Clinical trial NCT05070728
Conditions: Uveitis Uveitis, Posterior Uveitis, Intermediate
Keywords: EYP-2102 EyePoint Uveitis
Sponsor: EyePoint Pharmaceuticals, Inc.
Start date: 2021-10-13; Completion date: 2023-04-12
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A study to evaluate the safety and efficacy of a fluocinolone acetonide intravitreal (FAI) insert in the management of subjects with chronic non-infectious uveitis affecting the posterior segment of the eye.

Detailed description:
This was a phase 3, multicenter, randomized, masked, controlled study to evaluate the safety and efficacy of an injectable FAI insert for the management of subjects with chronic non-infectious uveitis affecting the posterior segment of the eye. Subjects were randomized to receive either a sham injection or the FAI insert and were observed for 1 year following treatment.

Arms: arm 1: Intravitreal sham injection arm 2: Fluocinolone acetonide (FA) intravitreal 0.05 mg insert (Yutiq 0.05 mg).
Interventions: intervention 1: Sham Injector intervention 2: FAI Insert
Intervention descriptions: intervention 1: Intravitreal sham injection intervention 2: Yutiq 0.05 mg contains 0.05 mg FA and was designed to deliver FA into the vitreous humor for at least 24 weeks.

Yutiq 0.05 mg was administered to the study eye by injection through the pars plana using a pre-loaded applicator with a 25-gauge needle.

Protocol documents:
Prot_000.pdf: 
Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 1 of 63
 
 
Yutiq 0.05 mg 
(Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
 
 
PROTOCOL EYP-2102-001 
 
 
A Phase 3, Multicenter, Prospective, Randomized, Masked, 
Controlled, Safety and Efficacy Study of a Fluocinolone Acetonide 
(FA) Intravitreal 0.05 mg Insert (Yutiq 0.05 mg) in Subjects with 
Chronic Non-Infectious Uveitis Affecting the Posterior Segment of 
the Eye 
 
 
 
 
IND Number 
113140 
Sponsor: 
EyePoint Pharmaceuticals, Inc. 
480 Pleasant Street 
Watertown, MA 02472 USA 
Version: 
3.0 
Protocol Release Date: 
20 Jul 2022 
 
 
 
Confidentiality Statement 
This document contains confidential information, which should not be copied, referred to, released, or 
published without written approval from EyePoint Pharmaceuticals, Inc.  Investigators are cautioned that 
the information given in this study protocol might be subject to change and revision.  Any conclusion 
regarding efficacy and safety must be considered provisional. 
 




Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 3 of 63
 
 
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 United States (US) Food and Drug Administration (FDA) regulations 
(21 CFR Parts 50, 54, 56 and 312) and International Conference on Harmonization (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 EyePoint Pharmaceuticals, Inc. 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 
 
 
 
 
 




Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 5 of 63
 
 
SYNOPSIS 
Name of Sponsor/Company: 
EyePoint Pharmaceuticals, Inc. 
Individual Study Table 
Referring to Part 
of the Dossier 
 
Volume: 
 
Page: 
 
 
(for National Authority 
Use only) 
Name of Investigational Product: 
EYP-2102 (Fluocinolone Acetonide Intravitreal 
0.05 mg Insert [Yutiq 0.05 mg]) 
Name of Active Ingredient: 
Fluocinolone Acetonide 
Title of Study:  A Phase 3, Multicenter, Prospective, Randomized, Masked, Controlled, Safety and 
Efficacy Study of a Fluocinolone Acetonide (FA) Intravitreal 0.05 mg Insert (Yutiq 0.05 mg) in 
Subjects with Chronic Non-Infectious Uveitis Affecting the Posterior Segment of the Eye 
Protocol Number:  EYP-2102-001 
Phase of Development:  3 
Study Centers:  Up to 40 study sites in the United States (US) 
Studied Period:  Up to 52 weeks of follow-up 
Objectives:  To evaluate the safety and efficacy of Yutiq 0.05 mg in the management of subjects with 
chronic non-infectious uveitis affecting the posterior segment of the eye. 
Methodology:  A 52-week, prospective, randomized, masked, controlled, safety and efficacy study of 
intravitreal Yutiq 0.05 mg compared to sham injection with a primary efficacy and safety readout at 
24 weeks. 
Number of Subjects (planned):  Approximately 60 subjects (30 subjects in the Yutiq 0.05 mg group 
and 30 in the sham treatment group) enrolled at approximately 40 sites in the US.  One eye in each 
subject will be designated as the study eye.  The Sponsor decided to stop enrollment in early May 2022 
for reasons other than safety or efficacy, following FDA advice received on January 24, 2022. Subjects 
who were randomized to Yutiq 0.05 mg will continue to be monitored on a modified-protocol 
schedule. The Sponsor is reevaluating the development program of Yutiq 0.05 mg. 
Key Inclusion Criteria: 
1. Male or non-pregnant female at least 18 years of age at time of consent. 
2. One or both eyes having a history of recurrent non-infectious uveitis affecting the posterior 
segment of the eye (intermediate, posterior, or panuveitis) with or without anterior uveitis 
>1 year duration. 
3. During the 52 weeks prior to enrollment (Day 1), the subject must have received treatment for 
uveitis in the study eye with: 
a) Systemic corticosteroid or other systemic therapies for at least 12 consecutive or 
non-consecutive weeks, 
AND/OR 
b) at least 2 intra- or peri-ocular administrations of corticosteroid for management of uveitis 
 
OR 
c) the study eye has experienced recurrence of uveitis at least 2 separate times requiring 
systemic, intra- or peri-ocular injection of corticosteroid. 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 6 of 63
 
 
4. At the time of enrollment (Day 1), the study eye has <10 anterior chamber cells/HPF (high-
power field) and a vitreous haze ≤ grade 2. 
5. Visual acuity of study eye ≥15 letters on the ETDRS chart. 
6. Not planning to undergo elective ocular surgery during the study. 
7. Able to understand and sign the Informed Consent Form (ICF). 
8. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures. 
Key Exclusion Criteria: 
Ocular Exclusion Criteria (for the study eye, unless indicated otherwise): 
1. History of posterior uveitis only that is not accompanied by vitritis or macular edema. 
2. History of iritis only associated with no vitreous cells, anterior chamber cells, or vitreous haze 
at Day 1. 
3. Uveitis with infectious etiology. 
4. Vitreous hemorrhage. 
5. Intraocular inflammation associated with a condition other than noninfectious uveitis (eg, 
intraocular lymphoma). 
6. Uveitis limited to the anterior segment, ie, anterior uveitis only. 
7. Ocular malignancy in either eye, including choroidal melanoma. 
8. Previous viral retinitis. 
9. Toxoplasmosis scar or scar related to previous viral retinitis in the study eye. 
10. Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex 
keratitis (dendritic keratitis), vaccinia, and varicella, mycobacterial infections of the eye, or 
fungal diseases of ocular structures. 
11. Media opacity precluding evaluation of retina and vitreous. 
12. Peripheral retinal detachment in area of insertion. 
13. Intraocular pressure > 22 mmHg or uncontrolled glaucoma (open angle or angle closure) in the 
study eye at Screening; subjects are not excluded if IOP is ≤ 22 mmHg in the study eye with no 
more than 2 classes of IOP lowering medications.  
14. Chronic hypotony (<6 mmHg). 
15. Ocular surgery within 12 weeks prior to Day 1. 
16. Capsulotomy within 30 days prior to Day 1. 
17. Prior intravitreal treatment with Retisert®, ILUVIEN®, or YUTIQ® (0.18 mg) within 
156 weeks prior to Day 1. 
18. Prior intravitreal treatment with OZURDEX® or sub-choroidal injection with XIPERE™ 
within 24 weeks prior to Day 1. 
19. Prior intravitreal treatment with Triesence® or TRIVARIS™ within 12 weeks prior to Day 1. 
20. Peri-ocular or subtenon steroid treatment within 12 weeks prior to Day 1. 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 7 of 63
 
 
21. Significant structural issues that put the subject at risk for implant migration to the anterior 
chamber (e.g. large iris defects or an anterior chamber lens). 
All other Exclusion Criteria: 
22. Allergy to fluocinolone acetonide or any component of Yutiq 0.05 mg. 
23. Requirement for chronic systemic or inhaled corticosteroid therapy (>15mg prednisone daily) 
or chronic systemic immunosuppressive therapy. 
24. History of certain skin cancers (specifically, basal cell carcinoma and squamous cell 
carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to 
Day 1. 
25. Positive test for human immunodeficiency virus (HIV) or syphilis during Screening. 
26. Mycobacterial uveitis or chorioretinal changes of either eye which, in the opinion of the 
Investigator, result from infectious mycobacterial uveitis. 
27. Systemic infection within 30 days prior to Day 1. 
28. Any severe acute or chronic medical or psychiatric condition that could increase the risk 
associated with study participation or could interfere with the interpretation of study results 
and, in the judgment of the Investigator, could make the subject inappropriate for study 
enrollment. 
29. Any other systemic or ocular condition which, in the judgment of the Investigator, could make 
the subject inappropriate for study enrollment. 
30. Treatment with an investigational drug or device within 30 days prior to Day 1. 
31. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to 
use an acceptable method of contraception as outlined in the protocol from at least 14 days 
prior to Day 1 until the 52-week Visit. 
32. Unlikely to comply with the study protocol or who are likely to be lost to follow-up within 
52 weeks. 
Treatment Assignment:  Study subjects will be randomly assigned to receive either Yutiq 0.05 mg 
(the test article) or an intravitreal sham injection in the designated study eye. 
Control:  Intravitreal sham injection 
Duration of Treatment:  Twenty-four weeks (based on in vivo release rates of Yutiq 0.05 mg in 
nonclinical study data) with expected tapering of FA release through 52 weeks. 
Test Article Therapy:  Fluocinolone acetonide intravitreal 0.05 mg insert (Yutiq 0.05 mg).  
Yutiq 0.05 mg contains 0.05 mg FA and is designed to deliver FA into the vitreous humor for at least 
24 weeks.  Yutiq 0.05 mg will be administered to the study eye by injection through the pars plana 
using a pre-loaded applicator with a 25-gauge needle. 
Designation/Randomization of Study Eye:  For subjects with unilateral uveitis, the study eye will be 
the affected eye; for subjects with bilateral uveitis, the study eye will be the more severely affected eye 
fitting the inclusion/exclusion criteria (ie, the eye having suffered more recurrences in the previous 
year, or if equal, the eye having received more therapy in the previous year, or if equal, the eye having 
the worse VA, or if equal, the eye clinically judged to be the more severely affected eye.)  If the eyes 
are symmetrically affected, the study eye will be the right eye. 
Study Procedures: 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 8 of 63
 
 
Screening (within 30 days prior to injection): 
Eligibility determination, informed consent, demographics, medical and ophthalmic history (including 
a detailed history of the management of their uveitis over the previous 52 weeks), vital signs, clinical 
laboratory testing, ophthalmic examinations (includes BCVA, IOP, dilated ophthalmoscopy, and 
anterior, posterior and intermediate slit lamp examination), subjective ocular tolerability and 
discomfort assessment, concomitant medications, and pregnancy testing as appropriate. 
Treatment Day (Day 1): 
Eligibility confirmation including meeting the entry criteria for anterior chamber cells, vitreous haze, 
IOP, and visual acuity on Study Day 1, and then randomization to either intravitreal Yutiq 0.05 mg or 
sham injection.  Following determination of study eye, subjects will receive either Yutiq 0.05 mg or the 
sham injection.  Assessments on that day will include vital signs, ophthalmic examinations, spectral-
domain – optical coherence tomography (SD-OCT), subjective ocular tolerability and discomfort 
assessment, pregnancy test if appropriate, concomitant medications, and adverse events (AEs). 
Follow-up Visits: 
Following injection on Study Day 1, subjects who were treated with Yutiq 0.05 mg will return for 
study visits on Days 7, 28, and at Months 2, 3, 6, and 12.  Evaluations on these days will include:  
review of concomitant medications, vital signs, ophthalmic examinations, IOP, SD-OCT, subjective 
ocular tolerability and discomfort assessment, and AEs.  All subjects treated with Yutiq 0.05 mg in the 
study will be followed for 52 weeks. In early May 2022, those subjects who had been treated with 
sham injection were discontinued from the study. Sham-treated subjects subsequently had their End of 
Study (EOS) evaluation. 
Masking:  Study subjects will receive either Yutiq 0.05 mg or a sham injection.  Subjects and study 
staff conducting clinical study assessments, except for the clinician performing the injection procedure, 
will be masked to randomized treatment assignment.  
Concomitant Medications: 
Subjects may be treated prior to study entry in order to meet study inclusion criteria and obtain a 
relatively quiet eye prior to enrollment.  If a subject is receiving a systemic treatment regimen or 
topical steroids to control uveitis prior to study enrollment, that subject will have such treatment ended 
within 12 weeks following Study Day 1, in a manner that follows the standard of care for ending the 
specific treatment.  For example, some systemic treatments may be ended immediately, while others 
require a period of gradual dose reduction (tapering). 
If a subject experiences a recurrence of uveitis in either eye that requires treatment during the study, 
local (topical, periocular, or intraocular) treatment will be used as the first line of therapy.  Systemic 
immunosuppressants or systemic steroids will be used only if local therapy fails.  Subjects who 
experience a recurrence of uveitis will continue in the study; once the subject’s recurrence is 
controlled, treatment will be ended in a manner that follows the standard of care for the specific 
treatment regimen. 
Criteria for Evaluation: 
Efficacy 
Primary Efficacy Endpoint:  Proportion of subjects who have a recurrence of uveitis in the study eye 
within 24 weeks (6 months) after receiving study treatment.  Recurrence is defined as: 
• 
An increase in the vitreous haze of ≥2 steps compared to baseline or any visit time point 
prior to the Week 24 visit; 
OR 
• 
A deterioration in visual acuity of at least 15 letters BCVA compared to baseline or any 
visit time point prior to the Week 24 visit. 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 9 of 63
 
 
Any criterion used to define recurrence must be attributable only to noninfectious uveitis.  To prevent 
post-procedural inflammatory reactions from being reported as uveitis recurrences, assessments for 
recurrence of uveitis begin after the Study Day 7 visit. 
Secondary Efficacy Endpoints: 
• 
Proportion of subjects who have a recurrence of uveitis in the study eye within 52 weeks 
• 
Proportion of subjects who have a recurrence of uveitis in the fellow eye within 24 and 52 
weeks 
• 
Mean change from baseline in BCVA letter score in the study eye at 24 and 52 weeks 
• 
Number of recurrences of uveitis within 24 and 52 weeks 
• 
Time to recurrence of uveitis through 24 and 52 weeks 
• 
Number of adjunctive treatments required to treat recurrences of uveitis at 24 and 52 
weeks 
• 
Proportion of subjects with recurrence of iridocyclitis defined as a >2-step increase in 
anterior chamber cells per HPF (1.6 × using a 1-mm beam) in the study eye compared to 
baseline at 24 and 52 weeks. 
• 
Proportion of subjects with resolution of macular edema as measured by SD-OCT imaging 
at Day 28 and at Months 2, 3, 6, and 12. 
Safety 
• 
Systemic AEs 
• 
Ocular AEs, including IOP elevation 
• 
Medications/procedures required to control elevated IOP 
• 
Development or worsening of cataract 
• 
Cataract-related procedures 
• 
Clinically significant ocular changes 
• 
Procedure related AEs 
• 
Subjective ocular tolerability and discomfort assessments 
Statistical Methods: 
Sample Size: 
A total of approximately 60 subjects will be enrolled in the study and receive either Yutiq 0.05 mg or a 
sham injection. The Sponsor decided to stop enrollment for reasons other than safety or efficacy, 
following FDA advice received on January 24, 2022. In early May 2022, subject enrollment into the 
study has been stopped; therefore, the sample size will represent the number of subjects enrolled at the 
time of the Sponsors decision to stop enrollment. 
Analysis Populations: 
The intent-to-treat (ITT) population will include all subjects enrolled in the study.  The Safety 
population will include all subjects enrolled in the study who received Yutiq 0.05 mg.  The per 
protocol (PP) population will be defined separately for the Week 24 and Week 52 analyses, and will 
exclude all subjects in the ITT population who meet any of the following criteria: 
• 
Received systemic treatment for recurrence of uveitis in fellow eye 
• 
Received an imputed endpoint at the Weeks 24 or 52 endpoints of the study 
• 
Failed screening, without exemption, but received Yutiq 0.05 mg 
• 
Had a major protocol deviation 
 
 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 10 of 63
 
 
Efficacy Analyses: 
Efficacy analyses will be performed on both the ITT and PP populations at 24 and 52 weeks.  The 
primary efficacy analysis will be performed on the ITT population at 24 weeks and will be the 
proportion of subjects who have a recurrence of uveitis.  The exact 95% confidence interval for the 
proportion will be derived.  Hypothesis testing using the exact binomial test will be conducted to test 
the difference between the proportion of subjects with a recurrence using a 2-sided alpha = 0.05.  The 
primary efficacy analysis will be conducted after all subjects in the study have completed at least 
24 weeks of study or have discontinued. 
In addition to recurrence based on vitreous haze increase or BCVA loss as defined above, recurrence 
will also be imputed in the following circumstances: 
• 
A subject who has not previously experienced a recurrence and does not complete the required 
eye examinations at Week 24 (or at Week 52 for the Week 52 analyses) for any reason will be 
considered as having a recurrence. 
• 
A subject who has not previously experienced a recurrence and takes a prohibited systemic 
concomitant medication or a prohibited local concomitant medication in the study eye at any 
time during the study prior to Week 24 (or prior to Week 52 for the Week 52 analyses) will be 
considered as having a recurrence. 
Systemic medications or topical steroids administered as part of gradual dose reduction (tapering) will 
not be considered prohibited medications.  Topical steroids, including those administered as part of 
short-term standard treatment following an ocular surgical procedure, will also not be considered 
prohibited medications. 
Safety Analyses: 
Safety analyses will be performed on the safety population at Weeks 24 and 52.  Descriptive statistics 
will be provided for all treatment-emergent adverse events (TEAEs).  Frequency counts and percentage 
of subjects within each treatment group will be provided by using the Medical Dictionary for 
Regulatory Activities (MedDRA) system organ class (SOC) and preferred term (PT) by treatment.  
Clinical laboratory results will be presented by treatment group using descriptive statistics.  Vital signs 
will be presented using descriptive statistics by treatment group and visit.  Subjective ocular tolerability 
and discomfort assessment results will be presented using descriptive statistics by treatment group and 
visit.  Concomitant medications will be presented by treatment group after coding with the World 
Health Organization (WHO) Drug Dictionary terms. 
 
 
 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 11 of 63
 
 
Table of Contents 
PROTOCOL APPROVAL PAGE ...................................................................................................................... 2 
INVESTIGATOR’S AGREEMENT ................................................................................................................... 3 
PERSONNEL CONTACT INFORMATION .................................................................................................... 4 
SYNOPSIS ............................................................................................................................................................. 5 
TABLE OF CONTENTS ................................................................................................................................... 11 
LIST OF TABLES .............................................................................................................................................. 13 
LIST OF FIGURES ............................................................................................................................................ 13 
LIST OF ABBREVIATIONS ............................................................................................................................ 14 
1 
INTRODUCTION ................................................................................................................................... 15 
1.1 
BACKGROUND................................................................................................................................. 15 
1.2 
UVEITIS 15 
1.3 
CURRENT TREATMENTS FOR UVEITIS ............................................................................................. 15 
2 
STUDY OBJECTIVES ........................................................................................................................... 16 
3 
INVESTIGATIONAL PLAN ................................................................................................................. 16 
3.1 
OVERALL STUDY DESIGN ............................................................................................................... 16 
3.2 
DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF CONTROL GROUPS ............................ 17 
3.3 
DURATION OF STUDY ...................................................................................................................... 17 
3.4 
ASSIGNMENT OF SUBJECT IDENTIFICATION NUMBER...................................................................... 18 
3.5 
DESIGNATION OF STUDY EYE AND RANDOMIZATION ..................................................................... 18 
3.5.1 
Unmasking .................................................................................................................... 18 
3.6 
RECORDING OF INJECTION PROCEDURE .......................................................................................... 19 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS ........................................................................ 20 
4.1 
INCLUSION CRITERIA ...................................................................................................................... 20 
4.2 
EXCLUSION CRITERIA ..................................................................................................................... 20 
4.3 
PREGNANCY AND CONTRACEPTION ................................................................................................ 22 
4.4 
STUDY TERMINATION CRITERIA ..................................................................................................... 23 
5 
STUDY PROCEDURES ......................................................................................................................... 24 
5.1 
MEASUREMENTS AND EVALUATIONS BY VISIT ............................................................................... 25 
5.1.1 
Days -30 to 0 (Screening Period) .................................................................................. 28 
5.1.2 
Day 1 (Study Treatment) ............................................................................................... 28 
5.1.3 
Day 7 ............................................................................................................................. 29 
5.1.4 
Day 28 ........................................................................................................................... 30 
5.1.5 
Months 2 and 3 .............................................................................................................. 30 
5.1.6 
Month 6 ......................................................................................................................... 31 
5.1.7 
Month 12 (End of Study) or Early Termination ............................................................ 31 
5.2 
APPROPRIATENESS OF MEASUREMENTS ......................................................................................... 32 
6 
INVESTIGATIONAL MATERIALS .................................................................................................... 32 
6.1 
STUDY DRUG IDENTIFICATION AND DESCRIPTION .......................................................................... 32 
6.1.1 
Yutiq 0.05 mg Composition .......................................................................................... 32 
6.1.2 
Yutiq 0.05 mg Packaging .............................................................................................. 32 
6.2 
YUTIQ 0.05 MG ADMINISTRATION .................................................................................................. 32 
6.2.1 
Yutiq 0.05 mg Injection Procedure ............................................................................... 32 
6.3 
CRITERIA FOR YUTIQ 0.05 MG REMOVAL ....................................................................................... 34 
6.4 
SHAM INJECTOR .............................................................................................................................. 34 
6.4.1 
Description .................................................................................................................... 34 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 12 of 63
 
 
6.4.2 
Sham Injector Packaging and Labeling ......................................................................... 34 
6.4.3 
Sham Injection Procedure ............................................................................................. 34 
6.5 
STORAGE AND DISPENSING OF STUDY TREATMENTS ...................................................................... 34 
6.6 
DRUG ACCOUNTABILITY ................................................................................................................ 34 
7 
CONCOMITANT MEDICATIONS/PROCEDURES ......................................................................... 35 
7.1 
PRIOR MEDICATIONS ...................................................................................................................... 35 
7.2 
TAPERING/ENDING SYSTEMIC OR TOPICAL UVEITIS TREATMENT FOLLOWING DAY 1 ................... 35 
7.3 
IOP REDUCTION THERAPY ............................................................................................................. 35 
7.4 
CATARACT REMOVAL AND OTHER ELECTIVE OCULAR SURGERY .................................................. 35 
7.5 
CONCOMITANT MEDICATIONS ........................................................................................................ 36 
7.6 
RESCUE TREATMENT OF RECURRENCE OF UVEITIS ........................................................................ 36 
7.7 
PROHIBITED MEDICATIONS ............................................................................................................. 36 
8 
ASSESSMENT OF SAFETY ................................................................................................................. 37 
8.1 
ADVERSE EVENTS ........................................................................................................................... 37 
8.1.1 
Ocular Adverse Events .................................................................................................. 38 
8.1.2 
Serious Adverse Events ................................................................................................. 38 
8.1.3 
Sight-Threatening Ocular Events Defined as SAEs in This Study ................................ 39 
8.1.4 
Clinical Laboratory Adverse Events ............................................................................. 40 
8.1.5 
Adverse Event Severity and Relationship ..................................................................... 40 
8.2 
RECORDING OF ADVERSE EVENTS .................................................................................................. 41 
8.3 
ADVERSE EVENT REPORTING ......................................................................................................... 42 
8.3.1 
Reporting of Serious Adverse Events............................................................................ 42 
8.4 
CLINICAL LABORATORY EVALUATIONS ......................................................................................... 44 
8.5 
VITAL SIGNS ................................................................................................................................... 45 
8.6 
SUBJECTIVE OCULAR TOLERABILITY AND DISCOMFORT ASSESSMENT ........................................... 45 
9 
REPORTING OF TECHNICAL PRODUCT COMPLAINTS ........................................................... 45 
10 
ASSESSMENT OF EFFICACY ............................................................................................................. 46 
10.1 
PRIMARY EFFICACY ENDPOINT ....................................................................................................... 46 
10.2 
SECONDARY EFFICACY ENDPOINTS ................................................................................................ 46 
11 
STATISTICAL METHODS AND DATA ANALYSIS ........................................................................ 46 
11.1 
DETERMINATION OF SAMPLE SIZE .................................................................................................. 47 
11.2 
ANALYSIS POPULATIONS ................................................................................................................ 47 
11.3 
GENERAL STATISTICAL CONSIDERATIONS ...................................................................................... 47 
11.3.1 
Data Summarization ...................................................................................................... 47 
11.3.2 
Definition of Baseline ................................................................................................... 47 
11.3.3 
Handling of Missing Data ............................................................................................. 47 
11.3.4 
Multicenter Considerations ........................................................................................... 47 
11.3.5 
Adjustment for Covariates ............................................................................................ 48 
11.3.6 
Interim Analyses ........................................................................................................... 48 
11.3.7 
Multiple Comparisons and Multiplicity ........................................................................ 48 
11.3.8 
Examination of Subgroups ............................................................................................ 48 
11.3.9 
Statistical Software ........................................................................................................ 48 
11.4 
ANALYSES ...................................................................................................................................... 48 
11.4.1 
Subject Disposition ....................................................................................................... 48 
11.4.2 
Demographic and Baseline Characteristics ................................................................... 48 
11.4.3 
Medical/Ophthalmic/Medication History ...................................................................... 48 
11.4.4 
Efficacy Analyses .......................................................................................................... 48 
11.4.5 
Use of Rescue and Prohibited Medications ................................................................... 49 
11.4.6 
Safety Analyses ............................................................................................................. 49 
12 
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS ................................................... 50 
12.1 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................................................. 50 
12.2 
INSTITUTIONAL REVIEW BOARDS/INDEPENDENT ETHICS COMMITTEE ........................................... 50 
12.3 
INFORMED CONSENT PROCESS ........................................................................................................ 51 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 13 of 63
 
 
12.4 
SOURCE DOCUMENTATION ............................................................................................................. 51 
12.5 
ELECTRONIC CASE REPORT FORMS ................................................................................................ 52 
12.6 
RETENTION OF STUDY RECORDS .................................................................................................... 52 
12.7 
MONITORING THE STUDY AND DATA QUALITY ASSURANCE .......................................................... 52 
12.8 
DISCONTINUATION OF THE STUDY .................................................................................................. 53 
12.9 
POLICY FOR PUBLICATIONS ............................................................................................................ 53 
13 
ETHICS .................................................................................................................................................... 53 
13.1 
ETHICS REVIEW .............................................................................................................................. 53 
13.2 
ETHICAL CONDUCT OF THE STUDY ................................................................................................. 54 
13.3 
WRITTEN INFORMED CONSENT ....................................................................................................... 54 
14 
REFERENCES ........................................................................................................................................ 54 
APPENDIX 1: 
MEASUREMENT OF BCVA BY ETDRS ........................................................................ 56 
APPENDIX 2: 
SLIT LAMP BIOMICROSCOPY, OPHTHALMOSCOPY, AND INTRAOCULAR 
PRESSURE .............................................................................................................................................. 57 
APPENDIX 3: 
SUBJECTIVE OCULAR TOLERABILITY AND DISCOMFORT ASSESSMENT ... 60 
APPENDIX 4: 
COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) 
VERSION 5.0 ........................................................................................................................................... 61 
APPENDIX 5: SUMMARY OF CHANGES .................................................................................................... 62 
 
List of Tables 
Table 1–1: 
Abbreviations and Specialist Terms ............................................................................... 14 
Table 5–1: 
Schedule of Study Procedures and Assessments, Study EYP-2102-001 ........................ 26 
 
List of Figures 
Figure 3-1: 
Study Design Schema, Study EYP-2102-001 ................................................................ 17 
 
 
 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
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List of Abbreviations 
Table 1–1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse event 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
ATC 
Anatomical Therapeutic Chemical 
BCVA 
Best corrected visual acuity 
BUN 
Blood urea nitrogen 
CFP 
Color fundus photography 
CFR 
(US) Code of Federal Regulations 
CI 
Confidence interval 
CPR 
Cardiopulmonary resuscitation 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
EC 
Ethics Committee 
eCRF 
Electronic case report form 
ESR 
Erythrocyte sedimentation rate 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA 
Fluocinolone acetonide 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice (guidelines) 
HIV 
Human immunodeficiency virus 
HPF 
High-power field 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IND 
Investigational New Drug application 
IOP 
Intraocular pressure 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IVRS 
Interactive Voice Response System 
MedDRA 
Medical Dictionary for Regulatory Activities 
OTC 
Over-the-counter 
PT 
Preferred term 
PVA 
Polyvinyl alcohol 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD-OCT 
Spectral-domain – optical coherence tomography 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected, unexpected serious adverse reaction 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
US/USA 
United States of America 
USPI 
US prescribing information 
WHO 
World Health Organization 
 
 
 


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1 INTRODUCTION 
1.1 Background 
YUTIQ® (fluocinolone acetonide intravitreal implant) 0.18 mg (180 mcg) is indicated for the 
treatment of chronic non-infectious uveitis affecting the posterior segment of the eye 
(intermediate, posterior, or panuveitis), and was approved for marketing by the United States 
(US) Food and Drug Administration (FDA) in Oct 2018.  In Mar 2019, the product received 
approval under the ILUVIEN® brand in the 17 countries under the Mutual Recognition 
Procedure for prevention of relapse in recurrent non-infectious uveitis affecting the posterior 
segment of the eye.  EyePoint Pharmaceuticals, Inc. (the Sponsor) developed this injectable 
intravitreal implant in a drug delivery system that contains 0.18 mg of fluocinolone acetonide 
(FA) designed to release FA at an initial rate of 0.25 µg/day into the vitreous humor for 36 
months.  YUTIQ® was designed to provide local steroid therapy to the eye for an extended 
period with the goals of eliminating the need for surgical implantation, providing extended, 
effective control of inflammation with an acceptable benefit/risk profile, and reducing the side 
effects associated with systemic administration of corticosteroids or immunomodulating drugs. 
The Sponsor is now developing Yutiq 0.05 mg (FA intravitreal implant) with 0.05 mg (50 mcg) 
of FA for the same indication as that noted above for YUTIQ® 0.18 mg.  Yutiq 0.05 mg is a non-
erodible intravitreal implant in a drug delivery system that contains 0.05 mg of FA and is 
designed to release FA at a rate of 0.25 μg/day into the vitreous humor for at least 6 months.  
Yutiq 0.05 mg is delivered through a siliconized 25-gauge needle using a pre-loaded injector. 
1.2 Uveitis 
Uveitis is defined as inflammation of the uveal tract (iris, ciliary body, choroids) or adjacent 
structures of the eye.  The cause of an inflammatory reaction in 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 affecting the posterior segment of the eye is responsible for approximately 10% of 
blindness in the US.  Chronic non-infectious uveitis affecting the posterior segment of the eye 
can occur at any age and affects people of different ethnic origins.  The inflammation that affects 
the choroid and retina may be a primary intraocular process or an ocular manifestation of 
systemic disease.  Uveitis of the posterior segment accounts for most of the loss of vision in 
patients with uveitis due to cystoid macular edema, glaucoma, retinal detachment, subretinal 
fibrosis, cataract, and optic disk atrophy. 
1.3 Current Treatments for Uveitis 
Uveitis is often a chronic disease requiring long-term medical therapy.  Currently, medical 
management of uveitis of the posterior segment includes the local administration of 
corticosteroid (topical, periocular, intravitreal) and/or systemic steroids or immunosuppressants.  
Immunosuppressive therapy is used for patients with severe uveitis who cannot tolerate or do not 
respond to systemic corticosteroid therapy.  The goal of therapy is to suppress the inflammation 
in the back of the eye. 


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There are disadvantages associated with these treatments and/or their routes of administration.  
All corticosteroid therapy, including systemic, is associated with ocular side effects, in particular 
cataract and corticosteroid-induced increased intraocular pressure (IOP), but these side effects 
are more commonly seen with local therapy.  Topical delivery is not effective for the treatment of 
uveitis of the posterior segment due to its limited intraocular penetration.  Periocular or 
intravitreal corticosteroid injections may be required frequently; however, injections have 
additional potential risks such as globe perforation, orbital fibrosis, endophthalmitis, and ptosis. 
In addition to Yutiq®, corticosteroids currently approved for the intravitreal treatment of chronic 
non-infectious uveitis affecting the posterior segment of the eye include Retisert® (invented by 
Eyepoint and licensed to Bausch and Lomb), OZURDEX®, and TRIVARIS®.  Despite the 
availability of these approved products as intravitreal therapy of uveitis of the posterior segment, 
systemic corticosteroids remain the mainstay of uveitis therapy (MUST Group 2011).  However, 
long-term use of systemic corticosteroids is associated with significant side effects (Brunton et 
al. 2006) and may not be a practical option for many patients. 
Yutiq 0.05 mg, a product that is relatively simple to administer and delivers the corticosteroid 
locally for at least 6 months, may offer significant benefits over existing local and systemic 
steroid therapies in the treatment of chronic non-infectious uveitis affecting the posterior 
segment of the eye. 
For more complete information regarding the safety profile and efficacy of Yutiq 0.05 mg, please 
refer to the current Yutiq Investigator’s Brochure (IB). 
2 STUDY OBJECTIVES 
The primary objective is to evaluate the safety and efficacy of Yutiq 0.05 mg in the management 
of subjects with chronic non-infectious uveitis affecting the posterior segment of the eye 
(intermediate, posterior, or panuveitis). 
3 INVESTIGATIONAL PLAN 
3.1 Overall Study Design 
The protocol was originally planned to be a 52-week, prospective, randomized, masked (subject 
and outcome assessor), controlled, safety and efficacy study of intravitreal Yutiq 0.05  mg 
compared to sham injection with a primary efficacy and safety readout at 24 weeks.  
The Sponsor has decided to stop enrollment for reasons other than safety or efficacy in early 
May 2022, following FDA advice received on January 24, 2022. The Sponsor is reevaluating the 
development program of Yutiq 0.05 mg. Subject enrollment has been stopped, and all subjects 
have been unmasked.  Subjects who were randomized to the sham injection were discontinued 
from the study and underwent their EOS visit. Subjects who were randomized to sham injection 
may have been treated with standard of care medication, if necessary.  Subjects who were 
randomized to Yutiq 0.05 mg will be followed on a modified protocol schedule through 
Month 12 (or ET) and evalulated for efficacy and safety.  
As depicted in Figure 3-1, subjects will receive either Yutiq 0.05 mg or a sham injection on 
Day 1 of the study. Subjects who were treated with Yutiq 0.05 mg will be assessed over the 
following 52 weeks on a modified protocol schedule according to the schedule presented in 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
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Table 5–1. Subjects who were randomized to the sham injection were discontinued from the 
study and underwent their EOS visit. 
 
Figure 3-1: 
Study Design Schema, Study EYP-2102-001 
 
Note: The sponsor decided to stop enrollment for reasons other than safety or efficacy in early May 2022, following 
FDA advice received on January 24, 2022. The Sponsor is reevaluating the development program of Yutiq 0.05 mg 
Subject enrollment in the study has been stopped. All subjects who were currently enrolled have been unmasked. 
Subjects who were to receive Yutiq 0.05 mg will be followed on a modified protocol schedule through Month 12 (or 
ET). 
3.2 Discussion of Study Design, Including the Choice of Control Groups 
A randomized, multicenter, masked, controlled study design has been selected in order to assess 
the safety and efficacy of the study treatment.  This study will utilize a sham injection as the 
control.  To minimize bias, two Investigators will be used at each study site.  One Investigator 
will serve as the unmasked treating Investigator (Investigator 1) and the other Investigator will 
serve as the masked assessing Investigator (Investigator 2).  On Day 1, Investigator 1 will inject 
Yutiq 0.05 mg or perform a sham injection. Either the Investigator 1 or a trained and delegated 
site staff member may also perform all Day 1 procedures and assessments.  At all other visits, 
study assessments will be performed by Investigator 2.  Only Investigator 1 will know the 
assigned treatment and should perform the post-injection indirect ophthalmoscopy to avoid 
unmasking of additional investigators.  Study personnel will use every reasonable effort to 
maintain the study mask. 
3.3 Duration of Study  
All subjects who were randomized to Yutiq 0.05 mg will be followed for 12 months after 
treatment on a modified protocol schedule.  Subjects who were randomized to the sham injection 
have been discontinued from the study and underwent their EOS visit. After the initial Screening 


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visit, subjects will have up to 30 days to be enrolled.  Study treatment will be administered on 
Day 1.  Eligible subjects who are enrolled in this study and randomized to receive Yutiq 0.05 mg 
will be seen for 8 scheduled study visits over approximately 12-14 months depending on the time 
between initial Screening, Day 1, and the final study visit at Month 12.  Screen failures will be 
recorded along with the reason(s) for not meeting the eligibility criteria. 
3.4 Assignment of Subject Identification Number 
Once a subject has provided written informed consent, and it has been determined that the 
subject will undergo screening, a Subject Identification (ID) Number will be assigned by the 
study site.  The first 2 digits of the ID number will be the assigned site number as followed by a 
3-digit number in sequential order (ie, 01-001, 01-002, etc.). 
The ID number is to be recorded on all study documents and will link the documents to the 
subject’s medical record.  To maintain confidentiality, the subject’s name should not be recorded 
on any study document other than the informed consent form (ICF). 
Only those patients who have been randomized will have Exclusion/Inclusion data recorded on 
the electronic case report form (eCRF). 
3.5 Designation of Study Eye and Randomization 
One eye in each subject will be designated as the study eye.  For subjects with unilateral uveitis, 
the study eye will be the affected eye; for subjects with bilateral uveitis, the study eye will be the 
more severely affected eye fitting the inclusion/exclusion criteria (ie, the eye having suffered 
more recurrences in the previous year, or if equal, the eye having received more therapy in the 
previous year, or if equal, the eye having the worse VA, or if equal, the eye clinically judged to 
be the more severely affected eye.)  If the eyes are symmetrically affected, the study eye will be 
the right eye. 
Following confirmation of eligibility on Day 1, subjects will be randomly assigned in a 1:1 ratio 
to either Yutiq 0.05 mg or sham injection through a central Interactive Voice Response System 
(IVRS).  Randomization will be stratified on the basis of whether the subject is receiving 
systemic treatment to control uveitis at the time of study entry. 
The randomization schedule will be prepared using a blocked randomization and will be 
generated by an independent statistician. 
The treatment assignment will be revealed to the assessing Investigator only in emergency 
situations when medical/supportive care cannot be provided without determining which study 
treatment the subject. 
3.5.1 
Unmasking 
Unmasking a subject’s treatment to the assessing Investigator should only be done in emergency 
situations for reasons of subject safety. 
At the initiation of the study, the clinical sites will receive instructions for unmasking a subject. 
In the event that an emergency unmasking is required, the assessing Investigator/medically 
qualified designee has the authority to unmask a subject’s treatment using IVRS, or its back-up 


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system if IVRS is not functioning.  If possible, the assessing Investigator/medically qualified 
designee should contact the Medical Monitor or designee before breaking the mask. 
When the masked treatment code is broken, the date and time of unmasking, name of person 
doing the unmasking, and the reason for unmasking must be fully documented in the source 
documentation. 
3.6 Recording of Injection Procedure 
The injection procedure of Yutiq 0.05 mg may be photographed or video-recorded according to 
the site’s standard procedures.  Images and/or video will be provided to the Sponsor who may 
distribute them to other participating sites or other appropriate parties.  Subject-identifying 
information must be redacted from all images and video prior to distribution. 


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4 SELECTION AND WITHDRAWAL OF SUBJECTS 
 Subject enrollment has been stopped for reasons other than safety or efficacy, following FDA 
advice received on January 24, 2022. See Section 3.1 for further details. Subjects will be enrolled 
in the study only if they meet all the following eligibility criteria. 
4.1 Inclusion Criteria 
Subjects will be considered eligible for participation in the study if all of the following inclusion 
criteria are satisfied: 
1. Male or non-pregnant female at least 18 years of age at time of consent. 
2. One or both eyes having a history of recurrent non-infectious uveitis affecting the 
posterior segment of the eye (intermediate, posterior, or panuveitis) with or without 
anterior uveitis >1 year duration. 
3. During the 52 weeks prior to enrollment (Day 1), the subject must have received 
treatment for uveitis in the study eye with:  
a) Systemic corticosteroid or other systemic therapies for at least 12 consecutive or non-
consecutive weeks, 
AND/OR 
b) at least 2 intra- or peri-ocular administrations of corticosteroid in the study eye, 
OR 
c) the study eye has experienced recurrence of uveitis at least 2 separate times requiring 
systemic, intra- or peri-ocular injection of corticosteroid. 
4. At the time of enrollment (Day 1), the study eye has <10 anterior chamber cells/HPF 
(high-power field) and a vitreous haze ≤ grade 2. 
5. Visual acuity of study eye ≥15 letters on the ETDRS chart. 
6. Not planning to undergo elective ocular surgery during the study. 
7. Able to understand and sign the ICF. 
8. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, 
and other study procedures. 
4.2 Exclusion Criteria 
Subjects who fulfill any of the following criteria will not be recruited into the study: 
Ocular Exclusion Criteria (for the study eye, unless indicated otherwise): 
1. History of posterior uveitis only that is not accompanied by vitritis or macular edema. 
2. History of iritis only associated with no vitreous cells, anterior chamber cells, or vitreous 
haze at Day 1. 
3. Uveitis with infectious etiology. 
4. Vitreous hemorrhage. 


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5. Intraocular inflammation associated with a condition other than noninfectious uveitis (eg, 
intraocular lymphoma). 
6. Uveitis limited to the anterior segment, ie, anterior uveitis only. 
7. Ocular malignancy in either eye, including choroidal melanoma. 
8. Previous viral retinitis. 
9. Toxoplasmosis scar or scar related to previous viral retinitis in the study eye. 
10. Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex 
keratitis (dendritic keratitis), vaccinia, and varicella, mycobacterial infections of the eye, 
or fungal diseases of ocular structures. 
11. Media opacity precluding evaluation of retina and vitreous. 
12. Peripheral retinal detachment in area of insertion. 
13. Diagnosis of any form of glaucoma or ocular hypertension at Screening, unless 
previously treated with an incisional surgery procedure that has resulted in stable 
intraocular pressure (IOP) in the normal range (10-21 mmHg). 
14. IOP >21 mmHg or concurrent therapy at Screening with any IOP-lowering 
pharmacologic agent. 
15. Chronic hypotony (<6 mmHg). 
16. Ocular surgery within 12 weeks prior to Day 1. 
17. Capsulotomy within 30 days prior to Day 1. 
18. Prior intravitreal treatment with Retisert®, ILUVIEN®, or YUTIQ® (0.18 mg) within 
156 weeks prior to Day 1. 
19. Prior intravitreal treatment with OZURDEX® or sub-choroidal injection with XIPERE™ 
within 24 weeks prior to Day 1. 
20. Prior intravitreal treatment with Triesence® or TRIVARIS™ within 12 weeks prior to 
Day 1. 
21. Peri-ocular or subtenon steroid treatment within 12 weeks prior to Day 1. 
All other Exclusion Criteria: 
22. Allergy to fluocinolone acetonide or any component of Yutiq 0.05 mg. 
23. Requirement for chronic systemic or inhaled corticosteroid therapy (>15mg prednisone 
daily) or chronic systemic immunosuppressive therapy. 
24. History of certain skin cancers (specifically, basal cell carcinoma and squamous cell 
carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to 
Day 1. 
25. Positive test for human immunodeficiency virus (HIV) or syphilis during Screening. 
26. Mycobacterial uveitis or chorioretinal changes of either eye which, in the opinion of the 
Investigator, result from infectious mycobacterial uveitis. 


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27. Systemic infection within 30 days prior to Day 1. 
28. Any severe acute or chronic medical or psychiatric condition that could increase the risk 
associated with study participation or could interfere with the interpretation of study 
results and, in the judgment of the Investigator, could make the subject inappropriate for 
study enrollment. 
29. Any other systemic or ocular condition which, in the judgment of the Investigator, could 
make the subject inappropriate for study enrollment. 
30. Treatment with an investigational drug or device within 30 days prior to Day 1. 
31. Pregnant or nursing females; females of childbearing potential who are unwilling or 
unable to use an acceptable method of contraception as outlined in the protocol from at 
least 14 days prior to Study Day 1 until the 52-week Visit. 
32. Unlikely to comply with the study protocol or who are likely to be lost to follow-up 
within 52 weeks. 
4.3 Pregnancy and Contraception 
Women of childbearing potential must be practicing and willing to continue using a highly 
effective method of birth control during the course of the study, such as:  oral contraceptive pill 
(eg, Ortho Tri-Cyclen®); injection (eg, Depo Provera®); implant (eg, Norplant®); patch (eg, 
Ortho Evra Patch®); vaginal ring (eg, NuvaRing®); intrauterine coil (eg, Mirena® coil); 
intrauterine device (IUD); or a barrier method (eg, latex condom, diaphragm, or cap) used with 
an additional form of contraception, ie, two methods (eg, sponge, spermicide, hormonal 
contraceptive pill, or injection).  A female is considered to be of childbearing potential UNLESS 
she is post-menopausal (no menses for two consecutive years) or without a uterus and/or both 
ovaries. 
Before enrolling a woman of childbearing potential, Investigators must review with the subject 
the following: 
• Pregnancy prevention information 
• Risks to unborn child(ren) 
• Risks if currently nursing 
• Any drug interactions with hormonal contraceptives 
• Contraceptives in current use; and 
• Guidelines for the follow-up of a reported pregnancy 
Subjects who become pregnant during the study should be discontinued from the study 
immediately.  Positive urine pregnancy results will be confirmed by a serum pregnancy test.  
Subjects should be instructed to notify the Investigator if it is determined after completion of the 
study that they became pregnant while participating in the study.  However, it is the 
Investigator’s responsibility to pursue the follow-up.  Whenever possible, a pregnancy should be 
followed to term, any premature terminations of pregnancy should be reported, and the status of 
the mother and the child should be reported to the Medical Monitor after delivery. 




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Subjects who are withdrawn due to AEs must be followed until there is either: 
• resolution 
• stabilization or severity to mild 
• returned to baseline status 
• subject is lost to follow-up 
• the event is otherwise explained by the Investigator 
Death:  The subject died during the study. 
Withdrawal of Consent:  The subject desired to withdraw from further participation in the study 
in the absence of a medical need to withdraw as determined by the Investigator.  If the subject 
gave a reason for this desire, this should be recorded. 
Major Protocol Violation:  There was failure to meet the protocol entry criteria or the subject 
failed to adhere to the protocol requirements or received prohibited medication (eg, subject 
failure to follow instructions, or inability to complete study assessments).  The violation 
necessitated premature termination from the study. 
Other:  The subject was terminated for a reason other than those listed above, such as termination 
of study by the Sponsor or a regulatory authority.  The Investigator must specify the reason. 
5 STUDY PROCEDURES 
To ensure the health of both eyes, observations of both the study eye and non-study (fellow) eye 
should be made at all visits as described in the Schedule of Study Procedures and Assessments 
(Table 5–1).  Data will be collected for both eyes at all visits except for the SD-OCT 
assessments, which will be collected in the fellow eye only at Day 1, Day 28, and at the early 
termination or Month 12 (end of study) visit. 
BCVA by ETDRS:  The equipment and procedures necessary for testing BCVA are presented in 
Appendix 1.  Visual acuity is always tested with the subject’s best correction, and should be 
measured prior to pupil dilation and slit lamp biomicroscopy examination or any drops or 
ointments being used.  BCVA by ETDRS will be measured at every study visit (Table 5–1).  
Visual acuity testing in this study is required at a distance of 4 meters, and for subjects with 
reduced vision at 1 meter.  Each site should have at least one certified refractionist available for 
the use of ETDRS charts.  An ETDRS-certified refractionist should perform all protocol 
refraction and BCVA measurements required by the protocol. 
Slit lamp Biomicroscopy:  Anterior chamber evaluation will be conducted using a slit beam of 
1 mm height and 1 mm width with maximum luminance through the highest powered lens using 
the Investigator’s standard slit lamp equipment and procedure.  This procedure will be the same 
for all subjects observed at the Investigator’s site.  Ocular structures, including vitreous haze, the 
presence of anterior chamber cells, and fundus examination will be measured according to the 
scales and conventions presented in Appendix 2.  Ocular examinations will be done at the study 
visits noted in (Table 5–1). 


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Dilated Ophthalmoscopy:  Will be performed according to the Investigator’s preferred 
procedure.  This procedure will be the same for all subjects observed at the Investigator’s site 
(Appendix 2).  Ocular examinations will be done at the study visits noted in Table 5–1. 
Intraocular Pressure/Tonometry:  IOP will be measured as described in Appendix 2 at the 
study visits noted in (Table 5–1). 
SD-OCT Assessments:  Spectral-domain – optical coherence tomography assessments of both 
eyes will be taken by a study-certified OCT technician according to the standardized procedures 
described in the Study Manual.  Because the eye must be dilated for OCT, it must be performed 
after testing visual acuity if these procedures are performed on the same day.  SD-OCT testing 
will be done at the study visits noted in (Table 5–1).   
Ocular and Non-ocular TEAEs:  Adverse events will be recorded at each study visit by asking 
the subject “How are you feeling today?” and additional questions as necessary, making an 
assessment of the reason for use of new concomitant medications or concurrent procedures (see 
Section 8.1). 
5.1 Measurements and Evaluations by Visit 
The schedule of study procedures and assessments by visit is presented in Table 5–1.  The 
Sponsor decided to stop enrollment for reasons other than safety or efficacy, following FDA 
advice received on January 24, 2022. The Sponsor is reevaluating the development program of 
Yutiq 0.05 mg. All subjects have been unmasked.  Subjects who had been assigned to sham were 
discontinued from the study in early May 2022 and were treated with standard of care 
medication, if necessary.  Subjects who had been treated with Yutiq 0.05 mg will be followed at 
Month 6 and 12 (or ET).  
 
 
 


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Table 5–1: 
Schedule of Study Procedures and Assessments, Study EYP-2102-001 
 
Screening 
Day 1 
Day 7 
Day 28 
Months 2, 3 
Months 6, 12 or ET 
Timing/Interval: 
-30 to 0 
1 
±2 days 
±3 days 
±7 days 
±28 days 
Informed Consent 
X 
 
 
 
 
 
Medical/Ophthalmic/Medication History 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Pregnancy Testa 
X 
X 
 
 
 
Xgh 
Vital Signsb 
X 
X 
X 
X 
X 
X 
Clinical Laboratoriescd 
X 
 
 
 
 
Xg 
ETDRS BCVA 
X 
X 
X 
X 
X 
X 
Ophthalmic Examinationsde 
X 
X 
X 
X 
X 
X 
Intraocular Pressure (IOP)e 
X 
X 
X 
X 
X 
X 
SD-OCTf 
 
X 
 
X 
X 
X 
Subjective Ocular Tolerability/Discomfort 
X 
X 
X 
X 
X 
X 
Yutiq 0.05 mg Placement or Sham Injection 
 
X 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
BCVA = Best corrected visual acuity; ET =  Early termination; ETDRS = Early treatment diabetic retinopathy study; HIV = Human immunodeficiency virus; SD-OCT = 
Spectral domain – optical coherence tomography 
Note: Yutiq 0.05 mg = Fluocinolone acetonide (FA) intravitreal 0.05 mg insert 
Note: For subjects with unilateral uveitis, the study eye will be the affected eye; for subjects with bilateral uveitis, the study eye will be the more severely affected eye fitting 
the inclusion/exclusion criteria (ie, the eye having suffered more recurrences in the previous year, or if equal, the eye having received more therapy in the previous year, 
or if equal, the eye having the worse VA, or if equal, the eye clinically judged to be the more severely affected eye.)  If the eyes are symmetrically affected, the study 
eye will be the right eye. 
Note: All ocular procedures and assessments will be performed on both the study eye and non-study (fellow) eye and data will be collected for both eyes with the exception of 
SD-OCT assessments (see footnote “g” below). 
(table footnotes on next page) 


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Footnotes for Table 5-1: 
a. 
Females of child-bearing potential only.  Urine pregnancy test done at Screening, Day 1, and Month 12. 
b. 
Vital signs will include systolic/diastolic blood pressure and pulse rate measured after the subject is in the sitting position for at least 5 minutes, height and weight (at 
Screening only). 
c. 
Routine clinical laboratory tests will include:  hematology (including erythrocyte sedimentation rate); serum chemistry; urinalysis; HIV and syphilis serology testing; 
tuberculosis testing (Screening only). 
d. 
Ophthalmic examinations will include:  dilated indirect ophthalmoscopy, and anterior, posterior, and intermediate slit lamp examinations. 
e. 
IOP will be recorded in the eCRF as the mean of three measurements. 
f. 
SD-OCT assessments will only be collected in the fellow eye at Day 1, Day 28, Month 6, and Month 12 (end of study) visits or at ET. 
g. 
To be done at Month 12 (end of study) visit, or for ET only. 
 
 
 


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5.1.1 
Days -30 to 0 (Screening Period) 
The following procedures must be completed during the initial Screening period (Table 5–1). 
Informed Consent:  Properly executed informed consent (written and verbal) is to be obtained 
prior to completion of any trial related procedures.  A subject may take as long as needed to 
review the ICF and consider trial participation; they may take the document with them and return 
for Day 1 at a later date (provided the study is still open for enrollment).  The subject must 
review, sign and date the document and receive a copy. 
Inclusion/Exclusion Criteria:  Inclusion/exclusion criteria (Section 4.1 and Section 4.2, 
respectively) will be reviewed to determine the subject’s eligibility to participate in the trial with 
the Investigator verifying enrollment eligibility. 
Demography, Medical/Ophthalmic History, and Medication History:  Demography, medical 
history, complete ophthalmic surgical and medical history, and recent (previous 30 days) 
ophthalmic and systemic concomitant medications are to be recorded.  Please document current 
contact lens use or ocular trauma in the study eye. 
Ocular Procedures to be Performed with Data Collected for Both Eyes: 
• BCVA (Appendix 1) 
• Intraocular pressure (Appendix 2) 
• Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
• Subjective ocular tolerability and discomfort assessment (Appendix 3) 
Non-Ocular Procedures to be Performed: 
• Collect urine sample for pregnancy testing in female subjects of childbearing potential 
(Section 4.3) 
• Vital sign measurements (Section 8.4) 
• Collect blood and urine samples for clinical laboratory evaluations (Section 8.2) 
• Prior and concomitant mediations (Section 7.1 and Section 7.5, respectively) 
• Adverse events, which will be collected from the time the ICF is signed (Section 8.1) 
5.1.2 
Day 1 (Study Treatment) 
The following procedures will be completed during the Day 1 visit (Table 5–1). 
Inclusion/Exclusion Criteria:  Will be reviewed again (Section 4.1 and Section 4.2, respectively) 
to confirm the subject’s eligibility to keep participating in the trial with the Investigator verifying 
eligibility. 
Randomization and Study Eye:  If still meeting the eligibility criteria, study subjects will then be 
randomized using the IVRS to receive either intravitreal Yutiq 0.05 mg or sham injection in the 
designated study eye on Day 1 (Section 3.5). 
Study Treatment Administration:  Yutiq 0.05 mg will be administered to the designated study eye 
by injection through the pars plana into the vitreous humor using a pre-loaded applicator with a 


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25-gauge siliconized needle.  The complete intravitreal injection procedure is presented in 
Section 6.2.1.  The intravitreal injection procedure is the same as that described in the current US 
prescribing information (USPI) for the marketed product YUTIQ® 0.18 mg (YUTIQ® USPI, 
2021). 
Subjects assigned to the sham injection control group will be prepared for injection in the same 
manner as subjects in the Yutiq 0.05 mg treatment group and will receive the same post-
treatment evaluations and medications.  However, when the Investigator opens the treatment 
packaging for a subject assigned to the sham injection control group, the package will contain an 
empty syringe with a blunt needle attached.  The sham injection will consist of pressing the blunt 
needle against the sclera of the eye with approximately the same pressure as would be used 
during the injection of Yutiq 0.05 mg (Section 6.4.3). 
Ocular Procedures to be Performed with Data Collected for Both Eyes (unless otherwise 
specified): 
• BCVA (Appendix 1) 
• Intraocular pressure (Appendix 2) 
• Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
• SD-OCT assessment 
• Subjective ocular tolerability and discomfort assessment (Appendix 3) 
Non-Ocular Procedures to be Performed: 
• Vital sign measurements (Section 8.4) 
• Collect urine sample for pregnancy testing in female subjects of childbearing potential 
(Section 4.3) 
• Prior and concomitant mediations (Section 7.1 and Section 7.5, respectively) 
• Adverse events (Section 8.1) 
5.1.3 
Day 7 
The following procedures will be completed during the Day 7 visit (Table 5–1). 
Ocular Procedures to be Performed with Data Collected for Both Eyes (unless otherwise 
specified): 
• BCVA (Appendix 1) 
• Intraocular pressure (Appendix 2) 
• Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
• Subjective ocular tolerability and discomfort assessment (Appendix 3) 
Non-Ocular Procedures to be Performed: 
• Vital sign measurements (Section 8.4) 
• Concomitant and rescue mediations (Section 7.5 and Section 7.6, respectively) 


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• Adverse events (Section 8.1) 
Unscheduled visit assessments may be performed as necessary at the discretion of the 
Investigator following Sponsor approval. 
5.1.4 
Day 28 
The following procedures will be completed during the Day 28 visit (Table 5–1). 
Ocular Procedures to be Performed with Data Collected for Both Eyes (unless otherwise 
specified): 
• BCVA (Appendix 1) 
• Intraocular pressure (Appendix 2) 
• Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
• SD-OCT assessment 
• Subjective ocular tolerability and discomfort assessment (Appendix 3) 
Non-Ocular Procedures to be Performed: 
• Vital sign measurements (Section 8.4) 
• Concomitant and rescue mediations (Section 7.5 and Section 7.6, respectively) 
• Adverse events (Section 8.1) 
Unscheduled visit assessments may be performed as necessary at the discretion of the 
Investigator following Sponsor approval. 
5.1.5 
Months 2 and 3 
The following procedures will be completed during the Month 2 and Month 3 visits (Table 5–1). 
Ocular Procedures to be Performed with Data Collected for Both Eyes (unless otherwise 
specified): 
• BCVA (Appendix1) 
• Intraocular pressure (Appendix 2) 
• Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
• SD-OCT assessment (study eye only) 
• Subjective ocular tolerability and discomfort assessment (Appendix 3) 
Non-Ocular Procedures to be Performed: 
• Vital sign measurements (_Vital_Signs_1) 
• Concomitant and rescue mediations (_Concomitant_Medications and 
_Rescue_Medications, respectively) 
• Adverse events (_Adverse_Events) 


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5.1.6 
Month 6  
The following procedures will be completed during the Month 6 visit (Table 5–1). 
Ocular Procedures to be Performed with Data Collected for Both Eyes (unless otherwise 
specified): 
• BCVA ( 
• Intraocular pressure (Appendix 2) 
• Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
• SD-OCT assessment (study eye only) 
• Subjective ocular tolerability and discomfort assessment (Appendix 3) 
Non-Ocular Procedures to be Performed: 
• Vital sign measurements (_Vital_Signs_1) 
• Concomitant and rescue mediations (_Concomitant_Medications and 
_Rescue_Medications, respectively) 
• Adverse events (_Adverse_Events) 
5.1.7 
Month 12 (End of Study) or Early Termination 
The following procedures will be completed during the Month 12 (End of Study) visit, or at early 
termination (Table 5–1).  Subjects who terminate the study prior to the Month 12 visit should 
undergo all procedures noted below. 
Ocular Procedures to be Performed with Data Collected for Both Eyes (unless otherwise 
specified): 
• BCVA (Appendix 1) 
• Intraocular pressure (Appendix 2) 
• Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
• SD-OCT assessment 
• Subjective ocular tolerability and discomfort assessment (Appendix 3) 
Non-Ocular Procedures to be Performed: 
• Collect urine sample for pregnancy testing in female subjects of childbearing potential 
(Section 4.3) 
• Vital sign measurements (Section 8.4) 
• Collect blood and urine samples for clinical laboratory evaluations (Section 8.2) 
• Concomitant and rescue mediations (Section 7.5 and Section 7.6, respectively) 
• Adverse events (Section 8.1) 




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equivalent).  Adequate anesthesia and a broad-spectrum microbicide should be given prior to the 
injection.  The injection procedure for Yutiq 0.05 mg is as follows: 
1. Just prior to injection, administer topical and/or subconjunctival anesthesia at the 
injection site (inferotemporal quadrant recommended). 
2. Administer 2-3 drops of a broad-spectrum microbicide into the lower fornix.  The lids 
may be scrubbed with cotton-tipped applicators soaked with a broad-spectrum 
microbicide.  Place a sterile lid speculum.  Have the patient look up and apply additional 
microbicide solution to the injection site.  Allow 30-60 seconds for the topical antiseptic 
to dry prior to injection of Yutiq 0.05 mg. 
3. Optimal placement of Yutiq 0.05 mg 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. 
4. Using sterile procedure, open the sterile foil pouch containing Yutiq 0.05 mg. 
5. Remove the Yutiq 0.05 mg applicator from the sterile pouch by grasping the barrel of the 
applicator; do not grasp the plunger. 
6. Remove the black plunger stop from the plunger. 
7. Carefully remove the protective cap from the needle and inspect the needle tip to ensure 
it is not bent. 
8. Remove the trombone wire from the distal end of the needle.  Prior to injection, keep the 
applicator tip above the horizontal plane to ensure that the Yutiq 0.05 mg implant does 
not fall out of the applicator. 
9. 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. 
10. Insert the needle through the conjunctiva and sclera up to the positive stop of the 
applicator. 
11. Depress the plunger at the back of the applicator fully to deliver the Yutiq 0.05 mg 
implant into the back of the eye. 
12. Remove the Yutiq 0.05 mg applicator from the eye and discard in a biohazard sharps 
container. 
13. 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 implant.  Scleral depression may enhance visualization of the implant.  Immediate 
measurement of IOP may be performed at the discretion of the Investigator. 
Following the injection, subjects should be monitored for change in IOP and for endophthalmitis.  
Monitoring may consist of a check for perfusion of the optic nerve head immediately after the 
injection, tonometry within 30 minutes following the injection, and biomicroscopy.  Subjects 
should be instructed to report without delay any symptoms suggestive of endophthalmitis. 


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6.3 Criteria for Yutiq 0.05 mg Removal 
The Investigator should consider removing Yutiq 0.05 mg 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 marketed product YUTIQ® 0.18 mg, the likelihood 
that insert removal will become necessary is very small. 
6.4 Sham Injector 
6.4.1 
Description 
The sham applicator is an empty 1-mL syringe attached to a blunt needle; it does not contain an 
intravitreal insert. 
6.4.2 
Sham Injector Packaging and Labeling 
Sham injectors will be supplied as individual finished products in primary, secondary, and 
tertiary packaging.  The primary packaging is the sham applicator, which includes a blunt needle.  
The sham 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 for investigational use in accordance with applicable regulations.  
The assembled units are subsequently sterilized by gamma irradiation, resulting in the sham 
injector, a sterile, single-use product. 
6.4.3 
Sham Injection Procedure 
The sham injection will consist of pressing the blunt needle against the sclera of the eye with 
approximately the same pressure as would be used during the injection of Yutiq 0.05 mg. 
6.5 Storage and Dispensing of Study Treatments 
Yutiq 0.05 mg and the sham injectors must be stored in a secure place and at controlled room 
temperature (15°C to 30°C/59°F to 86°F) and in the original containers. 
The Investigator has the overall responsibility for ensuring that study treatments are stored in a 
safe location with limited-access under the specified storage conditions.  Limited responsibility 
may be delegated to a pharmacy representative; however, this delegation must be documented. 
6.6 Drug Accountability 
The Investigator is responsible for ensuring adequate accountability of all used and unused study 
treatments.  While the Investigator may delegate components of drug accountability tasks to 
documented designee(s) (eg, pharmacist or staff designee), the ultimate responsibility for drug 
control and accountability resides with the Investigator.  This includes acknowledgment of 
receipt of each shipment (quantity and condition), maintenance of subject dispensing records and 
returned (as required) documentation.  Dispensing records will document quantities received 
from the Sponsor (or designee) and quantities dispensed to subjects, including treatment 


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kit/package number, date dispensed, subject identification number, subject initials, and the 
initials of the person dispensing drug will be recorded on the drug accountability log. 
During study initiation, the study monitor (Clinical Research Associate, CRA) will evaluate and 
obtain a copy of each site’s written standard operating procedure for study drug disposal/ 
destruction or return to ensure that it complies with Sponsor requirements if supplies will not be 
returned. 
An inspection for inventory and accounting purposes, and the assurance of proper storage, will 
also be conducted during monitoring visits.  Any significant accounting or storage discrepancy 
will be recorded and reported to the Sponsor and a plan for resolution will be documented.  After 
the monitor has checked and verified drug accountability during interim site visits and at the end 
of the study, any expired, partially-used, and used product should be handled according to the 
Sponsor’s instructions (ie, returned or destroyed). 
7 CONCOMITANT MEDICATIONS/PROCEDURES 
7.1 Prior Medications 
Prior medications are defined as all prescription, vaccinations, supplements, herbal therapies, any 
prohibited medications, and over-the-counter (OTC) medications taken within the 30 days 
(whether continuing or not) prior to Day 1.  All prior medications must be documented on the 
concomitant medications eCRF. 
7.2 Tapering/Ending Systemic or Topical Uveitis Treatment Following Day 1 
Subjects may be treated prior to entry in order to meet study inclusion criteria.  The objective of 
prior treatment is to obtain a relatively quiet eye prior to enrollment.  If a subject is receiving 
systemic corticosteroids or immunosuppressants, or topical steroids to control uveitis prior to 
study enrollment, that subject will have such treatment ended within 3 months following Day 1, 
in a manner that follows the standard of care for ending the specific treatment.  For example, 
some systemic treatment regimens may be ended immediately, while others require a period of 
gradual dose reduction (tapering).  Systemic medications or topical steroids administered as part 
of gradual dose reduction are not considered prohibited medications. 
7.3 IOP Reduction Therapy 
Pharmacologic treatment (eyedrops) of elevated IOP must be instituted whenever the IOP is 
>30 mmHg, and may be instituted at lower IOP levels at the discretion of 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 (laser, trabeculectomy).  The Investigator should obtain 
information on the treatment administered by non-study ophthalmologists for inclusion in the 
study records. 
7.4 Cataract Removal and Other Elective Ocular Surgery 
Cataracts are recommended to be removed by extra-capsular extraction with 
phacoemulsification.  A cataract may be removed prior to a subject’s enrollment.  Because of the 
importance of VA evaluations in this study, the timing of cataract removal or any elective surgery 


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during the post-treatment follow-up period should be scheduled at least 4 weeks prior to any 
study visit involving VA assessment. 
7.5 Concomitant Medications 
All prescription and OTC concomitant medications used concurrently (from the time of ICF 
signing through Month 12) must be documented on the concomitant medication eCRF. 
Information on the concomitant medication/therapy eCRF includes the name of the 
medication/therapy, dose, frequency, route, dates of use, and indication for use.  Subjects should 
be instructed not to take any medication including OTC products, without first consulting with 
the Investigator.  Any AE(s) that result(s) from taking a concomitant medication/therapy 
following the first study dose should be recorded on the AE eCRF. 
7.6 Rescue Treatment of Recurrence of Uveitis 
In the event of a uveitis recurrence in either eye (defined as an “Endpoint”), peri-ocular or 
intraocular corticosteroid injections, or topical medications should be administered as first line 
local therapy, in accordance with the protocol.  Investigators should consider treatment with 
topical steroids as first line therapy for a recurrence that involves only an increase in anterior 
chamber cells with no increase in vitreous opacity.  Systemic immunosuppressants or systemic 
steroids should be used only if local therapy fails. 
Subjects who experience a recurrence of uveitis will continue participation in the study.  Once 
the subject’s recurrence is controlled, the treatment regimen (local or systemic therapy) will be 
ended in a manner that follows the standard of care for ending the specific treatment regimen. 
Details of each recurrence and its treatment will be documented in the eCRF. 
7.7 Prohibited Medications 
Other than the exceptions described in Section 7.2, Section 7.6, or below, the following 
concomitant medications are not permitted during the study: 
• Oral, systemic, injectable, or topical steroids 
• Systemic immunosuppressants 
Systemic medications or topical steroids administered as part of gradual dose reduction 
(tapering), as described in Section 7.2, are not considered prohibited medications.  Additionally, 
topical steroids administered as short-term standard treatment following an ocular surgical 
procedure are not considered prohibited medications. 
It is advisable for the Investigator to discuss treatment with the Medical Monitor before 
administering any prohibited medication unless it is an emergency. 
Any medications or therapies that the subject is using during the study period and that would 
preclude eligibility as indicated in the Exclusion Criteria (Section 4.2), are prohibited 
medications. 
All prohibited medications used concurrently (from Day 1 through Month 12) must be 
documented in the eCRF. 


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8 ASSESSMENT OF SAFETY 
Safety assessments will include the incidence and severity of TEAEs reported after Screening, 
safety data collected from ocular examinations and IOP measurements, ocular tolerability and 
discomfort assessments, vital sign measurements, clinical laboratory tests, and the use of rescue 
and concomitant medications. 
8.1 Adverse Events 
The following are specific definitions of terms guided by the International Conference on 
Harmonization (ICH E2) Guidelines for Good Clinical Practice (GCP) and the US Code of 
Federal Regulations (CFR) that apply to the following sections.  The severity of AEs will be 
graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 5 
(Appendix 4). 
Definition of Adverse Event: 
An 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 and that does not necessarily have a causal relationship with the product.  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 an 
investigational product, whether or not considered related to the investigational product. 
AEs may also include pre- or post-treatment complications that occur as a result of protocol-
specified procedures (eg, invasive procedures such as venipuncture, delivery procedure, etc).  
Pre-existing conditions that increase in severity or change in nature during (or as a consequence 
of use of a medicinal product in) the study will also be considered AEs. 
An AE Will Not Include: 
• Medical or surgical procedures (eg, surgery, endoscopy, tooth extraction, transfusion) for 
events that led to the procedure 
• Pre-existing diseases, conditions, or laboratory abnormalities present or detected prior to 
the Screening visit, unless they worsen during the study 
• Situations where an AE or untoward medical occurrence has not occurred (eg, 
hospitalization for elective surgery, social and/or convenience admissions) 
Associated with the Use of the Drug (Causality): 
There is a reasonable possibility that the event may have been caused by the investigational drug 
(and/or the administration procedure). 
Unexpected Adverse Event: 
Any event that is not identified in nature, severity, or frequency in the current version of the IB.  
For example, if the IB referred to elevated hepatic enzymes or hepatitis, then an event of hepatic 
necrosis would be considered unexpected by the virtue of the greater severity.  The Sponsor or 
designee will determine AE expectedness. 


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8.1.1 
Ocular Adverse Events 
The following ocular events will be considered AEs for the purposes of this study: 
• Decrease in BCVA of at least ≥15 letters or ≥3 lines from the previous BCVA 
measurement 
• Moderate or severe (Grade 3 or 4) ocular findings compared to the last ocular 
examination 
• Worsening of >2 steps in anterior chamber cell count or vitreous haze compared to the 
last ocular examination 
• Increase in IOP of >10 mmHg at two visits at least 1 week apart or an increase in IOP to 
>25 mmHg 
8.1.2 
Serious Adverse Events 
An SAE is any AE that results in one of the following outcomes: 
• Death/Fatal 
• 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 (formal admission to a hospital for medical reasons for 
any length of time), or prolongs existing hospitalization. 
• Results in a persistent or significant disability/incapacity, or substantial disruption of the 
ability to conduct normal life functions. 
• Congenital anomaly/birth defect (in the child of a subject who was exposed to the study 
treatment). 
• Other important medical event.  Medical and scientific judgment should be exercised in 
determining whether an event is an important medical event.  An important medical event 
may not be immediately life-threatening and/or result in death or hospitalization but 
required medical intervention in order to prevent a SAE outcome.  However, if it is 
determined that the event may jeopardize the subject and/or may require intervention to 
prevent one of the other SAE outcomes, the important medical event should be reported 
as serious.  Examples of such events are intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse. 
The following hospitalizations will not be considered SAEs: 
• A visit to the emergency room or other hospital department for <24 hours that does not 
result in in-patient admission (unless considered an “important medical event” or a “life-
threatening event”). 
• Elective surgery or planned surgery prior to signing the ICF. 
• Admissions as per protocol for a planned medical/surgical procedure. 


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• Routine health assessments requiring admission for baseline/trending of health status (eg, 
routine colonoscopy). 
• Medical/surgical admission for a purpose other for healthcare purposes 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/or requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, care-giver respite, family circumstances, administrative). 
Clarification of SAEs: 
• Death is an outcome of an AE, and not an AE in itself. 
• All deaths, regardless of cause or relationship, must be reported. 
• Complications that occur during hospitalizations are AEs.  If a complication prolongs 
hospitalization, it is an SAE. 
• “In-patient hospitalization” means the subject has been formally admitted to a hospital for 
medical reasons for any length of time.  This may or may not be overnight.  It does not 
include presentation to, and/or care within, an emergency department. 
• The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. 
8.1.3 
Sight-Threatening Ocular Events Defined as SAEs in This Study 
In addition to the standard SAE categories described above, this study defines these additional 
ocular events as SAEs: 
• An AE that causes a decrease in visual acuity of ≥30 letters or ≥6 lines from the most 
recent previous measurement of visual acuity, lasting more than 1 hour. 
• An AE that causes a decrease in visual acuity to light perception or worse, lasting more 
than 1 hour. 
• An AE that requires surgical intervention (eg, 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 that is associated with severe intraocular inflammation (ie, 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 IOP-lowering medications. 
• An IOP <6 mmHg requiring medical intervention. 
• An AE that in the opinion of the Investigator requires medical or surgical intervention to 
prevent permanent loss of sight. 
The Investigator must employ all necessary therapeutic measures to resolve the SAE.  Any 
medications or therapies used to treat the SAE must be recorded in the eCRF. 


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8.1.4 
Clinical Laboratory Adverse Events 
An abnormal laboratory result should be considered an AE if it: 
• Results in the initiation or change of an intervention (eg, increased dose of medication), 
based on medical evaluation (eg, packed red cells for low hemoglobin). 
• Results in any out of range laboratory value that in the Investigator’s judgment fulfills the 
definitions of an AE. 
• Increases in severity compared to baseline. 
Abnormal laboratory values should not be listed as separate AEs if they are considered to be part 
of the clinical syndrome that is being reported as an AE.  Any laboratory abnormality considered 
to constitute an AE should be reported on the AE eCRF.  It is the responsibility of the 
Investigator to review all laboratory findings in all subjects and determine if they constitute an 
AE.  Medical and scientific judgment should be exercised in deciding whether an isolated 
laboratory abnormality should be classified as an AE. 
All laboratory AEs should be repeated and reassessed by the Investigator to track resolution and 
especially to confirm if they meet the definition of serious.  If serious, they will be reported as 
SAEs. 
The Investigator or a licensed designee must review all laboratory results in a timely manner as 
demonstrated by signature/date. 
8.1.5 
Adverse Event Severity and Relationship 
Adverse event severity is defined as a qualitative assessment of the intensity of an AE as 
determined by the Investigator.  The assessment of severity is made irrespective of the 
relationship or seriousness of the event to study treatment or the injection device. 
In the absence of an assigned severity per the CTCAE v5.0 (Appendix 4) grading criteria, the 
Investigator will grade AEs according to the following severity criteria: 
Mild/Grade 1: 
The event may be noticeable to subject; does not influence daily 
activities; usually does not require intervention. 
Moderate/Grade 2: 
The event may be of sufficient severity to make subject 
uncomfortable; performance of daily activities may be influenced; 
intervention may be needed. 
Severe/Grade 3: 
The event may cause severe discomfort; usually interferes with 
daily activities; subject may not be able to continue in the study; 
treatment or other intervention usually required. 
Life- or Sight- 
Threatening/Grade 4: The event requires urgent intervention to preserve life and/or 
permanent loss of vision. 
Death/Grade 5: 
The event resulted in the subject’s death. 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 41 of 63
 
 
The relationship of study treatment (ie, Yutiq 0.05 mg), the injector, or the injection procedure, to 
each AE must be determined by the Investigator according to the following: 
Not Related: 
Evidence indicates no plausible direct relationship to the study 
treatment, device, or procedure, or there is a reasonable causal 
relationship between non-investigational product, concurrent 
disease, or circumstance and the AE; and/or a causal relationship is 
considered biologically implausible. 
Possibly Related: 
There is reasonable causal relationship between the study treatment, 
device, or procedure and the AE. There may or may not be a 
clinically-plausible temporal sequence between the onset of the AE 
and study treatment, device, or procedure; the AE is not reasonably 
supported by other conditions. 
Probably Related: 
The study medication, device, or procedure and AE occurrence are 
reasonably related in time; a clinically-plausible temporal sequence 
between the onset of the AE and study treatment, device, or 
procedure is likely; based upon the Investigator’s clinical 
experience, the association of the AE with study medication, 
device, or procedure is likely; all other potential causes have been 
ruled out. 
If the relationship between the AE/SAE and the sequence study treatment, device, or procedure is 
determined to be “possible” or “probable”, the event will be considered related for the purposes 
of expedited regulatory reporting. 
8.2 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 may be spontaneously reported or elicited at each study visit through open-ended 
questioning, examination, or evaluation of a subject.  To prevent reporting bias, subjects should 
not be questioned regarding the specific occurrence of one or more AEs. 
The Investigator will record all AEs in the eCRF.  Where a diagnosis is possible, it is preferable 
to report the diagnosis rather than a series of terms (signs/symptoms) relating to the diagnosis.  If 
a definitive diagnosis is not possible, the individual symptoms and signs should be recorded. 
The following information must be captured for all AEs: 
• onset and end date 
• severity 
• seriousness 
• relationship to study treatment or the injection device, procedure 
• action taken 


Yuti q  0. 0 5 m g  ( Fl u oci n ol o ne Acet o ni de I ntra vitreal 0. 0 5 m g  I nsert) 
E ye P oi nt P h ar m ace utic als, I nc.  
Pr ot oc ol E Y P -2 1 0 2 -0 0 1 (Ve r s i o n  3 . 0) 
 
 
Fi nal:  2 0  J ul 2 0 2 2  
C O N FI D E N TI A L  
Pa ge 4 2  of 6 3  
 
 
 
 
•  a n y treat me nt re q uire d  
•  o utc o me 
If treat me nt f or t he A E was a d mi nistere d, it s h o ul d be rec or de d o n t he a p pr o priate c o nc o mita nt 
me dicati o n/ pr oce d ure e C R F pa ge.  Eac h disti nct A E s h o ul d be rec or de d se paratel y. 
8. 3  A d verse E ve nt Re p orti n g  
All s u bjects e nr olle d i n t he st u d y will be e val uate d f or A Es, w hic h will be c ollecte d fr o m t he 
ti me t he I C F is si g ne d u ntil st u d y c o m pleti o n ( Ta ble  5 – 1). 
All A Es will be e val uate d fr o m o nset u ntil res ol uti o n or sta bilizati o n, w hic he ver is first.  A d verse 
e ve nts t hat c o nti n ue after t he s u bject’s disc o nti n uati o n or c o m pleti o n of t he st u d y will be 
f oll o we d u ntil t heir me dical o utc o mes are deter mi ne d or u ntil no f urt her c ha n ge i n t he c o n diti o n 
is e x pecte d.  T he e ve nt a n d o utc o me will be re p orte d i n writi n g b y t he I n vesti gat or t o t he 
S p o ns or.  T he I n vesti gat or s hall s u p pl y t he S p o ns or a n d I nstit uti o nal Re vie w B oar d (I R B)/ Et hics 
C o m mittee ( E C)  wit h a n y a d diti o nal re q ueste d i nf or mati o n, n ota bl y f or re p orte d deat hs. 
8. 3. 1  
Re p orti n g of Seri o us A d verse E ve nt s 
All S A Es, re gar dless of ca use(s) or relati o ns hi p t o st u d y dr u g, m ust be rec or de d o n t he 
a p pr o priate e C R F pa ge a n d re p orte d t o t he S p o ns or wit hi n 2 4 h o urs of t he I n vesti g at or’s 
first a w are ness usi n g t he st u d y’s desi g nate d S A E Re p ort F or m. 
Mi ni mal i nf or mati o n t o be pr o vi de d o n t he S A E Re p ort F or m i ncl u des: 
•  Pr ot oc ol n u m ber 
•  Site a n d I n vesti gat or i de ntifiers  
•  S u bject n u m ber 
•  Brief descri pti o n of t he e ve nt(s)  
•  O nset date of t he e ve nt  
•  O utc o me of t he e ve nt as of t he date of re p ort, if k n o w n 
•  Res ol uti o n date a n d ti me, if t he e ve nt(s) res ol ve d  
•  A n y me dicati o n a d mi nistere d t o treat t he e ve nt  
•  I n vesti gat or’s assess me nt of t he ca usal relati o ns hi p of t he S A E t o t he i n vesti gati o nal 
pr o d uct 
•  A d diti o nal a n d f oll o w- u p i nf or mati o n as re q ueste d b y S p o ns or or its desi g nee 
S A Es m ust be re p orte d usi n g t he st u d y’s desi g nate d S A E Re p ort F or m a n d se nt t o: 
E m ail:  
  
F a x:  
 
T he I n vesti gat or will als o c o m pile wit h ur ge nt pri orit y ot her rele va nt d oc u me ntati o n (e g, c o pies 
of test res ults, h os pital disc har ge s u m mar y, a ut o ps y re p ort, etc.) a n d se n d t his i nf or mati o n t o t he 
S p o ns or ( or S p o ns or’s desi g nee). 
P P D
P P D


Yuti q  0. 0 5 m g  ( Fl u oci n ol o ne Acet o ni de I ntra vitreal 0. 0 5 m g  I nsert) 
E ye P oi nt P h ar m ace utic als, I nc.  
Pr ot oc ol E Y P -2 1 0 2 -0 0 1 (Ve r s i o n  3 . 0) 
 
 
Fi nal:  2 0  J ul 2 0 2 2  
C O N FI D E N TI A L  
Pa ge 4 3  of 6 3  
 
 
 
 
T he F D A a n d all partici pati n g I n vesti gat ors s hall be n otifie d b y a writte n I n vesti gati o nal Ne w 
Dr u g A p plicati o n (I N D) safet y re p ort of a n y A E ass ociate d wit h t he use of t he i n vesti gati o nal 
pr o d uct t hat is b ot h seri o us a n d u ne x pecte d n o later t ha n 1 5 cale n dar da ys fr o m t he S p o ns or’s 
a ware ness date of t he e ve nt.  A n S A E is c o nsi dere d t o be ass ociate d wit h t he use of t he 
i n vesti gati o nal pr o d uct if t he relati o ns hi p bet wee n t he S A E a n d t he i n vesti gati o nal pr o d uct is 
classifie d b y t he I n vesti gat or as “ p ossi bl y re late d” or “ pr o ba bl y relate d” (ie, s us pecte d, 
u ne x pecte d seri o us a d verse reacti o n [ S U S A R]) .  A n y u ne x pecte d fatal or life-t hreate ni n g S A E 
ass ociate d wit h t he use of t he i n vesti gati o nal pr o d uct will be re p orte d t o t he F D A b y t he S p o ns or 
wit hi n 7 cale n dar da ys. 
T he I R B/ E C s h o ul d be n otifie d of S A Es  as re q uire d i n acc or da nce wit h t he l ocal i nstit uti o nal 
p olic y. 
All I n vesti gat or s partici pati n g i n t he st u d y will be n otifie d of u ne x pecte d S A Es deter mi ne d t o be 
relate d t o st u d y treat me nt/i njecti o n pr oce d ure. 
Pre g n a nc y  Re p orti n g  
Pre g na nc y t hat occ urs d uri n g t he st u d y m ust be i m me diatel y re p orte d t o t he I n vesti gat or w h o 
will i m me diatel y n otif y t he S p o ns or or desi g nee wit hi n 2 4 h o urs of first a ware ness usi n g t he 
st u d y’s desi g nate d Pre g na nc y Re p ort F or m.  T his i ncl u des a n y pre g na nc y f oll o wi n g mater nal or 
pater nal e x p os ure t o t he i n vesti gati o nal pr o d uct. 
T he pre g na nc y s h o ul d be f oll o we d t o ter m.  T he o utc o me, i ncl u di n g pre mat ure ter mi nati o n m ust 
als o be re p orte d t o t he S p o ns or or desi g nee wit hi n 2 4 h o urs of t he I n vesti gat or ’s a ware ness usi n g 
t he Pre g na nc y Re p ort F or m.  All li ve birt hs m ust be f oll o we d f or a mi ni m u m of 4 wee ks or t o t he 
first well- ba b y visit.  All re p orts of c o n ge nital a b n or malities/ birt h defects a n d s p o nta ne o us 
a b orti o ns/ miscarria ges s h o ul d be re p orte d as S A Es.  Electi ve a b orti o n pr oce d ures wit h o ut 
c o m plicati o ns s h o ul d n ot be c o nsi dere d as A Es . 
If t he I n vesti gat or bec o mes a ware of a pre g na nc y occ urri n g i n a n y male s u bject’s part ner d uri n g 
t he male s u bject’s treat me nt wit h t he i n vesti gati o nal pr o d uct, t he I n vesti gat or m ust s u b mit t his 
i nf or mati o n t o t he S p o ns or o n t he Pre g na nc y Re p ort F or m. 
T he Pre g na nc y Re p ort F or m s h o ul d be se nt t o: 
E m ail:  
  
F a x:  
 
S peci al Sit u ati o ns  
N otificati o n m ust be ma de t o t he S p o ns or or desi g nee of a n y s pecial sit uati o n t hat i ncl u des t he 
f oll o wi n g, re gar dless of a n y ass ociate d A E : 
•  A me dicati o n err or, defi ne d as a n y u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g, or 
a d mi nistrati o n of a me dici nal pr o d uct w hile i n t he c o ntr ol of t he healt h care pr o vi der or 
s u bject. 
•  A b use, defi ne d as persiste nt or s p ora dic i nte nti o nal e xcessi ve use of a me dici nal or ot her 
pr o d uct. 
•  Mis use, defi ne d as a n y i nte nti o nal or i na p pr o priate use of a me dici nal pr o d uct t hat is n ot 
i n acc or da nce wit h t he pr ot oc ol i nstr ucti o ns or l ocal prescri bi n g i nf or mati o n. 
P P D
P P D


Yuti q  0. 0 5 m g  ( Fl u oci n ol o ne Acet o ni de I ntra vitreal 0. 0 5 m g  I nsert) 
E ye P oi nt P h ar m ace utic als, I nc.  
Pr ot oc ol E Y P -2 1 0 2 -0 0 1 (Ve r s i o n  3 . 0) 
 
 
Fi nal:  2 0  J ul 2 0 2 2  
C O N FI D E N TI A L  
Pa ge 4 4  of 6 3  
 
 
 
 
•  A n o ver d ose, defi ne d as a n acci de ntal or i nte nti o nal a d mi nistrati o n of a q ua ntit y of a 
me dici nal pr o d uct gi ve n per a d mi nistrati o n or c u m ulati vel y w hic h is a b o ve t he ma xi m u m 
rec o m me n de d d ose per pr ot oc ol or i n t he pr o d uct la beli n g.  I n cases of a discre pa nc y i n 
dr u g acc o u nta bilit y, o ver d ose will be deter mi ne d o nl y w he n it is clear t hat t he s u bject 
recei ve d a n e xcess d ose(s). 
S pecial sit uati o ns s h o ul d be re p orte d o n t he st u d y’s desi g nate d S pecial Sit uati o n Re p ort F or m 
e xce pt pre g na ncies f or w hic h t here is a de dicate d f or m.   If a n y s pecial sit uati o n res ults i n cli nical 
se q uela(ae)/A E(s) , t he e ve nt(s) m ust be rec or de d o n t he A E e C R F.  If t he A E  is seri o us, t he S A E 
e C R F m ust be c o m plete d a n d a S A E Re p ort F or m m ust be c o m plete d a n d s u b mitte d t o t he 
S p o ns or or desi g nee wit hi n 2 4 h o urs of first a ware ness. 
S pecial sit uati o ns i n v ol vi n g c o nc o mita nt me dicati o n d o n ot nee d t o be re p orte d o n t he S pecial 
Sit uati o n re p ort f or m.   H o we ver, s pecial sit uati o ns i n v ol vi n g c o nc o mita nt me dicati o n t hat res ult 
i n cli nical se q uelae/ A Es s h o ul d be re p orte d o n t he A E e C R F.  I n a d diti o n, a n y i na p pr o priate use 
of pr o hi bite d c o nc o mita nt me dicati o ns s h o ul d n ot be re p orte d as “ mis use” b ut ma y be m o re 
a p pr o priatel y d oc u me nte d as a pr ot oc ol de viati o n. 
T he S pecial Sit uati o n Re p ort F or m s h o ul d be se nt t o: 
E m ail:  
  
F a x:  
 
8. 4  Cli nic al L a b or at or y E v al u ati o ns  
T he r o uti ne cli nical la b orat or y tests n ote d bel o w will be perf or me d at Scree ni n g a n d M o nt h 1 2 
( or earl y ter mi nati o n) o nl y (Ta ble  5 – 1): 
•  He mat ol o g y (sta n dar d tests)  
•  E r yt hr oc yte se di me ntati o n rate (E S R ) 
•  Ser u m electr ol ytes:  s o di u m, p otassi u m, c hl ori de, calci u m , bicar b o nate 
•  Re nal f u ncti o n tests:  ser u m creati ni ne, bl o o d urea nitr o ge n ( B U N) 
•  H e patic f u ncti o n  tests:  ser u m bilir u bi n, al kali ne p h os p hatase, as partate  tra nsa mi nase 
( A S T), ala ni ne tra nsa mi nase ( A L T), al b u mi n, t otal pr otei n 
•  HI V a n d s y p hilis ser ol o g y testi n g  
•  Scree ni n g test f or late nt m yc o bacteri u m t u berc ul osis ( T B) i nfecti o n ( Scree ni n g o nl y) 
•  Uri nal ysis (sta n dar d tests)  
•  Uri ne pre g na nc y test (f or fe male  su bjects  of c hil d beari n g p ote ntial) 
I n vesti gat ors m ust re vie w a n d d oc u me nt la b orat or y test res ults, as well as a d dress t he cli nical 
si g nifica nce a n d ca usalit y (f or si g nifica nt a b n or malities).  Cli nicall y si g nifica nt a b n or mal 
la b orat or y res ults s h o ul d be re peate d as s o o n as p ossi ble.  Secti o n 7. 1. 4  pr o vi des f urt her 
g ui da nce as t o w he n a b n or mal la b orat or y res ults are t o be re p orte d as A Es. 
P P D
P P D


Yuti q  0. 0 5 m g  ( Fl u oci n ol o ne Acet o ni de I ntra vitreal 0. 0 5 m g  I nsert) 
E ye P oi nt P h ar m ace utic als, I nc.  
Pr ot oc ol E Y P -2 1 0 2 -0 0 1 (Ve r s i o n  3 . 0) 
 
 
Fi nal:  2 0  J ul 2 0 2 2  
C O N FI D E N TI A L  
Pa ge 4 5  of 6 3  
 
 
 
 
8. 5  Vit al Si g ns  
Vital si g ns , i ncl u di n g meas ure me nts of hei g ht a n d wei g ht, will i ncl u de s yst olic/ diast olic bl o o d 
press ure a n d p ulse rate meas ure d after t he s u bject is i n t he sitti n g p ositi o n f or at least 5 mi n utes  
at t he visits i n dicate d i n Ta ble  5 – 1. 
8. 6  S u bjecti ve Oc ul ar T oler a bilit y a n d Disc o mf ort Assess me nt  
T hese s u bject assess me nts will be meas ure d as descri be d i n A p pe n di x 3 .  Oc ular disc o mf ort will 
be meas ure d usi n g a 6 -p oi nt scale (fr o m “a bse nt” t o “i nt olera ble”) a n d oc ular t olera bilit y will be 
meas ure d usi n g a vis ual a nal o g scale.  T hese s u bject assess me nts will be meas ure d at e ver y st u d y 
visit ( Ta ble  5 – 1). 
9  R E P O R TI N G O F T E C H NI C A L P R O D U C T C O M P L AI N T S  
A Pr o d uct C o m plai nt is defi ne d as a n y writte n, electr o nic, or ver bal e x pressi o n of dissatisfacti o n 
re gar di n g t he i de ntit y, q ualit y, relia bilit y, safet y, p urit y, p ote nc y, effecti ve ness, or perf or ma nce of 
a n i n vesti gati o nal or c o m mercial pr o d uct after it is release d f or distri b uti o n. (e g, a n y fail ure of 
t he a p plicat or t o deli ver t he i ntra vitreal i nsert), or dissatisfacti o n wit h a n y ot her c haracteristic(s) 
of t he dr u g pr o d uct (e g, la beli n g, pac ka gi n g, etc). 
A n y/all Pr o d uct C o m plai nts s h o ul d be re p orte d t o E ye P oi nt wit hi n 2 4 h o urs usi n g t he desi g nate d 
Pr o d uct C o m plai nt Re p ort F or m.  T he c o m plai nt re p ort s h o ul d i ncl u de t he f oll o wi n g 
i nf or mati o n: 
•  Pr o d uct i de ntificati o n n u m ber  
•  I n vesti gat or na me, st u d y ce nter na me, a n d c o ntact p h o ne n u m ber 
•  Date t he c o m plai nt occ urre d  
•  Brief descri pti o n of t he c o m plai nt  
•  S u bject i n v ol ve d? ( yes or n o); if yes, were a n y A Es ass ociate d wit h t he c o m plai nt? ( yes 
or n o).  If ( yes) a n A E is ass ociate d wit h t he c o m plai nt, please refer t o Secti o n 8. 1 . 
O nce all i nf or mati o n is c ollecte d  please re p ort t o:  
E m ail:  
 
P h o ne:  
 
T he dr u g c o ntai ner (a p plicat or, f oil p o uc h, a n d cart o n) f or w hic h t he c o m plai nt was i nitiate d 
s h o ul d be retai ne d f or ret ur n t o E ye P oi nt f or a nal ysis. 
Atte nti o n: 
Pr o d uct Ret ur ns 
E ye P oi nt P har mace uticals, I nc.  
4 8 0 Pleasa nt Street  
Watert o w n, M A 0 2 4 7 2 U S A 
A n y c o m plai nt a b o ut a n i n vesti gati o nal pr o d uct m ust be re p orte d re gar dless of w het her t he 
defect or deficie nc y ha d a n y effect o n a s u bject or o n st u d y pers o n nel. 
P P D
P P D


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 46 of 63
 
 
10 
ASSESSMENT OF EFFICACY 
10.1 Primary Efficacy Endpoint 
The primary efficacy endpoint will be the proportion of subjects who have a recurrence of uveitis 
in the study eye within 24 weeks (6 months) after receiving study treatment.  Recurrence is 
defined as: 
• An increase in the vitreous haze of ≥2 steps compared to baseline or any visit time point 
prior to the Week 24 visit; 
OR 
• A deterioration in visual acuity of at least 15 letters BCVA compared to baseline or any 
visit time point prior to the Week 24 visit. 
Any criterion used to define recurrence must be attributable only to noninfectious uveitis.  To 
prevent post-procedural inflammatory reactions from being reported as uveitis recurrences, 
assessments for recurrence of uveitis begin after the Study Day 7 visit. 
Refer to Appendix 2 for additional information. 
10.2 Secondary Efficacy Endpoints 
The secondary efficacy endpoints will include: 
• Proportion of subjects who have a recurrence of uveitis in the study eye within 52 
weeks 
• Proportion of subjects who have a recurrence of uveitis in the fellow eye within 24 and 
52 weeks 
• Mean change from baseline in BCVA letter score in the study eye at 24 and 52 weeks 
• Number of recurrences of uveitis within 24 and 52 weeks 
• Time to recurrence of uveitis through 24 and 52 weeks 
• Number of adjunctive treatments required to treat recurrences of uveitis at 24 and 52 
weeks 
• Proportion of subjects with recurrence of iridocyclitis defined as a >2-step increase in 
anterior chamber cells per HPF (1.6 × using a 1-mm beam) in the study eye compared 
to baseline at 24 and 52 weeks. 
• Proportion of subjects with resolution of macular edema as measured by SD-OCT 
imaging at Day 28 and at Months 2, 3, 6, and 12. 
11 
STATISTICAL METHODS AND DATA ANALYSIS 
Detailed methodology for statistical analyses of the data collected in this study will be 
documented in a Statistical Analysis Plan (SAP), which will be developed and maintained by the 
Sponsor. 


Yutiq 0.05 mg (Fluocinolone Acetonide Intravitreal 0.05 mg Insert) 
EyePoint Pharmaceuticals, Inc.
Protocol EYP-2102-001 (Version 3.0) 
 
Final:  20 Jul 2022 
CONFIDENTIAL 
Page 47 of 63
 
 
The SAP may modify the plans outlined in the protocol; however, any major modifications of the 
primary endpoint definition and/or its analysis will also be reflected in a protocol amendment. 
All study data will be presented in by-subject listings. 
11.1 Determination of Sample Size 
Subject enrollment has been stopped due to reassons other than safety or efficacy. See 
Section 3.1 for further details. 
11.2 Analysis Populations 
The intent-to-treat (ITT) population will include all subjects enrolled in the study.  The Safety 
population will include all subjects enrolled in the study who received Yutiq 0.05 mg.  The per 
protocol (PP) population will be defined separately for the Week 24 and Week 52 analyses, and 
will exclude all subjects in the ITT population who meet any of the following criteria: 
• Received systemic treatment for recurrence of uveitis in fellow eye 
• Received an imputed endpoint at the Weeks 24 or 52 endpoints of the study 
• Failed screening, without exemption, but received Yutiq 0.05 mg 
• Had a major protocol deviation 
11.3 General Statistical Considerations 
11.3.1 Data Summarization 
Tabular data summaries for variables measured on a continuous scale will include descriptive 
statistics (n, mean, median, standard deviation, minimum, and maximum) by treatment group. 
For variables evaluated on a categorical scale, data summaries will include the number and 
percentage of subjects who provide each possible category, by treatment group.  The 95% 
confidence interval (CI) of the proportions will be constructed for each dose cohort, as 
appropriate. 
11.3.2 Definition of Baseline 
Baseline measurements are those taken at Screening or prior to receiving study treatment on 
Day 1, whichever is the latest. 
11.3.3 Handling of Missing Data 
In general, missing data will not be imputed, unless otherwise specified.  Early termination visits 
will be mapped to the next scheduled visit for inclusion in summary tables, where appropriate.  
Every effort will be made to ensure completeness of data collection. 
11.3.4 Multicenter Considerations 
Up to 40 investigative study centers will participate in the study.  All centers will be located in 
the United States.  Data will be pooled for all study centers for data analysis, unless otherwise 
specified.  


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11.3.5 Adjustment for Covariates 
Not applicable. 
11.3.6 Interim Analyses 
No formal interim analyses are planned for this study. 
11.3.7 Multiple Comparisons and Multiplicity 
Not applicable. 
11.3.8 Examination of Subgroups 
Subgroup analyses will be performed on the primary efficacy variable.  Analyses will be 
performed to determine the treatment effect within specific subgroups of interest, and to 
determine if the treatment effect is consistent across different subgroup levels.  Subgroups will 
be defined on the basis of baseline characteristics, including severity of edema, duration of 
disease, lens status, IOP, presence/absence of vitrectomy, and BCVA.  Further details will be 
provided in the SAP. 
11.3.9 Statistical Software 
All statistical summaries and analyses will be produced using SAS, Release 9.3 or higher. 
11.4 Analyses 
11.4.1 Subject Disposition 
A summary table will be prepared indicating the number and percentage of subjects in each 
treatment group who were included in each analysis population.  Within the ITT population, the 
number and percentage of subjects who did/did not complete the study will be presented.  Screen 
failures, including reasons for failing to satisfy eligibility criteria will also be summarized.  
Subjects who discontinue any time during the study will be categorized by reason for 
termination, and the percentage within each category will be provided.  Duration of study 
participation and insert duration will also be tabulated. 
11.4.2 Demographic and Baseline Characteristics 
Demographics and baseline characteristics will be summarized by treatment group using 
descriptive statistics for the ITT population. 
11.4.3 Medical/Ophthalmic/Medication History 
Medical history data will be coded and listed by treatment group. 
11.4.4 Efficacy Analyses 
Efficacy analyses will be performed on both the ITT and PP populations at 24 and 52 weeks.  
The primary efficacy analysis will be performed on the ITT population at 24 weeks and will be 
the proportion of subjects who have a recurrence of uveitis.  The exact 95% CI for the proportion 
will be derived.  Hypothesis testing using the exact binomial test will be conducted to test the 


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difference between the proportion of subjects with a recurrence using a 2-sided alpha = 0.05.  
The primary efficacy analysis will be conducted after all subjects in the study have completed at 
least 24 weeks of study or have discontinued. 
In addition to recurrence based on vitreous haze increase or BCVA loss as defined above, 
recurrence will also be imputed in the following circumstances: 
• A subject who has not previously experienced a recurrence and does not complete the 
required eye examinations at Week 24 (or at Week 52 for the Week 52 analyses) for any 
reason will be considered as having a recurrence. 
• A subject who has not previously experienced a recurrence and takes a prohibited 
systemic concomitant medication or a prohibited local concomitant medication in the 
study eye at any time during the study prior to Week 24 (or prior to Week 52 for the 
Week 52 analyses) will be considered as having a recurrence. 
Systemic medications or topical steroids administered as part of gradual dose reduction 
(tapering) will not be considered prohibited medications.  Topical steroids, including those 
administered as part of short-term standard treatment following an ocular surgical procedure, will 
also not be considered prohibited medications. 
11.4.5 Use of Rescue and Prohibited Medications 
During the study, some subjects may require rescue treatments in the study eye as a result of AEs 
or lack of efficacy of the study treatment.  Prior to database lock, the Sponsor will conduct a 
blinded data review to classify concomitant treatments as either rescue (Section 7.6) or 
prohibited (Section 7.7).  The proportion of subjects receiving these medications will be 
summarized by treatment type (rescue or prohibited), treatment group, and time point. 
11.4.6 Safety Analyses 
Safety analyses will be performed on the Safety population at Weeks 24 and 52.  Descriptive 
statistics will be provided for all treatment-emergent adverse events (TEAEs).  Both ocular and 
non-ocular TEAEs are defined as events that start after the study drug administration, and occur 
before termination of the study, or were present before study drug administration and worsened 
after dose administration. 
Frequency counts and percentage of subjects within each treatment group will be provided by 
using the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) 
and preferred term (PT) by treatment.  Within each level of summarization (SOC, PT), subjects 
who experience more than one occurrence will only be counted once.  Adverse events will also 
be presented by severity (mild, moderate, severe, life- or sight-threatening), and by relationship 
to study drug (not related, possibly related, probably related).  Listings of deaths, SAEs, and 
withdrawals due to AEs will be presented. 
Clinical laboratory results will be presented by treatment group using descriptive statistics.  
Laboratory values will be listed by subject, and values outside of a normal reference range will 
be flagged.  Pregnancy test results will be summarized separately. 
Vital signs will be presented using descriptive statistics by treatment group and visit. 


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Subjective ocular tolerability and discomfort assessment results will be presented using 
descriptive statistics by treatment group and visit. 
Prior and concomitant medications for both ocular and non-ocular indications will be coded 
using the World Health Organization (WHO) Drug Dictionary.  These medications (prescription, 
OTC, and nutritional supplements) will be summarized by anatomical therapeutic chemical 
(ATC) classification levels, WHO generic name, and treatment group.  Subjects will only be 
counted once at each level of the generic name or ATC level. 
12 
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS 
12.1 Quality Control and Quality Assurance 
The Sponsor’s 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 the Sponsor 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. 
12.2 Institutional Review Boards/Independent Ethics Committee 
Prior to the study initiation, the protocol and ICF will be submitted to the IRB/EC for approval.  
The IB may also be submitted as supplemental information.  By signing the “Statement of 
Investigator” form (FDA Form 1572), the Investigator is assuring that an IRB/EC that complies 
with the requirements set forth in 21 CFR Part 56 will be responsible for the initial and 
continuing review of the 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 the 
Sponsor or its designee prior to release of investigational supplies to the study site.  The approval 
letter must refer to the specific protocol and ICF.  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 the Sponsor 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 the Sponsor or designee for approval prior to IRB/EC submission. 
The Investigator is responsible for notifying the IRB/EC of any SAEs.  A copy of the notification 
must be forwarded to the Sponsor 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.  


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A final report must be provided to the IRB/EC and the Sponsor 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. 
12.3 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 
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.  One or two signed originals of the ICF will be prepared, 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 the other signed original of the ICF will be given to the subject, in 
accordance with applicable local requirements. 
12.4 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 the Sponsor 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 the Sponsor 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 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 link 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. 
• 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. 


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• The date when subject exited the study and a notation as whether the subject competed 
the study or was discontinued, including the reason for discontinuation. 
Upon request, the Investigator will provide the Sponsor with any required background data from 
the study documentation or clinic records.  This is particularly important when source documents 
are illegible or when errors in data transcription are suspected.  In case there are issues or 
governmental queries or requests for audit inspections, it is also necessary to have access to the 
complete study records, provided that subject confidentiality is protected. 
12.5 Electronic Case Report Forms 
All study data must be incorporated in the corresponding eCRFs which are designed for 
computer processing and analysis.  The Investigator will be responsible for recording all data in 
the eCRFs and must ensure the accuracy, completeness, legibility, and timeliness of the data 
reported to the Sponsor in the eCRF and in all required reports. 
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. 
If corrections are made following official final review and sign-off by the Investigator, the 
Investigator must be made aware of the changes and provide written acknowledgement. 
This study will be conducted in compliance with the regulations contained within 21 CFR 
Part 11, electronic records/electronic signatures regulations. 
12.6 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 US (or Product License outside the 
US) for this drug or 2 years after the withdrawal of the IND.  These records include the protocol 
and copies of all documents submitted to the Sponsor or to government authorities, subject 
records (including signed ICFs, 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 the Sponsor.  
If the Investigator cannot guarantee the archiving requirement at the site for any or all of the 
documents, special arrangements must be made between the Investigator and the Sponsor to 
store these in a sealed container outside of the study site so that they can be returned sealed to the 
Investigator in case of a regulatory audit.  When source documents are required for the continued 
care of the subject, appropriate copies will be made for storing outside of the study site. 
12.7 Monitoring the Study and Data Quality Assurance 
Representatives of the Sponsor (or designees) will contact the Investigator and his/her 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 facility’s readiness to conduct the trial. 
It will be the monitor’s responsibility to inspect the eCRFs at regular intervals throughout the 
study, to verify the adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them.  The monitor must have access to all study related reports and 


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records needed to verify the entries on the eCRF.  The Investigator (or designee) must agree to 
cooperate with the monitor to ensure that any problems detected in the course of these 
monitoring visits are resolved and agree to provide missing information and grant access to all 
study documentation. 
Every attempt must be made to follow the protocol, obtain and record all data requested for each 
subject at the specified times.  However, ethical reasons may warrant the failure to obtain and 
record certain data or to record data at the times specified.  If data is not recorded per protocol, 
the reasons must be clearly documented on the eCRF/records. 
Accurate and reliable data collection will be ensured by the verification of the eCRFs against the 
Investigator’s records by the monitor (source documentation verification).  Collected data will be 
entered into a computer database and subject to electronic and manual quality assurance 
procedures. 
The study data must be verifiable with the source data, which requires access to all original 
recordings, laboratory reports, product accountability records, including access to the subject 
electronic medical record, and source data must be made available for all study data.  Subjects 
must also allow access to their medical records.  They will be informed of this and must consent 
to permission by providing their signature on the ICF prior to enrollment. 
Representatives of the Sponsor (or designees) may audit the study periodically to ensure that all 
records are correct and complete.  The verification of the eCRF data must be by direct inspection 
of source documents. 
12.8 Discontinuation of the Study 
The Sponsor reserves the right to discontinue this study for administrative reasons at any time. 
The trial may also be terminated prematurely if unexpected AEs occur or if the Investigator does 
not adhere to the protocol. 
12.9 Policy for Publications 
The detailed procedures for the review of publications are set out in the clinical trial agreement 
entered into with the Sponsor in connection with this study.  Results from the study shall not be 
made available to any third party by the Investigator or staff outside of the publication policy. 
13 
ETHICS 
13.1 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 IB may also be provided as 
required.  The Investigator must submit written approval from an IRB/EC to the Sponsor or a 
designee such as a Contract Research Organization (CRO) before the 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. 


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The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  The Sponsor or the CRO 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. 
13.2 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. 
13.3 Written Informed Consent 
A properly executed, written informed consent document, in compliance with 21 CFR 50, the 
ICH guidelines, and relevant local regulatory requirements, will be obtained from each subject 
before the subject is enrolled into the study and before any study-related procedure is performed.  
Attention will be directed to the basic elements required for incorporation into the informed 
consent under US Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a]) and 
(21 CFR 50.25[b]). 
The informed consent document will be reviewed by the Sponsor or designee for inclusion of all 
required elements prior to submission to the IRB/EC.  The Sponsor must also review any 
revisions to the approved informed consent document prior to submission to the IRB/EC.  The 
final IRB/EC-approved document must be provided to the Sponsor for regulatory purposes.  It is 
the responsibility of the Investigator, or a person designated by the Investigator, to obtain written 
informed consent from each subject (or the subject’s legally authorized representative) 
participating in the study after adequate explanation of the aims, methods, anticipated benefits, 
and potential hazards of the study.  In the case where the subject is unable to read the form, an 
impartial witness will be present during the entire informed consent discussion.  After the subject 
has orally consented to participate in the study, the witness’ signature on the form will attest that 
the information in the consent form was accurately explained and understood. 
A copy of the fully executed informed consent document must be provided to the subject or the 
subject’s legally authorized representative.  If applicable, it will be provided in a certified 
translation of the local language by the site under the guidance of the Investigator.  Signed 
informed consent documents must remain in each subject’s medical record and be made 
available for verification by the monitor at any time. 
If new safety information results in significant changes in the risk/benefit assessment, the 
consent form will be reviewed and updated as necessary.  All subjects (including those who have 
already been treated with Yutiq 0.05 mg) will be informed of the new information and given a 
copy of the revised form to provide their consent in order to continue participation in the study. 
14 
REFERENCES 
Brunton LL, Lazo JS, Parker KL. Adrenocorticotropic hormone: adrenocortical steroids and their 
synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones.  In:  


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Brunton LL (Ed.) Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 2006: 
1593-1600. 
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;140:509-516. 
Maca SM, Amon M, Findl O, Kahraman G, Barisani-Asenbauer T. Efficacy and tolerability of 
preservative-free and preserved diclofenac and preserved ketorolac eyedrops after cataract 
surgery. Am J Ophthalmol. 2010; 149: 777-784. 
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Writing Committee: 
Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Louis TA, Sugar EA, Thorne JE. 
Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide 
implant for intermediate, posterior and panuveitis: the multicenter uveitis steroid treatment trial. 
Ophthalmol. 2011;118:1916–1926. 
Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory 
activity in intermediate and posterior uveitis. Ophthalmol. 1985;92:467-471. 
Scoville B, Krieglstein GK, Then E, Yokoyama S, Yokoyama T. Measuring drug-induced eye 
irritation: a simple new clinical assay. J Clin Pharmacol. 1985; 25: 210-218. 
YUTIQ® US Prescribing Information, May 2021. 
 
 
 


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APPENDIX 1: Measurement of BCVA by ETDRS 
The procedure for carrying out the testing of best-corrected visual acuity (BCVA) measured 
according to the standard procedure originally developed for Early Treatment Diabetic 
Retinopathy Study (ETDRS) will be covered in a separate document with instructions provided 
by the independent certification vendor selected by the Sponsor. 
 
 
 






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Intraocular Pressure 
Intraocular pressure will be assessed by applanation tonometry (preferably, Goldmann) 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 measurement for a given subject.  Measurement should 
be performed before dilated ophthalmoscopy. 
 
 
 


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APPENDIX 3: Subjective Ocular Tolerability and Discomfort Assessment 
Subjects will be asked to grade ocular tolerability and discomfort in both eyes at all study visits. 
Subjective Ocular Discomfort Grading 
Subjects will assess discomfort using the following subjective scale (Maca et al. 2010).  This 
parameter will consist of questioning about superficial pain, foreign body, or gritty sensation, 
itching, burning, and other forms of non-specific discomfort. 
• Grade 0: Absent 
• Grade 0.5: Very mild 
• Grade 1: Mild 
• Grade 2: Moderate 
• Grade 3: Severe 
• Grade 4: Intolerable 
Subjective Tolerability Using a Visual Analog Scale for Pain 
Subjects will assess tolerability using the following subjective visual analog scale (Scoville et al. 
1985).  A visual analogue scale is performed by asking subjects to indicate on an unmarked 
100-mm line the intensity of their pain.  A mark of “0” represents no sensation while “100” 
indicates the worst imaginable pain.  The location of the mark on the line is then measured with a 
ruler (in mm) to provide a numeric score. 
 


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APPENDIX 4: Common Terminology Criteria for Adverse Events (CTCAE) 
Version 5.0 
 
Adapted from: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_5x7.pdf  
 
 
 
 


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APPENDIX 5: Summary of Changes 
The following changes were made to Protocol EYP-2102-001 as Amendment 3 (v2.0): 
Section(s) 
Description of Change / Rationale 
Synopsis 
Section 3.1, Overall Study Design 
Figure 3-1, Study Design Schema, Study 
EYP-2102-001 
Section 5.1, Measurements and 
Evaluations by Visit 
 
• 
Added details to state that the Sponsor has decided to 
stop subject enrollment and will continue to monitor 
subjects randomized to Yutiq 0.05 mg. 
• 
Enrollment has been stopped due to reasons other 
than safety or efficacy, following FDA advice 
received on January 24, 2022. The Sponsor is 
reevaluating the development program of 
Yutiq 0.05 mg. 
• 
Updated these sections to describe the modified 
protocol schedule for those subjects randomized to 
Yutiq 0.05 mg.  
• 
Added the information that subjects who were 
randomized to sham injection will be discontinued 
from the study and will undergo their EOS visit. 
Section 3.2, Discussion of Study Design, 
Including the Choice of Control Groups 
• 
Clarified the masked versus unmasked personnel 
requirements that were included in Administrative 
Letter #2 (dated January 3, 2022). 
Section 3.3, Duration of Study 
• 
Clarified the modified protocol scheduled  
Section 4, Selection and Withdrawal of 
Subjects 
• 
Added text to state that subject enrollment has been 
stopped. 
Synopsis 
Section 4.1, Inclusion Criteria #3 
• 
Clarified the inclusion criteria #3 that was included 
in Administrative Amendment 3 (March 1, 2022). 
Synopsis 
Section 4.1, Inclusion Criteria #19 
• 
Added the marketed uveitis treatment XIPERE™ 
that was included in Administrative Amendment 3 
(March 1, 2022). 
Section 5.1, Measurements and 
Evaluations by Visit 
Table 5–1,  Schedule of Study Procedures 
and Assessments, Study EYP-2102-001 
• 
Removed Month 9 to align with modified protocol 
schedule for the subjects were were treated with 
Yutiq 0.05 mg. 
Table 5–1, Schedule of Study Procedures 
and Assessments, Study EYP-2102-001 
(footnote “c”). 
Section 8.4, Clinical Laboratory 
Evaluations 
• 
Added “Screening only” for the tuberculosis testing. 
Tuberculosis testing will not be performed at the 
final visit. 
Section 6.2.1, Yutiq 0.05 mg Injection 
Procedure 
• 
Clarified the timing for biomicroscopy post-injection 
that was provided in the Administrative Letter #2 
(dated January 3, 2022). 
Section 11.1, Determination of Sample 
Size 
• 
Added text that the Sponsor has stopped enrollment 
of the study. 


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Section(s) 
Description of Change / Rationale 
Appendix 2, Slit Lamp Biomicroscopy, 
Ophthalmoscopy, and Intraocular 
Pressure 
• 
Clarified the requirement for dilation for the slit lamp 
examination assessment that was included in the 
Administrative Letter #3 dated March 1, 2022. 
Appendix 5 Summary of Changes 
• 
Added Appendix 5 due to Amendment 3 changes. 
Global protocol changes 
• 
Miscellaneous typographical and formatting issues 
were corrected, and some hyperlinks were fixed 
and/or added. 
 

SAP_001.pdf: 
EyePoint Pharmaceuticals, Inc.
Protocol Number: EYP-2102-001
Statistical Analysis Plan
Page 1 of 27
EyePoint Pharmaceuticals, Inc.
Protocol Number: EYP-2102-001
A Phase 3, Multicenter, Prospective, Randomized, Masked, Controlled, Safety and Efficacy Study of 
Fluocinolone Acetonide (FA) Intravitreal 0.05 mg Insert (Yutiq 0.05 mg) in Subjects with Chronic 
Non-Infectious Uveitis Affecting the Posterior Segment of the Eye
Statistical Analysis Plan
Version: 1.0 08MAY2023


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E ye P oi nt P har mace uticals, I nc.
Pr ot oc ol N u m ber: E Y P- 2 1 0 2- 0 0 1
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T his d oc u me n
ctr o nic all y o n t he fi n al p a ge b y t he 
f oll o wi n g:
A p pr o ve d b y: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Date
E ye P oi nt P har mace utical I n c.
P P D
P P D
P P D
P P D


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
Page 4 of 27
Table of Contents
Author Signature Page..................................................................................................................2 
Sponsor Signature Page................................................................................................................3 
Table of Contents...........................................................................................................................4 
Version History..............................................................................................................................6 
1. 
Introduction....................................................................................................................7 
1.1. 
Objectives and Endpoints.................................................................................................7 
1.2. 
Study Design ....................................................................................................................8 
1.2.1. 
Randomization..................................................................................................................9 
2. 
Statistical Hypotheses ..................................................................................................10 
2.1. 
Multiplicity Adjustment.................................................................................................10 
3. 
Analysis Sets..................................................................................................................11 
3.1. 
Intent-to-Treat Analysis Set ...........................................................................................11 
3.2. 
Safety Analysis Set.........................................................................................................11 
4. 
Statistical Analyses.......................................................................................................12 
4.1. 
General Considerations ..................................................................................................12 
4.1.1. 
Data Summarization.......................................................................................................12 
4.1.2. 
Definition of Baseline ....................................................................................................12 
4.1.3. 
Analysis Visit Windows.................................................................................................12 
4.1.4. 
Handling of Missing Data ..............................................................................................12 
4.1.5. 
Multicenter Considerations ............................................................................................13 
4.1.6. 
Adjustment for Covariates..............................................................................................13 
4.1.7. 
Multiple Comparisons and Multiplicity .........................................................................13 
4.1.8. 
Statistical Software.........................................................................................................13 
4.2. 
Primary Efficacy Endpoint Analysis..............................................................................13 
4.2.1. 
Definition of Endpoint....................................................................................................13 
4.2.2. 
Analytical Approach for Primary Efficacy Endpoint.....................................................15 
4.2.3. 
Sensitivity Analysis........................................................................................................15 
4.3. 
Secondary Endpoints Analysis.......................................................................................15 
4.3.1. 
Definition of Secondary Endpoints ................................................................................15 
4.3.2. 
Analytical Approach for Secondary Efficacy Endpoints ...............................................16 
4.4. 
Safety Analyses..............................................................................................................16 
4.4.1. 
Extent of Exposure .........................................................................................................16 
4.4.2. 
Adverse Events...............................................................................................................16 
4.4.3. 
Subjective Ocular Tolerability and Discomfort Assessment .........................................17 
4.4.4. 
Intraocular Pressure........................................................................................................18 
4.4.5. 
Slit Lamp Examination...................................................................................................18 
4.4.6. 
Indirect Ophthalmoscopy ...............................................................................................19 
4.4.7. 
Prior and Concomitant Medications...............................................................................19 
4.4.8. 
Clinical Laboratory Evaluation ......................................................................................20 
4.4.9. 
Vital Signs, Physical Findings and Other Observations Related to 
Safety..............................................................................................................................20 
4.5. 
Interim Analysis ............................................................................................................20 


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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4.6. 
Primary Analysis............................................................................................................20 
4.7. 
Final Analysis.................................................................................................................20 
4.8. 
Changes to Protocol-planned Analyses..........................................................................20 
5. 
Sample Size Determination .........................................................................................21 
6. 
Supporting Documentation .........................................................................................22 
6.1. 
Appendix 1: List of Abbreviations.................................................................................22 
6.2. 
Appendix 2: Supporting Study Information...................................................................23 
6.2.1. 
Disposition of Subjects...................................................................................................23 
6.2.2. 
Demographics.................................................................................................................23 
6.2.3. 
Baseline and Disease Characteristics .............................................................................23 
6.2.4. 
Protocol Deviations ........................................................................................................23 
6.2.5. 
Medical History and Concurrent Illnesses .....................................................................23 
6.2.6. 
Prior/Concomitant Medications .....................................................................................23 
6.3. 
Appendix 3: Data Handling Conventions ......................................................................25 
6.3.1. 
Missing Date Imputation................................................................................................25 
7. 
References .....................................................................................................................27 


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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Version History
SAP 
Version
Date
Change
Rationale
1.0
08MAY2023
Not applicable
Original version


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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1.
Introduction
This document presents the statistical analysis plan (SAP) for the protocol EYP-2102-001, a
phase 3, multicenter, prospective, randomized, masked, controlled, safety and efficacy study of 
fluocinolone acetonide (FA) intravitreal 0.05 mg insert (Yutiq 0.05 mg) in subjects with chronic 
non-infectious uveitis affecting the posterior segment of the eye.
This SAP was developed in accordance with ICH E9 guideline. This SAP is to provide details of 
the statistical analyses based on the protocol version 3.0, dated July 20, 2022. The SAP will be 
finalized prior to database lock. Any deviations from the SAP after database lock and reasons for 
such deviations will be described and documented in the clinical study report.
The Sponsor decided to stop enrollment in early May 2022. Subjects who were randomized to 
Yutiq 0.05 mg will continue to be monitored on a modified-protocol schedule. The subjects who 
had been treated with sham injection were discontinued from the study. Consider the fact that the 
study was terminated early, the analyses described in this SAP has been limited to the scope per 
the interest of EyePoint Pharmaceuticals, Inc.  For such a reason, the list of endpoints and 
analyses in this SAP is a reduced list from the study protocol. 
1.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
Primary Efficacy Endpoint
To evaluate the safety and efficacy of Yutiq 
0.05 mg in the management of subjects with 
chronic non-infectious uveitis affecting the 
posterior segment of the eye.
The proportion of subjects who have a 
recurrence of uveitis in the study eye within 24 
weeks (6 months) after receiving study 
treatment
Secondary
Secondary Efficacy Endpoints
x
Proportion of subjects who have a 
recurrence of uveitis in the study eye 
within 52 weeks
x
Mean change from baseline in best 
corrected visual acuity (BCVA) letter 
score in the study eye at 24 and 52 
weeks 
x
Number of recurrences of uveitis within 
24 and 52 weeks 
x
Proportion of subjects with resolution of 
macular edema as measured by Spectral-
domain Optical Coherence Tomography
(SD-OCT) imaging at Day 28 and at 
Months 2, 3, 6, 9, and 12.
Safety


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Statistical Analysis Plan
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x
Systemic Adverse Events (AEs)
x
Ocular AEs, including IOP elevation 
x
Medications/procedures required to 
control elevated IOP 
x
Development or worsening of cataract 
x
Cataract-related procedures 
x
Clinically significant ocular changes 
x
Procedure related AEs 
x
Subjective ocular tolerability and
discomfort assessments
x
Vital signs
x
Clinical laboratory assessments
x
Use of rescue and concomitant 
medications
1.2.
Study Design
The protocol was originally planned to be a 52-week, prospective, randomized, masked (subject 
and outcome assessor), controlled, safety and efficacy study of intravitreal Yutiq 0.05 mg 
compared to sham injection with a primary efficacy and safety readout at 24 weeks.  A total of 
approximately 60 subjects (30 subjects in the Yutiq 0.05 mg group and 30 in the sham treatment 
group) were to be enrolled at approximately 40 sites in the US.  One eye in each subject will be 
designated as the study eye.
The Sponsor decided to stop enrollment in early May 2022 for reasons other than safety or 
efficacy, following FDA advice received on January 24, 2022. Subjects who were randomized to 
Yutiq 0.05 mg will continue to be monitored on a modified-protocol schedule through Month 12
(or ET) and evaluated for efficacy and safety. Those subjects who had been treated with sham 
injection were discontinued from the study and subsequently had their End of Study (EOS) 
evaluation.
Subjects will receive either Yutiq 0.05 mg or a sham injection on Day 1 of the study on the study 
eye and will be assessed over the following 52 weeks according to the schedule of study 
procedures and assessment. 
Yutiq 0.05 mg is a non-erodible intravitreal implant in a drug delivery system that contains 
0.05 mg of FA and is designed to relHDVH)$DWDUDWHRIȝJGD\LQWRWKHYLWUHRXVKXPRUIRU
at least 6 months. Yutiq 0.05 mg is preloaded into a single-dose applicator to facilitate injection 
of the implant directly into the vitreous.
To ensure the health of both eyes, observations of both the study eye and non-study (fellow) eye 


EyePoint Pharmaceuticals, Inc.
Protocol Number: EYP-2102-001
Statistical Analysis Plan
Page 9 of 27
should be made at all visits as described in the schedule of study procedures and assessments.
Ocular data will be collected for both eyes at all visits except for the SD-OCT assessments.
Figure 1. Study Design Schema
1.2.1.
Randomization 
One eye in each subject will be designated as the study eye. Following confirmation of eligibility 
on Day 1, subjects will be randomly assigned in a 1:1 ratio to either Yutiq 0.05 mg or sham 
injection through a central Interactive Voice Response System (IVRS). Randomization will be 
stratified based on whether the subject is receiving systemic treatment to control uveitis at the 
time of study entry. 


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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2.
Statistical Hypotheses
Not applicable.
2.1.
Multiplicity Adjustment
Not applicable.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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3.
Analysis Sets
For the purposes of analysis, the following analysis populations are defined:
3.1.
Intent-to-Treat Analysis Set
The Intent-to-Treat (ITT) analysis set will include all subjects who are randomized. Subject will 
be classified according to the assigned treatment. The ITT set will be used for analysis of 
efficacy, unless otherwise specified.
3.2.
Safety Analysis Set 
The Safety Analysis Set (SAS) will include all subjects who are randomized and received Yutiq 
0.05 mg or sham injection. Subjects will be classified according to the actual treatment received.
The SAS set will be used for the analysis of safety data.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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4.
Statistical Analyses
4.1.
General Considerations
4.1.1.
Data Summarization 
The Sponsor decided to stop enrollment in early May 2022. Subjects who were randomized to 
Yutiq 0.05 mg will continue to be monitored on a modified-protocol schedule. The subjects who 
had been treated with sham injection were discontinued from the study. Consider the fact that the 
study was terminated early, no statistical hypothesis testing will be performed.  All data 
summaries will be descriptive only, based on observed data.
Tabular data summaries for variables measured on a continuous scale will include descriptive 
statistics (n, mean, median, standard deviation, minimum, and maximum) by treatment group and 
visit.
For variables evaluated on a categorical scale, data summaries will include the number and 
percentage of subjects who provide each possible category, by treatment group and visit when 
applicable. The 95% confidence interval (CI) of the proportions will be constructed for each 
treatment group, as appropriate.
All study data will be presented in by-subject listings.
4.1.2.
Definition of Baseline 
Baseline measurements are those taken at Screening or prior to receiving study treatment on 
Day 1, whichever is the latest.
4.1.3.
Analysis Visit Windows
There will not be visit date re-mapping for the data analyses.  All analyses will be descriptive. 
Descriptive summary tables will be based on nominal visits.
x
Efficacy endpoints labelled as Week 24 endpoint will use the assessments from Month 6 
visit.   
x
Efficacy endpoints labelled as Week 52 endpoints will use the assessments of Month 12 
visit.  
4.1.4.
Handling of Missing Data 
In general, missing data will not be imputed, unless otherwise specified. For missing and partial 
dates imputation, refer to section 6.3.1.


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Statistical Analysis Plan
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4.1.5.
Multicenter Considerations 
Up to 40 investigative study centers will participate in the study. All centers will be in the United 
States. Data will be pooled for all study centers for data analysis, unless otherwise specified.
4.1.6.
Adjustment for Covariates 
Not applicable.
4.1.7.
Multiple Comparisons and Multiplicity 
Not applicable.
4.1.8.
Statistical Software 
All statistical summaries and analyses will be produced using SAS, Release 9.4 or higher.
4.2.
Primary Efficacy Endpoint Analysis
4.2.1.
Definition of Endpoint
The primary efficacy endpoint is the proportion of subjects who have a recurrence of uveitis 
in the study eye within 24 weeks (6 months) after receiving study treatment. Recurrence is 
defined as: 
x
$QLQFUHDVHLQWKHYLWUHRXVKD]HRIVWHSVFRPSDUHGWREDVHOLQHat the Week 24 visit,
or any visit time point prior to the Week 24 visit after the Study Day 7 visit
Or 
x
A deterioration in visual acuity of at least 15 letters BCVA compared to baseline at the 
Week 24 visit, or any visit time point prior to the Week 24 visit after the Study Day 7 
visit.
Any criterion used to define recurrence must be attributable only to noninfectious uveitis. To 
prevent post-procedural inflammatory reactions from being reported as uveitis recurrences, 
assessments for recurrence of uveitis begin after the Study Day 7 visit. 
The study protocol stated to impute subjects who don’t complete Week 24 eye examinations and 
subjects who take prohibited medications as having a recurrence.  Consider the fact that the study 
was terminated early, no imputation will be implemented.  Summary of the primary efficacy 
endpoint will be based only on the observed data from the subjects who reached Week 24.
4.2.1.1.
Vitreous Haze


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Statistical Analysis Plan
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Dilated indirect ophthalmoscopy will be performed to assess retinal and choroid appearances and 
vitreous haze for study eye and fellow eye at all study visits.
The following scale will be used to define the extent of vitreous haze.
Vitreous Haze Grading Scale
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
The diagram below presents the scoring convention that will be used to identify a minimum of 
“> 2 step increase” of vitreous haze for the primary efficacy endpoint.
Vitreous Haze Scoring Convention
4.2.1.2.
Measurement of BCVA by ETDRS 
Visual acuity testing in this study is required at a distance of 4 meters, and for subjects with 
reduced vision at 1 meter. Visual acuity is always tested with the subject’s best correction and 
should be measured prior to pupil dilation and slit lamp biomicroscopy examination or any drops 
or ointments being used. BCVA by ETDRS will be measured at every study visit.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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4.2.2.
Analytical Approach for Primary Efficacy Endpoint
The recurrence of uveitis rate will be summarized with the number and percentage of subjects 
with the recurrence and 95% confidence interval (CI) based on binomial distribution using the 
Clopper-Pearson (Exact) method.
The vitreous haze score and measurement of BCVA results will be summarized by treatment 
group at each scheduled visit. Mean change from baseline and proportion of subjects who have an 
increase of vitreous haze score of VWHSV, and proportion of subjects who have a deterioration of 
at least 15 letters BCVA from baseline will be presented at each scheduled visit.
Abnormal vitreous haze for the study eye and fellow eye will be summarized by treatment group 
and visit.
4.2.3.
Sensitivity Analysis
No sensitivity analysis will be performed.
4.3.
Secondary Endpoints Analysis
4.3.1.
Definition of Secondary Endpoints
The secondary efficacy endpoints will include the following endpoints:
4.3.1.1.
Proportion of subjects who have a recurrence of uveitis in the study eye within 52 
weeks 
The recurrence of uveitis will be assessed the same as the primary efficacy endpoint within 52 
weeks.
4.3.1.2.
Mean change from baseline in BCVA letter score in the study eye at 24 and 52 
weeks 
The change from baseline in BCVA as measured by ETDRS letter at each visit will be calculated.
4.3.1.3.
Number of recurrences of uveitis within 24 and 52 weeks 
The recurrences of uveitis on the study eye will be assessed as described in the primary efficacy 
endpoint and the incidence will be counted.
4.3.1.4.
Proportion of subjects with resolution of macular edema as measured by SD-
OCT imaging at Day 28 and at Months 2, 3, 6, 9, and 12.
The number and percentage of subjects who had macular edema from SD-OCT imaging will be 
summarized for each assessment timepoint through Week 24 and Week 52.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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4.3.2.
Analytical Approach for Secondary Efficacy Endpoints
The secondary efficacy analyses will be conducted using the ITT analysis set based on 
observed data.
x
The proportion of subjects with recurrent of uveitis will be summarized for the timepoint
of interest using the same method described for the primary efficacy endpoint.
x
The mean change from baseline in BCVA as measured by ETDRS letter score at each 
visit will be summarized for week 24 and 52 using descriptive statistics.
4.4.
Safety Analyses
Safety data will include adverse events reported after screening, data collected from ocular 
examinations and IOP measurements, ocular tolerability and discomfort assessments, vital sign 
measurements, clinical laboratory tests, and the use of rescue and concomitant medications.
All safety analyses will be performed on the safety analysis set based on actual treatment 
received. Ocular safety data will be summarized on the study eye and fellow eye separately,
where applicable. 
4.4.1.
Extent of Exposure
Subjects will receive either intravitreal Yutiq 0.05 mg or sham injection in the designated study 
eye on Day 1 and will be followed for 52 weeks after treatment for change in IOP and for 
endophthalmitis. The number and percentage of subjects who remain on the study will be 
summarized for each visit by treatment group. The number of subjects in each treatment group 
will be presented based on the actual treatment they have received.
4.4.2.
Adverse Events
Adverse event data will be coded using the Medical Dictionary for Regulatory Activities
(MedDRA). The severity of each AE will be graded by the investigator per CTCAE v5.0 criteria.
Descriptive statistics will be provided for all treatment-emergent adverse events (TEAEs). Both 
ocular and non-ocular TEAEs are defined as events that start after the study drug administration, 
and occur before termination of the study, or were present before study drug administration and 
worsened after dose administration.
Frequency counts and percentage of subjects within each treatment group will be provided by 
system organ class (SOC) and preferred term (PT) by treatment. Within each level of
summarization (SOC, PT), subjects who experience more than one occurrence will only be 
counted once. Adverse events will also be presented by severity (mild, moderate, severe, life- or 
sight-threatening), and by relationship to study drug (not related, possibly related, probably
related). Listings of deaths, and AEs leading to withdrawal will be presented.


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Statistical Analysis Plan
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Summaries will be sorted in descending order of frequency in the Yutiq 0.05 mg arm, when 
applicable. A listing of treatment-emergent AEs, treatment-emergent ocular events, and serious 
AEs will be provided.  
Ocular Adverse Events 
The following ocular events will be considered AEs for the purposes of this study: 
x
'HFUHDVHLQ%&9$RIDWOHDVWOHWWHUVRUOLQHVIURPWKHSUHYLRXV%&9$
measurement 
x
Moderate or severe (Grade 3 or 4) ocular findings compared to the last ocular examination 
x
Worsening of >2 steps in anterior chamber cell count or vitreous haze compared to the
last ocular examination 
x
Increase in IOP of >10 mmHg at two visits at least 1 week apart or an increase in IOP to 
>25 mmHg
4.4.3.
Subjective Ocular Tolerability and Discomfort Assessment 
Ocular discomfort will be measured using a 6-point scale (from “absent” to “intolerable”) and 
ocular tolerability will be measured using a visual analog scale. Subjects will be asked to grade 
ocular tolerability and discomfort for the study eye and fellow eye at all study visits. 
Subjective Ocular Discomfort Grading 
Subjects will assess discomfort using the following subjective scale (Maca et al. 2010). This 
parameter will consist of questioning about superficial pain, foreign body, or gritty sensation, 
itching, burning, and other forms of non-specific discomfort. 
x
Grade 0: Absent 
x
Grade 0.5: Very mild 
x
Grade 1: Mild 
x
Grade 2: Moderate 
x
Grade 3: Severe
x
Grade 4: Intolerable 
Subjective Tolerability Using a Visual Analog Scale for Pain 
Subjects will assess tolerability using the following subjective visual analog scale (Scoville et al. 
1985). A visual analogue scale is performed by asking subjects to indicate on an unmarked 100-
mm line the intensity of their pain. A mark of “0” represents no sensation while “100” indicates 
the worst imaginable pain. The location of the mark on the line is then measured with a ruler (in 
mm) to provide a numeric score.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
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The number and percentage of subjects in each ocular discomfort grading will be summarized by 
treatment group and visit. The VAS pain scale and change from baseline will be summarized
using descriptive statistics by treatment group and visit.
4.4.4.
Intraocular Pressure 
Intraocular pressure (IOP) will be measured after slit lamp examination has been completed at 
every study visit. The mean of 3 measurements per eye will be recorded as the IOP.  
Measurement should be performed before dilated ophthalmoscopy. The IOP measurement and 
change from baseline will be summarized using the descriptive statistics by treatment group and 
visit.
4.4.5.
Slit Lamp Examination
A routine slit lamp examination will collect clinical findings from the anterior and posterior 
segment of both study and fellow eye with pupil dilation and should be conducted after IOP 
measurement has been completed. 
Abnormal slit-lamp biomicroscopy results for the study eye and fellow eye will be summarized 
by treatment group and visit through week 24 and 52, respectively.
4.4.5.1.
Anterior Chamber Cell Grading Scale 
Anterior chamber cells will be measured at all study visits and assessment will be made using the 
following scale (Jabs et al. 2005).
Field size: 1 mm by 1 mm slit beam 
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 
Anterior Chamber Cell Scoring Convention 
The diagram presents the scoring convention that will be used to identify a minimum of “ 2 step 
increase” of anterior chamber cells compared to baseline at the Week 24 visit, or any visit time 
point prior to the Week 24 visit after the Study Day 7 visit.
Anterior Chamber Cell 2 Step Increase:


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The grading scale and measurement of anterior chamber cell results will be summarized by 
treatment group at each scheduled visit. The proportion of subjects who have an increase of 
DQWHULRUFKDPEHUFHOORIVWHSLQFUHDVH will be presented.
Abnormal anterior chamber assessment results will be summarized by treatment group and visit.
4.4.6.
Indirect Ophthalmoscopy 
Indirect ophthalmoscopy will be performed to assess retinal and choroid appearances and vitreous 
haze (Nussenblatt et al. 1985). Indirect ophthalmoscopy will be performed for study eye and 
fellow eye with pupil dilation and should be conducted after IOP measurement has been 
completed.
Abnormal indirect ophthalmoscopy results for the study eye and fellow eye will be summarized 
by visit through week 24 and 52 separately.
4.4.7.
Prior and Concomitant Medications
Prior and concomitant medications for both ocular and non-ocular indications will be coded 
using the World Health Organization (WHO) Drug Dictionary. These medications (prescription, 
OTC, and nutritional supplements) will be summarized by anatomical therapeutic chemical 
(ATC) classification level 2 term, WHO generic name, and treatment group. Subjects will only be 
counted once at each level of the generic name or ATC level.
4.4.7.1.
Use of Rescue and Prohibited Medications 
All prohibited medications used concurrently (from Day 1 through Month 12) must be
documented in the eCRF. During the study, some subjects may require rescue treatments in the 
study eye as a result of AEs or lack of efficacy of the study treatment. Prior to database lock, the 
Sponsor will conduct a data review to classify concomitant treatments as either rescue or 
prohibited. The proportion of subjects receiving these medications will be summarized by
treatment type (rescue or prohibited), treatment group, and time point.


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Statistical Analysis Plan
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4.4.8.
Clinical Laboratory Evaluation
Clinical laboratory results of hematology, chemistry, and urinalysis will be presented by 
treatment group using descriptive statistics. For hematology, shift tables of the worst on-study 
laboratory toxicity based on CTCAE grading relative to baseline will be presented. Subject 
LQFLGHQFHWDEOHVRIJUDGHODERUDWRU\WR[LFities will be provided for hematology and chemistry.
Laboratory values will be listed by subject, and values outside of a normal reference range will 
be flagged. 
4.4.9.
Vital Signs, Physical Findings and Other Observations Related to Safety
Observed and change from baseline for each vital sign parameter will be summarized 
descriptively by treatment group.
4.5.
Interim Analysis
No formal interim analyses are planned for this study.
4.6.
Primary Analysis
Not applicable.
4.7.
Final Analysis
The final analysis will be performed at the end of study when all subjects have completed the 
week 52 visit or terminate early from the study. 
4.8.
Changes to Protocol-planned Analyses
There are modifications from the clinical study protocol amendment (protocol version 3.0, 20 
July 2022) that impact statistical analysis.
x
Hypothesis testing using the exact binomial test will not be conducted to test the 
difference between the proportion of subjects with a recurrence using a 2-sided alpha 
= 0.05 due to insufficient sample size. Instead, the number and proportion of subjects 
who experience the uveitis recurrence will be summarized by treatment group.
x
Analysis populations are defined to include subjects who are randomized for the 
study. 


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Statistical Analysis Plan
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5.
Sample Size Determination
A total of approximately 60 subjects will be enrolled in the study and receive either 
Yutiq 0.05 mg or a sham injection. The Sponsor decided to stop enrollment for reasons other than 
safety or efficacy, following FDA advice received on January 24, 2022. In early May 2022, 
subject enrollment into the study has been stopped; therefore, the sample size will represent the 
number of subjects enrolled at the time of the Sponsors decision to stop enrollment.


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Statistical Analysis Plan
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6.
Supporting Documentation
6.1.
Appendix 1: List of Abbreviations
Abbreviation / Acronym
Definition / Expansion
AE
Adverse event
ATC
Anatomical Therapeutic Chemical 
BCVA
Best corrected visual acuity
BMI
Body Mass Index
CI
Confidence interval
CRF
Case Report Form
CTCAE
Common Terminology Criteria for Adverse Events
EDTRS
Early Treatment Diabetic Retinopathy Study
FA
Fluocinolone acetonide
IOP
Intraocular pressure
ITT
Intent-to-treat
IVRS
Interactive Voice Response System
MedDRA
Medical Dictionary for Regulatory Activities
OTC
Over-the-counter
PD
Protocol deviation
PT
Preferred Term
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SD-OCT
Spectral-domain Optical Coherence Tomography
SOC
System Organ Class
TEAE
Treatment-emergent adverse event
WHO-DD
World Health Organization - Drug Dictionary


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Statistical Analysis Plan
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6.2.
Appendix 2: Supporting Study Information
6.2.1.
Disposition of Subjects
A summary table will be prepared indicating the number and percentage of subjects in each 
treatment group who are included in each analysis population. Within the ITT population, the 
number and percentage of subjects who did/did not complete the study will be presented. Screen 
failures, including reasons for failing to satisfy eligibility criteria will also be summarized. In
addition, randomization stratification and subgroups will be summarized. 
Subjects who discontinue any time during the study will be summarized by reason for 
termination. Duration of study participation and insert duration will also be tabulated.
6.2.2.
Demographics
Demographics and baseline characteristics data include age (in years, at time of signing informed 
FRQVHQWDQGDJHFDWHJRU\YVUDFHVH[childbearing potential, ethnicity, height, 
weight, calculated BMI, and geographic region, and will be summarized by treatment group using 
descriptive statistics for the ITT population.
6.2.3.
Baseline and Disease Characteristics
Optical baseline characteristics include dilated indirect ophthalmoscopy results, baseline BCVA 
JURXSYV!OHWWHUV%&9$(7'56OHWWHUVFRUHintraocular pressure, ocular tolerability, 
and anterior, posterior and intermediate slit lamp examinations, and SD-OCT, and will be
summarized by treatment group using descriptive statistics with the ITT analysis set.
6.2.4.
Protocol Deviations
Protocol Deviations (PDs) data will be identified and recorded. The study team will conduct on-
going reviews of the PD data throughout the study. A summary of incidence of major PDs will be 
tabulated using number and percentage of subjects by deviation type.
Listings of subjects with PDs will be provided. 
6.2.5.
Medical History and Concurrent Illnesses
Medical history data including ophthalmic history will be coded using the MedDRA version 24.1
or higher and summarized by SOC and PT for each treatment group.
6.2.6.
Prior/Concomitant Medications
Prior medications are defined as all prescription, vaccinations, supplements, herbal therapies, any 


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
Page 24 of 27
prohibited medications, and over-the-counter (OTC) medications taken within the 30 days to day 
1 whether subjects continue to take or not. All prior medications must be documented on the 
concomitant medications eCRF.
Concomitant Medications are all prescription and OTC concomitant medications used
concurrently from the time of ICF signing through Month 12 and documented on the concomitant 
medication eCRF. 
Information on the concomitant medication/therapy eCRF includes the name of the 
medication/therapy, dose, frequency, route, dates of use, and indication for use. 
Prior and concomitant medications will be coded using the World Health Organization-Drug 
Dictionary (WHO-DD) version September 2021 B3 and will be summarized by preferred name.
The number and percentage of subjects using each medication will be presented by treatment 
group using the safety analysis set. Subjects taking more than one medication in the same 
preferred name will be counted once for the number of subjects taking that preferred name.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
Page 25 of 27
6.3.
Appendix 3: Data Handling Conventions
6.3.1.
Missing Date Imputation 
6.3.1.1.
Missing/Incomplete AE and Medication Start Date 
For AEs and Prior/Concomitant medications, the following imputation rules will be applied to 
impute partial or missing start dates.
x
If year, month, and day are all missing, then assign the date of study drug 
administration.
x
If month and day are missing and year is:
o
the same as the year of study drug administration then assign the month-day of 
study drug administration
o
earlier than the year of study drug administration then assign December 31
o
after the year of study drug administration then assign January 1.
x
If only day is missing, and month-year is:
o
the same as the month-year of study drug administration then assign the day of 
study drug administration
o
earlier than the month-year of study drug administration then assign the last 
day of the month
o
after the month-year of study drug administration then assign the first day of 
the month.
If the imputed start date is after the stop date, then there is a data error and do not impute the start 
date.
The imputed dates will be used to assess whether AEs should be considered as treatment 
emergent and if medications should be included in the safety summaries as prior or concomitant.
The original, partial dates will be included in data listings.
6.3.1.2.
Missing/Incomplete AE and Medication End Date 
Imputation rules for partial or missing stop dates
x
if day is missing, assign the last day of the month.
x
if month-day is missing, assign December 31 of the year.
x
if year, month, and day are all missing, do not impute.
If the stop date imputation leads to a date that is after the death date, then impute the stop date as 
the death date.
If the stop date imputation leads to a date that is before the start date, then there is a data error and 
do not impute the stop date.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
Page 26 of 27
6.3.1.3.
Missing/Incomplete Death Date
Imputation rules for partial or missing death dates
x
If death year and month are available but day is missing:
o
If “mmyyyy” for last contact date = “mmyyyy” for death date, set death date to the 
day after the last contact date.
o
If “mmyyyy” for last contact date < “mmyyyy” for death date, set death date to the 
first day of the death month.
o
If “mmyyyy” for last contact date > “mmyyyy” for death date, data error and do
not impute.
x
If both month and day are missing for death date or a death date is totally missing, set 
death date to the day after the last contact date.


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Protocol Number: EYP-2102-001
Statistical Analysis Plan
Page 27 of 27
7.
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