to Treat (ITT) Population 
The ITT population will include all eyes randomized into the study; analyzed as randomized. 
14.2.2. 
Safety Population 
The safety population will include all eyes randomized into the study; analyzed as treated. 
14.3. 
Analyses 
14.3.1. 
Analyses of Demographic and Baseline Data 
Demographic and baseline characteristics of the ITT population will be presented in tabular 
summaries by treatment group.  Continuous variables will be summarized using the mean, 
standard deviation, median, minimum and maximum; categorical variables will be summarized 
using counts and percentages of eyes in each category. The number of subjects will also be 
presented and have this data described. 
14.3.2. 
Disposition and Exposure 
Tabulation of study completion and premature study termination along with reasons for 
termination will be provided by treatment group.  Duration of study participation and insert 
duration will also be tabulated by treatment group. The number of subjects will also be presented 
and have this data described. 
14.3.3. 
Schedule of Analyses of Utilization and Safety 
Analyses of study data will be performed at the following two time points during the study: 
1. After all eyes have completed the Day 7 visit (or have been discontinued from the study 
prior to this visit).  The primary analysis of utilization will occur at the Day 1 time point. 
2. After all eyes have completed the Month 12 visit (or have been discontinued from the 
study prior to this visit). 


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14.3.4. 
Analyses of Utilization 
Utilization analyses will be performed on the ITT population, at Day 1. All primary and 
secondary utilization endpoints will be analyzed using the ITT population.  Descriptive statistics 
will be used in all utilization analyses. 
14.3.4.1. Primary Utilization Variable and Analysis 
The primary utilization analysis will be performed on the ITT population at Day 1 and will 
present the ease of intravitreal administration reported by Investigators, including the satisfactory  
ratings proportion, for the Mk I inserter and the Mk II inserter groups of eyes employing 
descriptive statistics including 95% confidence intervals using the exact binomial methodology. 
The primary utilization analysis will be conducted after all eyes in the study have completed 
study Day 7 or have discontinued study participation.  
The trial will be deemed a success for the Mk II inserter if the following condition is met:  
The proportion of Mk II procedures scored as satisfactory (i.e., VE, E or R) is not 
numerically lower than the corresponding proportion of Mk I procedures. 
14.3.5. 
Secondary Utilization Analyses 
The following endpoints will be analyzed employing descriptive statistics: 
• Clarity of the instructions for use, as assessed by the Investigator  
• Differences between observed procedure and instructions for use, as assessed by an 
Observer 
14.3.6. 
Analyses of Safety 
Safety analyses will be performed on the safety population at Day 7 and Month 12.  Eyes 
randomized but not receiving treatment will have all safety data listed only but will not be 
included in safety tabulations.  Descriptive statistics will be provided for all adverse events. 
Frequency counts and percentage of eyes within each category will be provided for categorical 
data.  Treatment Emergent Adverse Events (TEAEs; those that occurred on the day or after 
treatment) will be coded to a corresponding preferred term from the MedDRA coding dictionary. 
Ocular safety will be assessed by evaluating ocular TEAEs, visual acuity, IOP, concomitant 
medications, and slit lamp / dilated indirect ophthalmoscopy exams.  Systemic safety will be 
assessed by evaluating all TEAEs, vital signs, concomitant medications and clinical laboratory 
tests by treatment group. 
Adverse events will be summarized by presenting the number and percentage of eyes having at 
least one occurrence of any TEAE during the study, having at least one occurrence of a TEAE 
within each system organ class, and having at least one occurrence of each individual TEAE 
(preferred term) in each treatment group.  Occurrence of TEAEs using MedDRA preferred term, 
System Organ Class (SOC), by severity and relationship will be provided by treatment group.  If 
a patient experiences multiple events that map to a single preferred term, the greatest severity 
and strongest Investigator assessment of relation to the investigational product will be assigned 
to the SOC and preferred term for the appropriate summaries.   


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Treatment-emergent serious adverse events (SAEs) and TEAEs related to FAI insert treatment 
will be provided by preferred term, SOC and severity for each treatment group.  Again, if a 
patient experiences multiple events that map to a single preferred term, the greatest severity and 
strongest Investigator assessment of relation to the investigational product will be assigned to the 
SOC and preferred term for the appropriate summaries.  Adverse events leading to study 
discontinuation and any deaths will be listed. 
Vital signs will be presented using descriptive statistics by visit in each treatment group.  
Concomitant medication will be summarized by presenting the number and percentage of 
subjects receiving each medication by term and treatment after coding with WHO-Drug 
Dictionary terms.  Laboratory assessments will be presented by descriptive statistics. 
15. 
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS 
15.1. 
Quality Control and Quality Assurance 
pSivida Corp. employees and/or their contracted representatives utilize standard operating 
procedures (SOPs) designed to ensure that research procedures and documentation are 
consistently conducted/prepared to the highest quality standards.  These SOPs also require 
compliance with Health Authority regulations and GCP guidance. 
A Quality Assurance audit may be conducted by pSivida Corp. or a designee at any time during 
or after completion of this study.  The Investigator will be given adequate notice if he/she is 
selected for an audit.  The audit will include, but is not limited to, a review of all ICFs, a review 
of eCRFs, associated source documents and medical records, a review of regulatory 
documentation, an assessment of study conduct and protocol compliance, and a review of the 
investigational drug accountability.  At the conclusion of an audit, the auditor will conduct a 
brief meeting with the Investigator to review the audit findings. 
15.2. 
Institutional Review Boards / Ethics Committees 
Prior to the initiation of the study, the protocol, the ICF and the Investigator’s Brochure will be 
submitted to the IRB/EC for approval.  By signing the "Statement of Investigator" form (FDA 
form 1572), the Investigator is assuring that an IRB/EC which complies with the requirements 
set forth in 21 CFR Part 56 will be responsible for the initial and continuing review of the 
proposed clinical study.  A copy of the IRB/EC approval letter for the protocol, and the informed 
consent, as well as the protocol signature page must be submitted to pSivida Corp. or its designee 
prior to release of investigational supplies to the study site.  The approval letter must refer to the 
specific protocol and informed consent form.  The study site must maintain an accurate and 
complete record of all reports, documents and other submissions made to the IRB/EC concerning 
this protocol.  A list of the IRB/EC members, their titles or occupations, and their institutional 
affiliation, or an IRB/EC assurance number must be provided to pSivida Corp. or its designee 
prior to release of study supplies. 
FDA/relevant health authority regulations require that all advertisements for subject recruitment 
be approved by an IRB/EC prior to implementation.  The complete text and format must be 
submitted to pSivida Corp. or designee for approval prior to IRB/EC submission. 


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The Investigator is responsible for notifying the IRB/EC of any SAEs.  A copy of the notification 
must be forwarded to pSivida Corp. or its designee. 
Status reports must be submitted to the IRB/EC at least once a year (or more frequently as 
required by the IRB/EC) and the IRB/EC must be notified of study completion or termination.   
A final report must be provided to the IRB/EC and pSivida Corp. within 6 months of study 
completion or termination.  This report should include: any protocol deviations, the number of 
subjects evaluated, the number of subjects who withdrew or were withdrawn and the reasons for 
withdrawal, any significant AEs and the Investigator's summation of the study. 
15.3. 
Informed Consent Process 
It is the responsibility of the Investigator to inform each subject, prior to the screening 
evaluation, of the purpose of this clinical trial, including possible risks and benefits, and to 
document the informed consent process in the subject’s chart.  Prior to entry into the study or 
initiation of any study-related procedures, the subject must read, sign and date the IRB/EC 
approved ICF.  The person executing the consent must also sign and date the final consent form 
page.  The subject must have a copy of the signed and dated ICF, which will be either a copy of 
the signed original or another signed original, in accordance with applicable local requirements. 
A signed original copy of the ICF must be retained by the study site. 
15.4. 
Source Documentation 
The Investigator must maintain adequate and accurate source documents upon which eCRFs for 
each subject are based.  These documents are to be separate and distinct from eCRFs, except for 
cases in which pSivida Corp. has predetermined that direct data entry into specified pages of the 
subject’s eCRF is appropriate.  The Investigator must allow access to the source documents by 
representatives of pSivida Corp. and regulatory authorities as needed.  These records should 
include detailed notes on: 
• The date the subject entered the study, study protocol number and name of the 
sponsor. 
• The oral and written communication with the subject regarding the study treatment 
(including the risks and benefits of the study).  The date of informed consent must be 
recorded in the source documentation. 
• The subject’s relevant medical history prior to participation in the study and evidence 
that the subject meets study eligibility requirements. 
• The subject’s basic identifying information, such as demographics, that links the 
subject’s source documents with the eCRFs. 
• The dates of all study related subject visits. 
• The results of all diagnostic tests performed, diagnoses made, therapy provided, and 
any other data on the condition of the subject. 
• The subject’s exposure to study treatment and documentation of study treatment 
accountability. 


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• All AEs. 
• The subject’s exposure to any concomitant therapy (including start and stop dates, 
route of administration, and dosage). 
• All relevant observations and data on the condition of the subject throughout the 
study. 
• The date when subject exited the study and a notation as to whether the subject 
completed the study or discontinued study participation, including the reason for 
discontinuation. 
15.5. 
Electronic Case Report Forms 
All study data must be incorporated in the corresponding electronic case report forms.  The 
Investigator will be responsible for recording all data in the eCRFs.   
Data from clinical laboratory reports, etc. will be incorporated into the eCRFs either by direct 
transcription into appropriate eCRF pages or by inclusion of photocopies of these reports with 
printouts of the appropriate eCRF pages and stored in the site’s Study Binder. 
This study will be conducted in compliance with the regulations contained within CFR Part 11, 
electronic records/electronic signatures regulations. 
15.6. 
Retention of Study Records 
GCP regulations require that the Investigator retain all documentation related to this clinical trial 
for a period of 2 years after the approval of the NDA in the U.S. (or Product License outside the 
U.S.) for this drug or 2 years after the withdrawal of the IND.  These records include the protocol 
and copies of all documents submitted to pSivida Corp., or to government authorities, subject 
records (including signed informed consent forms, subject charts, eCRFs, and other source 
documents), IRB/EC approvals and correspondence, records of drug accountability, and all study 
communications, whether written, telephonic, or electronic.  None of the required documents 
will be destroyed or transferred to the control of another party without the written approval of 
pSivida Corp. 
15.7. 
Monitoring of the Study 
pSivida Corp. representatives will contact the Investigator and site staff prior to the start of the 
trial to review the procedures to be followed in conducting the study and recording the findings, 
and to confirm the site’s readiness to conduct the trial. 
Monitors may observe all aspects of subject treatment as frequently as necessary to ensure 
adherence to the protocol.  The Investigator and site staff will cooperate with pSivida Corp. 
representatives and will provide any missing information and grant access to all study 
documentation. 
pSivida Corp. representatives may audit the study periodically to ensure that all records are 
correct and complete.   


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15.8. 
Discontinuation of the Study 
pSivida Corp. reserves the right to discontinue this study for administrative reasons at any time. 
The trial may also be discontinued at a site before study completion, if unexpected adverse 
events occur or if the Investigator does not adhere to the protocol. 
15.9. 
Policy for Publications 
Procedures for the review of publications associated with this trial are described in the clinical 
trial agreement between the Investigator/institution and pSivida Corp. 


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16. 
ETHICS 
16.1. 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB/EC as appropriate.  The Principal Investigator must 
submit written approval from an IRB/EC to pSivida Corp. or its representative before the 
Principal Investigator may initiate this study. 
The Principal Investigator is responsible for informing the IRB/EC of any amendment to the 
protocol in accordance with local requirements.  In addition, the IRB/EC must approve all 
advertising used to recruit subjects for the study.  The protocol must be re-approved by the 
IRB/EC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB/EC with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  pSivida Corp. representatives will provide this information to the Principal 
Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the 
IRB/EC 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 ICH/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, possible risk and benefit of the study.  
Subjects must also be notified that they are free to discontinue participation in 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 ICF must be obtained before conducting any study procedures.  
The subject must have a copy of the signed and dated ICF, which will be either a copy of the 
signed original or another signed original, in accordance with applicable local requirements. 
A signed original copy of the ICF must be retained by the study site. 


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17. 
REFERENCES 
Campochiaro P, Nguyen QD, Hafiz G, Bloom S, Brown DM, Busquets M, Ciulla T, Feiner L, Sabates N, Billman 
K, Kapik B, Green K, Kane FE. Aqueous levels of fluocinolone acetonide after administration of fluocinolone 
acetonide inserts or fluocinolone acetonide implants. Ophthalmology 2013; 120: 583-587. 
Iluvien Prescribing Information (December 2014). 
Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. 
Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop, Am 
J Ophthalmol 2005; 140: 509-16. 
Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory activity in 
intermediate and posterior uveitis. Ophthalmology 1985; 92: 467–71. 
Retisert Prescribing Information (June 2011). 
Suttorp-Schulten MS, Rothova A. The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol 
1996; 80: 844-848. 


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18. 
APPENDIX 1: MEASUREMENT OF BCVA BY ETDRS 
Introduction: 
The procedure for performing the testing of best-corrected distance visual acuity is described in 
this appendix.  Visual acuity is always tested with the subject’s best correction.  Visual acuity 
should be measured without the pupils being dilated and before slit lamp biomicroscopy 
examination or any drops or ointments are used. 
Equipment and Facilities: 
The best-corrected visual acuity (BCVA) of participants will be measured according to the 
standard procedure originally developed for Early Treatment Diabetic Retinopathy Study 
(ETDRS) and adapted for the Age Related Eye Disease Study (AREDS) protocol.  To ensure 
best-corrected visual acuity measurement, manifest refraction must be completed prior to visual 
acuity testing.  The study requires a set of three Lighthouse Distance Visual Acuity Test Charts 
(Lighthouse 2nd edition or Precision Vision “ETDRS”) and a rear illuminated box providing 
standardized chart illumination. For participants who are illiterate or not familiar with the 
English alphabet, BCVA will be determined using the Tumbling E ETDRS charts. 
The charts and the box are manufactured by:    
Lighthouse Low Vision Products 
36-02 Northern Boulevard 
Long Island City, New York 11101 
Telephone: (718) 937-6959 
Or 
Precision Vision 
745 North Harvard Ave. 
Villa Park, IL 60181 
Telephone: (630) 833-1454 
Visual acuity testing in this study is required at a distance of 4 meters and for participants with 
reduced vision, at 1 meter.  The 4-meter distance should be clearly and permanently marked.  
The 1-meter distance is to be measured with a 1-meter stick with the participant seated in a chair. 
Visual acuity charts: 
Chart R is used for refraction.  Chart 1 is used for testing visual acuity of the right eye.  Chart 2 
is used to test visual acuity of the left eye.  The features of the charts are 5 high-contrast Sloan 
letters in each of the 14 lines.  Lines are of equal difficulty, and follow a geometric progression 
of letter size from line to line.  Further, charts 1, 2 and R have different letter sequences to avoid 
memorization by the participants.  Participants should be prevented from seeing Chart 1 and 
Chart 2 until refraction has been completed, and the visual acuity testing is to begin. 


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Rear illumination box: 
The dimensions of the light box are 24 ¾ inches by 25 ¾ inches by 7 inches.  The box can be 
mounted on a wall or on a 5-pronged wheel-based stand, manufactured by Lighthouse Low 
Vision Products.  Each prong is about 14 inches long, and 2 of the 5 wheels are lockable.  When 
the box is mounted on the stand, the height can be varied.  The charts are stored in the back of 
the light box. 
Room lights should be off during refraction and visual acuity testing.  The box itself provides 
sufficient illumination for the examiner to record the test results.  Additional light can have an 
adverse effect.  If absolutely necessary, a small desk type light may remain on; however, the 
light beam should be directed away from the light box and the subject.  The light box is equipped 
with two General Electric Cool Daylight 20-watt fluorescent tubes and ballast.  As the 
illumination of fluorescent tubes diminishes by 5% during the first 100 hours and by another 5% 
during the next 2,000 hours, the following should be done: 
• New tubes should be kept on for about four days (approx. 96 hours) to “warm-up”, time 
“on” does not have to be continuous. 
• All tubes should be replaced once a year. 
• It is advisable to periodically check the fluorescent tubes for proper function. 
Replacement tubes can be purchased at a local hardware store or Lighthouse Low Vision 
Product. 
Visual acuity lanes (4-meter and 1-meter): 
A distance of exactly 4 meters (13 feet, 1 ½ inches, or 157 ½ inches) is required between the 
participant’s eye and the visual acuity chart for the 4-meter test.  A distance of exactly 1 meter 
(39 ⅜ inches) is required for the 1-meter test. 
The room for visual acuity testing must have enough room for the 4-meter lane as well as the 
light box and the participant.  
Mounting the light box: 
The light box should be mounted at such a height that the top of the third row of letters (0.8 Log 
MAR) is 49 ± 2 inches from the floor. 
Wall mounting:  In addition to the 4-meter lane, 7 inches must be allowed for the depth of the 
box, plus space for the participant to sit or stand. 
Stand mounted box:  In addition to the 4-meter lane, 13 inches must be allowed for two of the 
stand’s casters to touch the rear wall or a line marked on the floor if there is no wall, plus space 
for the participant to sit or stand. 
Marking the distance (4 meters): 
If the chair and visual acuity box are permanently affixed, distance measurements need only to 
be made once.  If the box is mounted on the wall, but the participant’s chair is not permanently 
affixed, the 4-meter distance from the participant’s eye to the chart must be clearly and 
permanently marked. 


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If the box is mounted on a movable stand, the 4-meter distance must be clearly and permanently 
marked on the floor.  The location of the box must also be clearly and permanently marked on 
the floor and placement should be checked between participants.  When the stand touches the 
rear wall, two of the casters should touch the wall. 
Marking the distance (1 meter): 
The 1-meter distance is measured from the eye of the participant, with his or her back firmly 
against the back of the chair, to the second or fourth letter of the third line of the eye chart.  A 1-
meter measuring stick should be used. 
18.1. 
Refraction Technique 
All visual acuity will be measured with the participant’s best-corrected vision.  No pinhole 
testing will be done.  It is strongly advised that the refraction be done with the 4-meter distance.  
If for practical reasons, the 10-foot distance must be used, the same refraction procedure should 
be performed as for the 4-meter distance (visual acuity scores will be adjusted accordingly).  The 
right eye should be refracted first, then the left eye. 
If the participant wears contact lenses and has glasses, the participant should be reminded that 
the participant would be unable to wear contact lenses for the duration of the BCVA procedure.  
At the screening visit, if the participant is wearing contact lenses, the lenses should be removed 
and refraction and visual acuity should not be determined for at least half an hour for soft lenses 
and one hour for hard lenses. 
18.1.1. 
Approximate Refraction 
If results of a previous subjective refraction are available, they can be used as the beginning of 
approximate refraction.  Otherwise the following procedures should be used: 
• If the participant’s uncorrected visual acuity is 20/200 or better, and the participant does 
not have glasses for distance vision, the beginning approximate refraction is no lens 
correction (plano). 
• If the participant’s uncorrected visual acuity is less than 20/200 in either eye with the 
participant’s present distance glasses, or without correction if the subject does not have 
glasses, retinoscopy should be performed by an examiner proficient in this procedure.  
An acceptable alternative is to conduct an arbitrary trial with any lens to bring visual 
acuity to 20/200 or better.  The lens corrections obtained are used as the beginning 
approximate refraction for determining best-corrected acuity. 
• If the participant’s visual acuity is 20/200 or better with participant’s current distance 
glasses, the glasses are measured with a lensometer, and these measurements are to be 
used as the beginning approximate refraction. 
18.1.2. 
Subjective Refraction 
The trial frame is placed and adjusted on the subject’s face so that the lens cells are parallel to 
the anterior plane of the orbits and centered in front of the pupil.  The left eye is occluded and the 
beginning approximate refraction, as previously determined, is placed in the right lens cells with 
the cylindrical correction anterior. 


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• It is permissible to use a Phoropter for subjective refraction.  However, for testing visual 
acuity, the lenses from the last Phoropter refraction must be placed in trial frames and the 
final sphere must be rechecked as described in “Refining Final Spherical Power” (Section 
18.1.5). 
• If the participant’s visual acuity is too poor to see the largest letters on the chart at the 4-
meter distance, refer to “Refraction for Participants with Poor Visual Acuity” (Section 
18.1.7). 
18.1.3. 
Determination of Spherical Refraction 
With the beginning refraction in place, the visual acuity of the right eye is assessed and noted.  A 
+0.50 sphere is then held in front of the right eye and the participant is asked if the vision is  
“better”, “worse”, or “no different”, while looking at the smallest line the participant can read 
well. 
• If vision is improved, or there is no change, the sphere in the trial frame is replaced with 
one that is one-half diopter more plus.  The +0.50 sphere is held in front of the study eye 
and participant is asked again if the vision is “better”, “worse” or “no different”.  This 
process is repeated until the participant says that the additional +0.50 sphere makes the 
vision worse.  The lens should be left in place for 10 to 15 seconds in an attempt to 
evaluate whether the participant is accommodating.  If the vision clears during this 
period, the +0.50 sphere may be added again.  Successive attempts to evaluate additional 
plus lenses should be made with the 10 to 15 second delay.  If there is no evidence of 
unrelaxed accommodation, the delay period is no longer necessary. 
• Whenever the participant says that the vision is worse and no longer improves, the +0.50 
sphere is removed from the front of the trial frame.  By this process, the highest plus 
sphere that is tolerated without blurring the participant’s vision has been determined. 
• Next, a –0.37 sphere is held in front of the trial frame and the participant is asked if 
vision is “better”, “worse” or “no different”.  If vision is improved, the participant is 
requested to read the chart, and if at least one more letter is read on the smallest line 
noted previously or the next smaller line, the sphere in the trial is replaced by a sphere 
that is 0.25 diopter less.  In certain situations, the participant is unable to read more 
letters, but is convinced that the vision is actually improved.  If the examiner believes that 
this is the case, the additional minus sphere lens can be added.  At any stage in the 
examination, no more than 0.25 diopters of minus sphere should be added without an 
increase in the number of letters read correctly.  The additional minus sphere lens should 
not be added if the participant reads fewer letters but states that visual acuity is better. 
• If the participant says the vision is “no different” or “worse”, no minus power should be 
added and the determination of the sphere correction is complete. 
18.1.4. 
Determination of Cylindrical Refraction 
• Cylinder Axis Determination 
 
If the beginning approximate refraction contains a cylinder correction, changes in 
cylindrical axis are tested by adding a 0.25, 0.37 or 0.50 diopter cross-cylinder axis, first 


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with the positive axis at 45 degrees to one side of the cylinder axis and then with the 
positive axis 45 degrees to the opposite side of the cylinder axis.  Since neither position 
may produce a clear image, the participant is encouraged to select the position producing 
less blur while focusing on a single round letter on the line above the lowest line on the 
chart the participant can read when the cross cylinder is not held up before the trial frame.  
If the participant cannot choose between the two positions of the cross-cylinder at the 
beginning of this test, the axis is moved 5 to 15 degrees, first in one direction and then in 
the other, with the cross-cylinder being checked in each position to confirm that the 
original axis was correct.  If the participant prefers one position of the cross-cylinder to 
the other and the cylinder in the trial frame is plus, the axis of the cylinder is moved 5 to 
15 degrees toward the positive axis of the cross-cylinder when it is in the position found 
to be less blurry by the participant. 
 
When the power of the cylinder is low or the participant’s discrimination is poor, larger 
shifts will produce more clear-cut answers.  The cross-cylinder is held again with the 
positive axis 45 degrees, first to one side, then to the opposite of the new cylinder axis, to 
determine which position produces less blur. 
• Cylinder Power Determination 
 
Change in cylinder power is tested by adding the cross-cylinder, first with the positive 
axis and then with the negative axis coincident with the cylinder axis.  The participant is 
requested to focus on a round letter on the lowest line of the chart the participant can 
read.  If the participant prefers the positive axis coincident with the cylinder axis, the 
power of the correcting plus cylinder is increased by a +0.25 diopter.  If the participant 
prefers the negative axis coincident with the cylinder axis, the total power of the 
correcting plus cylinder is reduced by 0.25 diopter.  This process is repeated until the 
participant finds neither position is better than the other.  As the plus cylinder is added, 
the examiner should notice that the spherical equivalent of the refraction is changed.  
More minus sphere may be needed as the plus cylinder is added.  For every 0.50 diopter 
of cylinder power added, the sphere changes by –0.25 diopter.  If the beginning refraction 
is a pure sphere, the presence of an astigmatism is tested by arbitrarily placing a +0.25 
cylinder at 180 degrees in the trial frame, after having determined the highest-plus or 
least-minus sphere producing minimal blurring of vision, as described previously in 
Section 18.1.3.  The refraction is continued by using the cross-cylinder to test for the axis 
and the cylinder power using the cross-cylinder technique outlined above. 
18.1.5. 
Refining Final Spherical Power 
When neither the power nor the axis of the cylinder can be improved, the power of the sphere is 
refined by testing with +0.25 sphere and –0.37 sphere and changing the spherical power as 
indicated previously in Section 18.1.3.  If the sphere is changed at this point, the cylinder should 
be rechecked.  
This process is repeated until no further significant lens changes are made. 


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18.1.6. 
Summary of Refraction Protocol 
At the end of the refraction, the sphere is checked and the participant neither tolerates increased 
plus nor improves with increased minus spheres.  Then the axis is checked and no change in this 
is indicated.  At this point, the refraction is considered complete. 
If, at the time of the refraction, the subject’s pupil is dilated it must be noted on the visual acuity 
worksheet. 
18.1.7. 
Refraction for Participants with Poor Visual Acuity 
If it is not possible to perform a subjective refraction at 10 feet or 4 meters because visual acuity 
is too poor for the participant to see the largest letters on the chart at this distance, the refraction 
should be attempted at 1 meter.  The procedure at 1 meter is the same as the procedure for 4 
meters.  However, the increments of lens power can be larger.  For the sphere, ± 1.00 diopter or 
more can be tested.  Cylindrical refraction can be assessed with the 0.5 or 1.00 diopter. If 
subjective refraction can be performed successfully at 1-meter, a +0.75 sphere should be 
subtracted from the 1-meter refraction to make the correction appropriate for the 4-meter 
distance. 
18.2. 
4-Meter Test and 1-Meter Test 
18.2.1. 
4-MeterTest: 
The distance from the participant’s eyes to the visual acuity chart must be exactly 4 meters (13 
feet and 1.5 inches). 
• The examiner should insure that the participant is sitting or standing comfortably, and 
that the head does not move back and forth during the test.  The participant’s eyes should 
always remain at the 4-meter distance. 
• The participant should be told the chart contains only letters and no numbers.  Should the 
participant forget these instructions and read a number, the examiner will remind the 
participant that the chart contains letters only and request a letter response in lieu of a 
number. 
• The examiner should ask the participant to read slowly. 
• The examiner should never point to the chart or to specific letters on the chart or read any 
letters during the test. 
• Each letter is scored as correct or wrong.  If the participant changes a response aloud 
before he or she has read the next letter aloud, that response is acceptable.  If the 
participant changes the response after the next letter has been read aloud, that next 
response is unacceptable. 
• Participants should be encouraged to guess.  The reasons are: a) it will help maximize the 
participant’s effort and help ensure uniformity among different clinical sites; b) it will 
help prevent bias if the participant has become unmasked. 
• The participant should be requested to give only one letter as a response. 


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• The participant can turn or shake his or her head if this improves visual acuity while the 
fellow eye remains securely covered. 
18.2.2. 
1-Meter Test: 
Eyes reading less than 20 letters correctly at 4 meters will be tested at 1 meter. 
• Before testing at 1-meter, a +0.75 sphere should be added to the 4-meter correction 
already in the trial frame to compensate for the closer distance. 
• The participant will be asked to read only the first six lines at 1 meter, making 30 the 
highest possible score at this distance. 
• After the test of the right eye with chart 1 is completed, repeat the test for the left eye 
with chart 2, starting at 4 meters.  When testing of the left eye is completed, chart 1 and 2 
should be removed from view and chart R mounted.  At this time refraction used for the 
right and left eyes should be introduced to the trial frame or the Phoropter and binocular 
visual acuity should be assessed using the same protocol as noted above. 
18.2.3. 
Scoring Best Corrected Visual Acuity: 
The examiner will record each letter correctly identified by circling the corresponding letter on 
the Visual Acuity Worksheet.  Letters read incorrectly or for which there was no guess will be 
marked with a slash mark through the corresponding letter. 
• Each letter read correctly is scored as one point. 
• The score of each line (which is zero if no letter was read) is recorded on the Visual 
Acuity Worksheet. 
• If testing at 1 meter is not required, 30 points are automatically added to the total number 
of letters read correctly. 
• If testing at 1 meter is done the score is determined by adding the total number of letters 
read at 4 meters to the total number read correctly at 1 meter. 
The total combined score (sum of the 4-meter and 1-meter test scores) is recorded on the Visual 
Acuity Worksheet.  Snellen-equivalent is calculated from the lowest line read with ≤ 2 letter 
errors (≥ 3 letters correct). 
18.2.4. 
Visual Acuity Grading Scale 
Measurement of best corrected visual acuity is measured with logarithmic visual acuity charts at 
a distance of 4 meters, and at 1 meter if visual acuity is worse than 20/100.  Participants are 
encouraged to make a maximum effort to read as many lines as possible. 


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19. 
APPENDIX 2: METHODS OF CLINICAL EVALUATION 
19.1. 
Ophthalmoscopy and Grading of Vitreous Haze 
Ophthalmoscopy will be performed to assess retinal and choroid appearances and vitreous haze 
(Nussenblatt 1985).  Indirect ophthalmoscopy will be performed for each eye with pupil dilation 
and should be completed after IOP measurement has been completed. 
Vitreous Haze Grading Scale 
The following scale will be used to define the extent of vitreous haze: 
Grade 
Description 
Absent 
Clear view of optic disc, retinal vessels and nerve fiber layer 
Trace 
Slight blurring of optic disc margin and of normal striations and 
reflex of nerve fiber layer 
1+ 
Mild blurring of optic disc margin and slight loss of retinal vessel 
definition 
2+ 
Moderate blurring of optic disc margin and loss of retinal vessel 
definition 
3+ 
Optic nerve head and large vessels visible but borders quite (very) 
blurry 
4+ 
Optic nerve head obscured 


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19.2. 
Anterior Chamber Cells Grading 
Anterior Chamber Cells Grading Scale  
Anterior chamber cells will be measured using a Haag/Streit or similar slit lamp at high 
magnification (1.6 X) 1-mm beam.  The same instrument, and when possible the same examiner 
should be used on each patient throughout the study.  Assessment will be made using the 
following scale (Jabs 2005). 
 
Field size: 1 mm by 1 mm slit beam 
Grade 
Description 
0 
<1 cell / high power field (hpf) 
0.5+ 
1-5 cells/hpf 
1+ 
6-15 cells/hpf 
2+ 
16-25 cells/hpf 
3+ 
26-50 cells/hpf 
4+ 
>50 cells/hpf 
 
19.3. 
Fundus Examination 
The fundus assessments should be conducted using indirect ophthalmoscopy with a 20 diopter, 
28 diopter or 30 diopter condensing lens.  In order to minimize variability, every effort should be 
made to have a single examiner conduct all assessments on a given subject. 
19.4. 
Intraocular Pressure 
Intraocular pressure will be assessed, preferably by Goldmann applanation tonometry, and 
should be measured only after slit lamp examination has been completed.  The mean of 3 
measurements per eye will be recorded as the IOP.  All reasonable efforts should be made to 
have the same examiner obtain all IOP measurements for a given subject, using the same 
instrument.  Measurement should be performed before dilated ophthalmoscopy. 
19.5. 
Visual Field Measurement 
The 24-2 program will be used. The same program should be used for all measurements for a 
given subject, using the same instrument.  Measurement should be performed before 
ophthalmoscopy. 
 


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20. 
APPENDIX 3: QUESTIONNAIRES 
20.1. 
Mk I Questionnaires  
20.1.1. 
Investigator Questionnaire 
 
1. Were the instructions for the use of the Mk I inserter clear and understandable? 
If not, please explain. 
 
2. The ease of intravitreal administration using the Mk I inserter was:  
a. Very easy 
b. Easy 
c. Routine 
d. Difficult 
e. Very difficult 
 
3. Were you able to deliver the insert into the vitreous using the Mk I inserter?  
If not, please explain. 
 
20.1.2. 
Observer Questionnaire 
 
1. Was sterile technique used to remove the Mk I inserter from the pouch? 
If not, please explain. 
 
2. Did the Investigator follow the Mk I inserter instructions for use? 
If not, please explain. 
 
3. Did you observe any difficulty experienced by the Investigator during use of the  
Mk I inserter?  
If yes, please explain. 
 
4. Do you have any other observations to report? 
If yes, please explain. 


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20.2. 
Mk II Inserter Questionnaires 
20.2.1. 
Investigator Questionnaire 
 
1. Were the instructions for the use of the Mk II inserter clear and understandable? 
If not, please explain. 
 
2. The ease of intravitreal administration using the Mk II inserter was:  
a. Very easy 
b. Easy 
c. Routine 
d. Difficult 
e. Very difficult 
 
3. Were you able to deliver the insert into the vitreous using the Mk II inserter?  
If not, please explain. 
 
 
20.2.2. 
Observer Questionnaire 
 
1. Was sterile technique used to remove the Mk II inserter from the tray? 
If not, please explain. 
 
2. Did the Investigator follow the Mk II inserter instructions for use? 
If not, please explain. 
 
3. Did you observe any difficulty experienced by the Investigator during use of the  
Mk II inserter?  
If yes, please explain. 
 
4. Do you have any other observations to report? 
If yes, please explain. 
 

SAP_001.pdf: 
 
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Confidential 
 
 
 
 
 
 
 
 
 
pSivida Corp. 
 
PSV-FAI-006 
 
A Controlled, Multi-center Study of the Utilization and Safety of 
the MK II Inserter and the Safety of the FAI Insert in Subjects 
with Non-infectious Uveitis Affecting the Posterior Segment of 
the Eye 
 
12 APRIL 2016 
 
Statistical Analysis Plan 
 
Version 1.0 
 
Prepared by: 
 
PPD 
3900 Paramount Parkway 
Morrisville, NC 27560 
 
 
 


pSivida Corp. 
 
                       Statistical Analysis Plan 
PSV-FAI-006 
 
Date Issued: 12APR2016 
 
  
 
 
 
II
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... IV 
1. 
INTRODUCTION ............................................................................................................ 1 
2. 
OBJECTIVES ................................................................................................................... 2 
2.1. PRIMARY OBJECTIVE .......................................................................................................... 2 
2.2. SECONDARY OBJECTIVE ..................................................................................................... 2 
3. 
INVESTIGATIONAL PLAN .......................................................................................... 2 
3.1. OVERALL STUDY DESIGN AND PLAN .................................................................................. 2 
3.2. STUDY ENDPOINTS ............................................................................................................. 3 
4. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................... 4 
4.1. SAMPLE SIZE ...................................................................................................................... 6 
4.2. DESIGNATION OF STUDY EYE(S) AND RANDOMIZATION ..................................................... 6 
4.3. MASKING OF STUDY SUBJECTS ........................................................................................... 6 
4.4. ANALYSIS POPULATION ...................................................................................................... 6 
4.4.1. 
Intent-to-Treat (ITT) Population................................................................................. 6 
4.4.2. 
Safety Population ........................................................................................................ 7 
5. 
SUBJECT DISPOSITION ............................................................................................... 7 
5.1. DISPOSITION ....................................................................................................................... 7 
5.2. PROTOCOL DEVIATIONS ..................................................................................................... 7 
6. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................... 7 
6.1. DEMOGRAPHICS .................................................................................................................. 7 
6.2. BASELINE OCULAR CHARACTERISTICS ............................................................................... 8 
6.3. MEDICAL HISTORY ............................................................................................................. 9 
6.3.1. 
Non-ocular Medical History ....................................................................................... 9 
6.3.2. 
Ocular Medical History .............................................................................................. 9 
6.4. INCLUSION AND EXCLUSION CRITERIA ............................................................................... 9 
7. 
TREATMENTS AND MEDICATIONS ......................................................................... 9 
7.1. PRIOR AND CONCOMITANT MEDICATIONS .......................................................................... 9 
7.1.1 
Prior Medications ..................................................................................................... 10 
7.1.2 
Concomitant Medications ......................................................................................... 10 
7.1.3 
IOP Lowering Medications ................................................................................ 11 
7.2. OCULAR SURGERIES ......................................................................................................... 11 
7.2.1 
Surgical Intervention to Control Elevated IOP ........................................................ 12 
7.2.2 
Cataract Surgeries .................................................................................................... 12 
7.3. STUDY TREATMENTS ........................................................................................................ 12 
7.3.1. 
Extent of Exposure .................................................................................................... 13 
8. 
UTILIZATION ANALYSIS .......................................................................................... 14 
8.1. PRIMARY UTILIZATION ENDPOINT .................................................................................... 14 
8.1.1. 
PRIMARY UTILIZATION ANALYSIS ................................................................................ 14 


pSivida Corp. 
 
                       Statistical Analysis Plan 
PSV-FAI-006 
 
Date Issued: 12APR2016 
 
  
 
 
 
III 
8.2. SECONDARY UTILIZATION ENDPOINTS AND ANALYSIS .................................................... 15 
9. 
SAFETY ANALYSIS ..................................................................................................... 15 
9.1. ADVERSE EVENTS ............................................................................................................. 15 
9.1.1. 
Incidence of Adverse Events ..................................................................................... 16 
9.1.2. 
Relationship of Adverse Events to Study Treatment ................................................. 17 
9.1.3. 
Severity of Adverse Event.......................................................................................... 17 
9.1.4. 
Serious Adverse Events ............................................................................................. 18 
9.1.5. 
Adverse Events Leading to FAI Insert Removal ....................................................... 18 
9.1.6. 
Adverse Events Leading to Study Discontinuation ................................................... 19 
9.1.7. 
Adverse Events Leading to Death ............................................................................. 19 
9.1.8. 
Adverse Events of Special Interest ............................................................................ 19 
9.1.9. 
Procedure Related Adverse Events ........................................................................... 19 
9.1.10 
Other Meaningful Adverse Events ......................................................................... 20 
9.2. OPHTHALMIC EXAMINATION ............................................................................................ 20 
9.2.1. 
Best-corrected Visual Acuity (BCVA) ....................................................................... 20 
9.2.2. 
Intraocular Pressure (IOP) ....................................................................................... 21 
9.2.3. 
Dilated Indirect Ophthalmoscopy ............................................................................. 21 
9.2.4. 
Slit Lamp Examination .............................................................................................. 22 
9.2.5. 
Vitreous Haze and Anterior Chamber Cells ............................................................. 22 
9.3. HUMPHREY 24-2 VISUAL FIELD TEST ............................................................................... 23 
9.4. CLINICAL LABORATORY EVALUATIONS ........................................................................... 23 
9.5. VITAL SIGN MEASUREMENTS ........................................................................................... 23 
9.6. PHYSICAL EXAMINATION ................................................................................................. 23 
10. 
INTERIM ANALYSIS ................................................................................................... 23 
11. 
CHANGES IN THE PLANNED ANALYSIS .............................................................. 24 
12. 
REFERENCES ................................................................................................................ 24 
13. 
APPENDICES ................................................................................................................. 25 
13.1. 
SCHEDULE OF STUDY PROCEDURES AND ASSESSMENTS ............................................... 25 
13.2. 
QUESTIONNAIRES ................................................................................................... 26 
13.2.1. 
Mk I Questionnaires .............................................................................................. 26 
13.2.2. 
Mk II Inserter Questionnaires ............................................................................... 26 
 


pSivida Corp. 
 
                       Statistical Analysis Plan 
PSV-FAI-006 
 
Date Issued: 12APR2016 
 
  
 
 
 
IV 
 
List of Abbreviations 
AE 
Adverse Event 
BCVA 
Best Corrected Visual Acuity 
eCRF 
Electronic Case Report Form 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA 
Fluocinolone Acetonide 
FAI Insert 
Fluocinolone Acetonide Intravitreal Insert 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
hpf 
High power field 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IOP 
Intraocular Pressure 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System 
PT 
Preferred Term 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
SOP 
Standard Operational Procedure 
TEAE 
Treatment-Emergent Adverse Event 
WHO 
World Health Organization 
VA 
Visual Acuity 
 
 


pSivida Corp. 
 
                       Statistical Analysis Plan 
PSV-FAI-006 
 
Date Issued: 12APR2016 
 
  
 
 
 
1
1. Introduction 
pSivida Corp. is developing a drug product candidate to treat chronic non-infectious uveitis 
affecting the posterior segment of the eye. This includes posterior uveitis, intermediate uveitis, 
with or without anterior uveitis, and panuveitis. pSivida’s product candidate is an intravitreal 
insert that contains 0.18 mg of fluocinolone acetonide (FA) and releases FA into the vitreous 
humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day. In this study, this 
specific drug product candidate is abbreviated as“FAI insert” (for Fluocinolone Acetonide 
Intravitreal insert). 
 
Uveitis is defined as inflammation of the uveal tract (iris, ciliary body, choroids) or adjacent 
structures. The cause of inflammatory reaction of the inner eye can be infectious, traumatic, 
neoplastic or autoimmune. According to the classification scheme recommended by the 
International Uveitis Study Group, the disease can be classified on the basis of anatomic 
locations: anterior, intermediate, posterior, or panuveitis.  
 
Generally, posterior uveitis occurs in all age groups and affects people of different ethnic origins.  
The inflammation that affects the choroid and retina may be a primary intra-ocular process or 
may be an ocular manifestation of systemic disease. Posterior uveitis accounts for most of the 
loss of vision in eyes with uveitis, due to any one or more of the following: cystoid macular 
edema, choroidal neovascularization, glaucoma, retinal detachment, subretinal fibrosis, cataract, 
or optic disk atrophy. 
 
A product that is relatively simple to administer and delivers corticosteroid locally for an 
extended period of time may offer significant benefits over existing local and systemic steroid 
therapies. 
 
The FAI insert to be used in the present study contains the same drug product as IluvienTM, an 
intravitreal fluocinolone acetonide product candidate that is commercially available in the United 
States and Europe for the treatment of diabetic macular edema (DME) [Iluvien prescribing 
information (December 2014)].  
 
Additionally, Retisert®, a larger FDA-approved intraocular product that requires surgical 
implantation, also contains the same active ingredient as the FAI insert.  Compared to the FAI 
insert, Retisert delivers approximately 3 times as much FA at rates approximately 3 times faster.  
Retisert has been approved by FDA for the treatment of chronic non-infectious uveitis affecting 
the posterior segment of the eye [Retisert prescribing information (June 2001)]. 
 
pSivida Corp. has developed the FAI insert to provide local steroid therapy with an improved 
benefit/risk profile. The FAI insert is currently being evaluated in PSV-FAI-001, a phase III 
clinical study in subjects with chronic non-infectious uveitis affecting the posterior segment of 
the eye. 
 
Based on information reported in the Iluvien phase 3 trials and in PSV-FAI-001, pSivida Corp. 
has modified the inserter used in intravitreal administration of the FAI insert. This modified 
inserter (the Mk II inserter) is expected to be easier to use than the Mk I inserter used in 


pSivida Corp. 
 
                       Statistical Analysis Plan 
PSV-FAI-006 
 
Date Issued: 12APR2016 
 
  
 
 
 
2
PSVFAI-001. PSV-FAI-006 is designed to assess the utilization and safety of the Mk II inserter, 
compared to the Mk I inserter, and also assesses the safety of the FAI insert. 
2. Objectives 
To evaluate the utilization and safety of the Mk II inserter and to evaluate the safety of the FAI 
insert in eyes with non-infectious uveitis affecting the posterior segment of the eye. 
2.1. 
Primary Objective  
To assess the utilization and the safety of the Mk II inserter, and the safety of the FAI insert, 
from the day of treatment through 7 days following treatment. 
2.2. 
Secondary Objective  
To assess the safety of the FAI insert during 12 months following treatment. 
3. Investigational Plan 
3.1. 
Overall Study Design and Plan 
This trial is a 12 month, phase 3, multi-center, randomized, single-masked (subject), controlled 
study designed to evaluate the utilization and safety of the Mk II inserter and the safety of the 
FAI insert, in subjects with non-infectious uveitis affecting the posterior segment of the eye. This 
study will be conducted in at least 3 study sites. Enrollment of approximately 25 subjects is 
expected. A total enrollment of approximately 30 eyes is planned for this study (20 Mk II 
inserter: 10 Mk I inserter) in one or both eyes in each subject.    
                                                                                                                                                                                    
All subjects will receive the FAI insert on Day 1 of the study, administered using either an Mk I 
inserter or an Mk II inserter.  If both eyes in a subject with bilateral uveitis satisfy the study’s 
inclusion/exclusion criteria, both eyes may be enrolled in the study. In this case, randomization 
of a subject’s second eye will occur independently and will occur no earlier than the study Day 7 
visit for the subject’s first study eye.  
 
At least 10 different investigators will administer the FAI insert. Each time a subject’s eye is 
enrolled in the study, one investigator will serve as the treating investigator (Investigator); 
another staff member in the study site will serve as the trained observer (Observer). On study 
Day 1, the Investigator will administer the FAI insert, and the Observer will observe the 
procedure used by the Investigator to administer the FAI insert. The Investigator and the 
Observer will complete questionnaires related to the administration of the FAI insert on Day 1. 
The Investigator (or designee) will perform all subsequent study assessments. Study personnel 
will not disclose to the subject which inserter was used for intravitreal administration of the FAI 
insert.  
 
Subjects will receive standard care in the study eye(s) and any non-study eye for 12 months 
following enrollment, in accord with medical need and the Investigator’s standard practice. Eyes 
will be assessed according to the schedule of procedures and assessments (Appendix 13.1).   
 
Analyses of study data will be performed at the following two time points during the study: 


pSivida Corp. 
 
                       Statistical Analysis Plan 
PSV-FAI-006 
 
Date Issued: 12APR2016 
 
  
 
 
 
3
1. After all subjects have completed the Day 7 visit (or have been discontinued from the 
study prior to this visit).  The primary utilization and safety analyses of the inserters will 
be conducted at Day 7 time point. 
2. After all subjects have completed the Month 12 visit (or have been discontinued from the 
study prior to this visit).  The safety analyses of the FAI insert will be conducted at 
Month 12 time point. 
3.2. 
Study Endpoints 
The primary utilization and safety analyses of the inserters will be conducted at Day 7; safety 
analyses of the FAI insert will be conducted at Day 7 and Month 12. Analyses will be based on 
individual eyes. 
 
Evaluation of Mk II inserter and Mk I inserter 
 
Utilization evaluation (based on individual eye):  
The primary utilization endpoint is defined as the proportion of intravitreal insertion procedures 
that are assessed by the Investigator as satisfactory.  A satisfactory procedure is defined as one 
receiving a score from the Investigator as either Very Easy (VE), Easy (E), or Routine (R), 
according to the following categories: 
• Very Easy (VE) 
• Easy (E) 
• Routine (R) 
• Difficult (D) 
• Very Difficult (VD) 
 
Secondary utilization endpoints include: 
• Clarity of the Instructions for Use, as assessed by the Investigator 
• Differences between observed procedure and instructions for use, as assessed by an Observer  
 
 
Safety evaluation (based on individual eye): 
Safety will be evaluated over one period: Day 1- Day 7, and will include:  
• Ocular adverse events, including: procedure-related adverse events, IOP increase/decrease, 
medications/procedures required to treat adverse events, clinically significant ocular changes 
 
Evaluation of the FAI insert 
 
Safety will be evaluated for two periods: through Day 7 and through Month 12. Descriptive 
statistics will be used to present the results of all safety evaluations and will include:  
• Ocular adverse events (base on individual eye), including: IOP increase/decrease, 
medications/procedures required to control elevated/low IOP, development or worsening of 
cataract, cataract-related procedures, clinically significant ocular changes 
• Systemic adverse events 


pSivida Corp. 
 
                       Statistical Analysis Plan 
PSV-FAI-006 
 
Date Issued: 12APR2016 
 
  
 
 
 
4
4. General Statistical Considerations 
Continuous data will be described using descriptive statistics (i.e. n, mean, standard deviation, 
median, minimum, and maximum). Categorical data will be described using the eye/subject 
count and percentage in each category. For the summary statistics of all numerical variables 
unless otherwise specified, minimum and maximum will be displayed to the same level of 
precision as reported. Mean and median will be displayed to one level of precision greater than 
the data collected. Standard deviation / standard error will be displayed to two levels of precision 
greater than the data collected. P-values will be rounded to three decimal places. If a p-value is 
less than 0.001 it will be reported as “<0.001”. If a p-value is greater than 0.999 it will be 
reported as “>0.999”.  
 
Data will be displayed in all listings sorted by treatment group, unless otherwise specified. A 
subject will be assigned by the study site. The first 3 digits of the ID number will be the assigned 
site number, followed by a 3-digit subject number in sequential order (i.e., 201001, etc.).  Within 
the IWRS system, at the time of randomization, a 1-digit eye identification number will be 
added: the subject’s first eye (if eligible) to be randomized will be assigned the additional digit 
“1” (e.g., 201001-1); the subject’s second eye (if eligible) to be randomized will be assigned the 
additional digit “2” (e.g., 201001-2).  However all data within the clinical data base will be 
recorded based on the subject number (without the eye id) and eye level data will be recorded as 
OD or OS.  For non-ocular/systemic assessments, subjects who have more than one eye 
randomized/treated will have data listed once for each different treatment received.  (e.g., the 
data could be listed for both the Mk II and Mk I injectors.) 
 
When count data are presented, the percentage will be suppressed when the count is zero in order 
to draw attention to the non-zero counts. A row denoted “Missing” will be included in count 
tabulations where specified on the shells to account for dropouts and missing values. For by 
treatment summaries, the denominator for percentages will be the number of eyes in each 
category in that treatment within the analysis population of interest, unless otherwise specified.  
For summaries for all subjects for data summarized at the subject level, the denominator for 
percentages will be the number of subjects who have at least one eye within the analysis 
population of interest, unless otherwise specified. 
 
Unless otherwise specified, baseline will be defined as the last non-missing evaluation prior to or 
on the date of treatment injection (Day 1). The study day will be calculated as assessment date – 
date of treatment injection (Day 1) + 1. Study day for non-ocular events and assessments will be 
determined using the date of treatment in the first treated study eye.  Study day for ocular 
assessments for the first treated eye will be determined using the date of treatment in the first 
treated study eye.  If the second eye is also treated, study day for the ocular assessments in that 
eye will be based on the date of treatment in that eye.  If the second eye is not treated, study day 
for ocular assessments in that eye will be based on the date of treatment in the treated study eye. 
 
For all utilization and safety analyses, analysis visit windows will be used for assigning 
assessments to an analysis visit, as follows: 
 
Scheduled Visit 
Target Day 
Visit Window (Days) 
Screening 
-60 to 0 
Not applicable 


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Day 1 
1 
Not applicable 
Day 7 
7 
4 to 10 
Day 28 
28 
14 to 42 
Month 3 
90 
69 to 111 
Month 12 
360 
332 to 388 
Only those assessments which are assigned to an analysis visit will be included in the summary 
tables and figures which are presented by visit. If there are multiple assessments assigned to the 
same visit window, the observation to be used for analysis will be determined as follows: 
If there is only one observation falling into a defined visit window, then that observation 
will be flagged for inclusion in by-visit analyses. 
If there is more than one observation falling in a defined visit window and one of the 
observations was made in a “scheduled ” study visit (e.g., day 7, day 28, Month 3, etc.) and 
the other observation(s) was made in an unscheduled visit , then the observation from the 
scheduled study visit  will be used for by-visit analyses.     
If there is more than one observation falling into a defined visit window and all 
observations are from unscheduled visits, then the earliest observation with non-missing 
data for a given assessment will be used for by-visit analyses. 
 
All assessments will be presented in the data listings.  
 
The Day 7 analysis will include all assessments with a start day on or before the upper limit of 
the Day 7 visit window (study day 10). The analysis at Month 12 will include all data in the 
database. 
 
Subjects may have more than one eye randomized to treatment; therefore, for summaries 
counting patients by treated eye, a subject may be included more than once in a given summary.  
The same subject may be included more than once in the same treatment group if both eyes are 
randomized to the same inserter.  Similarly, a subject may be counted more than once in the total 
eyes column if both eyes are randomized. 
 
Subjects will be counted at most once for total subject summaries even if the subject has both 
eyes randomized.    
 
Eyes not receiving assigned treatment and non-study eyes will have all safety data listed and will 
be included in selected AE and SAE summaries only.  In the listings, randomized eyes that did 
not receive treatment will be grouped separately by their randomized treatment assignment (i.e., 
Mk I inserter - Not Treated, Mk II inserter - Not Treated). Non-randomized eyes which do not 
receive treatment will be grouped in listings.  Percentages for Safety population summaries will 
be based on the number of eyes that received treatment. 
 
All analyses will be conducted using SAS Version 9.2 or higher. 


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4.1. 
Sample Size 
This study is not statistically powered to detect a difference between the Mk I and Mk II inserters 
for the proportion of satisfactory procedures.   
 
With a sample size of 20 eyes in the Mk II inserter group, the 95%, two-sided confidence 
interval of satisfactory procedures in the Mk II inserter group will be no larger than 27.2% - 
72.8% when the exact binomial method and a proportion of 10 satisfactory procedures out of 20 
Mk II inserter procedures are employed. All other satisfactory procedure proportions for the Mk 
II inserter will result in two-sided, 95% confidence bounds that are narrower than that described 
above. 
 
With a sample size of 10 eyes in the Mk I inserter group, the 95%, two-sided confidence interval 
of the satisfactory procedures proportion will be no larger than 18.7% - 81.3% when the exact 
binomial method and a satisfactory procedures proportion of 5 out of 10 are employed. All other 
satisfactory procedures proportions for the Mk I inserter will result in two-sided, 95% confidence 
bounds that are narrower than that described above.  
 
These confidence bounds, based on eye, are thought to adequately characterize the ease of use 
and other performance characteristics of the two inserters being studied. 
4.2. 
Designation of Study Eye(s) and Randomization 
For subjects with unilateral uveitis, the study eye will be the affected eye. For subjects with 
bilateral uveitis, the study eye(s) will be the eye(s) meeting eligibility criteria. If both eyes satisfy 
eligibility criteria, both eyes may be enrolled in the study. In a subject with both eyes eligible for 
enrollment, randomization of the subject’s second study eye may occur no sooner than study Day 
7 of that subject’s first study eye. 
 
Following confirmation of eligibility at Day 1, eyes will be randomly assigned (2:1) to receive 
the FAI insert using either the Mk II inserter or the Mk I inserter, respectively. Randomization 
assignments will be administered through a central Interactive Web Response System (IWRS). 
Randomization will be stratified on the basis of the investigator administering the treatment.  
The randomization schedule will be prepared using a blocked randomization and will be 
generated by an independent statistician. Only those subjects who have been enrolled in the 
study will have data recorded on the electronic case report forms (eCRF). 
4.3. 
Masking of Study Subjects 
Treatment assignments will be masked to study subjects. Any non-study eye may receive any 
standard treatment at the discretion of the Investigator. 
4.4. 
Analysis Population 
4.4.1. Intent-to-Treat (ITT) Population 
The ITT population will include all eyes randomized into the study; analyzed as randomized. A 
given subject may have more than one eye included in the ITT population. All eyes in the ITT 
population will be analyzed according to the treatment they were randomized to receive and not 
according to what they actually received, in the event there is a discrepancy.  


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4.4.2. Safety Population 
The safety population will include all eyes randomized into the study; analyzed as treated. A 
given subject may have more than one eye included in the Safety population. All eyes in the 
Safety population will be analyzed according to the treatment actually received and not 
according to the treatment they were randomized to receive, in the event there is a discrepancy. 
5. Subject Disposition 
5.1. 
Disposition 
Disposition will be summarized for the ITT population at the subject level and at the eye level.  
 
Disposition summarized at the subject level will include the number and percentage of subjects 
for the following categories: number of eyes randomized (one, two),  subject randomization (one 
eye randomized to the MK I Inserter, one eye randomized to the MK II Inserter, both eyes 
randomized to the MK I inserter, both eyes randomized to the MK II Inserter, and one eye 
randomized to the MK I inserter and one eye randomized to the MK II Inserter),subjects who 
completed the study, subjects who discontinued from the study, and reasons for study 
discontinuation. The reason includes the following: adverse event, lack of efficacy, lost to 
follow-up, death, subject voluntarily withdrew, physician decision, sponsor decision, and study 
cancelled.  Percentages will be based on the number of subjects who have at least one eye 
randomized. 
 
Disposition will also be summarized at the eye level for the ITT population, summarizing eyes in 
the Safety population, eyes that completed the study, eyes that discontinued the study, and  the 
reason for premature study termination by treatment group and for all treated eyes. Percentages 
will be based on the number of eyes randomized. 
 
All disposition data will be presented in a listing. 
5.2. 
Protocol Deviations 
All protocol deviations will be reviewed and assessed as to significance prior to each database 
lock. The protocol deviations will be summarized by treatment group for the ITT population.  
 
Protocol deviations will be presented in a listing for the ITT population.   
6. Demographics and Baseline Characteristics 
6.1. 
Demographics 
Demographics will be summarized by treatment group and at the subject level for all subjects for 
the ITT population and Safety populations. Summaries will be generated for the Safety 
population only if there are randomized eyes that do not receive treatment.  Summaries by 
treatment group will be based on the number of randomized (ITT) or treated eyes (Safety); 
therefore a subject who has both eyes randomized (treated) will be counted more than once, 
“repeating” the subject level demographics information once for each treated eye.   Percentage 
for the by treatment summaries will be based on the number of randomized eyes and percentages 


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for the total subjects summary will be based on the number of subjects who have at least one eye 
randomized (treated). 
 
The demographics data consist: 
• 
Age (years)  calculated using the date of the informed consent and date of birth 
• 
Sex 
• 
Race 
• 
Ethnicity 
• 
Iris color 
• 
Height (cm) 
• 
Weight (kg) 
• 
Body Mass Index (BMI) (kg/m^2) calculated as (body weight in kilograms) / (height in 
meters)2 
 
Age (years), height (cm), weight (kg), and BMI (kg/m^2) will be summarized as continuous 
variables. The number and percentage of eyes/subjects by age category (<=20, 20 - < 40, 40 - < 
60, >= 60), sex (Male, Female), race (White, Black, Asian, American Indian or Alaska Native, 
Native Hawaiian or Other Pacific Islander, and Other) and ethnicity (Hispanic or Latino, Not 
Hispanic or Latino), and iris color (Black, Brown, Hazel, Green, Blue, Grey, and Other) will also 
be reported.  
 
Demographics data will be presented in a listing for the ITT population. 
6.2. 
Baseline Ocular Characteristics 
Baseline ocular characteristics will be summarized by treatment group and for all treated eyes for 
the ITT and Safety populations. Summaries will be generated for the Safety population only if 
there are randomized eyes that do not receive treatment.   
 
The baseline ocular characteristics to be summarized include: 
• 
Treated Eyes (OD, OS) 
• 
Duration of uveitis (years) calculated as (screening date – date of onset of uveitis +1)/ 
365.25 
• 
Number of recurrences in the last 12 months 
• 
Lens status 
• 
Presence of cataract (if with lens status of phakic) 
• 
History of vitrectomy procedure(s) 
• 
Prior incisional anti-glaucoma surgeries 
• 
Baseline BCVA (letters) 
• 
Baseline IOP (mmHg) 
 
Duration of uveitis, baseline BCVA (letters), and baseline IOP (mmHg) will be summarized as 
continuous variables. For partial uveitis onset dates, a missing month will be imputed as January 
and a missing day will be imputed as the first of the month. The number and percentage of eyes 
by duration of uveitis (< 2 years, 2 to 5 years, > 5 years), number or recurrences in the last 12 


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months (<= 2, >2), lens status (phakic, aphakic, and pseudophakic), presence of cataract (if with 
lens status of phakic), and history of  related procedure(s) and surgeries will also be reported.  
 
Baseline ocular characteristics will be summarized for randomized eyes only. Summaries will be 
presented at the eye level.  Percentage will be based on the number of randomized eyes (ITT) or 
treated eyes (Safety).  
 
All collected baseline ocular characteristics data for all eyes will be presented in a listing for the 
ITT population.  
6.3. 
Medical History 
6.3.1. Non-ocular Medical History 
Non-ocular medical history and current non-ocular conditions will be summarized by treatment 
group for each body system for the ITT population. Body systems will be included as recorded 
on the eCRF. The non-ocular medical history data will be also summarized for all subjects at the 
subject level.  Summaries by treatment group will be based on the number of randomized eyes; 
therefore a subject who has both eyes randomized will be counted more than once, “repeating” 
and counting the non-ocular history once for each treated eye.   Percentage for the by treatment 
summaries will be based on the number of randomized eyes and percentage for the total subjects 
summary will be based on the number of subjects who have at least one eye randomized. 
 
Non-ocular medical history data, including specific details on the condition/diagnosis and 
start/end dates, will be presented in a listing for the ITT populations. 
6.3.2. Ocular Medical History  
Any clinically significant ocular conditions within the past 12 months prior to Screening will be 
recorded on the eCRF. Ocular medical history data, including specific details on the 
condition/diagnosis, location (OS, OD, and OU), study eye(s) designation, treatment required, 
and start/end dates, will be presented in a listing for the ITT populations. 
6.4. 
Inclusion and Exclusion Criteria 
Prior to randomization, the investigator will assess whether the eye fulfills all the requirements 
of the inclusion and exclusion criteria outlined in the protocol. If an eye does not fulfill all of the 
requirements, the specific inclusion criterion not met or exclusion criterion which was met will 
be recorded on the eCRF. This information and whether the sponsor granted a waiver will be 
presented in a listing.  
7. Treatments and Medications 
7.1. 
Prior and Concomitant Medications 
Prior and concomitant medication will be summarized by drug class and preferred term after 
coding with WHO Drug (WHO201209 version or higher) Dictionary terms. 
 
All summaries will be provided for ocular medications and non-ocular medications, separately. 
Systemic steroids and immunosuppressants that have been prescribed for uveitis will be 


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summarized as ocular medications, but are not considered prohibited in this study.  Summaries 
will include the total number of medications, the number  and percentage of eyes or subjects 
receiving at least one medication, and the number and percentage of eyes or subjects receiving a 
medication summarized at the summarized by ATC level 1 term, ATC level 2 term, and 
preferred term.  Eyes and/or subjects may receive more than one medication per ATC level 1 
category, ATC level 2 category, and preferred term. At each level of summarization, an eye or 
subject is counted once if the eye or subject received one or more medications. 
 
All prior and concomitant medication, including pre- and post-ocular procedure medications will 
be presented in listings for the Safety population.  
7.1.1 Prior Medications 
Prior medications are defined as those medications with a recorded end date prior to the initiation 
of study treatment. 
 
Prior non-ocular medication will be summarized by treatment group for each drug class and 
preferred term for the Safety population. The prior non-ocular medication data will be also 
summarized for all subjects at subject level. Summaries by treatment group will be based on the 
number of treated eyes; therefore a subject who has both eyes treated will be counted more than 
once, “repeating” the non-ocular medication and counting once for each treated eye.   
Percentages for the by treatment summaries will be based on the number of treated eyes and 
percentages for the total subjects summary will be based on the number of subjects who have at 
least one eye treated. 
 
Prior ocular medication will be summarized by treatment group and for all treated eyes for each 
drug class and preferred term for the Safety population.  Percentages will be based on the 
number of treated eyes. 
7.1.2 Concomitant Medications 
Concomitant medications are defined as those medications which are taken on or after the 
initiation of study treatment (Day 1). This includes medications which start prior to Day 1 but 
continue while the subject is on treatment.  
 
Concomitant non-ocular medication will be summarized by treatment group for ATC level 1 
term, ATC level 2 term and preferred term for the Safety population. The concomitant non-
ocular medication data will be also summarized for all subjects at the subject level.  Summaries 
by treatment group will be based on the number of treated eyes; therefore a subject who has both 
eyes treated will be counted more than once, “repeating” and counting the non-ocular medication 
once for each treated eye.   Percentages for the by treatment summaries will be based on the 
number of treated eyes and percentages for the total subjects summary will be based on the 
number of subjects who have at least one eye treated. 
 
Concomitant ocular medication will be summarized by treatment group and for all treated eyes 
for each drug class and preferred term for the Safety population.   Percentages will be based on 
the number of treated eyes. 
 


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An additional summary of concomitant medication for each of the specified reasons for 
medication (recurrence of uveitis, treatment emergent AE, increased IOP, cataract, other) will be 
reported as well. 
7.1.3 
IOP Lowering Medications 
The number and percentage of eyes requiring IOP lowering medication to control elevated IOP 
will be summarized by treatment group and for all treated eyes.  Any systemic medications will 
be summarized as received in both eyes. IOP lowering medications will be identified as those 
medications with a reason for medication of “Increased IOP”. Incidence will be summarized 
through 12 months and for 3 month time intervals through 12 months.   
 
The number of medications (one, two, ≥ three) required to achieve adequate IOP control will 
also be included in the summary. IOP medications will be counted at the “ingredient” level.  For 
example, if the subject is receiving COSOPT (which contains two ingredients TIMOLOL 
MALEATE and DORZOLAMIDE HYDROCHLORIDE) and TIMOLOL MALEATE at the 
same time, the subject will be included in analysis as receiving two medications.  
 
A single medication must be used for a minimum of 7 days. Multiple medications must be used 
concurrently for a minimum of 14 days.  A subject does not need to be taking the same 
medication(s) over a given period to be counted for analysis.  For example, if a subject is taking 
Medication A from days 50 to day 55, then Medication B from days 56 to 62, the patient will be 
counted as receiving 1 medication to control IOP, because the subject required at least one IOP 
medication/ingredient for 7 consecutive days, even though each medication/ingredient was used 
for less than 7 days.   In a similar example, if a subject was receiving Medication A from days 50 
to 60, Medication B on days 61 to 70, and Medication C on Days 52 to 70, then the subject will 
be counted in the analysis as receiving 2 medications, because the subject received two unique 
medications/ingredients over days 52 to 70. 
 
Because medications can start and stop at various times in the analysis periods (up to month 3, 
month 3 to month 6, etc.) a medication will be counted in a given period if the start date(s) for 
the required number days of consecutive use (7 days for a single medication, 14 days for 
multiple medications) occurs within the period, even if the end of the 7 or 14 days of consecutive 
use falls after the end of the given analysis period.   Medication(s) which begin in one analysis 
period and continue to the “next” analysis period will be counted in the “next” analysis period 
only if the medication(s) were received for at least 7 or 14 days (for single or multiple 
medications, respectively) in the “next” period. 
 
A summary of IOP lowering medications will also be presented by history of incisional surgery 
to control elevated IOP (History of Incisional Surgery, No History of Incisional Surgery). All 
summaries will be performed using the Safety population for the final analysis at Month 12 only.   
 
7.2. 
Ocular Surgeries 
All ocular surgeries during a subject’s participation in the study will be recorded on the eCRF.  


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A summary of surgery/procedure for each of the specified reasons (recurrence of uveitis, 
treatment emergent AE, increased IOP, cataract, other) will be reported. Summaries will be 
provided by treatment group and for all treated eyes for the Safety population. 
 
Ocular surgery data, including details on the procedure, eye, start date, and reason for the 
surgery, will be presented in a listing for the Safety population. 
 
7.2.1 Surgical Intervention to Control Elevated IOP 
The number and percentage of eyes requiring any surgical intervention to control elevated IOP 
will be summarized by treatment group and for all treated eyes.  Ocular surgeries with a reason 
of “Increased IOP” will be included in the summary.  Surgery data will be reviewed to ensure all 
IOP surgeries including those with “Other” indication are also identified using the specification 
text.  Incidence will be summarized overall through 12 months and for 6 month time intervals 
through 12.  
 
A summary of incidence of surgical interventions to control elevated IOP will also be presented 
by history of incisional surgery to control elevated IOP (History of Incisional Surgery, No 
History of Incisional Surgery). All summaries will be performed using the Safety population for 
the final analysis at Month 12 only.   
 
A listing of all subjects requiring surgical interventions to control elevated IOP will be provided.   
This listing will include details relating to the IOP-lowering surgical intervention (procedure, 
eye, study eye designation, and date procedure performed), demographic and baseline ocular 
characteristics including BCVA and IOP, and the last available BCVA and IOP values as of the 
data cut-off.   
7.2.2 Cataract Surgeries 
The number and percentage of eyes requiring cataract surgery will be summarized by treatment 
group and for all treated eyes.  Only eyes which are indicated as phakic at study entry will be 
included for analysis. Ocular surgeries with a reason of “Cataract” will be included in the 
summary. Incidence will be summarized overall through 12 months and for 6 month time 
intervals through 12 months. All summaries will be performed using the Safety population and 
percentages will be based on the number of phakic eyes in the Safety population.  Analysis will 
be performed for the final analysis at Month 12 only. 
 
7.3. 
Study Treatments  
Fluocinolone acetonide (FA) is the active ingredient in the FAI insert. The FAI insert is an 
injectable intravitreal sustained-release FA delivery system pre-loaded into an injection device 
and is administered as an intravitreal injection through the pars plana.  For this study, the FAI 
insert will be provided in one of two sterile preloaded inserters: the Mk I inserter or the Mk II 
inserter. The FAI insert is designed to release FA for a period of 36 months at a nominal rate of 
approximately 0.2 μg FA/day. 
 
The Mk I inserter is a sterile, pre-loaded, modified syringe that uses a 25 gauge XX-thin wall 


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needle to penetrate the conjunctiva and sclera; the needle is not retracted after intravitreal 
injection has been completed. The Mk I inserter has been used previously in clinical study 
PSVFAI-001. 
 
The Mk II inserter is a sterile, pre-loaded applicator that uses a 27 gauge standard wall needle to 
penetrate the conjunctiva and sclera; the needle is retracted during intravitreal injection. 
 
Data related to the study treatment procedure will be presented in a listing for the Safety 
population.  
7.3.1. Extent of Exposure 
Duration of insert (days) is defined as the total number of days a study eye is exposed to study 
drug and will be presented as the total number of days from the injection date (Day 1) to either 
the FAI insert removal date, for those eyes which have the insert removed while in the study, or 
the last visit date (date of insert removal or last visit - the date of injection + 1) as recorded on 
the End of Study/Early Termination page. If the last visit date on the End of Study/Early 
Termination page is missing, or if a subject is lost to follow-up, the latest available visit date will 
be used. Duration of insert at Day 7 is defined similarly to overall insert duration, using either 
the FAI insert removal date, if removal occurred prior to Day 7 visit date, or the Day 7 visit date 
as the cut-off date. If a subject’s Day 7 visit date occurs later than the data cut off for the Day 7 
analysis (upper limit of Day 7 visit window) then the upper limit of the Day 7 visit date will be 
used as the end date of the insert duration.   
 
Duration of insert up to Day 7 (or Month 12) will be summarized by treatment group and for all 
treated eyes for the Safety population. The duration of insert will be classified into following 
categories: <= 7 days, 8 to 28 days, 29 to 90 days, 91 to 360 days, and >= 360 days and the 
number and percentage of eyes in each duration category will be presented for the Safety 
population.  
 
Duration of study participation (days) is calculated as date of last visit as recorded on the End of 
Study/Early Termination page – date of Day 1 visit + 1. If the last visit date on the End of 
Study/Early Termination page is missing, or if a subject is lost to follow-up, the latest available 
visit date will be used. Duration of study participation at Day 7 is calculated as the date of Day 7 
visit – date of Day 1 visit + 1. If a subject’s Day 7 visit date occurs later than the data cut-off for 
the Day 7 analysis (upper limit of Day 7 visit window), then the upper limit of the Day 7 visit 
date will be used as the end date of participation. 
 
Duration of study participation up to Day 7 (or Month 12) will be summarized by treatment 
group and for all subjects at the subject level for the Safety population. The durations of study 
participation will be classified into one of the following categories: <= 7 days, 8 to 28 days, 29 to 
90 days, 91 to 360 days, and >= 360 days and the number and percentage of eyes or subjects in 
each duration category will be presented for the Safety population.  Summaries by treatment 
group will be based on the number of treated eyes; therefore a subject who has both eyes treated 
will be counted more than once, “repeating” and including the duration of subject participation 
once for each treated eye.   Percentages for the by treatment summaries will be based on the 


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number of treated eyes and percentage for the total subjects summaries will be based on the 
number of subjects who have at least one eye treated. 
 
Duration of insert and duration of study participation will be presented in a listing for the Safety 
population. 
8. Utilization Analysis 
Utilization analyses will be performed by treatment group, at Day 1 based on the questionnaires 
from Investigator and the Observer (Appendix 13.2).  
 
All primary and secondary utilization endpoints will be analyzed using the ITT population. 
 
 
Data related to the utilization will be presented in a listing for the ITT population.  
8.1. 
Primary Utilization Endpoint 
The primary utilization endpoint is defined as the proportion of intravitreal insertion procedures 
that are assessed by the Investigator as satisfactory. A satisfactory procedure is defined as one 
receiving a score from the Investigator as either Very Easy (VE), Easy (E), or Routine (R), 
according to the following categories: 
• Very Easy (VE) 
• Easy (E) 
• Routine (R) 
• Difficult (D) 
• Very Difficult (VD)  
If more than one inserter is used for the same eye, the results from the first inserter will be used 
for completing the questionnaires and analysis. Comments related to the second inserter will be 
presented in a listing.  Any injector which penetrates the eye but does not deliver the FAI insert 
into the eye will be scored as Very Difficult for analysis. 
8.1.1. Primary Utilization Analysis 
 
The primary utilization analysis will compare the proportion of intravitreal insertion procedures 
that are assessed by the Investigator as satisfactory (i.e., VE, E or R), in the Mk I inserter and the 
Mk II inserter groups.  
 
The number and percentage of eyes with satisfactory intravitreal insertion procedures will be 
presented, for the Mk I inserter and the Mk II inserter groups of eyes employing descriptive 
statistics including 95% confidence intervals using the exact binomial methodology. The 
difference in proportions, the 95% exact unconditional confidence interval for the treatment 
difference (Mk II vs Mk I) in proportions, and the Fisher’s exact test p-value will also be 
provided, however this comparison is considered exploratory only as the study is not powered to 
detect a difference between the inserters. 
 


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The primary utilization analysis will be conducted after all eyes in the study have completed 
study Day 7 or have discontinued study participation. 
 
The study will be deemed a success for the Mk II inserter if the following condition is met: The 
proportion of Mk II procedures scored as satisfactory is not numerically lower than the 
corresponding proportion of Mk I procedures. 
8.2. 
Secondary Utilization Endpoints and Analysis 
Secondary endpoints include: 
• Clarity of the instructions for use, as assessed by the Investigator (yes, no) 
• Differences between observed procedure and instructions for use, as assessed by an 
Observer (yes, no) 
 
These secondary utilization endpoints will be analyzed employing descriptive statistics.  
Additionally descriptive statistics for other items on the investigator and observer questionnaires 
will be presented.   
9. Safety Analysis 
Safety analyses will be performed by treatment group for the Safety population at Day 7 and 
Month 12. Descriptive statistics will be used in safety analyses. Summary at the subject level 
will also be provided. 
 
Non-treated randomized eyes and non-study eyes will only have all safety data listed.  Adverse 
events will be summarized for these eyes, but otherwise they will not be included in safety 
tabulations.   
9.1. 
Adverse Events 
A treatment-emergent AE (TEAE) is defined as any new untoward medical occurrence or 
worsening of a pre-existing medical condition in a subject administered an investigational 
product; an AE does not necessarily have a causal relationship with this treatment. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of investigational product, 
whether or not considered related to the investigational product. 
 
For the purpose of inclusion in TEAE tables, incomplete AE start and end dates will be imputed 
as follows: 
Missing onset dates (where UK and UKN indicate unknown or missing day and month 
respectively):  
• 
UK-MMM-YYYY: If the month and year are different from the month and year of the 
date of injection, assume 01-MMM-YYYY. If the month and year are the same as the 
month and year for the date of injection, and the end date (after any imputation) is on or 
after the date of injection, then assume the date of injection (Day 1). If the month and 
year are the same as the date of injection, and the end date (after any imputation) is prior 
to the date of injection, then assume the end date for the start date.  


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• 
DD-UKN-YYYY/UK-UKN-YYYY: If the year is different from the year of the date of 
injection, assume 01-JAN-YYYY of the collected year. If the year is the same as the date 
of injection year, and the end date (after any imputation) is on or after the date of 
injection, then assume the date of injection (Day 1). If the year is the same as the date of 
injection, and the end date (after any imputation) is prior to the date of injection, then 
assume the end date for the start date.  
 
Missing end dates (where UK and UKN indicate unknown or missing day and month 
respectively):  
• UK-MMM-YYYY: Assume the last day of the month; 
• DD-UKN-YYYY/UK-UKN-YYYY: Assume 31-DEC-YYYY. 
 
All adverse events will be classified by System Organ Class (SOC) and Preferred Term (PT) 
according to the Medical Dictionary for Regulatory Activities (MedDRA, Version 15.1 or 
higher). 
 
An overview summary of any TEAE, serious TEAE, treatment-related TEAE, treatment-related 
serious TEAE, TEAE leading to FAI insert removal, TEAE leading to study discontinuation, and 
AE leading to death will be provided.  
 
All TEAE summaries will be provided for ocular events and non-ocular events, separately.  All 
adverse events starting on or after the date of treatment in the first study eye are considered 
TEAE, however ocular events occurring in non-treated eyes and events occurring in the second 
treated eye between the date of treatment in the first treated eye and the date of treatment in the 
second treated eye will be summarized separately from ocular events that occur in treated eyes 
after the date of treatment within the respective eye.   
 
All AEs will be presented in a listing. 
9.1.1. Incidence of Adverse Events 
Summaries of the total number of ocular TEAEs and the number and percentage of eyes having 
at least one ocular TEAE will be provided by treatment group and for all treated eyes.  Similarly, 
summaries of the total number of non-ocular TEAEs and the number and percentage of subjects 
having at least one non-ocular TEAE will be provided by treatment group.  Ocular events and 
non-ocular events will be also summarized at the subject level for all subjects.  Ocular events 
which occur in non-treated eyes and ocular events which occur in the second treated eye with a 
start date on or after the date of treatment in the first study eye but before the date of treatment in 
the second eye will be summarized separately as noted in section 9.1.10. 
 
Ocular and non-ocular TEAEs will be summarized by SOC and PT. At each level of 
summarization, eye or subject level, an eye or subject is counted once for multiple events within 
PT/SOC.  
 
Summaries by treatment group and for all treated eyes will be based on the number of treated 
eyes; therefore non-ocular events for subjects who have both eyes treated may be counted more 


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than once, “repeating” and counting the adverse event once for each treated eye.  A non-ocular 
event will be counted for a given eye if the event start date is on or after the treatment date in the 
given eye. (i.e., non-ocular events which occur on or after the date of treatment in the first treated 
eye but before the date of treatment in the second eye will be counted once for the first eye only.  
If the event start date was on or after the treatment date in the second treated eye, the event 
would be counted twice, once for each eye.)  Ocular events will be counted for a given study 
eye/treatment if the event start date is on or after treatment date within the given treated eye.  
Percentages will be calculated out of the number of treated eyes in the Safety Population. 
 
Subject level summaries for all subjects will be based on the number of subjects who have at 
least one treated eye and a subject will be counted as having an event in the total subject 
summary if the subject has an event in at least one treated eye.  Percentages will be calculated 
out of the number of subjects in the Safety Population with at least one treated eye. 
  
The summary of TEAEs will be presented in descending order from the SOC with the highest 
subject incidence to the SOC with the lowest subject incidence. If the incidence for any two or 
more SOC is equal, the SOC will be presented in alphabetical order. Within each SOC, the PTs 
will be presented in alphabetical order.  
 
A separate summary of protocol defined ocular TEAEs, overall and by criteria, will be provided. 
This summary will include the following ocular events, as reported on the AE eCRF page: 
• decrease in visual acuity of ≥ 15 letters, compared to the most recent previous 
measurement of visual acuity 
• moderate or severe (grade 3 or 4) ocular findings compared to the last ophthalmic 
examination 
• worsening of ≥ 2 steps in anterior chamber cell count or vitreous haze, compared to the 
last ophthalmic examination 
• increase in IOP of ≥ 10 mmHg at two visits at least 1 week apart or an increase in IOP to 
≥ 25 mmHg 
9.1.2. Relationship of Adverse Events to Study Treatment 
A summary of TEAEs by relationship to study treatment will be presented in a table by incidence 
of occurrence by treatment group. The investigator will provide an assessment of the relationship 
of the event to the study treatment. The possible relationships are “Unrelated”, “Possibly 
Related”, and “Probably Related”. TEAEs that are missing a relationship will be presented in the 
summary table as “Probably Related” but will be presented in the data listing with a missing 
relationship.  
 
The TEAE data will be categorized and presented by SOC, PT, and relationship in a manner 
similar to that described in Section 9.1.1.    
9.1.3. Severity of Adverse Event 
A summary of TEAEs by severity will be presented in a table by incidence of occurrence by 
treatment group. The severity will be captured on the eCRF page. The possible severities are 
“Mild,” “Moderate,” and “Severe.” TEAEs that are missing severity will be presented in tables 
as “Severe” but will be presented in the data listing with a missing severity. 


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A summary of TEAEs related to study treatment by severity will be presented in a table. Events 
with a relationship if “Possibly Related” and “Probably Related” will be considered related to 
study treatment and included in this summary. 
 
The TEAE data will be categorized and presented by SOC, PT, and severity in a manner similar 
to that described in Section 9.1.1. 
9.1.4. Serious Adverse Events 
Serious treatment-emergent adverse events (SAEs) as below will be presented in a table by 
incidence of occurrence by treatment group. 
•  Results in death 
•  Is life-threatening 
•  Requires in-patient hospitalization or prolongs existing hospitalization 
•  Results in persistent or significant disability / incapacity 
•  Is a congenital anomaly / birth defect 
•  Is a medically important event or reaction 
 
The SAE data will be categorized and presented by SOC and PT in a manner similar to that 
described in Section 9.1.1 and by severity as described in Section 9.1.3. 
 
A separate summary of protocol defined SAEs, overall and by criteria, will be provided. This 
summary will include the following sight-threatening ocular events, as reported on the AE/SAE 
eCRF page: 
• An AE which causes a decrease in visual acuity of  ≥ 30 letters, compared to the most 
recent previous measurement of visual acuity, lasting more than 1 hour 
• An AE which causes a decrease in visual acuity to light perception or worse, lasting more 
than 1 hour 
• An AE which requires surgical intervention (e.g., conventional surgery, vitreous tap or 
biopsy with intravitreal injection of anti-infective, or laser or retinal cryopexy with gas) 
to prevent permanent loss of sight 
• An AE which is associated with severe intraocular inflammation (i.e., 4.0 anterior 
chamber cell score, 4+ flare or 4+ vitritis) 
• Two consecutive IOP measurements of 30 mmHg or higher taken at least 72 hours apart 
when a subject is already being treated with two glaucoma medications 
• An IOP < 6 mmHg requiring medical intervention 
• An AE which in the opinion of the Investigator requires medical or surgical intervention 
to prevent permanent loss of sight 
9.1.5. Adverse Events Leading to FAI Insert Removal 
A summary of TEAEs with an action taken with study treatment of “FAI Insert Removal” will be 
presented in a table by treatment group and all treated eyes. These TEAEs will be also 
summarized for subject level. 
 


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The summary of TEAEs with an action taken with study treatment of “FAI Insert Removal” will 
be presented by SOC and PT in a manner similar to that described in Section 9.1.1.  
9.1.6. Adverse Events Leading to Study Discontinuation  
All eyes having an AE where the answer to “Was eye terminated from study due to this AE?” is 
“Yes” will be presented in a listing.   
9.1.7. Adverse Events Leading to Death 
All subjects who have an AE with an outcome of “Fatal” will be presented in a listing.  
9.1.8. Adverse Events of Special Interest 
A summary of TEAEs of cataract and elevated IOP will be presented in a table by treatment 
group and all treated eyes. These TEAEs will be also summarized for subject level. Events will 
be included in the summary based on a list of PTs for each event category. Cataract events will 
include any event whose MedDRA higher lever coded term is “CATARACT CONDITIONS" is 
contained in the preferred term.  IOP elevations will be based on the specific preferred term 
“INTRAOCULAR PRESSURE INCREASED” or if the preferred term contains the phrase 
“GLAUCOMA”.   
 
A summary of ocular TEAEs which are considered complications of IOP lowering medications 
to control IOP will be presented by treatment group and all treated eyes. These TEAEs will be 
also summarized for subject level. Events will be included in the summary based on manual 
review of AEs with an onset date on or after the date of first use of any IOP lowering medication.  
 
A summary of ocular TEAEs which are considered complications of surgical interventions to 
control IOP will be presented by treatment group and all treated eyes. These TEAEs will be also 
summarized for subject level. Events will be included in the summary based on manual review of 
all AEs with an onset date on or after the date of surgical intervention. A similar summary will 
be presented for complications of cataract surgeries.  
 
At each level of eye summarization, an eye is counted once for multiple events within PT. 
Percentages will be calculated out of the number of eyes in the Safety population. At each level 
of subject summarization, a subject is counted once for multiple events within PT. Percentages 
will be calculated out of the number of subjects in the Safety population. The summary will be 
sorted by PT in alphabetical order.  Adverse events of special interest will be summarized at Day 
7 and Month 12. 
 
A manual data review memo will be written at the time the manual data reviews are performed.    
Because investigators may report similar events differently, the memo will be written a the time 
of the manual review to document the specific details on the preferred terms and other text 
specifications that are used to identify IOP lowering medications, IOP surgeries, and Cataract 
surgeries.   
9.1.9. Procedure Related Adverse Events  
 


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Adverse events with an onset date within 7 days of the insert procedure will be clinically 
reviewed to assess the relationship to the injection procedure.  Events that could be considered 
related to the injection procedure could include but is not limited to events such as decreased IOP, 
increased IOP, eye pain, eye erythema, etc.  The process by which the manual review is 
conducted will be summarized in a manual data review memo.   Events which are deemed 
related to the injection will be summarized in similar manner as incidence of adverse events 
detailed in section 9.1.1. 
9.1.10 Other Meaningful Adverse Events  
Ocular events which occur in non-treated eyes and ocular events which occur in the second 
treated eye with a start date on or after the date of treatment in the first study eye but before the 
date of treatment in the second eye will be summarized by SOC and PT.  At each level of 
summarization, an eye is counted once for multiple events within PT/SOC.  Summaries will be 
for total eyes and not by randomized treatment group(s) for the first/second eye.  Percentages 
will be based on the number of non-treated eyes or the number of second treated eyes, 
respectively. A similar summary of serious adverse events will also be provided.  Ocular events 
in non-treated eyes will be presented.  Events in the second study eye prior to date of treatment 
in the second study eye will be presented in data listings under the treatment of the second 
treated eye.    
9.2. 
Ophthalmic Examination 
All ophthalmic examinations are performed on both eyes.  
9.2.1. Best-corrected Visual Acuity (BCVA) 
BCVA will be measured according to the standard procedure developed for ETDRS at 4 meters 
(or at 3 meters if the electronic ETDRS system is employed). Corrected-distance VA is to be 
reported as number of letters read correctly by the subject. The Snellen Fraction will also be 
recorded. If the subject is unable to read any letters at 4 meters or 1 meter, the investigator will 
assess the subject’s ability to count fingers, recognize hand motion, or light perception. 
 
A summary table presenting the observed values and changes from baseline in BCVA (letters) 
will be presented by treatment group for the Safety population. Changes from baseline to each 
scheduled post-baseline visit will be presented. In addition, a categorical summary of change 
from baseline in BCVA will present the letter change at Day 7 (or Month 12) and the maximum 
letter change at any time point up to Day 7 (or Month 12), including categories of ≥ 15 letters 
lost, ≥ 10 letters lost, ≥ 5 letters lost, no change, ≥ 5 letters gained, ≥10 letters gained, and ≥ 15 
letters gained.  
 
The BCVA summaries will also be presented for the following subgroups: 
• IOP lowering medication [No IOP lowering medication, Required IOP lowering 
medication] 
• Surgical Intervention to Control Elevated IOP [No surgical intervention, Required 
surgical intervention] 
• Lens status at Baseline [Phakic, Aphakic, Pseudophakic] 
 


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IOP lowering medication status will be based on a subject’s use of any IOP lowering medication 
up to the time point of interest (Day 7 and Month 12). Surgical intervention status will be defined 
in a similar manner.   
  
For eyes with phakic lens status at study entry who undergo cataract surgery while in the study, 
the change in BCVA (letters) from the last BCVA measurement prior to surgery to the first 
BCVA measurement after surgery will be summarized by treatment group for the Safety 
population. In addition, a summary of change from baseline in BCVA (letters) will be presented 
by treatment group with phakic eyes at study entry who undergo cataract surgery while in the 
study vs. eyes with a lens status of pseudophakic at study entry. 
 
BCVA data will be presented in a listing.  
9.2.2. Intraocular Pressure (IOP) 
Applanation tonometry (preferable Goldman) will be used for IOP measurements, where the 
value recorded on the eCRF is an average of 3 measurements. On Day 1, this assessment will be 
performed pre- and post-administration of study treatment.  
 
A summary table presenting the observed values and changes from baseline in IOP (mmHg) will 
be presented by treatment group for the Safety population. Changes from baseline to each 
scheduled post-baseline visit, as well as the Day 1 post-administration of study treatment, will be 
presented.  
 
The number and percentage of eyes with an IOP measurement > 21 mmHg at any post-
administration assessment will be presented for each treatment group. Incidence will be 
summarized through Day 7 and month 12.  
 
Additionally, the number and percentage of eyes with an IOP measurement meeting any of the 
IOP elevation criteria at any post-administration assessment and by visit will be presented by 
treatment group for the Safety population. The IOP elevation criteria include:  
• Increase in IOP from baseline of  > 5 mmHg  
• Increase in IOP from baseline of  ≥ 12 mmHg 
• IOP measurement > 25 mmHg 
• IOP measurement > 30 mmHg 
 
IOP data will be presented in a listing. 
9.2.3. Dilated Indirect Ophthalmoscopy 
The investigator will assess the status (Normal, Abnormal – Clinically Significant, Abnormal – 
Not Clinically Significant) of the vitreous, macula, retina, optic nerve, choroid, and retinal 
periphery. On Day 1, this assessment will be performed pre- and post-administration of study 
treatment. Post-administration of study treatment, the investigator will assess the adequacy of the 
central retinal artery perfusion and indicate the presence of any complications.  
 
Data from the indirect ophthalmoscopy examination will be presented in a listing.   


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9.2.4. Slit Lamp Examination 
The investigator will assess any changes in lens or cataract status and the status (Normal, 
Abnormal – Clinically Significant, Abnormal – Not Clinically Significant) of the conjunctiva, 
cornea, iris, anterior chamber, and posterior chamber.  
 
A summary table presenting the number and percentage of eyes with a change in lens/cataract 
status since screening or a worsening of an existing cataract since the previous visit will be 
presented by baseline lens status, treatment group for the Safety population with a phakic or 
pseudophakic lens status at study entry for the given eye.  
 
Data from the slit lamp examination will be presented in a listing.   
9.2.5. Vitreous Haze and Anterior Chamber Cells 
Indirect ophthalmoscopy will be performed for each eye with pupil dilation.  The following scale 
(Nussenblatt 1985) will be used to define the extent of vitreous haze:  
Grade 
Description 
Absent 
Clear view of optic disc, retinal vessels and nerve fiber layer 
Trace 
Slight blurring of optic disc margin and of normal striations and reflex 
of nerve fiber layer 
1+ 
Mild blurring of optic disc margin and slight loss of retinal vessel 
definition 
2+ 
Moderate blurring of optic disc margin and loss of retinal vessel 
definition 
3+ 
Optic nerve head and large vessels visible but borders quite (very) 
blurry 
4+ 
Optic nerve head obscured 
 
Anterior chamber cells will be measured using a Haag/Streit or similar slit lamp at high 
magnification (1.6 X) 1-mm beam. Assessment will be made using the following scale (Jabs 
2005). 
 
Field size: 1 mm by 1 mm slit beam 
Grade 
Description 
0 
<1 cells/hpf 
0.5+ 
1-5 cells/hpf 
1+  
6-15 cells/hpf 
2+ 
16-25 cells/hpf 
3+  
26-50 cells/hpf 
4+ 
>50 cells/hpf 
 
Frequency distributions of the vitreous haze and anterior chamber cells grading at each 
scheduled visit will be summarized in a table by treatment group in the Safety population.   
 
All vitreous haze and anterior chamber cell data will be presented in a listing. 


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9.3. 
Humphrey 24-2 Visual Field Test 
A summary table presenting the observed values and changes from baseline will be presented for 
mean deviation (dB) by treatment group for the Safety population. Changes from baseline to 
each scheduled post-baseline visit will be presented.  
 
Visual field test data will be presented in a listing.  
9.4. 
Clinical Laboratory Evaluations 
Laboratory assessments will be performed by a local laboratory at the Screening visit only. 
Laboratory results will not be included in the clinical database. Any clinically significant 
laboratory values at Screening will be entered into the subject’s medical history.   
 
The eCRF data of laboratory testing (HIV and syphilis serology), including confirmation that the 
lab tests were performed, an explanation if they were not performed, and whether there were any 
clinically significant values, will be presented in a listing.  
 
Female subjects of child-bearing potential will have urine pregnancy tests conducted throughout 
the study. Any subjects with positive pregnancy test results at any time during the study will be 
presented in a listing. The listing will also include the subject’s fertility status collected at the 
Screening visit.  
9.5. 
Vital Sign Measurements 
Summary tables will be presented for vital sign data, including sitting systolic blood pressure 
(mmHg), sitting diastolic blood pressure (mmHg) and pulse rate (bpm), by treatment group and 
all subjects for the Safety population. Observed results at each visit and changes from baseline to 
each scheduled post-baseline visit will be presented.  
 
Summaries by treatment group will be based on the number of treated eyes; therefore non-ocular 
vital sign assessments for subjects who have both eyes treated will be included more than once, 
“repeating” and including the assessments once for each treated eye.   
 
All vital sign data will be presented in a listing. 
9.6. 
Physical Examination 
Any abnormalities noted during the physical examination will be presented in a listing for all 
subjects.  
10. Interim Analysis 
No interim analysis is planned for this study. The primary utilization analysis and safety analyses 
will be conducted at the Day 7; i.e., after all subjects have completed the Day 7 visit or have 
been discontinued from the study prior to this visit. Analysis of the study data through Month 12 
(the complete study data) will be performed after all subjects have either completed the Month 
12 visit, or have been discontinued from the study prior to the Month 12. 


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11. Changes in the Planned Analysis 
No changes in the planned analysis at present. 
12. References 
Iluvien Prescribing Information (December 2014).  
 
Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) 
Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of 
the First International Workshop, Am J Ophthalmol 2005; 140: 509-16. 
 
Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory 
activity in intermediate and posterior uveitis. Ophthalmology 1985; 92: 467–71. 
 
Retisert Prescribing Information (June 2011). 
 


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13. Appendices 
 
13.1. Schedule of Study Procedures and Assessments 
 
Assessments 
Screening 
Day 
1 
Day 
7 
Day 
28 
Month 
3 
Month 
12 
Timing/Interval 
-60  
1 
±3D 
±14D 
±21D 
±28D 
Medical/Ophthalmic History 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
Vital Signsa 
X 
X 
X 
X 
X 
X 
Clinical Labsb 
X 
 
 
 
 
 
Ophthalmic Examinationc 
X 
X 
X 
X 
X 
X 
Visual Field 
X 
 
 
 
 
X 
Pregnancyd 
X 
X 
 
 
 
X 
Randomization 
 
X 
 
 
 
 
FAI Insert Administration 
 
X 
 
 
 
 
Post-Administration Assessmente 
 
X 
 
 
 
 
Questionnairef 
 
X 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Adverse Event (AEs) 
 
X 
X 
X 
X 
X 
 
                                                 
a Include systolic/diastolic blood pressure and pulse rate after subject is in the sitting position for at least 5 
minutes.  Height and weight at Screening visit only. 
b HIV and syphilis serology testing. 
c Ophthalmic examination includes: BCVA, IOP [recorded as the mean of three measurements], dilated 
indirect ophthalmoscopy, and anterior, posterior, and intermediate slit lamp examinations.  
d Females of child-bearing potential only: urine test conducted only at Screening, Day 1 and Month 12 
e includes indirect ophthalmoscopy to verify adequate central retinal artery perfusion, absence of any other 
complications, verification of insert placement; IOP [recorded as the mean of three measurements]; follow-
up contact with the subject the day following Study Day 1 regarding the subject’s ocular condition, and any 
complaint and/or adverse event. 
f Following each administration of the FAI insert, the Investigator and the Observer will each complete a 
questionnaire related to the administration procedure. 
 


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13.2. QUESTIONNAIRES 
13.2.1. Mk I Questionnaires 
Investigator Questionnaire 
1. 
Were the instructions for the use of the Mk I inserter clear and understandable? 
If not, please explain. 
 
2. 
The ease of intravitreal administration using the Mk I inserter was: 
a. Very easy 
b. Easy 
c. Routine 
d. Difficult 
e. Very difficult 
 
3. 
Were you able to deliver the insert into the vitreous using the Mk I inserter? 
If not, please explain. 
 
Observer Questionnaire 
1. 
Was sterile technique used to remove the Mk I inserter from the pouch? 
If not, please explain. 
 
2. 
Did the Investigator follow the Mk I inserter instructions for use? 
If not, please explain. 
 
3. 
Did you observe any difficulty experienced by the Investigator during use of the Mk I inserter? 
If yes, please explain. 
 
4. 
Do you have any other observations to report? 
If yes, please explain. 
 
13.2.2. Mk II Inserter Questionnaires 
Investigator Questionnaire 
1. 
Were the instructions for the use of the Mk II inserter clear and understandable? 
If not, please explain. 
 
2. 
The ease of intravitreal administration using the Mk II inserter was: 
a. Very easy 
b. Easy 
c. Routine 
d. Difficult 
e. Very difficult 
 
3. 
Were you able to deliver the insert into the vitreous using the Mk II inserter? 
If not, please explain. 
 


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Observer Questionnaire 
1. 
Was sterile technique used to remove the Mk II inserter from the tray? 
If not, please explain. 
 
2. 
Did the Investigator follow the Mk II inserter instructions for use? 
If not, please explain. 
 
3. 
Did you observe any difficulty experienced by the Investigator during use of the Mk II inserter? 
If yes, please explain. 
 
4. 
Do you have any other observations to report? 
If yes, please explain.