Conditions: Macular Edema
Keywords: Macular Edema Dexamethasone Branch Retinal Vein Occlusion Central Retinal Vein Occlusion Diabetic Macular Edema Noninfectious Uveitis Ozurdex Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 54
Healthy volunteers: no

Brief summary:
The Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) Applicator is used to deliver an implant with medicine to the eye. AbbVie is updating the DEX PS DDS Applicator. This purpose of this study is to show that the updated DEX PS DDS Applicator works in adult participants with macular edema due to retinal diseases.

The DEX PS DDS is approved for the treatment of macular edema. Participants will be placed into 1 of 2 groups, called treatment arms. Each group receives the same treatment drug delivered using different applicators. Around 54 adult participants with macular edema will be enrolled in the study in approximately 7-10 sites in the United States.

Participants will receive a single intravitreal (into the eye) administration of DEX PS DDS implant using either the currently-approved DEX PS DDS Applicator or the the updated Applicator. The participants will be observed for a duration of 7 days, with the DEX PS DDS implant received on day 1 and follow-up through day 7.

The updates being evaluated in this study are related to the DEX PS DDS Applicator only, with the safety and efficacy of the DEX PS DDS implant well characterized and the same as the currently marketed product. Participants will attend regular visits during the study at a hospital or clinic. The applicator function will be checked by medical assessment, checking for side effects, procedural complications and/or product complaints, and evaluating the administration procedure.

Detailed description:

Arms:
arm 1: DEX PS DDS 0.7 mg implant was administered intravitreally into the study eye using updated applicator at Day 1 and followed until Day 7. arm 2: DEX PS DDS 0.7 mg implant was administered into the study eye using currently approved applicator at Day 1 and followed until Day 7.

Interventions: intervention 1: Updated DEX PS DDS Applicator intervention 2: Approved DEX PS DDS Applicator intervention 3: Dexamethasone
Intervention descriptions: intervention 1: Intravitreal Administration intervention 2: Intravitreal administration intervention 3: Dexamethasone 0.7 mg in a solid polymer drug delivery system

Protocol document:
Prot_000.pdf: 


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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
7
2.1
BACKGROUND AND RATIONALE
7
2.2
BENEFITS AND RISKS TO SUBJECTS
7
3
OBJECTIVES AND ENDPOINTS
8
3.1
OBJECTIVES, HYPOTHESES, AND ESTIMANDS
8
3.2
PRIMARY ENDPOINT
8
3.3
SECONDARY ENDPOINT
8
3.4
ADDITIONAL ENDPOINTS
9
3.5
SAFETY ENDPOINTS
9
4
INVESTIGATIONAL PLAN
9
4.1
OVERALL STUDY DESIGN AND PLAN
9
4.2
DISCUSSION OF STUDY DESIGN
10
5
STUDY ACTIVITIES
11
5.1
ELIGIBILITY CRITERIA
11
5.2
CONTRACEPTION RECOMMENDATIONS
13
5.3
PROHIBITED MEDICATIONS AND THERAPY
14
5.4
PRIOR AND CONCOMITANT THERAPY
14
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
16
5.6
FOLLOW-UP AFTER SUBJECT DISCONTINUATION OF STUDY DRUG OR FROM STUDY
17
5.7
STUDY DRUG
17
5.8
RANDOMIZATION/DRUG ASSIGNMENT
17
5.9
PROTOCOL DEVIATIONS
18
5.10 DATA MONITORING COMMITTEE
18
6
SAFETY CONSIDERATIONS
18
6.1
COMPLAINTS AND ADVERSE EVENTS
18
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
21
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7.1
STATISTICAL AND ANALYTICAL PLANS
21
7.2
DEFINITION FOR ANALYSIS POPULATIONS
21
7.3
HANDLING POTENTIAL INTERCURRENT EVENTS FOR THE PRIMARY AND KEY SECONDARY ENDPOINTS
22
7.4
STATISTICAL ANALYSES FOR EFFICACY
22
7.5
STATISTICAL ANALYSES FOR SAFETY
22
7.6
INTERIM ANALYSIS
22
7.7
OVERALL TYPE I ERROR CONTROL
22
7.8
SAMPLE SIZE DETERMINATION
22
8
ETHICS
23
8.1
INSTITUTIONAL REVIEW BOARD (IRB)
23
8.2
ETHICAL CONDUCT OF THE STUDY
23
8.3
SUBJECT CONFIDENTIALITY
23
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
23
10 DATA QUALITY ASSURANCE
23
11 COMPLETION OF THE STUDY
24
12 REFERENCES
24
LIST OF TABLES
TABLE 1.
ALLOWED CONCOMITANT MEDICATIONS/THERAPY
15
TABLE 2.
STUDY DRUG IDENTIFICATION
17
LIST OF FIGURES
FIGURE 1.
SCHEMATIC
10
LIST OF APPENDICES
APPENDIX A.
STUDY-SPECIFIC ABBREVIATIONS AND TERMS
25
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
27
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APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
28
APPENDIX D.
ACTIVITY SCHEDULE
29
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
30
APPENDIX F.
OPERATIONS MANUAL
33
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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted?
Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) is a Food and Drug 
Administration (FDA)-approved, biodegradable, NOVADUR® solid polymer drug delivery system 
containing 0.7 mg of dexamethasone.  The DEX PS DDS Implant comes preloaded and is delivered in the 
vitreous cavity by a single-use DEX PS DDS Applicator with a 22 gauge needle that leaves a sutureless 
self-sealing wound.  The sustained release formulation was designed to release dexamethasone from 
the DEX PS DDS Implant for up to 6 months into the posterior segment of the eye.  The DEX PS DDS is 
approved for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central 
retinal vein occlusion (CRVO), for the treatment of noninfectious uveitis affecting the posterior segment 
of the eye, and for the treatment of diabetic macular edema (DME). 
AbbVie is updating the DEX PS DDS Applicator to include a change of the implant retention feature, 
other minor changes to the DEX PS DDS Applicator (i.e., change of safety tab color, shortening of the 
safety tab, linkage hole alignment, lever clasp), as well as the change to the visual/physical depth of
penetration feature (needle sleeve). 
There is no defined clinical hypothesis for this study.  This study is designed to demonstrate that the 
updated DEX PS DDS Applicator (that incorporates the final, to be-marketed design) delivers the 
DEX PS DDS Implant to the vitreous cavity and is suitable for commercial use in patients with macular 
edema due to retinal diseases.  No changes are being made to the DEX PS DDS Implant.  As the safety of 
the DEX PS DDS Implant is already well characterized and is the same as the currently marketed product, 
the duration of the proposed study is designed to capture investigator experience and any complaints 
associated with the DEX PS DDS Implant administration using the updated DEX PS DDS Applicator.  The 
planned assessments include best-corrected visual acuity (BCVA), biomicroscopic slit lamp examination, 
ophthalmoscopy, and intraocular pressure (IOP).  Adverse events (AEs) will also be collected.  The 
treatment administration assessment form will be collected to evaluate investigator experience with 
and performance of the updated DEX PS DDS Applicator and the currently-approved DEX-PS DDS 
Applicator as a comparator.  These parameters are sufficient to determine whether the updated DEX PS 
DDS Applicator delivers the DEX PS DDS Implant to the vitreous cavity.
2.2 Benefits and Risks to Subjects
The DEX PS DDS Implant was developed to address the problems associated with conventional 
corticosteroid therapies.  The DEX PS DDS Implant administered into the posterior segment of the eye 
releases a total dose of approximately 0.7 mg dexamethasone.  Other routes of administration (topical, 
periocular, systemic, and standard intravitreal injection of corticosteroid suspensions) require much 
higher daily doses to deliver equivalent levels of corticosteroid to the posterior segment while also 
exposing non-target organs to corticosteroids.  With DEX PS DDS Implant, substantially lower daily doses 
of dexamethasone are released directly to the posterior segment, thereby minimizing potential systemic 
side effects.  The DEX PS DDS Implant gradually degrades over time while releasing dexamethasone until 
it ultimately disappears from the vitreous.  Therefore, there is no need to remove the DEX PS DDS 
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Implant.  By delivering a drug directly into the vitreous cavity, the blood-eye barriers are circumvented, 
and intraocular therapeutic levels can be achieved with minimal risk of systemic toxicity.
The updates being evaluated in this study are related to the DEX PS DDS Applicator only; the DEX PS DDS
Implant remains unchanged.  The safety of the DEX PS DDS Implant is already well characterized and is 
the same as the currently marketed product.
Based on the information mentioned above, no additional or new risks are anticipated other than those 
previously known for DEX PS DDS Implant.
For further details, please see findings from completed studies, including safety data in the current 
DEX PS DDS investigator's brochure.
Considering the Coronavirus Disease – 2019 (COVID-19) pandemic, the benefit and risk to subjects 
participating in this study have been re-evaluated.  Based on the limited information to date, and given 
the minimal systemic exposure to the active ingredient, no additional risk to study subjects is 
anticipated with the use of DEX PS DDS Implant.
3 OBJECTIVES AND ENDPOINTS
3.1 Objectives, Hypotheses, and Estimands
Primary
The primary objective is to demonstrate that the updated DEX PS DDS Applicator (that incorporates the 
final, to-be-marketed design) delivers the DEX PS DDS Implant to the vitreous cavity and is suitable for 
commercial use in patients with macular edema due to retinal diseases.
There is no defined clinical hypothesis or estimands for this study.
Secondary
No secondary objective is defined for this study.
3.2 Primary Endpoint
No primary efficacy endpoint is defined for this study.  The study is not designed to assess efficacy of the 
study drug.  The DEX PS DDS Implant is an FDA-approved drug, and its efficacy is already well
established.
3.3 Secondary Endpoint
No secondary efficacy endpoint is defined for this study.  The study is not designed to assess efficacy of 
the study drug.  The DEX PS DDS Implant is an FDA-approved drug, and its efficacy is already well
established.
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3.4 Additional Endpoints
Additional endpoints are the updated and currently-approved DEX PS DDS Applicator performance 
(assessed via treatment administration assessment form, completed by the investigator) on Day 1.  
Further details regarding the treatment administration assessment form are in the Operations Manual
(Appendix F).
3.5 Safety Endpoints
This study is not designed to assess safety of the study drug, but AEs will be collected.  The DEX PS DDS 
Implant is an FDA-approved drug, and its safety is already well established.
Safety variables that will be evaluated in the study include vital signs, AEs, and ocular parameters as 
determined through assessments of BCVA, biomicroscopic slit-lamp examination, ophthalmoscopy, and 
IOP.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a Phase 3b, prospective, randomized, open-label, two-arm, 7-day clinical study in subjects with 
macular edema due to retinal vein occlusion (RVO) (BRVO or CRVO) or DME to support the evaluation of 
the updated DEX PS DDS Applicator (that incorporates the final, to-be-marketed design) and 
demonstrate that it delivers the DEX PS DDS Implant to the vitreous cavity and is suitable for commercial 
use in patients with macular edema due to retinal diseases.  The schematic of the study is shown in 
Figure 1.  Further details regarding study procedures are in the Operations Manual.
The study will consist of a single administration of the DEX PS DDS Implant (0.7 mg) in the study eye (SE) 
using either the updated DEX PS DDS Applicator (that incorporates the final, to-be-marketed design) or 
the currently-approved DEX PS DDS Applicator; approximately 54 subjects will be enrolled in the study 
and randomly assigned in a 2:1 ratio to receive the DEX PS DDS implant using the updated applicator or 
the currently-approved applicator, respectively.
Enrollment duration is planned to be approximately 3 months.
See Section 5 for information regarding eligibility criteria.
No interim analysis is planned for this study.
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Figure 1.
Schematic
DEX PS DDS = Dexamethasone Posterior Segment Drug Delivery System
4.2 Discussion of Study Design
Choice of Control Group
This is a two-arm, open-label study where approximately 54 subjects will be randomized in a 2:1 ratio to 
receive the same DEX PS DDS implant using either an updated applicator (test arm) or the currently-
approved applicator (comparator arm), respectively.
Appropriateness of Measurements
Standard statistical and clinical procedures will be utilized in this study.  All measurements in this study 
are standard for assessing disease activity in subjects with macular edema due to RVO (BRVO or CRVO) 
or DME.  All clinical and laboratory procedures in this study are standard and generally accepted.
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Day: 
Test= Updated applicator 
Study eye will be intravitreally administered with DEX PS DDS 0. 7 mg using 
Updated applicator at Day 1 and followed unt il Day 7 
Comparator= Currently-approved applicator 
Study eye will be intravitreally administered with DEX PS DDS 0.7 mg using 
Currently-approved applicator at Day 1 and followed until Day 7 
1 
2 
3 
4 
5 
6 
Purple Days = Study Visits 
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Suitability of Subject Population
Adult subjects with macular edema due to RVO (BRVO or CRVO) or DME will be included in this study, 
consistent with the currently marked product.  The SE will be selected by the investigator.  Qualified 
subjects will be administered DEX PS DDS Implant using either the updated or currently-approved 
DEX PS DDS Applicator in the SE.  To avoid confounding results, ocular conditions in the SE in which DEX 
PS DDS Implant is contraindicated are prohibited during the study.
Selection of Doses in the Study
The study will consist of a single fixed-dose administration of the DEX PS DDS Implant (0.7 mg) in the SE, 
which is same as the currently marketed product.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all the following criteria to be included in the study.  Anything other than a positive 
response to the questions below will result in exclusion from study participation.
Consent
1. Subject or legally authorized representative must voluntarily sign and date an informed 
consent, approved by an institutional review board (IRB), prior to the initiation of any screening 
or study-specific procedures.
2. Subject is willing to provide written documentation in accordance with the relevant country 
and local privacy requirements, where applicable.
3. In the opinion of the investigator, willing and able to follow study instructions and likely to 
complete all required study visits.
Demographic and Laboratory Assessments
4. Male and female.
5. Subject must be ≥ 18 years of age and the legal age of consent, at the time of signing the 
informed consent.
6. Subject is willing and able to comply with procedures required in this protocol.
Disease/Condition Activity
7. Diagnosis of 
a.
Macular edema due to RVO (BRVO or CRVO) in the SE
OR
b.
DME in the SE
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Subject History
8. No ocular conditions in the SE for which DEX PS DDS Implant is contraindicated.
a.
No active or suspected ocular or periocular infections in the SE including most viral 
diseases of the cornea and conjunctiva, including active epithelial herpes simplex 
keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal 
diseases.
b.
No glaucoma, with cup to disc ratios of greater than 0.8 in the SE.
c.
No torn or ruptured posterior lens capsule in the SE.  Note: Laser posterior capsulotomy 
in subjects with a pseudophakic eye is not a contraindication for DEX PS DDS Implant use.
d.
No known hypersensitivity to any components of DEX PS DDS Implant.
9. No known or suspected allergy or sensitivity to study diagnostic agents or medications.
10. Subject does not have a condition and is not in a situation that, in the investigator's opinion, 
may put the subject at significant risk, may confound the study results, or may interfere 
significantly with participation in the study.
11. The study investigator should consider the subject's overall health condition, including 
COVID-19 infection, to determine the subject's eligibility to be enrolled in the current study.  
This should include assessing if the subject is suspected of, quarantined for, or diagnosed with 
active COVID-19 infection; or whether the subject has any symptoms, as these could be 
exclusionary based on eligibility criterion 10 above.
Contraception
12. For all females of child-bearing potential; a negative urine pregnancy test at the 
Screening/Baseline Visit, prior to study drug administration.
13. Female subjects of childbearing potential must practice at least 1 protocol-specified method 
of birth control, that is effective from Study Day 1 through at least 3 months after study drug 
administration.  Female subjects of non-childbearing potential do not need to use birth control.
14. Female who is not pregnant or breastfeeding, and is not considering becoming pregnant or 
donating eggs during the study or for approximately 3 months after study drug administration.
Concomitant Medications
15. Subject must not have been treated with any investigational drug or device within 30 days 
prior to study drug administration or is currently enrolled in another clinical study or was 
previously enrolled in this study.
16. Subject is not expected to receive and has not been receiving the following during the study:
a.
SE: intravitreal injections of any sort other than the study treatment
b.
SE: sub-tenon, subconjunctival or topical corticosteroids 
c.
SE: anti-vascular endothelial growth factor therapies 
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0 
0 
0 
0 
0 
0 
0 
0 
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d.
SE: additional invasive non-study ocular procedures or intraocular surgery (including 
laser)
e.
Systemic corticosteroids (oral, inhaled, intranasal, intravenous, intramuscular, epidural, 
rectal, or extensive dermal)
f.
Systemic immunosuppressants (e.g., cyclosporine), immunomodulators 
(e.g., interferon), antimetabolites (e.g., methotrexate) or alkylating agents 
(e.g., cyclophosphamide)
g.
Systemic carbonic anhydrase inhibitors (e.g., acetazolamide)
h.
Anticoagulants for treatment of ophthalmic vascular disease
5.2 Contraception Recommendations
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified:

Females, Non-Childbearing Potential
Females do not need to use birth control during the study if considered of non-childbearing 
potential due to meeting any of the following criteria:
1.
Premenopausal female with permanent sterility or permanent infertility due to one of the 
following:

Permanent sterility due to a hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy

Non-surgical permanent infertility due to Mullerian agenesis, androgen insensitivity, or 
gonadal dysgenesis; investigator discretion should be applied to determining study entry 
for these individuals.
2.
Postmenopausal female

Age > 55 years with no menses for 12 or more months without an alternative medical 
cause.

Age ≤ 55 years with no menses for 12 or more months without an alternative medical 
cause AND documentation of a follicle-stimulating hormone level > 30 IU/L.

Females, of Childbearing Potential

Females of childbearing potential must avoid pregnancy during the study and for at least 
3 months after study drug administration.

Females must commit to one of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation-initiated at 
least 30 days prior to study Day 1.
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
Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to study Day 1.

Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).

Intrauterine device

Intrauterine hormone-releasing system

Vasectomized partner (provided the partner has received medical confirmation of the 
surgical success of the vasectomy and is the sole sexual partner of the trial subject).

Practice true abstinence, defined as:  Refraining from heterosexual intercourse when 
this is in line with the preferred and usual lifestyle of the subject (periodic abstinence 
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are 
not acceptable).
Contraception recommendations related to use of concomitant therapies prescribed should be based on 
the local label.
Contraception Requirements for Males
Not applicable for this study.
5.3 Prohibited Medications and Therapy
Prohibited concomitant medications are listed in the eligibility criteria.
During the study, all other investigational drugs are prohibited.
5.4 Prior and Concomitant Therapy
Allowed concomitant medications/therapies are presented in Table 1.
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Table 1.
Allowed Concomitant Medications/Therapy
Allowed Concomitant Medications/Therapy
Comments/Notes
IOP-lowering treatment 
If elevated IOP is observed in the SE after DEX PS DDS Implant 
administration during the study, IOP lowering treatment will be 
initiated at the discretion of the investigator.
Medications required for treatment 
administration
Medications required for DEX PS DDS Implant administration are 
permitted at the investigator's discretion.
Use of systemic NSAIDs 
Systemic NSAIDs regularly used prior to enrollment will be 
allowed to continue during the study and should be 
administered at a dosage that remains constant throughout the 
course of the study.
Treatment in the non-SE
Treatment in the non-SE is not restricted during the study, and 
the non-SE will receive standard of care per investigator 
discretion.
DEX PS DDS = Dexamethasone Posterior Segment Drug Delivery System; IOP = intraocular pressure; NSAIDs = nonsteroidal 
anti-inflammatory drug; SE = study eye
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject is receiving at the time of enrollment or receives during the study 
must be recorded from Screening/Baseline Visit prior to study drug administration through the 
Day 7/Premature Discontinuation (PD) Visit.
Any questions regarding concomitant or prior therapy should be raised to the AbbVie emergency 
contact.  Information regarding potential drug interactions with DEX PS DDS Implant can be located in 
the DEX PS DDS investigator's brochure.
Subjects must be able to safely discontinue any prohibited medications as described in the eligibility 
criteria.  Subjects must be consented for the study prior to discontinuing any prohibited medications for 
the purpose of meeting study eligibility.
COVID-19 Pandemic-Related Vaccination Guidance
Given the ongoing COVID-19 pandemic, selected non-live vaccines (e.g., messenger ribonucleic acid, 
non-replicating viral vector, protein subunit, etc.) to prevent severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) infection may be administered during screening or the study period, as long 
as components of the vaccine are not contraindicated.
The decision to receive a locally available vaccine should be based on local guidance and an individual 
discussion between the treating physician and the subject.
The potential impact of DEX PS DDS Implant on SARS-CoV-2 vaccination is unknown.  Therefore, study 
drug should be administered as follows:

Implantation of the DEX PS DDS Implant, when possible, is preferred to be performed at least 
± 7 days from the SARS-CoV-2 vaccine administration. 
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Note:  The above guidance applies to all SARS-CoV-2 vaccine doses given as part of the complete 
treatment course.
These recommendations may be subject to change based on the evolving knowledge around the use of 
SARS-CoV-2 vaccines and as more data are collected in real-world scenarios and clinical trials.
Any SARS-CoV-2 vaccine information must be documented on the COVID-19 vaccine electronic case 
report form (eCRF).  Refer to the Operations Manual for instructions on reporting any AEs associated 
with the COVID-19 vaccine.
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including, 
but not limited to, the following:

Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the Sponsor.

The investigator believes it is in the best interest of the subject.

The subject requests withdrawal from the study.

Eligibility criteria violation was noted and continuation of study procedure would place the 
subject at risk.

Introduction of prohibited medications or dosages and continuation of study procedure would 
place the subject at risk.

The subject becomes pregnant before study drug administration.

Subject is significantly noncompliant with study procedures, which would put the subject at risk 
for continued participation in the trial.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.
COVID-19 Pandemic-Related Acceptable Protocol Modification
During the COVID-19 pandemic, it has been necessary to employ mitigation strategies to enable the 
investigator to ensure subject safety and continuity of care.  Acceptable mitigation strategies are 
identified and included in the Operations Manual in Appendix F.
The investigator should contact the sponsor medical contact before discontinuing a subject from the 
study for a reason other than described in the protocol to ensure all acceptable mitigation steps have 
been explored.
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5.6 Follow-Up After Subject Discontinuation of Study Drug or from 
Study
Subjects should be advised on the continued scientific importance of their data.  If a subject prematurely 
discontinues study participation (withdrawal of informed consent), the procedures outlined for the 
PD visit should be completed as soon as possible, preferably within 2 days.  In addition, if subject is 
willing, follow-up after study drug administration may be completed to ensure all treatment-emergent 
AEs/serious adverse events (SAEs) have been resolved. 
5.7 Study Drug 
Study drug will be administered on Day 1, and subjects will not be retreated.
Table 2.
Study Drug Identification
Investigational Product
Mode of 
Administration
Dosage Form
Strength
Manufacturer
Dexamethasone 
Posterior Segment Drug 
Delivery System
Implant 0.7 mg
Intravitreal 
Injection –
updated 
applicator
Implant
0.7 mg
Allergan 
Dexamethasone 
Posterior Segment Drug 
Delivery System
Implant 0.7 mg
Intravitreal 
Injection –
currently-
approved 
applicator
Implant
0.7 mg
Allergan 
The DEX PS DDS Implant 0.7 mg is supplied in a foil pouch with a single-use updated DEX PS DDS 
Applicator (that incorporates the final, to-be-marketed design) or the currently-approved single-use DEX 
PS DDS Applicator.  Quantities will be sufficient to accommodate study design.  Each kit will be labeled 
per local requirements and this label must remain affixed to the kit.  Upon receipt, study drug should be 
stored as specified on the label and kept in a secure location.  Each kit will contain a unique kit number.  
This kit number is assigned to a subject via interactive response technology (IRT) and encodes the 
appropriate study drug to be dispensed at the subject's corresponding study visit.  Site staff will 
complete all blank spaces on the label before dispensing to subjects.  Study drug will only be used for 
the conduct of this study.
5.8 Randomization/Drug Assignment
All subjects will be assigned a unique identification number by the IRT at the screening visit.
All subjects will be treated with DEX PS DDS Implant in an unmasked, open-label manner.  Subjects will 
be randomly assigned in a 2:1 ratio to receive the DEX PS DDS implant using either the updated 
applicator (test) or the currently-approved applicator (comparator), respectively.
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Study drug will be labeled with study kit numbers.  The IRT system will provide the designated site 
personnel with the specific study kit number for each subject after eligibility is confirmed on Day 1.  The 
designated site personnel will receive and maintain the IRT confirmation notifications for each 
transaction.
5.9 Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol except when necessary to 
eliminate an immediate hazard to study subjects.  The investigator is responsible for complying with all 
protocol requirements, written instructions, and applicable laws regarding protocol deviations.  If a 
protocol deviation occurs (or is identified, including those that may be due to the COVID-19 pandemic), 
the investigator is responsible for notifying the IRB, regulatory authorities (as applicable), and AbbVie.
5.10 Data Monitoring Committee
Not applicable for this study.  
Criteria for subject withdrawal from the study are provided in Section 5.5.  Details about reporting 
adverse events, product complaints, and intercurrent illnesses is provided in Section 4.2 of Appendix F.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product/device.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device damage or not 
working properly, or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event.  
Reporting will be done via electronic data capture (EDC).  The date the product complaint details are 
entered into EDC and the form is saved represents the date reported to AbbVie.  A back-up paper form 
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will be provided for reporting complaints related to unassigned product or in the event of an EDC system 
issue.  If a back-up paper form is used, the date the form is emailed to RD_PQC_QA@abbvie.com 
represents the date reported to AbbVie.
All follow-up information is to be reported to the sponsor (or an authorized representative) and 
documented in source as required by the sponsor.  Product complaints associated with adverse events 
will be reported in the study summary.  All other complaints will be monitored on an ongoing basis.  
Product complaints occurring during the study will be followed up to a satisfactory conclusion.
Medical Complaints/Adverse Events and Serious Adverse Events:  DEX PS DDS
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
"special situations" such as accidental or intentional overdose, medication error, occupational or 
accidental exposure, off-label use, drug abuse, drug misuse, or drug withdrawal, all which must be 
reported whether associated with an AE or not.  Any worsening of a pre-existing condition or illness is 
considered an AE.  Worsening in severity of a reported adverse event should be reported as a new AE.  
Laboratory abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the investigator 
considers them to be AEs.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and/or the surgery/procedure has 
been pre-planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
during the study (e.g., surgery performed earlier than planned), then the deterioration of the condition 
for which the elective surgery/procedure is being done will be considered an adverse event.
If an AE, whether associated with DEX PS DDS or not, meets any of the following criteria, it is to be 
reported to AbbVie clinical pharmacovigilance (as appropriate) as an SAE within 24 hours of the site 
being made aware of the SAE (refer to Section 4.2 of the Operations Manual for reporting details and 
contact information):
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not been 
taken.  This does not include an event that would have been fatal if it 
had occurred in a more severe form.
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Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any length 
of time or prolongs the subject's hospital stay.  This does not include 
an emergency room visit or admission to an outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with 
the activities of daily living of a study subject.  Disability is not 
intended to include experiences of relatively minor medical 
significance such as headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle).
Important Medical Event 
Requiring Medical or Surgical 
Intervention to Prevent 
Serious Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require 
medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life threatening, hospitalization, 
prolongation of hospitalization, congenital anomaly, or persistent or 
significant disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or 
drug abuse.
All AEs reported from the time of study drug administration through study exit will be collected, 
whether solicited or spontaneously reported by the subject.  In addition, study procedure-related 
serious and nonserious AEs will be collected from the time the subject signs the study-specific informed 
consent.
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions reporting for DEX PS 
DDS in accordance with global and local requirements.
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk to subjects.
Adverse Event Severity and Relationship to DEX PS DDS
The investigators will rate the severity of each AE as mild, moderate, or severe.
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The investigator will use the following definitions to rate the severity of each AE:
Mild
The AE is transient and easily tolerated by the subject.
Moderate
The AE causes the subject discomfort and interrupts the subject's usual 
activities.
Severe
The AE causes considerable interference with the subject's usual activities 
and may be incapacitating or life threatening.
The investigator will use the following definitions to assess the relationship of the AE to the use of DEX 
PS DDS:
Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 24 hours after the site 
becomes aware of the pregnancy.  Subjects who become pregnant during the study before planned 
study drug administration must not receive study drug and must be discontinued (Section 5.5).  If a 
pregnancy occurs in a study subject, information regarding the pregnancy and the outcome will be 
collected.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth, or congenital anomaly is 
considered a SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol will be focused on safety analyses.  Complete and 
specific details of the statistical analysis will be described in the statistical analysis plan (SAP).
7.2 Definition for Analysis Populations
All subjects who have received DEX PS DDS Implant will contribute to the Safety Analysis Set (SAF). The 
SAF will be used for all safety analyses.
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7.3 Handling Potential Intercurrent Events for the Primary and Key 
Secondary Endpoints
Not applicable for this study.
7.4 Statistical Analyses for Efficacy
This study is not designed to assess efficacy of the study drug.  The DEX PS DDS Implant is an 
FDA-approved drug, and its efficacy is already well established.
Therefore, the efficacy analyses for this study are not applicable.
7.5 Statistical Analyses for Safety
The safety analysis will be performed using the SAF.  General safety parameters will include AEs 
(including pregnancies that meet SAE criteria per Section 6.1) and vital signs.  Ocular safety parameters 
will include BCVA, IOP measurement, biomicroscopy, ophthalmoscopy.  The treatment administration 
assessment form will be collected to evaluate investigator experience with and performance of the 
updated and the currently-approved DEX PS DDS Applicators.
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).  The 
number and percentage of subjects reporting AEs will be tabulated based on primary system organ class 
and preferred terms.  Summary tables will be generated for all AEs regardless of causality as well as 
treatment-related AEs.  Descriptive statistics for vital signs will be presented.  Ocular safety parameters 
will be summarized.  The treatment administration assessment form will also be summarized.
7.6 Interim Analysis
Not applicable for this study.
7.7 Overall Type I Error Control
Not applicable for this study.
7.8 Sample Size Determination
The sample size is determined empirically based on discussions with FDA to evaluate a minimum of 
30 eyes using the updated applicator and a minimum of 15 eyes using the currently approved applicator. 
Assuming a drop out rate of about 15% and the need to achieve 30 and 15 subjects to use the updated 
applicator and currently-approved applicator, respectively, the total enrollment would require
approximately 54 subjects.
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8 ETHICS
8.1 Institutional Review Board (IRB)
The protocol, informed consent form(s) (ICF[s]), recruitment materials, and all subject materials will be 
submitted to the IRB for review and approval.  Approval of both the protocol and the ICF(s) must be 
obtained before any subject is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  In addition, all changes to the 
consent form(s) will be IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, 
applicable regulations, and guidelines governing clinical study conduct and the ethical principles that 
have their origin in the Declaration of Helsinki.  Responsibilities of the investigator are specified in 
Appendix B.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).  During the COVID-19 pandemic, remote data review/verification may be employed if 
allowed by the local regulatory authority, IRB, and the study site.
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
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11
COMPLETION OF THE STUDY
The end-of-study is defined as the date of end of study participation by the last subject in the study.
A subject is considered to have completed the study if he/she has completed all study visits including 
Day 7.
12
REFERENCES
None.
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APPENDIX A. STUDY-SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AE
Adverse event
BCVA
Best-corrected visual acuity
BRVO
Branch retinal vein occlusion
COVID-19
Coronavirus Disease – 2019
CRF
Case report form
CRO
Clinical research organization
CRVO
Central retinal vein occlusion
DEX PS DDS
Dexamethasone Posterior Segment Drug Delivery System 
DME
Diabetic macular edema
eCRF
Electronic case report form 
EDC
Electronic data capture
FDA
Food and Drug Administration
GCP
Good Clinical Practice
ICF
Informed consent form
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IOP
Intraocular pressure
IRB
Institutional review board
IRT
Interactive response technology
MedDRA
Medical Dictionary for Regulatory Activities
NSAIDs
Nonsteroidal anti-inflammatory drugs
OU
Both eyes
PD
Premature discontinuation
PSC
Posterior subcapsular
RSI
Reference safety information
RVO
Retinal vein occlusion
SAE
Serious adverse event
SAF
Safety analysis set
SAP
Statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SE
Study eye
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SUSAR
Suspected Unexpected Serious Adverse Reactions
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APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol 1491-801-007:  Evaluation of an Updated Dexamethasone Posterior Segment Drug Delivery 
System Applicator in Participants with Macular Edema due to Retinal Diseases
Protocol Date: 29 November 2021
Clinical research studies sponsored by AbbVie are subject to the ICH GCP and local laws and regulations 
and guidelines governing the study at the site location.  In signing the Investigator Agreement, the 
investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, 
current protocol and operations manual, and making changes to a protocol only after notifying 
AbbVie and the appropriate IRB, except when necessary to protect the subject from immediate 
harm.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed consent and 
ethics committees (e.g., IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments.
9.
Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie.
10. Providing direct access to source data documents for study-related monitoring, audits, IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
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APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Medical Writer
Medical Writing
Medical Monitor
Clinical Development
Study Project Manager
Clinical Study Leadership
Statistical Therapeutic Area Head and 
Statistics Senior Director
Statistics
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APPENDIX E. PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions 
Protocol
Date
Version 1.0
20 April 2021
Version 2.0
24 June 2021
The purpose of Version 3.0 is to update from Version 2.0 the following sections below:

Minor editorial changes were made throughout the protocol for clarity and consistency. 

On the Title page, the sponsor/emergency medical contact and the number of planned sites 
were updated.
Rationale: Updated due to personnel changes and revised number of planned sites.

In Section 1, Section 2.1, Section 3.4, Section 7.5, and Appendix D, treatment administration 
questionnaire was revised to treatment administration assessment form. 
Rationale: Revised to be consist with the terminology used on the eCRF.

In Section 5.1 (eligibility criteria 7), added that diagnosis of macular edema due to RVO or DME 
is in the study eye. 
Rationale: Revised for clarity and accuracy.

In Section 5.8, text indicating that subjects could rescreen under their initial screening number 
was removed. 
Rationale: Subjects are not to be rescreened using their initial screening number. 

In Section 5.10, location of criteria for subject withdrawal and adverse event reporting was 
provided. 
Rationale: Updated to align with currently approved protocol template. 

In Section 6.1, details about product complaint reporting were added. 
Rationale: Added to provide additional information on product complaint reporting.

In Section 6.1, removed text indicating that AEs meeting SAE criteria can be reported to CRO.
Rationale: AEs meeting SAE criteria are to be reported to AbbVie clinical pharmacovigilance. 

In Section 8.2, removed text about conduct of the study in the event of a significant 
disaster/crisis. 
Rationale: Removed to align with the currently approved protocol template. 

In Section 11, the end-of-study definition was revised from last subject's last visit to end of study 
participation by the last subject. 
Rationale: Revised for clarity and to align with the currently approved protocol template. 
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
In Appendix C, list of protocol signatories was updated
Rationale: Updated due to personnel changes

Appendix F – the Operations Manual was updated as follows  

In Section 1, the sponsor/emergency medical contact was updated, email address for SAE 
reporting was updated, and Product Complaints contact information was added. 
Rationale: Updated due to personnel changes and to align with additional product 
complaint reporting procedure details added to the protocol.  

In Section 2, guidance on timing administration of DEX PS DDS around the SARS-CoV-2 
vaccine was added. 
Rationale: To align with guidance in the protocol.

In Sections 2.1, 3.12, 3.13, and 6.4, treatment administration questionnaire was revised to 
treatment administration assessment form. 
Rationale: Revised to be consist with the terminology used on the eCRF.

In Section 2.1, timing of administering the treatment administration assessment form was 
clarified. 
Rationale: Timing of administration was clarified for consistency.

In Section 3.7, removed text indicating that the sponsor will provide the pregnancy test kits
to sites. 
Rationale: The sponsor will not be providing the pregnancy test kits. 

In Section 3.8, distance from chart was converted from centimeters to inches. 
Rationale: Revised to be consistent with the use of feet for the Snellen equivalent. 

In Section 3.12 (step 12 under Treatment Procedure), instructions to inspect the needle tip 
were added. 
Rationale: To align with applicator instructions. 

In Section 4.1, text was added to clarify collection of AEs. 
Rationale: Clarification added to align with currently approved Operations Manual. 

In Section 4.2, removed the use of paper SAE CRFs, except as a backup, when reporting SAEs 
to clinical pharmacovigilance; email address for SAE reporting was updated.
Rationale: To discontinue the use of paper SAE CRF forms except for use as a backup and to 
update contact information. 

In Section 4.2, added details about product complaints.
Rationale: Product complaints will be collected. 

In Section 6.2, additional instructions about storage and disposition of study drug were 
added. 
Rationale: To provide additional detail and align with the currently approved Operations 
Manual. 
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
In Section 7.2, subheading for the lens assessment was created.
Rationale: To separate out the lens assessment and ophthalmoscopy (indirect). 
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APPENDIX F. OPERATIONS MANUAL
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1 CONTACTS
Sponsor/
Emergency Medical 
Contact
 MD
AbbVie Inc.
2525 Dupont Drive
Irvine, California 92612
EMERGENCY 24 hour Number:  
+1 (973) 784-6402
Mobile:
Email:
Safety Concerns
Ophthalmology Safety Team
1 North Waukegan Road
North Chicago, Illinois 60064
Phone:
+1 (833) 942-2226
Email:
SafetyManagement_Ophthalmology@abbvie.com
SAE Reporting 
outside of EDC
Email:
IR-Clinical-SAE@abbvie.com
Fax:
+1 (714) 796-9504
Back-up: +1 (714) 246-5295
Product Complaints
Email:
RD_PQC_QA@abbvie.com
Phone:
N/A
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TABLE OF CONTENTS
1
CONTACTS
2
2
PROTOCOL ACTIVITIES BY VISIT
5
2.1
INDIVIDUAL TREATMENT PERIOD VISIT ACTIVITIES
5
2.2
INDIVIDUAL POST-TREATMENT PERIOD VISIT ACTIVITIES
7
3
STUDY PROCEDURES
7
3.1
STUDY SUBJECT INFORMATION AND INFORMED CONSENT
7
3.2
ELIGIBILITY CRITERIA
8
3.3
MEDICAL/SURGICAL HISTORY
8
3.4
ADVERSE EVENT ASSESSMENT
8
3.5
PRIOR/CONCOMITANT THERAPY (MEDICATIONS AND PROCEDURES)
8
3.6
VITAL SIGNS
9
3.7
URINE PREGNANCY TESTS
9
3.8
BEST-CORRECTED VISUAL ACUITY (SNELLEN EQUIVALENT) ASSESSMENT
9
3.9
INTRAOCULAR PRESSURE MEASUREMENT
11
3.10
BIOMICROSCOPY EXAM (SLIT LAMP)
11
3.11
OPHTHALMOSCOPY (INDIRECT)
12
3.12
DISPENSE STUDY DRUG AND TREATMENT ADMINISTRATION
12
3.13
TREATMENT ADMINISTRATION ASSESSMENT FORM
18
3.14
SUBJECT WITHDRAWAL FROM STUDY
19
3.15
UNSCHEDULED VISITS
19
4
SAFETY MANUAL
19
4.1
METHODS AND TIMING OF SAFETY ASSESSMENT
19
4.2
REPORTING ADVERSE EVENTS, PRODUCT COMPLAINTS, AND INTERCURRENT ILLNESSES
19
5
COUNTRY-SPECIFIC REQUIREMENTS
21
5.1
SUSAR REPORTING
21
6
STUDY DRUG
21
6.1
TREATMENTS ADMINISTERED
21
6.2
PACKAGING AND LABELING
21
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6.3
METHOD OF ASSIGNING SUBJECTS TO TREATMENT GROUPS
22
6.4
SELECTION AND TIMING OF DOSE FOR EACH SUBJECT
22
7
APPENDICES
24
7.1
BIOMICROSCOPY EXAM (SLIT LAMP)
24
7.2
LENS ASSESSMENT
26
7.3
OPHTHALMOSCOPY (INDIRECT)
28
8
REFERENCES
31
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2 PROTOCOL ACTIVITIES BY VISIT
Study visits may be impacted due to the Coronavirus Disease – 2019 (COVID-19) pandemic.  This may 
include changes such as visits at alternative locations, or changes in the visit frequency and timing of 
study procedures, among others.  Additional details are provided in the subsequent section.  Every 
effort should be made to ensure the safety of subjects and site staff, while maintaining the integrity of 
the study.  If visits cannot be conducted onsite due to travel restrictions or other pandemic-related 
reasons, follow the updates below on how to proceed.  Study visits and assessments must be conducted 
onsite and cannot be conducted virtually during the study.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
During the COVID-19 pandemic, if it is not possible for all study procedures to be performed as specified 
due to travel restrictions or other reasons, the following modifications are allowed:

Study visits and/or activities should be performed as scheduled whenever possible.  If it is not 
possible to do so due to the pandemic, the following modifications are allowed:

Day 1 can occur within 3 days of Screening/Baseline (including on the same day).

Implantation of the DEX PS DDS implant, when possible, is preferred to be performed at 
least ± 7 days from the SARS-CoV-2 vaccine administration.
2.1 Individual Treatment Period Visit Activities
This section presents a list of activities performed during each visit, organized by visit.  The dot pattern 
on the upper right indicates the place of the visit in the overall Treatment Period Activity Schedule.
Activities are grouped by category (Interview, Exam, etc.).  Further information about each activity is 
provided in Section 3.
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the person who administered the informed consent, and any other signatories according to local 
requirements.  A copy of the signed informed consent will be given to the subject and the original will be 
placed in the subject's medical record.  An entry must also be made in the subject's dated source
documents to confirm that informed consent was obtained prior to any study-related procedures and 
that the subject received a signed copy.
Information regarding benefits for subjects and information regarding provisions for treating and/or 
compensating subjects who are harmed because of participation in the study can be found in the 
informed consent form.
Due to the COVID-19 pandemic, it is possible that additional protocol modifications not outlined in this 
protocol may become necessary.  If this situation arises, in addition to the study informed consent, 
additional verbal consent may be obtained prior to these adaptations or substantial changes in study 
conduct in accordance with local regulations.
3.2 Eligibility Criteria
Eligibility criteria will be assessed at the Screening/Baseline visit (Section 2.1).
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for the eligibility criteria 
assessment, other than those specified in Section 2.
3.3 Medical/Surgical History
A complete medical/surgical history, including demographics and ophthalmic history, will be 
documented at the Screening/Baseline visit (Section 2.1).  The medical/surgical history will serve as the 
baseline for clinical assessment.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for the medical/surgical 
history assessment, other than those specified in Section 2.
3.4 Adverse Event Assessment
Please refer to Section 4.1.
3.5 Prior/Concomitant Therapy (Medications and Procedures)
Prior/concomitant therapy (medications and procedures) will be recorded at visits per Section 2.1 and 
Section 2.2, according to the Prior and Concomitant Therapy section of the protocol.
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COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for the prior/concomitant 
therapy (medications and procedures) assessment, other than those specified in Section 2.
3.6 Vital Signs
Vital sign determinations of systolic and diastolic blood pressures and pulse rate will be obtained at 
visits as specified in Section 2.1 and Section 2.2.  Systolic and diastolic blood pressures will be measured 
by sphygmomanometer after subjects have been at rest (seated) for at least 5 minutes.  Blood pressure 
will be recorded as millimeters of mercury (mmHg).  Pulse rate will be measured after the subject has 
been in a resting state (seated) for at least 5 minutes.  Pulse will be counted for 30 seconds, multiplied 
by 2, and recorded as beats per minute (bpm).
Measurements should be assessed consistently throughout the study.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for vital signs, other than 
those specified in Section 2.
3.7 Urine Pregnancy Tests
Pregnancy testing should not be performed for postmenopausal women.
A urine pregnancy test will be performed at the Screening/Baseline visit for all female subjects of 
childbearing potential.  Pregnancy test kits will be administered according to the instructions provided 
with the test kits.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for urine pregnancy tests, 
other than those specified in Section 2.
3.8 Best-Corrected Visual Acuity (Snellen Equivalent) Assessment
Best-corrected visual acuity (BCVA) will be measured at all visits using a 3 meter, logMAR chart.  
Best-corrected visual acuity assessments will be performed using the most recent manifest refraction.  
In order to provide standardized assessments, all BCVA measurements should be consistently performed 
using the same test distance and lighting conditions throughout the entire study.
The RIGHT eye will be tested first with the manifest refraction in place.
If 3 meters is not available in front of the phoropter, the results of the manifest refraction will be placed 
in a trial frame and the BCVA measured at 3 m.
The LogMAR chart should be set at approximately eye level to the average height of a seated subject.  
Mark a spot on the floor (e.g., with tape) that is 10 feet away from the chart.  The examiner should 
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ensure that the subject's head does not move back and forth during testing.  After careful instruction, 
the left eye is occluded, and testing begins with the right eye.
The subject should be told that the chart has letters only and no numbers.  If the subject states a 
number, he/she should be reminded that the chart contains no numbers and the examiner should 
request a letter in lieu of the number.
Starting at the top line, the subject should be asked to read slowly (at a rate not faster than about 
1 letter per second) in order to achieve the best identification of each letter.  Do not proceed until the 
subject has given a definite response.  If the subject loses his/her place in reading or the examiner loses 
his/her place, the examiner should ask the subject to go back to the line where the place was lost.  The 
examiner should never point to the chart or to a specific letter on the chart or read any of the letters on 
the chart during the test.
When the subject says they cannot read a letter, he/she should be encouraged to guess.  If the subject 
identifies a letter as 1 of 2 or more letters, they should be asked to choose 1 letter.  When it becomes 
evident that no further meaningful readings can be made, despite urging to guess, the examiner should 
stop the test for that eye.  
Each letter is scored as correct or incorrect.  Once a subject has identified a letter with a definite single 
letter response and has read the next letter, a correction of the previous letter cannot be accepted.  
If the subject changes a response aloud before he/she has read the next letter aloud, then the change 
should be accepted.
When the subject no longer correctly identifies any letters on a line, stop testing the eye.  The BCVA is 
the lowest line read with 1 or no misses.  Record the acuity in Snellen equivalent units (e.g., 20/63).  
Repeat procedures for the other eye when specified by protocol.
If the BCVA is worse than logMAR 1.0 (20/200), the subject should be moved to 29.5 inches from the 
chart.  The subject should be seated for testing at this distance.  Record the acuity as the lowest line 
read, multiplying the denominator by four, e.g., 20/80 × 4 = 20/320.  If no letters can be read, test for 
Count Fingers, Hand Motion, or Light Perception, and record.
The pinhole method for measuring BCVA is not acceptable.
REPEAT the entire process for the LEFT eye.
Please note, at the 20/50 line, the chart will separate into 3 sets of charts.  For testing the right eye, 
have the subject continue reading down the right chart.  The chart on the left side is for testing the left 
eye and the center chart can be used for refraction. 
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for BCVA tests, other than 
those specified in Section 2.
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3.9 Intraocular Pressure measurement
Intraocular pressure (IOP) must be measured prior to pupil dilation.  Measurements will be taken as 
specified in Section 2.1 and Section 2.2.
Measurements will be taken using a Goldmann applanation tonometer or a handheld tonometer affixed 
to a slit-lamp with the subject seated.  The subject and slit-lamp should be adjusted so that the subject's 
head is firmly positioned on the chin rest and against the forehead rest without leaning forward or 
straining.  Tight fitting neckwear should be loosened.  Both eyes will be tested, with the right eye 
preceding the left eye.  The measurer will look through the binocular viewer of the slit lamp at low 
power.  The tension knob will be preset at a low-pressure value (4 to 6 mm Hg).  The measurer will 
follow the image of the fluorescein-stained semicircles while slowly rotating the tension knob until the 
inner borders of the fluorescein rings touch each other at the midpoint of their pulsation in response to 
the cardiac cycle.  When this image is reached, the measurer will take his/her fingers off the tension 
knob and record the IOP reading along with the date and time of day.
A Goldmann applanation tonometer is preferred, however, contact tonometers, including hand-held 
tonometers are acceptable.  In either case, the same tonometer should be used throughout the study 
for each subject.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for IOP measurement, other 
than those specified in Section 2.
3.10 Biomicroscopy Exam (Slit lamp)
Biomicroscopic examinations will be performed using a slit lamp at visits as specified in Section 2.1 and 
Section 2.2.  The examinations will include determination of ophthalmic medical 
observations/complications, evaluation of the condition of the eyelids, conjunctiva, cornea, anterior 
chamber, iris/pupil, and lens.
See Section 7.1 for more information.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for biomicroscopic 
examination, other than those specified in Section 2.
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3.11 Ophthalmoscopy (Indirect)
Ophthalmoscopic examinations will be performed through a dilated pupil at visits as specified in 
Section 2.1 and Section 2.2.  The examinations will include evaluation of the lens, vitreous, optic nerve, 
macula, and retina.  Presence of DEX PS DDS Implant in the vitreous cavity of the study eye (SE) after 
implantation will also be evaluated.
See Section 7.3 for more information.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for ophthalmoscopic 
examination, other than those specified in Section 2.
3.12 Dispense Study Drug and Treatment Administration
On Day 1, study drug will be dispensed and administered to subjects as specified in Section 2.1.  The 
study drug will be administered by the investigator after all other Day 1 procedures are completed 
(except for the treatment administration assessment form [completed by the investigator] and 
ophthalmoscopy [indirect], which will be performed following study drug administration).  On Day 1, the 
site personnel will document the date and time study drug was administered to verify compliance.
DEX PS DDS Study Treatment Procedure 
Materials needed

Tropicamide 1% or local equivalent

Phenylephrine 2.5% or local equivalent

Tetracaine 0.5% or local equivalent topical anesthetic

Povidone iodine 5% or local equivalent antiseptic

Lidocaine 2% or local equivalent subconjunctival anesthetic

Fluorescein strips

Sterile surgical field

Sterile drape

27-gauge needles

1 mL and 3 mL syringes

Cotton tip applicators

Cellulose sponges

Eyelid speculum

Caliper

Toothed forceps
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
Drape scissors
Pre-Treatment
Pre-operative antibiotics to SE 4 times daily may be started up to 3 days prior to study drug 
administration on Day 1.
Preliminary Procedures
On the day of the study procedure:
1.
If necessary, perform tonometry using a previously unopened bottle of the topical anesthetic 
and a sterile fluorescein strip.
2.
Dilate the subject's eyes with fresh, previously unopened bottles of dilating drops.
3.
It is recommended that the treating investigator perform a dilated exam on the treated eye, 
paying special attention to the quadrant that is anticipated to be used for the study procedure.
Treatment Procedure Overview
The general order of steps as written is:

Conjunctival sterilization

Local anesthesia

Sterile field set-up (sterile technique)

Prep

Drape (sterile gloves)

Procedure (sterile gloves)
The procedure is written according to the following considerations:

Assuming that there is no assistant present for the majority of the steps

To allow adequate time for the local anesthesia to work

To avoid having the treating investigator re-glove multiple times

To avoid having the subject's conjunctiva and cornea exposed with the lid speculum for a 
prolonged period of time

To avoid having the subject's cornea and conjunctiva exposed to the povidone-iodine prep or 
local equivalent antiseptic for a prolonged period of time
Treatment Procedure
The exact order of Steps 3 to 17 of the Treatment Procedure is not mandated as long as sterility is 
maintained and all of the steps are followed in a logical fashion (i.e., prep done before drape).  For 
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example, if an investigator prefers to give local anesthetic after the prep and drape, it is allowed as long 
as it is done in a sterile fashion.  If an assistant is present, many of the steps can be done in parallel such 
as the subject prep and the sterile field set-up.
There are two different DEX PS DDS Applicators used in this study, the currently-approved applicator 
(comparator) and the updated applicator (test).  The following instructions applies to both applicators.
1.
For all subjects, anesthetize the treated eye with 1 or 2 drops of the freshly opened bottle of 
topical anesthetic.  If the pre-operative antibiotics were not administered prior to Day 1, give an 
additional 3 doses of antibiotics to the SE every 15 minutes, three times.  Irrigate conjunctiva, 
including fornices, with at least 10 mL of 5% povidone iodine or local equivalent antiseptic.
2.
Place 2 drops of the povidone iodine 5% solution or local equivalent antiseptic on the 
conjunctiva of the treated eye. 
3.
As needed, using a 27-gauge needle affixed to a 1 mL syringe, inject approximately 0.2 to 0.5 mL 
of local anesthetic subconjunctivally in the quadrant selected for the study procedure.

There is no restriction on where the study procedure can be performed with the exception 
that 3:00 and 9:00 should be avoided because of the ciliary arteries and nerves.  The 
infero-temporal quadrant is usually the most accessible.

Note: if it is your normal practice, the subconjunctival anesthetic may be given after the 
prep and drape as long as it can be drawn up and administered in a sterile fashion.  
Additionally, topical anesthetic may also be administered.
4.
Open the sterile field.
5.
Using sterile technique, open the following onto the sterile field:

Sterile eyelid speculum

Sterile caliper or 1 mL syringe depending on the surgeon's preference

Sterile drape

Sterile cotton tip applicators

Sterile cellulose sponges

Sterile toothed forceps

Sterile drape scissors
6.
Inspect the foil pouch containing the DEX PS DDS Applicator to ensure the seal is intact.
7.
Using sterile technique, open the foil pouch containing the DEX PS DDS Applicator and allow the 
DEX PS DDS Applicator to gently fall onto the sterile field.  Do not drop the DEX PS DDS 
Applicator onto the field from a great height since that may damage the DEX PS DDS Applicator 
or dislodge the DEX PS DDS Implant.  Remember that only the inside of the foil pouch is sterile.
8.
Paint the eyelids, eyelid margins, and lashes of the treated eye 3 times using cotton tip 
applicators saturated with povidone iodine 5% or local equivalent antiseptic.
9.
Place an additional 2 drops of povidone iodine 5% or local equivalent antiseptic on the 
conjunctiva of the treated eye.
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10. If you are using an indirect ophthalmoscope as your coaxial light source, put it on now and 
adjust it for comfortable viewing.  Set it to small pupil (if available) and brightest beam.
11. Put on sterile gloves.
12. Carefully remove the cap by pulling it straight out from the DEX PS DDS Applicator in line with 
the long axis of the DEX PS DDS Applicator, taking care not to contact the needle with the cap.  
There is a tube within the cap that closely surrounds the needle, and angling the cap as it is 
removed can damage the needle or blunt the tip. Inspect the needle tip for damage; the 
implant retention plug may be visible in the bevel of the updated applicator needle and should 
not be removed.
Currently-Approved and Updated Applicators:
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Currently-approved applicator 
(Comparator) 
Cap 
Safety Tab 
Actuator Button ---;.~ 
Updated applicator 
(Test) 
Cap 
Safety Tab 
Actuator Button 


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13. Remove the safety tab from the DEX PS DDS Applicator by pulling it out perpendicular to the 
long axis of the DEX PS DDS Applicator.  Gently place the DEX PS DDS Applicator back on the 
sterile field taking care to avoid damaging the needle.  Do not twist or bend the safety tab to 
remove it and do not re-cap the DEX PS DDS Applicator.

If the indirect ophthalmoscope was used for the visualization or if the treating investigator 
removed the indirect themselves, first re-glove with sterile glove(s), and then remove the 
safety tab.
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Currently-approved applicator 
(Comparator) 
Needle with -------.J 
sleeve 
Updated applicator 
(Test) 
Safety Tab 
Actuator Button -----~•J 
Actuator Button 
Currently-approved applicator 
(Comparator) 
Needle_...._ _ __., 
Sleeve ---.....ii 
Needle 
Updated applicator 
(Test) 
Sleeve -----., 
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
Note: If the safety tab is not removed prior to the injection, it will be extremely difficult if 
not impossible to depress the actuator button.
14. Apply the sterile drape to the treated eye so that the eyelashes are excluded from the surgical 
field.  If using a non-fenestrated drape, ask the subject to keep his/her eye open as the drape is 
applied and use the sterile drape scissors to cut a slit in the drape over the treated eye.
15. Place the sterile speculum between the eyelids of the treated eye.  Try to ensure the eyelashes 
are covered by the drape and are out of the surgical field.

If subconjunctival local anesthetic was not given earlier, inject it now and allow it a few 
minutes to work.
16. Using a sterile caliper or the hub of a 1 cc syringe, measure 4 mm posterior to the limbus in 
phakic eyes or 3.0-3.5 mm posterior to the limbus in pseudophakic eyes.  Avoid 3 and 9 o'clock 
due to the posterior ciliary arteries and nerves.
17. Displace the conjunctiva away from the injection site and stabilize the globe with sterile toothed 
forceps (recommended) or a sterile cotton tip applicator.
18. Holding the long axis of the DEX PS DDS Applicator parallel to the limbus, enter the sclera at a 
shallow tangential angle with the bevel of the needle up (away from the sclera).
19. Staying parallel to the limbus and 4 mm behind the limbus for phakic eyes or 3.0 – 3.5 mm 
behind the limbus for pseudophakes, advance the tip of the needle partial thickness within the 
sclera for 1-2 mm (approximately half to all of the bevel) then re-direct the needle towards the 
center of the vitreous cavity.
20. Advance the needle until the vitreous cavity is entered and the sleeve is against the conjunctiva.  
Do not advance the needle past the point where the sleeve touches the conjunctiva.

Avoid aiming towards the inferior retina.  This creates a bi-planar self-sealing needle tract 
similar to sclerotomies for 23 gauge vitrectomy.  When re-directing into the vitreous cavity, 
allow for the fact that the DEX PS DDS Implant can be up to 5.6 mm long.
21. Slowly depress the actuator button on the DEX PS DDS Applicator until an audible and/or 
palpable click is noted; on occasion, a smaller, softer click is heard or felt while the button is only 
partially depressed.  Before withdrawing the DEX PS DDS Applicator from the eye, ensure that 
the button is fully depressed and has locked flush with the DEX PS DDS Applicator surface.  
Remember that the speed of the DEX PS DDS injection is proportional to the speed that the 
button is depressed. 
22. Withdraw the needle from the eye, back-tracking along the original entry path if possible (first 
perpendicular then parallel).  If an assistant is present, have them use a sterile cotton tip 
applicator to put pressure on the injection site as the needle exits (as with an intravitreal gas 
injection).

Remember that the subject is only under subconjunctival anesthesia and is able to move 
his/her eye, so it is more important to keep control of the globe than it is to put pressure on 
the injection site as the needle exits.
23. Use a cellulose sponge to check for wound leaks and for vitreous incarceration in the wound.  
Note the injection site to the nearest clock hour.
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24. Slide the conjunctiva back into place.
25. Remove the lid speculum and sterile drape.  Clean off the povidone-iodine or local equivalent 
antiseptic prep.
26. Perform indirect ophthalmoscopy without scleral depression looking to see if the DEX PS DDS 
Implant is visible, and if there are any signs of procedure-related complications such as vitreous 
hemorrhage, retinal tears, or retinal detachment.  The DEX PS DDS Implant is not always visible 
immediately post-procedure so do not scleral depress solely to visualize the DEX PS DDS 
Implant.
Post Treatment
1.
Remind subject to use antibiotic drops in SE 4 times daily for the next 3 days.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications to dispense or administer 
study drug, other than those specified in Section 2.
3.13 Treatment Administration Assessment Form
The treatment administration assessment form, as part of the electronic case report form (eCRF), will be 
completed by the investigator on Day 1 after study drug administration per Section 2.1. 
The investigator will evaluate whether the updated (test) or the currently-approved (comparator)
DEX PS DDS Applicator dispensed the DEX PS DDS Implant in the vitreous cavity and performed as 
intended.  The position of the DEX PS DDS Implant in the vitreous cavity will be defined1 as follows:

Position 1 (P1) = presence of the DEX PS DDS Implant in contact with pars plana and/or ciliary 
processes.

Position 2 (P2) = presence of the DEX PS DDS Implant anterior to the equator but with no part of 
it in contact with pars plana and/or ciliary processes.  Equator is identified based on the location 
of the vortex veins. 

Position 3 (P3) = presence of the DEX PS DDS Implant posterior to the equator.  Equator is 
identified based on the location of the vortex veins.
If the DEX PS DDS Implant is visible between P2 and P3 positions, then it should be marked as P2.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
There are no pandemic or natural disaster-related protocol modifications for the treatment 
administration assessment form, other than those specified in Section 2.
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COVID-19 Pandemic-Related Acceptable Protocol Modifications
Supplemental study case report forms should be completed in the event of COVID-19-related missed 
visits, study drug interruptions or discontinuations, or AEs (including capture of specific signs/symptoms 
of infection and testing results).
Severe acute respiratory syndrome coronavirus 2 infections should be captured as AEs.  If the event 
meets the criteria for a SAE, then follow the SAE reporting directions per the protocol and above.  The 
following COVID-19-related supplemental eCRFs should be completed (for both serious and nonserious 
events):

COVID-19 Supplemental Signs/Symptoms

COVID-19 Status Form
Reactions known to be associated with the SARS-CoV-2 vaccine should be reported as AEs.  If the event 
meets the criteria for an SAE, then follow the SAE reporting directions.  All AEs associated with the 
SARS-CoV-2 vaccine will be linked to the vaccine on the COVID-19 Vaccine eCRF.
5 COUNTRY-SPECIFIC REQUIREMENTS
5.1 SUSAR Reporting
AbbVie will be responsible for SUSAR reporting for the study drug in accordance with global and local 
guidelines and the Appendix of the Investigator Brochure will serve as the reference safety information 
(RSI).  The RSI in effect at the start of a Development Safety Update Report reporting period serves as 
the RSI during the reporting period.  For follow-up reports, the RSI in place at the time of occurrence of 
the 'suspected' Serious Adverse Reaction will be used to assess expectedness.
6 STUDY DRUG
6.1 Treatments Administered
The study drug (DEX PS DDS Implant 0.7 mg) will be administered into the SE on Day 1 (Section 2.1).
Study drug must not be dispensed without contacting the interactive response technology (IRT) system.  
Study drug may only be dispensed to subjects enrolled in the study through the IRT system.
6.2 Packaging and Labeling
The DEX PS DDS Implant 0.7 mg will be preloaded in the updated DEX PS DDS Applicator that 
incorporates the final, to-be-marketed design (test) or the currently-approved DEX PS DDS Applicator
(comparator).
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Both the updated and currently-approved DEX PS DDS Applicators will be provided in a sealed pouch 
and the pouch will be contained within a carton.
Both the pouch and the carton will be labeled as required per country requirement.  The labels must 
remain affixed to the pouch and carton.  All blank spaces should be completed by site staff prior to 
dispensing to subject.
Storage and Disposition of Study Drug
Study drug must be stored at 15° to 30°C (59° to 86°F).
The study drug is for investigational use only and is to be used only within the context of this study.  The 
study drug supplied for this study must be maintained under adequate security and stored under the 
conditions specified on the label until dispensed for subject use or destroyed on site as appropriate.
Sites are responsible for maintaining the study drug according to the storage conditions specified on the 
clinical label and monitoring for temperature excursions with the use of a calibrated continuous 
temperature monitoring device (for example, chart recorders and/or acceptable calibrated min/max 
thermometers) or continuous monitoring systems.  Specific guidance on appropriate temperature 
monitoring and temperature excursions reporting requirements will be provided separately.
6.3 Method of Assigning Subjects to Treatment Groups
This is a Phase 3b, prospective, randomized, open-label, two- arm, 7-day clinical study in subjects with 
macular edema due to retinal vein occlusion (RVO) (branch retinal vein occlusion [BRVO] or central 
retinal vein occlusion [CRVO]) or diabetic macular edema (DME) to support the evaluation of the 
updated DEX PS DDS Applicator (that incorporates the final, to be marketed design) and demonstrate 
that it delivers the DEX PS DDS Implant to the vitreous cavity and is suitable for commercial use in 
patients with macular edema due to retinal disease.  Eligible subjects will be administered DEX PS DDS 
Implant 0.7 mg in the SE on Day 1. Approximately 54 subjects will be enrolled in this study and 
randomly assigned in a 2:1 ratio to receive the DEX PS DDS implant using either the updated applicator 
(test) or the currently-approved applicator (comparator), respectively.
At the Screening/Baseline visit, all subjects will be assigned a unique subject number using the IRT.  For 
subjects who do not meet the study selection criteria, the site personnel must contact the IRT system 
and identify the subject as a screen failure.
Subjects who are enrolled will retain their subject number assigned at the Screening/Baseline visit 
throughout the study.  Upon receipt of study drug, the site will acknowledge receipt in the IRT system.
Contact information and user guidelines for IRT use will be provided to each site.
6.4 Selection and Timing of Dose for Each Subject
Eligible subjects will be administered DEX PS DDS Implant 0.7 mg in the SE on Day 1, in an open-label 
manner. Approximately 54 subjects will be enrolled in this study and randomly assigned in a 2:1 ratio to 
receive the DEX-PS-DDS implant using either the updated applicator (test) or the currently-approved 
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
applicator (comparator), respectively. The study drug will be administered by the investigator after all 
other Day 1 procedures are completed (except for the treatment administration assessment form
[completed by the investigator] and ophthalmoscopy [indirect], which will be performed following study 
drug administration).
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7 APPENDICES
7.1 Biomicroscopy Exam (slit lamp)
Biomicroscopic examinations will be performed using a slit lamp.  The examinations will include 
determination of ophthalmic medical observations/complications, evaluation of the condition of the 
eyelids, conjunctiva, cornea, anterior chamber, iris/pupil, and lens.
Eyelid/Eyelid Margins/Lashes:
Edema
0 (None) = No edema
+0.5 (Trace) = Localized, minimal (trace) swelling
+1 (Mild) = Localized, mild swelling
+2 (Moderate) = Diffuse, moderate swelling
+3 (Severe) = Diffuse, severe swelling
Erythema
0 (None) = No erythema
+0.5 (Trace) = Localized, minimal (trace), flush reddish color 
+1 (Mild) = Localized, mild, flush reddish color
+2 (Moderate) = Diffuse reddish color encompassing the entire lid margin
+3 (Severe) = Deep diffuse reddish color of lid margins and superior and/or inferior eyelid
Conjunctiva (Bulbar):
Hyperemia 
0 (None) = No hyperemia
+0.5 (Trace) = Minimal (trace) flush, reddish color
+1 (Mild) = Mild flush, reddish color
+2 (Moderate) = Bright red color
+3 (Severe) = Deep, bright, diffuse redness
Edema
0 (None) = No edema
+0.5 (Trace) = Localized, minimal (trace) swelling
+1 (Mild) = Localized, mild swelling
+2 (Moderate) = Diffuse, moderate swelling
+3 (Severe) = Diffuse, severe swelling
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Conjunctiva (Palpebral):
Hyperemia
0 (None) = No hyperemia
+0.5 (Trace) = Minimal (trace) flush, reddish color
+1 (Mild) = Mild flush, reddish color
+2 (Moderate) = Bright red color
+3 (Severe) = Deep, bright, diffuse redness
Edema
0 (None) = No edema
+0.5 (Trace) = Localized, minimal (trace) swelling
+1 (Mild) = Localized, mild swelling
+2 (Moderate) = Diffuse, moderate swelling
+3 (Severe) = Diffuse, severe swelling
Cornea:
Edema
0 (None) = No edema
+0.5 (Trace) = Localized, minimal (trace) epithelial haze
+1 (Mild) = Dull glass appearance of epithelium that may include fine localized microcystic changes
+2 (Moderate) = Dull glass appearance of the epithelium with large number of cystic changes with or 
without stromal edema
+3 (Severe) = Epithelial bullae and/or stromal edema, localized or diffuse, with or without stromal striae
Punctate Epithelial Staining (includes superficial punctate keratopathy, punctate epithelial erosion, and 
punctate epithelial keratopathy)
0 = No staining
+0.5 = Trace
+1 = Mild
+2 = Moderate
+3 = Severe
Anterior Chamber:
For the measurements of cells and flare based on Standardized Uveitis Nomenclature (SUN) criteria2, the 
following settings should be used:

1 x 1 mm slit beam 

High magnification

Highest slit lamp voltage 

Low ambient lighting
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Illumination angle of 45°

Same grader and slit lamp whenever possible
The Anterior Chamber will be evaluated, at a minimum, for presence of the following pathologies:

Cells
0 = 0 cells
+0.5 = 1-5 cells (trace)
+1 = 6-15 cells
+2 = 16-25 cells
+3 = 26-50 cells
+4 = > 50 cells

Flare
0 = None: No flare seen
+1 = Faint: Faint flare seen
+2 = Moderate: Iris and lens details clear
+3 = Marked: Iris and lens details hazy
+4 = Intense: Fibrin or plastic aqueous

Anterior Synechiae

Hypopyon – if hypopyon is present provide details and if applicable levels in millimeters (mm)
Iris/Pupil:
The iris/pupil will be evaluated for pathology. If pathology is present, it will be described.
Rubeosis Iridis
0 = No visible rubeosis iridis
+0.5 = Trace visible rubeosis iridis
+1 = Obvious vessels in 1 quadrant (≤ 90 degrees)
+2 = Obvious vessels 2-3 quadrants (91-270 degrees)
+3 = Obvious vessels 4 quadrants (271-360 degrees)
7.2 Lens Assessment
Lens Status:
Lens status will be assessed as phakic, pseudophakic, or aphakic.  The lens (including the posterior 
capsule when visible, e.g., post-lens extraction) will also be evaluated for pathology.  If pathology is 
present, it will be described.
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Cataract Assessment (Phakic eyes only):
Under dilated examination, the presence and severity of nuclear, cortical, and posterior subcapsular 
cataract lens opacities will be evaluated according to the Age-Related Eye Disease Study Clinical Lens 
Grading Protocol.  Biomicroscopic findings will be compared with standard photographs.  AbbVie will 
supply the site with a copy of the standard photographs.3
Pupils should be dilated to at least 5 mm.  The slit lamp should be used at 10x magnification.  Grading 
will be performed as described below.

Nuclear Sclerosis

Adjust the slit beam to a width of 0.3 mm and a height of 8.0 mm.

Orient the slit beam at 45º to the viewing axis.

Compare the slit lamp appearance with Nuclear Standard Photograph #2.  The primary 
considerations are: the opalescence (reflectance) of the nucleus and the blurring of the 
normal landmarks, i.e., the dark interval at the center of the nucleus (the "sulcus") and the 
short, bright bands adjacent to it anteriorly and posteriorly (the "lentils," so named for their 
somewhat bean-like shape).

Standard Photographs.  Only Nuclear Standard Photograph #2 is used in grading.  Standard 
Photographs #1 and #3 are provided as examples of lenses that have less and more nuclear 
sclerosis than Standard Photograph #2.

Grading scale
I. Opacity is absent
II. Opacity is present, but less than Standard Photograph #2
III. Opacity is present and as severe as or worse than Standard Photograph #2

Posterior Subcapsular (PSC) Opacities

Use retroillumination and include PSC opacities visible with it.

Standard Photographs.  Only PSC Standard Photograph #2 is used for grading.  PSC Standard 
Photograph #2 with lines at the borders of the opacity is provided for reference.

Grading scale
IV. Opacity is absent
V. Opacity is present, but less than Standard Photograph #2
VI. Opacity is present and as severe as or worse than Standard Photograph #2

Cortical Opacities

Use retroillumination.

Include both anterior and posterior cortical opacities that are visible with retroillumination.

Combine all opacities and compare total area with Cortical Standard Photograph #2 (about 
25% of the visible lens).
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Standard photographs.  Only Cortical Standard Photograph #2 is used in grading.  Standard 
#2 with lines at the borders of the opacities is provided for reference.

Grading scale
VII. Opacity is absent
VIII. Opacity is present, but less than Standard Photograph #2
IX. Opacity is present and as severe as or worse than Standard Photograph #2
Posterior Capsule Assessment (aphakic or pseudophakic eyes only)
When visible, an assessment of the posterior capsule will be performed to determine the location of 
capsular opacification, if any, and whether the capsular bag is intact.
7.3 Ophthalmoscopy (indirect)
Dilated Fundoscopic Examination
The fundus assessments should be conducted through a dilated pupil.  The examinations will include 
evaluation of the lens, vitreous, optic nerve, macula, and retina.  The investigator should note if the 
pupil dilated normally.
Vitreous:
(1 × 3 mm beam in anterior vitreous).4
Cells
0 = None
+0.5 = 1-10 cells
+1 = 11-20 cells
+2 = 21-30 cells
+3 = 31-100 cells
+4 = > 100 cells
Note if the condition is not evaluable.
Vitreous Haze
Vitreous haze will be graded by viewing the optic disc and posterior retina using the following settings 
and by comparing the haze against a photographic standardized scale5 according to the chart provided 
by AbbVie.

Indirect ophthalmoscope and a 20-diopter lens

Illumination set to mid-power

Large beam

Low ambient lighting

Same grader and indirect ophthalmoscope whenever possible
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The scale is categorized as follows:
0 = No inflammation
+0.5 = Trace inflammation (slight blurring of the optic disc margins and/or loss of the nerve fiber layer 
reflex)
+1 = Mild blurring of retinal vessels and optic nerve
+2 = Moderate blurring of optic nerve head
+3 = Marked blurring of optic nerve head
+4 = Optic nerve head not visible
Note if the condition is not evaluable.
Vitreous Hemorrhage
Vitreous hemorrhage will be evaluated for severity.  Indicate whether or not it is localized to the 
injection site.
0 = No visible evidence of hemorrhage on fundus ophthalmoscopic exam
+0.5 = Retinal detail is visible; trace hemorrhage is present
+1 = Retinal detail is visible; mild hemorrhage is present
+2 = Large retinal vessels are visible; central retinal detail is not visible
+3 = Red reflex is visible; no central retinal detail is seen posterior to the equator
+4 = No red reflex
Posterior Vitreous Detachment
The presence or absence of a posterior vitreous detachment will be evaluated.  Note if the condition is 
not evaluable.
Optic Nerve:
The optic nerve will be evaluated for pathology.  If pathology is present, it will be described.  It will be 
noted if the condition is not evaluable.
Cup/Disc ratio will be reported using a 0.0 to 1.0 scale.  It will be noted if the condition is not evaluable.
Macula:
The macula will be evaluated, at a minimum, for the presence or absence of the following pathologies. 
Note if the condition is not evaluable.

Intraretinal fluid

Subretinal fluid

Intraretinal hemorrhage

Subretinal hemorrhage

Rhegmatogenous detachment

Tractional detachment

Pigment epithelial detachment
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Retina Periphery:
The retina periphery will be evaluated, at a minimum, for presence or absence of the following 
pathologies.  Note if the condition is not evaluable.

Retinal hemorrhage

Retinal tear (specify location in clock hours)

Rhegmatogenous retinal detachment with or without macular detachment

Tractional retinal detachment with or without macular detachment

Exudative retinal detachment with or without macular detachment

Round (atrophic) retinal hole

Lattice degeneration
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL 1491-801-007 Version 3.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8 REFERENCES
1.
Sudhalkar A, Kodjikian L, Chhablani J, et al.  Intraocular dexamethasone implant position in situ 
and ocular hypertension. Retina. 2018;38(12):2343-9.
2.
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(3):509-16.
3.
Age-Related Eye Disease Study Research Group. The age-related eye disease study (AREDS) 
system for classifying cataracts from photographs: AREDS report no. 4. Am J Ophthalmol.
2001;131(2):167-75.
4.
Mitchel Opremcak E. (1995). Symptoms and Signs of Uveitis. In: Uveitis. Springer, New York, 
NY. https://doi.org/10.1007/978-1-4612-4174-4_2.
5.
Nussenblatt RB, Palestine AG, Chan CC, et al. Standardization of vitreal inflammatory activity in 
intermediate and posterior uveitis. Ophthalmology. 1985;92(4):467-71.
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SAP_001.pdf: 
Updated DEX PS DDS applicator
1491-801-007 – Statistical Analysis Plan
Version 1.0 – 16Dec2021
1
Statistical Analysis Plan for Study 1491-801-007
Evaluation of an Updated Dexamethasone Posterior 
Segment Drug Delivery System Applicator in 
Participants with Macular Edema due to Retinal 
Diseases  
Date:  16Dec 2021 
Version 1.0
 
NCT04976777


Updated DEX PS DDS applicator
1491-801-007 – Statistical Analysis Plan
Version 1.0 – 16Dec2021
2
Table of Contents
1.0
Introduction .............................................................................4
2.0
Study Design and Objectives..................................................4
2.1
Objectives, Hypotheses and Estimands .....................................................4
2.2
Study Design Overview .............................................................................4
2.3
Treatment Assignment and Blinding .........................................................5
2.4
Sample Size Determination........................................................................5
3.0
Endpoints..................................................................................6
4.0
Analysis Populations ...............................................................6
5.0
Subject Disposition..................................................................7
6.0
Study Drug Duration and Compliance..................................7
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications ......................7
7.1
Demographics and Baseline Characteristics..............................................8
7.2
Medical History .........................................................................................8
7.3
Ophthalmic Medical History......................................................................8
7.4
Prior and Concomitant Medications ..........................................................8
8.0
Handling of Potential Intercurrent Events for the 
Primary and Key Secondary Endpoints................................9
9.0
Efficacy Analyses.....................................................................9
10.0
Safety Analyses ........................................................................9
10.1
General Considerations..............................................................................9
10.2
Adverse Events ..........................................................................................9
10.2.1
Treatment-Emergent Adverse Events ......................................................10
10.2.2
Adverse Event Overview .........................................................................10
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT .......................11
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure ..................................................................................................11
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation...............................................................................11
10.2.6
Adverse Events of Special Interest ..........................................................11


Updated DEX PS DDS applicator
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10.3
Analysis of Laboratory Data....................................................................12
10.4
Analysis of Vital Signs ............................................................................12
10.5
Other Safety Analyses..............................................................................12
10.5.1
Best Corrected Visual Acuity (BCVA)....................................................12
10.5.2
Intraocular Pressure (IOP) .......................................................................13
10.5.3
Biomicroscopy .........................................................................................13
10.5.4
Opthalmoscopy ........................................................................................15
11.0
Other Analyses.......................................................................16
12.0
Interim Analyses....................................................................16
12.1
Data Monitoring Committee....................................................................16
13.0
Overall Type-I Error Control ..............................................16
14.0
Version History......................................................................16
15.0
Reference................................................................................17
List of Tables
Table 1.
SAP Version History Summary...............................................................16
List of Figures
Figure 1.
Study Schematic.........................................................................................4
List of Appendices


Updated DEX PS DDS applicator
1491-801-007 – Statistical Analysis Plan
Version 1.0 – 16Dec2021
4
1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for updated DEX PS 
DDS applicator study 1491-801-007, evaluation of an updated dexamethasone posterior 
segment drug delivery system applicator in participants with macular edema due to retinal 
diseases.
The SAP will not be updated in case of administrative changes or amendments to the 
protocol unless the changes impact the analysis.
Unless noted otherwise, all analyses will be performed using SAS Version 9.4 (SAS 
Institute Inc., Cary, NC  27513) or later under either or both the Linux and UNIX 
operating systems.
This SAP includes changes to analyses described in the protocol.  Details are outlined in 
Section 14.0.
2.0
Study Design and Objectives
2.1
Objectives, Hypotheses and Estimands
The primary objective is to demonstrate that the updated DEX PS DDS applicator (that 
incorporates the final, to-be-marketed design) delivers the DEX PS DDS Implant to the 
vitreous cavity and is suitable for commercial use in subjects with macular edema due to 
retinal diseases.
There is no defined clinical hypothesis or estimands for this study.
2.2
Study Design Overview
The schematic of the study is shown in Figure 1.
Figure 1.
Study Schematic




Updated DEX PS DDS applicator
1491-801-007 – Statistical Analysis Plan
Version 1.0 – 16Dec2021
6
currently approved applicator. Assuming a dropout rate of about 15% and the need to 
achieve 30 and 15 subjects to use the updated applicator and currently-approved 
applicator, respectively, the total enrollment would require approximately 54 subjects.
3.0
Endpoints
3.1
Efficacy Endpoint(s)
The study is not designed to assess efficacy of the study drug.  The DEX PS DDS Implant
is an FDA-approved drug, and its efficacy is already well-established.
3.2
Safety Endpoint(s)
This study is not designed to assess safety of the study drug, but AEs will be collected.  
The DEX PS DDS Implant is an FDA-approved drug, and its safety is already well 
established.
Safety variables that will be evaluated in the study include vital signs, AEs, and ocular 
parameters as determined through assessments of BCVA, biomicroscopic slit-lamp 
examination, ophthalmoscopy, and IOP.
4.0
Analysis Populations
The following population sets will be used for the analyses.
The Safety Analysis Set (SAS) consists of all subjects who received DEX PS DDS 
Implant.  Subjects will be included in the analysis according to the updated applicator or 
currently-approved applicator that was used to deliver the DEX PS DDS Implant.


Updated DEX PS DDS applicator
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5.0
Subject Disposition
The total number of subjects who were screened, enrolled (randomized), and treated will 
be summarized.  Reasons for exclusion, including screen failure, will be summarized. A 
summary of subject accountability will be provided where the number of subjects in each 
of the following categories will be summarized for each treatment group:
●
Subjects enrolled (randomized) in the study;
●
Subjects who took the dose of study drug;
●
Subjects who prematurely discontinued study drug (all reasons and primary 
reason).
For end of study participation, the number and percentage of subjects who completed the 
protocol defined follow-up period (or did not with associated reasons) will be summarized 
overall and by treatment group.
6.0
Study Drug Duration and Compliance
Not applicable.
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications
Demographics, baseline or disease characteristics, medical history, and prior and 
concomitant medications will be summarized for the SAS overall and by treatment group.
Categorical variables will be summarized with the number and percentage of subjects; 
percentages will be calculated based on the number of non-missing observations.
Continuous variables will be summarized with descriptive statistics (number of 
non-missing observations, mean and standard deviation, median, minimum and
maximum).


Updated DEX PS DDS applicator
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7.1
Demographics and Baseline Characteristics
Continuous demographic variables include age. Categorical demographic variables 
include sex, ethnicity and race.
7.2
Medical History
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). The actual version of the MedDRA coding dictionary will be noted in the 
statistical tables and clinical study report. The number and percentage of subjects in each 
medical history category (by MedDRA system organ class and preferred term) will be 
summarized overall and by treatment group. The system organ class (SOC) will be 
presented in alphabetical order, and the preferred terms will be presented in alphabetical 
order within each SOC. Subjects reporting more than one condition/diagnosis will be 
counted only once in each row (SOC or preferred term).
7.3
Ophthalmic Medical History
Ophthalmic medical history is defined as indicated on the medical history eCRF form 
marked ‘OD’,’OS’ or ‘OU’ to the question of the location of the medical history. 
Ophthalmic medical history data will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). The actual version of the MedDRA coding dictionary 
will be noted in the statistical tables and clinical study report. The number and percentage 
of subjects in each ophthalmic medical history category (by MedDRA system organ class 
and preferred term) will be summarized overall and by treatment group. The system 
organ class (SOC) will be presented in alphabetical order, and the preferred terms will be 
presented in alphabetical order within each SOC. Subjects reporting more than one
condition/diagnosis will be counted only once in each row (SOC or preferred term).
7.4
Prior and Concomitant Medications
Prior and concomitant medications will be summarized by generic name. A prior 
medication is defined as any medication taken prior to the date of the study drug. 


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A concomitant medication is defined as any medication that started prior to the date
of the first dose of study drug and continued to be taken after the first dose of study drug
or any medication that started on or after the date of the first dose of study drug. The 
number and percentage of subjects taking medications will be summarized by generic 
drug name based on the World Health Organization (WHO) Drug Dictionary for both 
prior and concomitant medications.
8.0
Handling of Potential Intercurrent Events for the 
Primary and Key Secondary Endpoints
Not applicable.
9.0
Efficacy Analyses
Not applicable.
10.0
Safety Analyses
10.1
General Considerations
Safety data will be summarized for the SAS. Safety summaries will be presented by 
treatment group. For the safety analysis, subjects are assigned to a treatment group based 
on the treatment actually received, regardless of the treatment randomized.
Study eye is defined as the eye that received DEX PS DDS Implant.
10.2
Adverse Events
Adverse events (AEs) will be summarized and presented using primary MedDRA System 
Organ Classes (SOCs) and preferred terms (PTs) according to the version of the MedDRA 
coding dictionary used for the study at the time of database lock. The actual version of 
the MedDRA coding dictionary used will be noted in the AE tables and in the clinical 
study report. Specific adverse events will be counted once for each subject for calculating 
percentages, unless stated otherwise. In addition, if the same adverse event occurs 


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multiple times within a subject, the highest severity and level of relationship to 
investigational product will be reported.
10.2.1
Treatment-Emergent Adverse Events
Treatment-emergent AEs are defined as any AE with the onset that is after the first dose 
of study drug. Events where the onset date is the same as the study drug start date are 
assumed to be treatment-emergent. Each treatment-emergent AE will be determined as 
ocular or non-ocular AE. The ocular treatment-emergent AE is defined as indicated on the 
AE form of eCRF marked “OD” or “OS” to the question of “what was the location of the 
adverse event All treatment-emergent AEs, ocular treatment-emergent AEs in either the 
study eye or fellow eye, and non-ocular AEs will be summarized overall, as well as by 
primary MedDRA SOC and Preferred Term. The SOCs will be presented in alphabetical 
order, and the PTs will be presented in alphabetical order within each SOC.
The number and percentage of subjects experiencing treatment-emergent AEs will be 
summarized.
10.2.2
Adverse Event Overview
An overview of AEs will be presented consisting of the number and percentage of 
subjects experiencing at least one event for each of the following AE categories:
●
Any treatment-emergent AE
●
Any treatment-emergent AE related to study drug according to the investigator
●
Any severe treatment-emergent AE
●
Any serious treatment-emergent AE
●
Any treatment-emergent AE leading to death
●
Any ocular treatment-emergent AE
●
Any AEs of Special Interest
●
All deaths


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●
TEAEs related to COVID-19 infection.  
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
Treatment-emergent AEs, ocular treatment-emergent AEs in either the study eye or fellow
eye, and non-ocular AEs will be summarized by SOC and PT; by maximum relationship 
to study procedure as assessed by the investigator (e.g., reasonable possibility or no 
reasonable possibility) and SOC and PT; by maximum severity and SOC and PT; and by 
subject number and SOC and PT. Specific adverse events will be counted once for each 
subject for calculating percentages, unless stated otherwise. In addition, if the same 
adverse event occurs multiple times within a subject, the highest severity and level of 
relationship to investigational product will be reported.
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure
Not applicable.
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to 
Study Discontinuation
SAEs (including deaths) and AEs leading to study discontinuation will be summarized by 
SOC and PT and in listing format.
10.2.6
Adverse Events of Special Interest
There are no protocol-specific AEs of special interest.
However, AEs possibly related to DEX PS DDS implant position and administration will 
be tabulated by PT. These AEs include, but not limit to, conjunctival hemorrhage, 
conjunctival tear cataract, lens or lenticular abnormality or change from baseline, vitreous 


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haze, vitreous hemorrhage, vitreous leak, retinal hemorrhage, retinal tear, retinal hole, 
retinal detachment, other retinal abnormality or change, intraocular inflammation, 
blindness, visual acuity or vision decrease. Also, abnormality or change of best corrected 
visual acuity (BCVA) (≥2 lines or more worse than baseline) and IOP change by 10 
mmHg from baseline will be reported as AE, and will be included.
10.3
Analysis of Laboratory Data
Not applicable.
10.4
Analysis of Vital Signs
Vital sign measurements of systolic and diastolic blood pressure and heart rate will be 
summarized.
Each vital sign variable will be summarized for all visits (starting with Baseline) with the 
number of non-missing observations, mean and standard deviation, median, minimum and 
maximum. Mean change from baseline to each applicable post-baseline visit will be 
summarized for each vital sign variable, with the number of observations, baseline mean, 
and visit mean. 
10.5
Other Safety Analyses
10.5.1
Best Corrected Visual Acuity (BCVA)
BCVA will be performed for both eyes at each follow-up visit.
BCVA for the study eye and fellow eye will be summarized by a categorical tabulation 
of the number of line change from baseline at each follow-up visit for the following 
categories: 
•
3 lines or better than baseline (“Much Better”)
•
2 lines better than baseline (“Better”)


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•
Between 1 line worse and 1 line better than baseline (“No change”)
•
2 lines worse than baseline (“Worse”)
•
3 lines or worse than baseline (“Much Worse”)
10.5.2
Intraocular Pressure (IOP)
Intraocular pressure (IOP) is measured at each follow-up visit prior to pupil dilation for 
both eyes.
IOP of the study eye and fellow eye will be summarized for the raw IOP values and 
change from baseline at each visit with descriptive statistics by treatment group.
The IOP of the study eye will be summarized by three cut-off values at each follow-up 
visit:
•
35 mmHg, 
•
30 mmHg, and 
•
25 mmHg
In addition, the change from baseline IOP in the study eye of 10 mmHg increase will be 
analyzed. 
10.5.3
Biomicroscopy
The biomicroscopy examinations are performed for both eyes at every follow-up
visit. The following assessments are performed:

Findings from conjunctiva (edema, hyperemia and subconjunctival hemorrhage), 
cornea (edema and superficial punctuate keratopathy), and iris/pupil (rubeosis 
iridis) using a 5-point scale (0=none, 0.5=trace, 1=mild, 2=moderate, 3=severe)


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
Anterior chamber (flare) using a 5-point scale (0 = None, 1 = Faint, 2 = 
Moderate, 3 = Marked, 4 = Intense).

Cells of anterior chamber using a 6-point scale (0 = 0 cells, 0.5 = 1-5 cells, 1 = 6-
15 cells, 2 = 16-25 cells, 3 = 26-50 cells, 4 = >50 cells)

Iris/Pipil using a on a 5-scale in cells (0=no visible rubeosis iridis, +0.5= trace 
visible rubeosis iridis, +1=obvious vessels in 1 quadrant, +2= obvious vessels in 2-
3 quadrants, +3= obvious vessels in 4 quadrants).

Hypopyon of anterior chamber (not evaluable, present or not and the level 
estimated in millimeters)

Lens status as phakic, pseudophakic, or aphakic

Presence and severity of nuclear, cortical, and posterior subcapsular cataract lens 
opacities using a 3-point scale for each type of opacity (1 = opacity is absent, 2 = 
opacity is present, but less than standard photo #2, and 3 = opacity is present and 
as severe as or worse than standard photo #2)

Posterior capsule assessment for aphakic or pseudophakic eyes as not evaluable, 
intact or not
The number and percent of patients with clinically significant biomicroscopy findings at 
one or more visits will be tabulated for study eye and fellow eye. A clinically significant 
finding is defined as at least two severity grade increase (worsening) from baseline, or a 
status change from absent to present or non-evaluable to evaluable at follow-up visits. If a 


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pathology is recorded at a follow-up visit but not at baseline, the baseline will be imputed 
with the same pathology, with a grade of zero (none).
10.5.4
Ophthalmoscopy
The ophthalmoscopy examinations are performed for both eyes at each follow-up 
visit. The following assessments are performed:

Vitreous cells and vitreous haze using a 6-point rating scale plus not evaluable (0, 
0.5, 1, 2, 3, 4 and not evaluable)

Vitreous hemorrhage using a 6-point rating scale (0, 0.5, 1, 2, 3, and 4)

Posterior vitreous detachment evaluated as no, yes and not evaluable

Disc hemorrhage and other disc pathology as not evaluable, no finding or present

Fundus as no finding or present

Intraretinal fluid, subretinal fluid, intraretinal hemorrhage, rhegmatogenous 
detachment, tractional detachment, pigment epithelial detachment as no finding or 
present

Retinal hemorrhage, retinal tear, rhegmatogenous retinal detachment, tractional 
retinal detachment, exudative retinal, other retinal detachment, round (astrophic) 
retinal holes, and lattice degeneration as no finding or present

Cup to disc ratio value


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Similar to biomicroscopy data, the number and percent of patients with clinically 
significant ophthalmoscopy findings at one or more visits will be tabulated for study 
eye and fellow eye. A clinically significant finding is defined as at least two severity 
grade increase (worsening) from baseline, or a status change from absent to present or 
non-evaluable to evaluable at follow-up visits.  
11.0
Other Analyses
Not applicable.
12.0
Interim Analyses
Not applicable.
12.1
Data Monitoring Committee
Not applicable.
13.0
Overall Type-I Error Control
Not applicable.
14.0
Version History
Table 1.
SAP Version History Summary
Version
Date
Summary
1.0
16 Dec 2021
Original version


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15.0
Reference


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Appendix A.
Protocol Deviations
The number and percentage of subjects who reported at least one of the following 
protocol deviation categories will be provided.
●
Subject entered into the study even though s/he did not satisfy entry criteria.
●
Subject developed withdrawal criteria during the study and was not 
withdrawn.
●
Subject received wrong treatment or incorrect dose of study.
●
Subject took prohibited concomitant medication.


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Appendix B.
Definition of Adverse Events of Special Interest
Adverse Events of Special Interest (AESI) will be identified using the following search 
criteria:
Area of Safety Interest
Search Criteria
AEs related to Implant position and 
administration
Conjunctival hemorrhage, conjunctival tear cataract, lens or 
lenticular abnormality or change from baseline, vitreous haze, 
vitreous hemorrhage, vitreous leak, retinal hemorrhage, retinal 
tear, retinal hole, retinal detachment, other retinal abnormality 
or change, intraocular inflammation, blindness, visual acuity or 
vision decrease, abnormality or change of BCVA (≥2 lines or 
more worst then baseline), IOP change by 10 mmHg from 
baseline.
Adjudicated terms will be further identified using CECAT and 
CETERM from the CE SDTM dataset.