Clinical trial NCT05704725
Conditions: Chorioretinal Vascular Disease
Keywords: Chorioretinal vascular disease CVD ABP 938 EYLEA® aflibercept
Sponsor: Amgen
Start date: 2023-01-23; Completion date: 2023-03-24
Enrollment: 49 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to is to assess the ability of retina specialists to successfully administer, via an intravitreal (IVT) injection, a 2 mg dose of ABP 938, using the ABP 938 aflibercept prefilled syringe (PFS), compared to a 2 mg dose of aflibercept using the aflibercept PFS.

Detailed description:

Arms: arm 1: Participants will be randomized in a ratio of 2:1 to receive either a single IVT injection of ABP 938 in a PFS or a single injection of aflibercept in a PFS. arm 2: Participants will be randomized in a ratio of 2:1 to receive either a single IVT injection of ABP 938 in a PFS or a single injection of aflibercept in a PFS.
Interventions: intervention 1: ABP 938 intervention 2: Aflibercept
Intervention descriptions: intervention 1: IVT injection intervention 2: IVT injection

Protocol documents:
Prot_000.pdf: 
Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
Page 1 of 61
Confidential
CLINICAL STUDY PROTOCOL
Title:
An Open Label, Two-Arm Study in Subjects with Chorioretinal 
Vascular Disease to Evaluate ABP 938 and Aflibercept
(Eylea®) in a Prefilled Syringe
Protocol Number:
20210034
Study Phase:
Phase 3B
Test Product:
ABP 938
Regulatory Agency 
Identifier Number(s):
IND number 135489
EudraCT number 2019-002503-17 
Sponsor:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799
(805) 447-1000
Contract Research 
Organization (CRO):
ICON Clinical Research
South County Dublin Business Park,
Leopardstown, Dublin 18, D18X5R3
Ireland
Phone: +353-1-2912000
Fax: +353-1-2476260
Protocol Version and 
Date:
Version 1.0, 19 Oct 2022
This study will be performed in compliance with the principles of Good Clinical Practice.
This document is a confidential communication of Amgen Inc. Acceptance of this document 
constitutes agreement by the recipient that no unpublished information contained herein shall be 
published or disclosed without prior written approval, except that this document will be disclosed 
to the appropriate Institutional Review Board(s) under the condition that they keep it confidential.
NCT number: NCT05704725 
This NCT number has been applied to the document
for purposes of posting on clinicaltrials.gov


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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PROTOCOL SIGNATURE PAGE – SPONSOR
This protocol has been reviewed and approved by the representative(s) listed below. Any 
modification of the protocol must be agreed upon by Amgen and the investigator and must be 
documented in writing.
Amgen Inc. representative:
, MD, PhD
Executive Medical Director
Print Name
Title
Signature
Date
Electronically signed by:
Reason: I am approving this document
ate: Oct 25, 2022 02:55 PDT


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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PROTOCOL SIGNATURE PAGE – CONTRACT RESEARCH ORGANIZATION
This protocol has been reviewed and approved by the representative(s) listed below. Any 
modification of the protocol must be agreed upon by Amgen and the investigator and must be 
documented in writing.
ICON Clinical Research representatives:
Medical Director
Print Name
Title
Signature
Date
Electronically signed by:
MD
eason: I am approving this
ocument
Date: Oct 25, 2022 10:19 GMT+2


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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PROTOCOL SIGNATURE PAGE – INVESTIGATOR
I have read this protocol, which has been agreed by Amgen Inc. and given approval/favorable 
opinion by the Institutional Review Board (IRB), and I agree that it contains all necessary details 
for my staff and I to conduct this study as described. I will provide copies of the protocol and any 
amendments to all study personnel under my supervision and provide access to all information 
provided by Amgen Inc. or their specified designees. I will discuss the material with the study 
personnel to ensure that they are fully informed about the study.
I understand that information contained in or pertaining to this protocol is confidential and should 
not be disclosed, other than to those directly involved in the execution or the ethical review of the 
study, without written authorization from Amgen Inc.. It is, however, permissible to provide 
information to a subject in order to obtain consent.
I agree to conduct this study according to this protocol and to comply with its requirements, subject
to ethical and safety considerations and guidelines, and to conduct the study in accordance with 
the general guidelines indicated in the Declaration of Helsinki, International Council for 
Harmonisation guidelines on Good Clinical Practice (ICH GCP), and applicable national or
regional regulatory requirements.
I agree to comply with the procedures described for data recording and reporting and to permit 
monitoring and auditing by Amgen Inc., and inspection by the appropriate regulatory authorities.
I agree to make my subjects’ study records available to Amgen Inc. personnel, their 
representatives and relevant regulatory authorities in order to verify data that I have entered into 
the case report forms. I will retain the study-related essential documents until Amgen Inc.
indicates that they are no longer needed. I am aware of my responsibilities as an investigator as 
provided by Amgen Inc.
I agree to ensure that Financial Disclosure Statements will be completed by: myself (including, if 
applicable, my spouse or legal partner and dependent children) and my sub-investigators
(including, if applicable, their spouses or legal partners and dependent children) at the start of the 
study and for up to 1 year after the study is completed, if there are changes that affect my financial 
disclosure status.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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I understand that Amgen Inc. may decide to suspend or prematurely terminate the study at any 
time for whatever reason; such a decision will be communicated to me in writing. Conversely, 
should I decide to withdraw from execution of the study, I will communicate my intention 
immediately in writing to Amgen Inc.
Investigator:
Print Name
Title
Institution
Signature
Date


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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SERIOUS ADVERSE EVENT CONTACT INFORMATION
In the event of a serious adverse event, the investigator will send a safety report form within 
24 hours of becoming aware of the serious adverse event to Amgen Inc.
In the Americas:
Amgen Inc.
Fax: +1-888-814-8653
Email: svc-ags-in-us@amgen.com
Version 1.0, 19 Oct 2022
Initial creation


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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PROTOCOL SUMMARY
Protocol Number: 20210034
Protocol Title: An Open Label, Two-Arm Study in Subjects with Chorioretinal Vascular 
Disease to Evaluate ABP 938 and Aflibercept (Eylea®) in a Prefilled Syringe.
Sponsor: Amgen Inc.
Study Phase: Phase 3B
Indication: Chorioretinal vascular disease (CVD)
Study Sites: Approximately 4 sites in the United States (US).
Rationale: Amgen is developing ABP 938 as a biosimilar candidate to Eylea® (aflibercept). To 
administer ABP 938 as an intravitreal (IVT) injection, Amgen has also developed a prefilled 
syringe (PFS). The study will investigate whether the ABP 938 PFS can be used effectively and 
safely by retina specialists to administer the 2 mg dose of study drug, when descriptively 
compared to the US-licensed aflibercept PFS.
Objectives/Endpoints:
Objectives
Endpoints
Primary
The primary objective for this study is to 
assess the ability of retina specialists to 
successfully administer, via an IVT injection,
a 2 mg dose of ABP 938, using the ABP 938 
PFS, compared to a 2 mg dose of aflibercept 
using the aflibercept PFS.
The primary endpoint for the study is the 
proportion of IVT injections successfully 
administered to subjects with CVD by retina 
specialists, utilizing the ABP 938 PFS or 
aflibercept PFS.
Secondary
The secondary objective is to assess the 
safety of ABP 938 administered to subjects 
with CVD via an IVT injection, using the ABP 
938 
PFS 
compared 
to 
aflibercept 
administered using the aflibercept PFS.
The secondary endpoint for the study is the 
incidence of ocular adverse events (AEs) 
and serious adverse events (SAEs) in the 
study eye, and non-ocular SAEs until the 
end of study visit (Day 28 visit).
Study Design: This is an open label, two-arm, randomized, multi-site study within the US in 
adult subjects with CVD, including neovascular (wet) age-related macular degeneration (AMD), 
diabetic macular edema (DME), macular edema following retinal vein occlusion (RVO), or 
diabetic retinopathy (DR). Randomization will be stratified by retina specialist.
The study consists of a screening visit (Day -1), a baseline visit (Day 1) and an end of study 
visit (Day 28 ± 7 days). The screening and baseline visit may be combined into one visit (Day 1).


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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Study Procedures: After providing informed consent, subjects will be screened. After 
screening assessments are completed and if subject eligibility is confirmed, the subject will be 
enrolled into the study and randomized to either receive a single IVT injection of ABP 938 in a 
PFS or a single injection of aflibercept in a PFS and followed for safety events.
The use of the PFS will be evaluated by the ability of retina specialists to successfully administer 
the investigational product (IP) (test or reference product) 2 mg in PFS via IVT injections to 
subjects.
After completion of the IVT injection, the investigator will provide their assessment to report 
whether the injection was successfully administered or not.
Safety procedures for the study eye will include Best Corrected Visual Acuity (BCVA) by 
ETDRS (Early Treatment Diabetic Retinopathy Study), slit-lamp biomicroscopy, intraocular 
pressure (IOP), and indirect ophthalmoscopy and spectral domain- optical coherence 
Tomography (SD-OCT).
Study Duration: The study duration for each subject will be approximately 28 days (± 7 days) 
excluding screening and the study will end for subjects when they complete the end of study 
visit assessments.
The start of the study will be the date on which the first subject provides informed consent, 
and the end of the study will be when the last subject has completed the assessments for the 
end of study visit. Whenever possible, all procedures listed under the end of study visit should 
be completed for subjects who are prematurely discontinued.
Planned Number of Subjects: Approximately 48 adult male or female subjects with a 
minimum of 32 subjects in the ABP 938 PFS arm and a minimum of 16 subjects in the 
aflibercept PFS arm (randomization ratio 2:1).
Target Population: Subjects aged ≥ 18 years old with treatment-naïve or previously treated
neovascular (wet) AMD, DME, macular edema following RVO, or DR in the study eye, in 
whom treatment (IVT) with aflibercept is indicated.
Test Product:
Name: ABP 938
Dose: 2 mg/0.05 mL
Mode of administration: Single IVT injection using PFS
Reference Product:
Name: aflibercept
Dose: 2 mg/0.05 mL
Mode of administration: Single IVT injection using PFS


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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Statistical Methods: All analyses for this study will be summarized descriptively. The Full 
Analysis Set (FAS) will include all randomized subjects and will be analyzed according to 
randomized treatment. This analysis set will be used for summaries of the primary endpoint. 
The number and percentage of injections successfully administered utilizing the PFS will be 
provided descriptively separately by randomized treatment group. Percentages will be based 
upon the number of subjects in the FAS for each treatment group. The estimated primary 
endpoint success rate for each treatment group will be calculated by the average of each 
retina specialists’ individual success rate.
The Safety Analysis Set will include all randomized subjects who receive the IP and will be 
analyzed according to the actual treatment received. This analysis set will be used for 
summaries of safety data. All reported AEs will be assigned the system organ class and 
preferred term according to the Medical Dictionary for Regulatory Activities as of the time of 
analysis and graded by Common Terminology Criteria for Adverse Events, version 5.0. The 
number and percentage of subjects experiencing any ocular treatment emergent AEs 
(TEAEs) and serious treatment emergent adverse events (TE-SAEs) in the study eye, and 
non-ocular SAEs will be summarized descriptively and separately by actual treatment 
received.
Statistical Hypothesis: No formal statistical hypothesis testing will be conducted.
Protocol Version and Date: Version 1.0, 19 Oct 2022


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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STUDY SCHEMATIC
Figure 1
Study Schematic
IVT = intravitreal; mg = milligram; mL = milliliter; n = number of subjects.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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SCHEDULE OF ASSESSMENTS
Table 1
Schedule of Assessments
BCVA = Best Corrected Visual Acuity; ETDRS = Early Treatment Diabetic Retinopathy Study; 
IVT = Intravitreal; IOP = Intraocular pressure; SD-OCT = Spectral Domain-Optical Coherence Tomography
a The screening and baseline visits may be combined on Day 1.
b In the event of premature discontinuation, the subject should complete the assessments indicated at the end of 
study visit, whenever possible.
c Adverse events will be collected from the signing of the informed consent form until the end of study visit.
d All ophthalmic safety assessments should be performed on the study eye only.
e IOP will be measured pre-dose (prior to dilation) and 15-60 minutes after IP administration.
f
Indirect ophthalmoscopy will be performed pre-dose and after IP administration.
g Required for females of childbearing potential. Test will be performed by local laboratory.
Study Procedure
Screening
Baseline 
(Randomization 
and Injection)
End of Studyb
(! 7 days)
Day -1
Day 1a
Day 28
Informed Consent
X
Medical and Ophthalmic History
X
Demographic Data
X
Concomitant Medications
X
X
X
Adverse Events c
X
X
X
BCVA by ETDRS d
X
X
Slit-Lamp Biomicroscopy d
X
X
Intraocular Pressure (IOP) d
X
X e
X
Indirect Ophthalmoscopy d
X
X f
X
SD-OCT d
X
X
Urine Pregnancy g
X
Randomization
X
IVT Injection of Study Medication (ABP 938 or aflibercept) 
X


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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TABLE OF CONTENTS
CLINICAL STUDY PROTOCOL ...........................................................................1
PROTOCOL SIGNATURE PAGE – SPONSOR ...................................................2
PROTOCOL SIGNATURE PAGE – CONTRACT RESEARCH 
ORGANIZATION............................................................................................3
PROTOCOL SIGNATURE PAGE – INVESTIGATOR ..........................................4
SERIOUS ADVERSE EVENT CONTACT INFORMATION ..................................6
PROTOCOL SUMMARY ......................................................................................7
STUDY SCHEMATIC..........................................................................................10
SCHEDULE OF ASSESSMENTS.......................................................................11
TABLE OF CONTENTS......................................................................................12
LIST OF TABLES................................................................................................15
LIST OF FIGURES .............................................................................................15
LIST OF ABBREVIATIONS ................................................................................16
1
INTRODUCTION AND RATIONALE ............................................................18
1.1
Background..............................................................................................18
1.1.1
Disease...............................................................................................18
1.1.2
Amgen Test Product Background.......................................................18
1.1.3
Nonclinical Studies .............................................................................18
1.1.4
Clinical Studies ...................................................................................18
1.1.5
Non-Amgen Reference Product..........................................................18
1.2
Study Rationale........................................................................................19
1.3
Benefit/Risk Assessment .........................................................................19
2
OBJECTIVES AND ENDPOINTS.................................................................20
3
STUDY PLAN...............................................................................................20
3.1
Overall Study Design and Plan ................................................................20
3.2
Discussion of Study Design......................................................................21
3.3
End of Study.............................................................................................21
3.3.1
End of Study Definition .......................................................................21
3.3.2
Study Duration for Subjects ................................................................22
4
STUDY POPULATION .................................................................................22
4.1
Inclusion Criteria ......................................................................................22
4.2
Exclusion Criteria .....................................................................................22
4.3
Subject Enrollment...................................................................................23


Sponsor Name: Amgen Inc.
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4.4
Screen Failures........................................................................................24
4.5
Premature Discontinuation.......................................................................24
4.5.1
Premature Discontinuation of Investigational Products.......................24
4.5.2
Premature Discontinuation from the Study .........................................25
4.5.3
Lost to Follow-up ................................................................................26
5
DESCRIPTION OF STUDY ASSESSMENTS..............................................26
5.1
Demographics and Other Screening Assessments..................................26
5.1.1
Informed Consent ...............................................................................27
5.1.2
Medical and Ophthalmic History .........................................................27
5.1.3
Demographics.....................................................................................27
5.1.4
Urine Pregnancy.................................................................................27
5.2
Assessment of Administration of Intravitreal Injection..............................27
5.3
Safety Assessments.................................................................................27
5.3.1
Best Corrected Visual Acuity ..............................................................27
5.3.2
Slit-Lamp Biomicroscopy ....................................................................28
5.3.3
Intraocular Pressure ...........................................................................28
5.3.4
Indirect Ophthalmoscopy ....................................................................28
5.3.5
Spectral Domain Optical Coherence Tomography..............................28
5.3.6
Adverse Events...................................................................................28
5.3.7
Pregnancy...........................................................................................28
6
TREATMENTS.............................................................................................29
6.1
Investigational Products ...........................................................................29
6.1.1
Description of Investigational Products...............................................29
6.1.2
Handling and Storage .........................................................................29
6.1.3
Packaging, Labeling, and Shipment ...................................................29
6.1.4
Product Complaints ............................................................................30
6.2
Method of Assigning Treatment ...............................................................30
6.3
Dose and Administration ..........................................................................30
6.3.1
Intervention After the End of the Study...............................................30
6.4
Precautions and/or Lifestyle Considerations ............................................30
6.5
Prior and Concomitant Therapy ...............................................................30
6.5.1
Prior Treatment (Medications and Therapies).....................................31
6.5.2
Concomitant Treatments (Medications and Therapies) ......................31
6.5.2.1
Concomitant Treatment of the Fellow Eye.....................................31
6.5.3
Prohibited Concomitant Medications and Procedures ........................31


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6.5.4
Rescue Medication .............................................................................31
6.6
Overdose .................................................................................................32
6.7
Compliance ..............................................................................................32
6.8
Accountability...........................................................................................32
7
ADVERSE EVENTS.....................................................................................32
7.1
Definitions ................................................................................................32
7.1.1
Adverse Events...................................................................................32
7.1.1.1
Events Meeting the Adverse Event Definition................................33
7.1.1.2
Events NOT Meeting the Adverse Event Definition.......................33
7.1.2
Serious Adverse Events......................................................................34
7.1.3
Suspected Unexpected Serious Adverse Reactions...........................35
7.1.4
Other Abnormal Assessments ............................................................35
7.1.5
Events of Interest................................................................................35
7.1.6
Adverse Device Effects.......................................................................35
7.2
Assessment of Adverse Events................................................................36
7.2.1
Severity...............................................................................................36
7.2.2
Causality.............................................................................................36
7.3
Documenting and Reporting Adverse Events...........................................37
7.4
Reporting of Serious Adverse Events ......................................................38
7.5
Method of Detecting Adverse Events and Serious Adverse Events.........39
7.6
Adverse Event and Serious Adverse Event Follow-up.............................39
7.7
Safety Reporting Oversight ......................................................................39
8
STATISTICS.................................................................................................40
8.1
General Procedures.................................................................................40
8.2
Analysis Populations................................................................................40
8.3
Sample Size.............................................................................................40
8.4
Planned Analyses ....................................................................................41
8.4.1
Interim Analysis and Early Stopping Guidelines .................................41
8.4.2
Final Analysis......................................................................................41
8.5
Statistical Methods...................................................................................41
8.5.1
Primary Endpoint ................................................................................41
8.5.2
Secondary Endpoints..........................................................................41
8.5.3
Safety Endpoints.................................................................................42
8.5.4
Demographic and Baseline Characteristics ........................................42
8.5.5
Exposure to Investigational Products..................................................42


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8.5.6
Exposure to Concomitant Medications ...............................................43
8.5.7
Handling of Missing Values.................................................................43
9
ETHICS AND RESPONSIBILITIES..............................................................43
9.1
Good Clinical Practice..............................................................................43
9.2
Institutional Review Board........................................................................43
9.3
Informed Consent.....................................................................................44
9.4
Financing and Insurance..........................................................................45
9.4.1
Contractual and Financial Details .......................................................45
9.4.2
Insurance, Indemnity, and Compensation ..........................................45
9.4.3
Financial Disclosure............................................................................46
10 RECORDS MANAGEMENT.........................................................................46
10.1
Source Documentation.............................................................................47
10.2
Case Report Form Completion and Data Management ...........................47
10.3
Study Files and Record Retention............................................................48
11 AUDITING AND MONITORING ...................................................................48
11.1
Risk and Quality Tolerance Limits............................................................49
11.2
Protocol Adherence and Deviations.........................................................49
12 AMENDMENTS............................................................................................50
13 STUDY REPORT AND PUBLICATIONS......................................................50
14 STUDY START AND TERMINATION ..........................................................51
15 CONFIDENTIALITY......................................................................................52
16 REFERENCES.............................................................................................53
17 APPENDICES ..............................................................................................54
17.1
Appendix I - Study Administrative Structure.............................................54
17.2
Appendix II - Clinical Laboratory Tests.....................................................56
17.3
Appendix III - Contraceptive Guidance and Collection of Pregnancy 
and Lactation Information.........................................................................57
LIST OF TABLES
Table 1
Schedule of Assessments .............................................................11
LIST OF FIGURES
Figure 1
Study Schematic ...........................................................................10


Sponsor Name: Amgen Inc.
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LIST OF ABBREVIATIONS
ADR
Adverse Drug Reaction
AE
Adverse Event
AMD
Age-related Macular Degeneration
ATC
Anatomical Therapeutic Chemical
BCVA
Best Corrected Visual Acuity
COVID-19
Coronavirus Disease 2019
CRO
Contract Research Organization
CTCAE
Common Terminology Criteria for Adverse Events
CVD
Chorioretinal Vascular Disease
DME
Diabetic Macular Edema
DR
Diabetic Retinopathy
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
ETDRS
Early Treatment Diabetic Retinopathy Study
EU
European Union
EudraCT
European Union Drug Regulating Authorities Clinical Trials
EOI
Events of Interest
FAS
Full Analysis Set
FSH
Follicle-stimulating Hormone
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
HRT
Hormonal Replacement Therapy
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation
IND
Investigational New Drug
IOP
Intraocular Pressure
IP
Investigational Product
IRB
Institutional Review Board
IVT
Intravitreal 
IXRS
Interactive Voice Response System / Interactive Web Response System


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MedDRA
Medical Dictionary for Regulatory Activities
NCT
National Clinical Trial
PFS
Prefilled Syringe
PlGF
Placental Growth Factor
PT
Preferred Term
QTL
Quality Tolerance Limit
RVO
Retinal Vein Occlusion
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Standard Deviation
SD-OCT
Spectral Domain Optical Coherence Tomography
SOC
System Organ Class
SUSAR
Suspected Unexpected Serious Adverse Reaction
TEAE
Treatment Emergent Adverse Event
TE-SAE
Treatment Emergent Serious Adverse Event
TMF
Trial Master File
US
United States
USPI
United States Prescribing Information
VEGF
Vascular Endothelial Growth Factor
WHODDE
World Health Organization Drug Dictionary Enhanced


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1
Introduction and Rationale
1.1
Background
1.1.1
Disease
Chorioretinal vascular disease (CVD) constitutes the most common causes of moderate and 
severe vision loss in developed countries. These commonly include neovascular (wet) 
age-related macular degeneration (AMD), diabetic macular edema (DME), macular edema 
following retinal vein occlusion (RVO), and diabetic retinopathy (DR).(1)
AMD is a leading cause of blindness for people over the age of 65 in the United States (US). In 
the neovascular (wet or exudative) form of AMD, choroidal neovascular membranes disrupt 
the normal architecture of retina and adjacent tissues leading to retinal edema, submacular 
hemorrhage, as well as debilitating atrophy and scarring.(2)
The use of intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) therapy is currently 
the standard of care for CVD. The anti-VEGF agents inhibit choroidal neovascularization 
growth and fluid leakage, which enable visual improvement.(3)
1.1.2
Amgen Test Product Background
Amgen is developing ABP 938 as a biosimilar candidate to Eylea® (aflibercept). ABP 938
belongs to the pharmacologic class of VEGF inhibitors and acts as a soluble decoy receptor 
that binds VEGF type A (VEGF-A), placental growth factor (PlGF), and to a lesser extent 
VEGF type B (VEGF-B), and thereby prevents binding and activation of VEGF receptor 1 
(VEGFR1) and VEGF receptor 2 (VEGFR2).
1.1.3
Nonclinical Studies
A detailed summary of analytical and nonclinical data is provided in the Investigator’s 
Brochure (IB).
1.1.4
Clinical Studies
A detailed description of the chemistry, pharmacology, efficacy, and safety of ABP 938 is 
provided in the IB. A Phase 3 study to assess effectiveness and safety of ABP 938 compared 
to aflibercept in subjects with neovascular (wet) AMD is currently ongoing.
1.1.5
Non-Amgen Reference Product
Aflibercept belongs to the pharmacologic class of VEGF inhibitors. In the US, it is approved 
for indicated IVT administration in the treatment of neovascular (wet) AMD, macular edema 
following RVO, DME, and DR.(4) In the EU, aflibercept is approved for the treatment of the 
above indications with the exception of DR, and is also approved for the treatment of myopic 


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choroidal neovascularization (CNV).(5) Regeneron has developed a single dose prefilled 
syringe (PFS) for administration of aflibercept as an IVT injection.
1.2
Study Rationale
Amgen is developing ABP 938 as a biosimilar candidate to aflibercept. In an ongoing 
comparative clinical study ABP 938 is provided and used as a sterile aqueous solution for 
injection in single-use glass vials. Each vial used in that study provides a usable amount to 
deliver a single dose of 2 mg aflibercept in a volume of 50 μL. To administer ABP 938 as an 
IVT injection, Amgen has also developed a PFS. The study will investigate whether the 
ABP 938 PFS can be used effectively and safely by retina specialists, to administer the 2 mg 
dose of study drug, when descriptively compared to the US-licensed aflibercept PFS.
1.3
Benefit/Risk Assessment
ABP 938 is a biosimilar candidate to a reference product, aflibercept, for which the benefit-risk 
profile, following IVT administration for approved indications is well understood. A Phase 3 
study to assess effectiveness and safety of ABP 938 compared to aflibercept in subjects with 
neovascular (wet) AMD is currently ongoing.
The 2 mg dose of both study drugs and administration via PFS in this study is consistent with 
the Eylea® prescribing information for subjects with CVD.
More detailed information about the known and expected benefits, risks, and reasonably 
expected AEs of ABP 938 and aflibercept can be found in the ABP 938 IB, and in the Eylea® 
United States Prescribing Information (USPI), August 2022, respectively.(4)
Considering the measures taken to minimize risk to subjects participating in this study, the 
potential risks identified in association with ABP 938 are justified by the anticipated benefits 
that may be afforded to subjects with CVD.
Amgen closely monitors the Coronavirus disease 2019 (COVID-19) pandemic around the 
world. As part of this effort, Amgen performs a rigorous assessment, considering the study 
design, subject safety, public health risk, benefit-risk assessment, as well as the burden on 
country healthcare systems. Decisions are made on a study-by-study and country-by-country 
basis to minimize risk to subjects and avoid undue burden on healthcare facilities.
Subjects who display symptoms consistent with COVID-19 infections or who have tested 
positive for COVID-19 should contact the investigator to ensure appropriate care as well as 
documentation and management of study assessments.
Amgen considers that it is important to continue the proposed development of ABP 938 in this 
study in order to advance potential therapy options for subjects as rapidly as possible, while 


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balancing this with appropriate measures to monitor and mitigate the potential impact of 
COVID-19.
Study sites and subjects should follow the most recent local and institutional guidelines, as 
applicable, for the prevention of COVID-19 infection including COVID vaccinations. Based on 
general best practices for vaccination of immunocompromised individuals, it is recommended 
that the course of COVID-19 vaccinations is completed at least 2 weeks before study 
enrollment, or as per local guidance.
2
Objectives and Endpoints
Objectives
Endpoints
Primary
The primary objective for this study is to assess 
the ability of retina specialists to successfully 
administer, via an IVT injection, a 2 mg dose of 
ABP 938, using the ABP 938 PFS, compared to 
a 2 mg dose of aflibercept using the aflibercept 
PFS.
The primary endpoint for the study is the 
proportion of IVT injections successfully 
administered to subjects with CVD by 
retina specialists, utilizing the ABP 938 
PFS or aflibercept PFS.
Secondary
The secondary objective is to assess the safety 
of ABP 938 administered to subjects with CVD 
via an IVT injection, using the ABP 938 PFS 
compared to aflibercept administered using the 
aflibercept PFS.
The secondary endpoint for the study is 
the incidence of ocular adverse events 
(AEs) and serious adverse events 
(SAEs) in the study eye, and non-ocular 
SAEs until the end of study visit (Day 28 
visit).
3
Study Plan
3.1
Overall Study Design and Plan
This is an open label, two-arm, randomized, multi-site study within the US in adult subjects
with CVD. Approximately 48 adult male or female subjects will be randomized in a ratio of 2:1
to receive either a single IVT injection of ABP 938 in a PFS or a single injection of aflibercept 
in a PFS. Randomization will be stratified by retina specialist.
The study design is outlined in Figure 1, and the visit schedule and planned assessments at 
each visit are detailed in Table 1.
The study consists of a screening visit (Day -1), a baseline visit (Day 1) and an end of study 
visit (Day 28 ± 7 days).


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At the screening visit (Day -1), the investigator will obtain signed informed consent from the 
subject before any study procedures or assessments are performed. Once subject eligibility 
is confirmed the subject will be enrolled into the study. At this visit, the subject will undergo 
ocular safety procedures including the Best Corrected Visual Acuity (BCVA) scale, intraocular 
pressure (IOP), slit-lamp biomicroscopy, indirect ophthalmoscopy, and spectral domain 
optical-coherence tomography (SD-OCT).
At the baseline visit (Day 1), the subject will be randomized to receive a single IVT injection 
of either ABP 938 or aflibercept (open label) in a PFS administered by a retina specialist. Only 
one eye will be selected as the study eye. IOP will be measured, and indirect ophthalmoscopy 
will be performed before and after IP administration. The screening and baseline visit may be 
combined into one visit (Day 1).
At the end of study visit (Day 28 ± 7 days), the ocular safety procedures performed at the 
screening visit will be repeated.
AEs will be collected from the signing of the informed consent form (ICF) until the end of study 
visit.
The method of assigning subjects to treatment is discussed in Section 6.2.
No interim analyses are planned.
3.2
Discussion of Study Design
This is an open label, randomized study intended to assess if a PFS can be used effectively 
and safely by retina specialists to administer ABP 938. ABP 938 is intended to be developed 
as a biosimilar candidate to aflibercept which has been approved in many countries as an IVT 
injection for CVD. The dose of ABP 938 is the same as the reference product aflibercept. The 
secondary objective of the study is to assess ocular safety in the study eye and non-ocular 
SAEs.
3.3
End of Study
3.3.1
End of Study Definition
Primary completion/end of study: The primary completion date/end of study is the date when 
the last subject has completed the assessments for the end of study visit.
If the study concludes prior to the primary completion/end of study date originally planned in 
the protocol (i.e., early termination of the study), then the primary completion/end of study will 
be the date when the last subject is assessed or receives an intervention for evaluation in the 
study (i.e., last subject last visit).


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3.3.2
Study Duration for Subjects
The study duration for each subject will be approximately 28 days (± 7 days) excluding 
screening and the study will end for subjects when they complete the end of study visit 
assessments.
4
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted. The study population will include men or 
women with treatment-naïve or previously treated neovascular AMD, DME, macular edema 
following RVO, or DR, in whom treatment with aflibercept is indicated.
4.1
Inclusion Criteria
The following inclusion criteria must be met for a subject to be eligible for inclusion in the 
study:
1. The subject/subject’s legally acceptable representative must sign an Institutional 
Review Board (IRB) approved ICF before any study-specific procedures are initiated.
2. Men or women ≥18 years old at screening.
3. Treatment-naïve or previously treated neovascular (wet) AMD, DME, macular edema 
following RVO, or DR in the study eye.
4.2
Exclusion Criteria
A subject who meets any of the following exclusion criteria will not be eligible for inclusion in 
the study:
1. Active intraocular or periocular infection or active intraocular inflammation in either eye 
at baseline.
2. Uncontrolled intraocular pressure greater than (>) 25 millimeters of mercury (mmHg) 
in the study eye (uncontrolled defined as IOP > 25 mmHg despite intraocular 
pressure-lowering therapy).
3. Deemed legally blind in one or both eyes (count fingers or worse vision).
4. History of or any current indication of excessive bleeding or recurrent hemorrhages, 
including any prior excessive intraocular (including subconjunctival) bleeding or 
hemorrhages after IVT injection or intraocular procedures in either eye.
5. Current systemic infectious disease or on a therapy for active infectious disease.
6. History of any medical, ocular or non-ocular conditions that, in the opinion of the 
investigator, may interfere with the injection procedure or pose a safety concern.


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7. History of stroke or transient ischemic attacks or myocardial infarction within the last 
6 months prior to screening.
8. Treatment with anti-VEGF IVT injection in the study eye within 28 days prior to 
screening.
9. Any use of intraocular corticosteroids in the study eye within 3 months prior to 
screening.
10. Receipt of any systemic anti-VEGF within the last 6 months prior to screening.
11. Any invasive intraocular surgery, prior long-acting therapeutic agent, or ocular drug 
release device implantation (approved or investigational) in the study eye within the 
past 3 months prior to screening.
12. For women: pregnant or breast feeding, or planning to become pregnant while enrolled 
in the study and for 3 months after IP administration.
13. Sexually active subjects and their partners who are of childbearing potential (i.e., 
neither surgically sterile nor post-menopausal) who refuse to use adequate 
contraception (e.g., true abstinence, sterilization, injectable hormonal contraception, 
birth control pills, contraceptive implants, or other highly effective methods) while 
on-study and for 3 months after IP administration. Male subjects must agree not to 
donate sperm during study and for 3 months following dose of IP.
14. Allergy or hypersensitivity to the IP, to any of the excipients of ABP 938 or aflibercept, 
or to other study-related procedures/medications (e.g., anesthesia, antiseptic).
15. Previously enrolled in this study.
16. Participation in any interventional clinical study within 3 months prior to screening.
4.3
Subject Enrollment
Before subjects participate in any study-specific assessments/procedures, Amgen requires a 
copy of the site’s written IRB approval of the protocol and ICF.
The subject or the subject’s legally acceptable representative must personally sign and date 
the IRB and Amgen approved informed consent before the commencement of study-specific 
procedures.
A subject is considered enrolled when the investigator decides that the subject has met all 
eligibility criteria. The investigator is to document the decision and date, in the subject’s 
medical records.
Each subject will receive a unique 11-digit subject identification number obtained from the 
interactive web response system (IXRS). This will be assigned at the screening visit before 


 
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any study procedures are performed. The investigator will keep a record (the subject 
screening log) that includes limited information about the potential candidates (such as date 
of screening) for subjects who entered screening. The number will be used to identify the 
subject throughout the clinical study and must be used on all study documentation related to 
that subject. The unique 11-digit subject identification numbers will be assigned in sequential 
order for each site in the format 934XXXXX###, where “934XXXXX” refers to the site number, 
and ### refers to the sequential subject ordering as each subject at a site is entered into the 
IXRS system (i.e., 93412345001). If a subject withdraws from study participation, his/her 
unique identification number cannot be re-used for another subject. 
The subject identification number must remain constant throughout the entire clinical study 
and must not be changed after initial assignment. This number will be different from the 
randomization number assigned for the study. 
4.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but who 
do not meet did not meet entrance criteria required for participation and are not subsequently 
entered in the study. Data for subjects who fail screening will not be collected in the electronic 
data capture (EDC) system. Individuals who do not meet the criteria for participation in this 
study (screen failure) will not be rescreened. 
4.5 
Premature Discontinuation 
Subjects have the right to withdraw from protocol procedures, or the study as a whole at any 
time and for any reason without prejudice to their future medical care by the physician or at 
the institution. 
4.5.1 Premature Discontinuation of Investigational Products 
Subjects or their legally acceptable representative can decline to receive IP or undergo 
procedures but continue participation in the study. If this occurs, the investigator is to discuss 
with the subject the possibilities for continuation of the Schedule of Assessments 
(see Table 1) including different options of follow-up (e.g., in person, by phone/mail, through 
family/friends, in correspondence/communication with other treating physicians, from the 
review of medical records) and collection of data, including endpoints, AEs, and device-related 
events and must document this decision in the subject’s medical records. 
Subjects who have discontinued prior to or after receiving IP should not be automatically 
removed from the study. Whenever safe and feasible, it is imperative that subjects remain 
on-study to ensure safety surveillance and/or collection of outcome data. 


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Reasons for early removal from study or procedural assessments may include any of the 
following:
∀
Decision by Amgen.
∀
Lost to follow-up.
∀
Death.
∀
AE.
∀
Subject request.
∀
Pregnancy.
At the time of premature discontinuation, the subject should complete the assessments 
indicated at the end of study visit; see Table 1.
The study site will make every effort to ensure that subjects who receive ABP 938 or 
aflibercept, and subsequently prematurely discontinue the study complete the end of study 
visit.
4.5.2
Premature Discontinuation from the Study
Participation in the study is strictly voluntary. A subject has the right to withdraw from the study 
at any time for any reason, without any reprisal.
The investigator has the right to terminate participation of a subject for any of the following 
reasons:
∀
Difficulties conducting ophthalmic procedures.
∀
Violation of the protocol.
∀
Severe AEs or SAEs.
∀
Any other reason relating to the subject's safety or integrity of the study data.
If a subject is withdrawn from the study, the study monitor/Amgen will be informed 
immediately. Withdrawal of consent for a study means that the subject does not wish to 
receive IP or undergo procedures, and/or the subject does not wish to or is unable to continue 
further study participation. If there is a medical reason for withdrawal, the subject will remain 
under the supervision of the investigator until satisfactory health has returned.
If the subject withdraws consent for disclosure of further information, then Amgen may retain 
and continue to use any collected data before such a withdrawal of consent. Where permitted, 
publicly available data can be included after withdrawal of consent.


 
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Although a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a 
study, the investigator should make a reasonable effort to ascertain the reason(s), while fully 
respecting the subject's rights. 
At the time of premature study discontinuation, the investigator should make every effort to 
ensure the subject completes the assessments indicated at the end of study visit; see  
Table 1. 
Subjects who prematurely discontinue from the study cannot subsequently rejoin the study. 
For details on the discontinuation of study sites or the study as a whole, see Section 14. 
4.5.3 Lost to Follow-up 
A subject will be considered lost to follow-up if he/she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the study site for a required 
study visit: 
x 
The study site must attempt to contact the subject and reschedule the missed visit as 
soon as possible, counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study. 
x 
Before a subject is deemed lost to follow-up, the investigator (or designee) must make 
every effort to regain contact with the subject (where possible, 2 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). 
x 
Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
x 
For subjects who are lost to follow-up, the investigator can search publicly available 
records, where permitted, to ascertain survival status. This ensures that the data set(s) 
produced as an outcome of the study is/are as comprehensive as possible. 
5 
Description of Study Assessments 
Refer to Table 1 for the Schedule of Assessments. 
5.1 
Demographics and Other Screening Assessments 
Safety assessments that are also part of the screening assessments are described in 
Section 5.3. 


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5.1.1
Informed Consent
All subjects or their legally authorized representative must sign and personally date the IRB 
approved informed consent before any study-specific procedures are performed.
5.1.2
Medical and Ophthalmic History
Medical and ophthalmic history, including any ongoing illnesses, will be collected.
5.1.3
Demographics
Demographic data, including year of birth/age, sex, and race, will be collected.
5.1.4
Urine Pregnancy
A urine pregnancy test will be performed for female subjects of child bearing potential at a 
local laboratory at the screening visit.
5.2
Assessment of Administration of Intravitreal Injection
The use of the PFS will be evaluated by the ability of retina specialists, to successfully 
administer the IP 2 mg in a PFS via IVT injections to a subject’s study eye.
The preparation and administration of an ABP 938 or aflibercept IVT injection to dose subjects 
using a PFS will be guided by a list of tasks to be completed:
1. Firmly attach a 30 gauge needle (1/2 inch).
2. Carefully press/expel contents of the syringe to indicated line.
3. Perform IVT injection, injecting the full volume of drug.
4. Perform post injection safety check.
After completion of the injection, the investigator is required to provide their assessment to 
report whether the injection was successfully administered or not. If the response is no, a 
reason and details will be provided.
Refer to the pharmacy manual for detailed preparation and administration instructions.
5.3
Safety Assessments
The assessments described in the following sections will be performed for the study eye only.
5.3.1
Best Corrected Visual Acuity
The visual function of the study eye will be assessed prior to dilation at a distance of 4 meters 
at the screening and end of study visits using the Early Treatment Diabetic Retinopathy Study 
(ETDRS) BCVA letter score.


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5.3.2
Slit-Lamp Biomicroscopy
Slit-lamp biomicroscopy will be performed at the screening and end of study visits to assess 
the anterior eye structure prior to dilation.
5.3.3
Intraocular Pressure 
IOP will be measured via applanation tonometry at the screening, baseline and end of study
visits. For the baseline measurement, IOP will be measured pre-dose (prior to dilation) and 
15-60 minutes after IP administration. The method of IOP measurement should be consistent 
for each subject throughout the study.
5.3.4
Indirect Ophthalmoscopy
Indirect ophthalmoscopy for evaluating the posterior segment will be assessed and reported
at the screening, baseline, and end of study visits. For the baseline assessment, the indirect 
ophthalmoscopy will be performed pre-dose and after IP administration.
5.3.5
Spectral Domain Optical Coherence Tomography
SD-OCT will be performed at the screening and end of study visits to assess the structure of
the retina. The same device should be used for a subject throughout the study.
5.3.6
Adverse Events
AEs are defined in Section 7.1.1. AEs will be followed, collected, and reported in line with the 
procedures described in Section 7.3.
5.3.7
Pregnancy
Details of all pregnancies and/or lactation in female subjects and pregnancies in male 
subjects’ partners will be collected after the start of study treatment and until the end of study
visit.
If pregnancy/lactation is reported, the investigator must inform Amgen within 24 hours of 
learning of the pregnancy and/or lactation and is to follow the procedures outlined in 
Section 17.3. Amgen Global Patient Safety will follow-up with the investigator regarding 
additional information that may be requested.
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
Further details regarding pregnancy and lactation are provided in Section 17.3.


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6
Treatments
6.1
Investigational Products
6.1.1
Description of Investigational Products 
Test Product
Name:
ABP 938
Dose: 
2 mg/0.05 mL
Mode of administration:
Single IVT injection using PFS
Manufacturer:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799
Reference Product
Name:
aflibercept
Dose(s): 
2 mg/0.05 mL
Mode of administration:
Single IVT injection using PFS
Manufacturer:
Regeneron Pharmaceuticals, Inc.
777 Old Saw Mill River Road
Tarrytown, NY 10591
6.1.2
Handling and Storage
ABP 938 and aflibercept should be stored according to the storage information provided on 
the IP carton. The PFS should be stored in a refrigerator (2° to 8°C) and protected from light. 
Further details regarding handling and storage are provided in the IB and the pharmacy 
manual.
6.1.3
Packaging, Labeling, and Shipment
Open label ABP 938 and aflibercept will be packaged and labeled in accordance with all 
applicable regulatory requirements. ABP 938 and aflibercept will be shipped at a temperature 
of 2ºC to 8ºC and stored under controlled conditions according to the storage requirements.
Refer to the IB and pharmacy manual for full details for packaging, labeling, and shipment of 
the IP.
Amgen will supply ABP 938 and aflibercept as PFSs.


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6.1.4
Product Complaints
Any written, electronic, or oral communication that alleges deficiencies related to the identity, 
quality, durability, reliability, safety, effectiveness, or performance of a drug, combination 
product, or device after it is released for distribution to market or clinic by either: (1) Amgen or 
(2) distributors or partners for whom Amgen manufactures the material. This includes all 
components distributed with the drug, such as packaging, drug containers, delivery system, 
labeling, and inserts.
Any product complaint(s) associated with an investigational product, non-investigational 
products, devices, or combination products supplied by Amgen are to be reported according 
to the instructions provided in the pharmacy manual.
6.2
Method of Assigning Treatment
Once the subject has successfully met the criteria for enrollment the subject will be confirmed 
as enrolled within the IXRS.
Randomization will be performed through a centralized IXRS. On Day 1, eligible subjects will 
be assigned to ABP 938 or aflibercept in a 2:1 ratio. Each subject will receive a unique 
randomization number when he/she is assigned treatment. Subjects will be allocated to 
treatment according to the randomization code.
6.3
Dose and Administration
ABP 938 and aflibercept 2 mg/0.05 mL will be administered as a single IVT injection.
6.3.1
Intervention After the End of the Study
There are no planned interventions following the end of the study.
6.4
Precautions and/or Lifestyle Considerations
There are no lifestyle considerations (such as dietary or physical activity restrictions) for this 
study further to those listed in the inclusion/exclusion criteria (Section 4).
6.5
Prior and Concomitant Therapy
All medication (including vaccines, over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) taken from 30 days before the start of screening until the end of 
study visit will be collected.
The medical monitor should be contacted if there are any questions regarding prior or 
concomitant medications or procedures.


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6.5.1
Prior Treatment (Medications and Therapies)
Prior therapies, defined as those that were stopped at or within 30 days prior to the baseline 
visit, will be collected.
6.5.2
Concomitant Treatments (Medications and Therapies)
Throughout the study, investigators may prescribe any concomitant medications or treatments 
deemed necessary to provide adequate supportive care except for those described in 
Section 6.5.3.
Concomitant therapies are to be collected from screening until the end of study visit.
Concomitant therapies are defined as those that are ongoing at the time of IP administration 
and during the follow-up period. Generic names for concomitant medication should be used, 
if possible.
All subjects who do not receive IP should be offered alternative treatment, if applicable. 
Treatment should be given according to normal clinical practice after the end of study visit. 
6.5.2.1
Concomitant Treatment of the Fellow Eye
Standard-of-care treatment will be allowed for any ocular condition in the fellow eye at any 
time during the study. At the discretion of the qualified specialist, the subject’s fellow eye may 
receive treatment on the same day as the study eye or at an unscheduled visit. All fellow eye 
treatments must be collected on the electronic case report form (eCRF) as a concomitant 
medication and/or procedure for the fellow eye. The fellow eye will not be considered an 
additional study eye. Subjects who receive treatment for the fellow eye will not be required to 
be withdrawn from the study.
6.5.3
Prohibited Concomitant Medications and Procedures
Subjects may not receive any medications (approved or investigational) in the study eye other 
than the assigned study treatment as specified in this protocol, unless they have completed 
the end of study visit assessments.
This includes medications administered locally (e.g., IVT, topical, juxtascleral or periorbital 
routes), as well as those administered systemically, with the intent of treating the study eye.
6.5.4
Rescue Medication
Although the use of rescue medications is allowed at any time during the study, the use of 
rescue medications should be delayed, if possible. The date and time of rescue medication 
administration, as well as the name and dosage regimen of the rescue medication, must be 
collected.


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6.6
Overdose
The ABP 938 and aflibercept PFS are designed to deliver a single dose of 2 mg drug in a 
volume of 0.05 mL, therefore, the chances of overdose with a single IVT injection are minimal.
Overdosing of ABP 938 and aflibercept may increase intraocular pressure. Therefore, in case 
of overdose, intraocular pressure should be monitored and, if deemed necessary by the 
investigator, adequate treatment should be initiated.
6.7
Compliance
Subjects will be administered the IP by the investigator in a single dose on Day 1. Treatment 
compliance will be assured by the investigator who will record the date and time of each dose 
administered in the clinic in the source documents.
6.8
Accountability
The IP must not be used for any purpose other than that defined in this protocol. All supplies 
of IP will be accounted for in accordance with GCP.
The pharmacist or (designee) should maintain accurate records of all IP supplies received 
during the study. These records should include the dates and amounts of IP that were 
received at the study site, dispensed, and destroyed on site following guidance in the 
pharmacy manual. The records should include dates, quantities, lot numbers, expiration 
dates, and subject numbers. If errors or damage to the IP shipments occur, the investigator 
should contact Amgen (or its designee) immediately. Copies of the IP accountability records 
will be provided by each investigator for inclusion in the trial master file (TMF) after database 
lock. The study monitor will periodically check IP supplies held by the investigator or 
pharmacist to verify accountability of the IP used.
The investigator (or designee) will administer the IP only to the identified subjects in this study, 
according to the procedures described in this study protocol. Investigators should maintain 
records that adequately document that the subjects were provided the dose specified by the 
protocol and reconcile all IP received from Amgen (or designee).
After the end of the study, all unused IP and all medication containers should be destroyed at 
the study site and complete documentation will be returned to Amgen.
7
Adverse Events
7.1
Definitions
7.1.1
Adverse Events
An AE is any untoward medical occurrence in a clinical study subject. The event does not 
necessarily have a causal relationship with the IP. The investigator is responsible for ensuring 


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that any AEs observed by the investigator or reported by the subject are recorded in the 
subject’s medical records as well as in the eCRF.
The definition of AEs includes worsening of a pre-existing medical condition. Worsening 
indicates that a pre-existing medical condition (e.g., diabetes, migraine headaches, and gout) 
has increased in severity, frequency, and/or duration, and/or has an association with a 
significantly worse outcome. In the case of worsening of a pre-existing condition, the start 
date of the event is the date when the first signs of worsening were observed. A pre-existing 
condition that has not worsened during the study or involves an intervention such as elective 
cosmetic surgery or a medical procedure while on-study is not considered an AE.
Note: an AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) in the investigator’s opinion, is
temporally associated with the use of a treatment, combination product, medical device or 
procedure.
7.1.1.1
Events Meeting the Adverse Event Definition
Events that meet the AE definition are as follows:
∀
Any abnormal or worsening ocular safety result that is considered clinically significant 
in the medical and scientific judgment of the investigator.
∀
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
∀
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study.
∀
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses are to be reported regardless of sequelae.
7.1.1.2
Events NOT Meeting the Adverse Event Definition
Events not meeting the AE definition include:
∀
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.
∀
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).


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∀
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
7.1.2
Serious Adverse Events
An SAE is any event that meets at least 1 of the following serious criteria:
∀
Fatal.
∀
Life-threatening (places the subject at immediate risk of death).
∀
Requires inpatient hospitalization or prolongation of existing hospitalization.
∀
Results in persistent or significant disability/incapacity.
∀
Congenital anomaly/birth defect.
∀
Other medically important serious event.
Definition of Terms
Life-threatening: an AE is life-threatening if the subject was at immediate risk of death from 
the event as it occurred. For example, drug-induced hepatitis that resolved without evidence 
of hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. It does not include an AE or suspected adverse reaction that, had it occurred in 
a more severe form, might have caused death.
Hospitalization:
an AE
requiring hospitalization should be considered as an SAE.
Hospitalization for elective surgery, or for procedures planned prior to the subject providing 
informed consent, or routine clinical procedures that are not the result of an AE (e.g., elective 
surgery for a pre-existing condition that has not worsened) should not be considered AEs or 
SAEs. If anything untoward is reported during the procedure, that occurrence must be 
reported as an AE, either 'serious' or 'nonserious' according to the usual criteria. An AE would 
meet the criterion of “requires hospitalization”, if the event necessitated an admission to a 
health care facility (e.g., overnight stay). When in doubt as to whether hospitalization occurred 
or was necessary, the AE should be considered serious. Complications that occur during 
hospitalization are an AE. If a complication prolongs hospitalization or fulfills any other serious 
criteria, the event is serious.
Disability/incapacity: an AE is incapacitating or disabling if the experience results in a 
substantial and/or permanent disruption of the subject’s ability to carry out normal life 
functions. This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.


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Other medically important serious event: If an investigator considers an event to be clinically 
important, but it does not meet any of the serious criteria, the event could be classified as a 
SAE under the criterion of “other medically important serious event.” Examples of such events 
could include allergic bronchospasm, convulsions, blood dyscrasias, drug-induced liver injury, 
or events that necessitate an emergency room visit, outpatient surgery, or urgent intervention.
7.1.3
Suspected Unexpected Serious Adverse Reactions
A suspected unexpected serious adverse reaction (SUSAR) is defined as an untoward and 
unintended response to a IP, which is not listed in the applicable product information, and 
meets one of the following serious criteria: results in death, is life-threatening, requires 
hospitalization or prolongation of an existing hospitalization, results in persistent or significant 
disability or incapacity, or is a congenital anomaly or birth defect; and is assessed as causally 
related to the IP.
7.1.4
Other Abnormal Assessments
Where applicable, the investigator is responsible for reviewing other assessments and 
determining whether an abnormal value in an individual study subject represents a clinically 
significant change from the subject’s baseline values. Where applicable, clinical sequelae are 
to be recorded as the AE. In addition, abnormal assessments that are associated with signs 
and/or symptoms must be recorded as an AE or SAE if they meet the definition of an AE or 
SAE as described in Sections 7.1.1 and 7.1.2.
7.1.5
Events of Interest 
The adverse events of interest (EOIs) will be defined in the Statistical Analysis Plan (SAP) 
and will be reviewed on an ongoing basis as part of safety monitoring. There are no additional 
expedited reporting requirements for EOIs, beyond what is defined for any AE report that 
qualifies to be expedited as part of regulatory reporting rules for IPs.
7.1.6
Adverse Device Effects
The detection and documentation procedures for adverse device effects described in this 
protocol apply to all ABP 938 and aflibercept PFSs provided for use in the study.
An adverse device effect is any AE related to the use of a combination product or medical 
device. Adverse device effects include AEs resulting from insufficient or inadequate 
instructions for use, AEs resulting from any malfunction of the device, or AEs resulting from 
use error or from intentional misuse of the device.
In order to fulfill regulatory reporting obligations worldwide, the investigator is responsible for 
the detection and documentation of any adverse device effects that occur during the study 
with such devices.


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All adverse device effects are to be reported as AEs following the same reporting periods and 
procedures.
Product complaints are described in Section 6.1.4.
7.2
Assessment of Adverse Events
7.2.1
Severity
The terms serious and severe are not synonymous. The general term “severe” is often used 
to describe the intensity (severity) of a specific event; the event itself, however, may be of 
relatively minor medical significance (such as a grade 3 headache). This is NOT the same as 
serious, which is usually associated with events that pose a threat to a subject’s life or ability 
to function (see Section 7.1.2). A severe AE (classified as grades 3 or 4) does not necessarily 
need to be considered serious. For example, a white blood cell count of 1000/mm3 to less 
than 2000/mm3 is considered grade 3 (severe) but may not be considered serious.
Seriousness (not intensity) serves as a guide for defining regulatory reporting obligations.
The investigator will make an assessment of severity for each AE and SAE reported during 
the study using the CTCAE, version 5.0.
7.2.2
Causality
∀
The investigator is obligated to assess the relationship between the IP and each 
occurrence of an AE/SAE.
∀
Relatedness means that there are facts or reasons to support a relationship between 
the IP and the event.
∀
The investigator will use their clinical judgment to determine the relationship.
∀
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated.
∀
The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment.
∀
For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.
∀
There may be situations in which a SAE has occurred and the investigator has minimal 
information to include in the initial report. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data.


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∀
The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.
∀
The causality assessment is 1 of the criteria used when determining regulatory 
reporting requirements.
∀
A causal relationship is indicated by a “yes” or “no” response to the question: “Is there 
a reasonable possibility that the event may have been caused by the IP?”.
7.3
Documenting and Reporting Adverse Events
The investigator is responsible for ensuring that all AEs observed by the investigator or 
reported by the subject that occur from the signing of the ICF until the end of study visit using 
the applicable eCRF Adverse Event Summary page.
Occurrence of AEs may be volunteered spontaneously by the subject; discovered as a result 
of general, non-leading verbal questioning by the study staff; or determined by physical 
examination or other safety assessments.
When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) related to 
the event.
The investigator must assign the following AE attributes:
∀
AE diagnosis or syndrome(s), if known (if not known, signs or symptoms).
∀
Dates of onset and resolution.
∀
Severity.
∀
Assessment of relatedness to the IP, or devices.
∀
Action taken.
The investigator’s clinical judgment is used to determine whether a subject should be removed 
from treatment due to an AE. A subject, or subject’s legally acceptable representative, can 
also voluntarily withdraw from treatment due to an AE. If the subject withdraws consent, the 
subject is encouraged to undergo, at a minimum, an end of study assessment.
It is the investigator’s responsibility to review all documentation (e.g., hospital notes, 
laboratory reports, and diagnostic reports) related to an AE. Wherever possible, the 
investigator’s diagnosis, not the individual signs and symptoms, will be documented as the 
AE.


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It is not acceptable for the investigator to send photocopies of the subject’s medical records 
to sponsor/responsible contract research organization (CRO) in lieu of completion of the Event 
eCRF page.
If specifically requested, the investigator may need to provide additional follow-up information, 
such as discharge summaries, medical records, or extracts from the medical records. In this 
case, all subject identifiers, with the exception of the subject number, will be blinded on the 
copies of the medical records before submission to Amgen.
Investigators are not obligated to actively seek AEs or SAEs after the subject’s conclusion of 
study participation. However, if the investigator learns of any SAE, including death, at any 
time after a subject has been discharged from the study, and he/she considers the event to 
be reasonably related to the IP or study participation, the investigator must promptly notify 
Amgen.
7.4
Reporting of Serious Adverse Events
The SAE must be reported to Amgen, or its designee, within 24 hours following the 
investigator’s knowledge of the event using the paper Serious Adverse Event Report Form.
The investigator will submit any updated SAE data to Amgen within 24 hours of it being 
available.
The SAE can be reported by faxing a completed paper Serious Adverse Event Fax Cover 
Sheet and Serious Adverse Event Report Form at the number provided below.
Fax information to Safety Risk Management/ICON, for the attention of:
In the Americas:
Amgen Inc.
Fax: +1-888-814-8653
Email: svc-ags-in-us@amgen.com
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the Serious Adverse Event Report Form sent by overnight mail or 
courier service.
Initial notification via telephone does not replace the need for the investigator to complete and 
sign the Serious Adverse Event Report Form within the designated reporting time frames. The 
investigator may be asked to provide additional follow-up information, which may include a 
discharge summary or extracts from the medical record. Information provided about the SAE 
must be consistent with that recorded on the applicable eCRF (e.g., Adverse Event Summary 
eCRF).


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If a subject is permanently withdrawn from study because of an SAE, this information must be 
submitted to Amgen, or its designee.
Investigators will receive notification of related SAE reports sent to regulatory authorities in 
accordance with local requirements.
Determination of expectedness for Amgen products will be based on the IB for the IP and the 
regional prescribing information for products being studied for an approved use.
Expectedness assessments are to be made for all IPs (Amgen and non-Amgen) using the 
appropriate reference safety information per local regulatory reporting requirements. SUSARs
reported for subjects receiving a non-Amgen IP are to be expedited according to local 
requirements.
Amgen, or its designee, reports SAEs and/or SUSARs as required to regulatory authorities, 
investigators/institutions, and IRBs in compliance with all reporting requirements according to 
local regulations and GCPs.
The investigator is to notify the appropriate IRB of SAEs occurring at the study site and other 
AE reports received from Amgen, in accordance with local procedures and statutes.
After the protocol-required reporting period defined above, the investigator does not need to 
actively monitor subjects for SAEs. However, if the investigator becomes aware of a SAE after 
this protocol-required reporting period, the investigator will report the event to Amgen within 
24 hours following the investigator’s knowledge of the event. SAEs reported outside of the 
protocol-required reporting period will be captured within the safety database as clinical study
cases for the purposes of expedited reporting.
7.5
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about AE 
occurrence.
7.6
Adverse Event and Serious Adverse Event Follow-up
During the study AEs, EOIs and SAEs should be followed proactively by the investigator until 
the event resolves, or the condition stabilizes to a level acceptable to the investigator, until 
the event is otherwise explained, or until the subject is lost to follow-up. At the time the 
subject’s study participation ends, all related SAEs should be evaluated for resolution.
7.7
Safety Reporting Oversight
In accordance with ICH GCP, Amgen (or designee) will inform investigators of “findings that 
could affect adversely the safety of subjects, impact the conduct of the study, or alter the IRB’s 
approval/favorable opinion to continue the study.”


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An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (e.g., summary or listing of SAEs) from Amgen will file it along with the IB 
and will notify the IRB, if appropriate, according to local requirements.
Prompt notification by the investigator to Amgen of SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of subjects and the safety of a study treatment 
under clinical investigation are met. Amgen has a legal responsibility to notify both the local 
regulatory authority and other regulatory agencies about the safety of a study treatment under 
clinical investigation. Individual safety reports must be prepared for SUSARs according to 
local regulatory requirements and sponsor policy and forwarded to investigators as necessary.
8
Statistics
8.1
General Procedures
Analyses will be performed using SAS® (SAS Institute, Cary, NC, US) by Amgen or its 
representatives.
The SAP will be approved prior to first subject first visit. The SAP will provide a detailed 
description of the statistical methods and expand on the details provided in the protocol.
All data will be presented by treatment group. Descriptive statistics (number of observations, 
mean, standard deviation [SD], median, minimum, and maximum) will be provided for 
continuous variables, and counts and percentages will be presented for categorical variables.
Confidence intervals for the primary endpoint will also be presented.
Baseline is defined as the last non-missing measurement before IP administration.
8.2
Analysis Populations
The Full Analysis Set (FAS) will include all randomized subjects and will be analyzed 
according to randomized treatment. This analysis set will be used for summaries of the 
primary endpoint.
The Safety Analysis Set will include all enrolled subjects who receive the IP and will be 
analyzed according to the actual treatment received. This analysis set will be used for 
summaries of safety data.
8.3
Sample Size
For this study, no prospective calculations of statistical power have been made.
It is planned to enroll approximately 48 adult male or female subjects into the study, with a 
minimum of 32 subjects in the ABP 938 PFS arm and a minimum of 16 subjects in the 
aflibercept PFS arm, randomized in a ratio of 2:1.


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8.4
Planned Analyses
8.4.1
Interim Analysis and Early Stopping Guidelines
No interim analysis is planned for this study.
8.4.2
Final Analysis
The final analysis of the study will occur when all subjects completed the day 28 visit or
terminate early.
8.5
Statistical Methods
8.5.1
Primary Endpoint
The primary endpoint of the number of successful IP injections with the PFS will be 
summarized using the FAS based on observed data. The number and percentage of injections 
successfully administered utilizing the PFS will be provided descriptively for separately by 
randomized treatment group. Percentages will be based upon the number of subjects in the 
FAS for each treatment group. The estimated primary endpoint success rate for each 
treatment group will be calculated by the average of each retina specialists’ individual success 
rate. The variance of this estimator will be calculated as:
() =
∑
(̅)


()
where  is the proportion of successfully IVT injections administered for the i-th retina 
specialist and ̅ is the average of proportions of successfully administered IVT injections
across all retina specialists, K is the total number of retina specialists. T-distribution with (K-1) 
degrees of freedom will be used to calculate any corresponding confidence interval. No formal 
statistical comparisons will be performed between the two treatment groups. Missing data will 
not be imputed.
8.5.2
Secondary Endpoints
The secondary endpoints of ocular treatment emergent adverse events (TEAEs) and serious 
TEAEs (TE-SAEs) in the study eye and non-ocular TE-SAEs will be summarized with 
qualitative descriptive statistics for all subjects and separately by actual treatment received 
using the Safety Analysis Set.
For each secondary endpoint, the total number of TEAEs and the number and percentages 
of subjects experiencing at least one TEAE will be summarized for all subjects and by actual 
treatment received. Summaries will also include the number and percentages of subjects
experiencing at least one TEAE within a System Organ Class (SOC) and Preferred Terms 


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(PTs) within SOCs. Subjects with multiple TEAEs will be counted only once within each PT
and SOC.
AEs will be coded according to latest available version of the Medical Dictionary for Regulatory 
Activities (MedDRA).
TEAEs are defined as AEs with an onset after IP administration.
8.5.3
Safety Endpoints
The Safety Analysis Set will be used for the analysis of all safety data. Only TEAEs will be 
summarized.
An overall summary table of AEs will be presented which will include breakdowns of ocular 
TEAEs in the study eye, non-ocular TEAEs, TE-SAEs, TEAEs leading to study 
discontinuation, TEAEs leading to death, treatment related TEAEs, EOIs, etc. The number 
and percentage of subjects experiencing at least one event will be presented. Details of the 
overall summary table of AEs will be addressed in the SAP. Additional summaries of AEs by 
SOC and PTs by maximum severity may include ocular TEAEs in the study eye/fellow eye, 
injection procedure related ocular TEAEs in the study eye, etc. 
Quantitative safety assessments such as BCVA using ETDRS and IOP will be summarized 
at each time point and visit using continuous descriptive statistics for the study eye for all 
subjects and actual treatment received. Change from baseline, calculated as post-baseline 
value minus baseline value, will be summarized at each scheduled post-baseline assessment. 
Qualitative safety assessments such as slit-lamp biomicroscopy and indirect ophthalmoscopy 
will be summarized using counts and percentages for the study eye for all subjects and actual 
treatment received. Shifts from baseline will also be presented at each scheduled
post-baseline assessment.
Subject listings will be generated for all SAEs all safety assessments.
8.5.4
Demographic and Baseline Characteristics
Demographic characteristics (including age, sex, ethnicity, and race) and baseline 
characteristics will be presented by assigned treatment descriptively for the FAS and the 
safety analysis set.
8.5.5
Exposure to Investigational Products
Subject exposure to IP will be analyzed using the safety analysis set.


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8.5.6
Exposure to Concomitant Medications
Prior and concomitant medications used in this study will be coded using the latest available 
version of the World Health Organization Drug Dictionary Enhanced (WHODDE). The 
dictionary version will be detailed in the SAP. Concomitant medications will be summarized 
for the safety analysis set. 
8.5.7
Handling of Missing Values
Missing primary endpoint will not be imputed. Missing safety data will generally not be 
imputed. Missing dates for AEs, medical history, and concomitant medications may be 
imputed for the purposes of TEAE flags, concomitant flags, etc. Rules for imputation of 
missing dates will be detailed in the SAP.
9
Ethics and Responsibilities
9.1
Good Clinical Practice
This study will be conducted in accordance with the protocol and with the Note for Guidance 
on GCP ICH Harmonised Tripartite Guideline E6 (R1)/Integrated Addendum E6 (R2); US FDA 
CFR (Title 21 Parts 50, 56, 312), requirements for the conduct of clinical studies as provided 
in the EU Directive 2001/20/EC; the general guidelines indicated in the Declaration of Helsinki;
and all applicable regulatory requirements.
9.2
Institutional Review Board
Before initiating a study, the investigator/institution must have written and dated 
approval/favorable opinion from the IRBs for the study protocol/amendment(s), written ICF, 
any ICF updates, subject recruitment procedures (e.g., advertisements), and any written 
information to be provided to subjects and a statement from the IRBs that these comply with 
GCP requirements (if applicable). A current copy of the IB should be included as part of the 
written application to the IRB.
Amgen may amend the protocol at any time. A copy of the written approval of the protocol 
and ICF must be received by Amgen before recruitment of subjects into the study and IP
shipment.
The IRB approval(s) must identify the protocol version as well as the documents reviewed.
Any amendments to the protocol will require IRB/ approval before the implementation of the 
changes made to the study, except for changes necessary to eliminate an immediate hazard 
to the study subjects.
The investigator will be responsible for the following:


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∀
Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the IRB.
∀
Notifying the IRB of SAEs or other significant safety findings, including adverse drug 
reactions (ADRs) that are both serious and unexpected, as required by IRB 
procedures.
∀
Providing oversight of the conduct of the study at the study site and adherence to the 
requirements of all applicable regulations.
∀
Promptly reporting deviations from, or changes to, the protocol to eliminate immediate 
hazards to the study subjects.
∀
Obtaining annual IRB approval/renewal throughout the duration of the study. Copies 
of the investigator’s reports and the IRB continuance of approval must be sent to 
Amgen.
9.3
Informed Consent
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s) and should adhere to GCP and to the ethical principles 
that have their origin in the Declaration of Helsinki. Both the informed consent discussion and 
the written ICF and any other written information to be provided to subjects should include 
explanations of the following:
∀
The investigator or his/her representative will explain the purpose and nature of the 
study as well as possible adverse effects to the subject or his/her legally acceptable
representative and answer all questions regarding the study.
∀
Subjects must be informed that their participation is voluntary, and consent can be 
withdrawn at any point.
∀
Subject data up to withdrawal of consent will be included in the analysis of the study, 
and where permitted, publicly available data can be included after withdrawal of 
consent.
∀
Subjects or their legally acceptable representative will be required to sign a statement 
of informed consent that meets the requirements of US FDA CFR Title 21 Part 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements where applicable, and the IRB’s or study site.
∀
Prior to a subject’s participation in the study, the written ICF should be signed and 
personally dated by the subject or by the subject's legally acceptable representative, 
and by the person who conducted the informed consent discussion.


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∀
The medical record must include a statement that written informed consent was 
obtained before the subject was enrolled in the study and the date the written consent 
was obtained. Subject withdrawal of consent or discontinuation from study, study 
treatment and/or procedures must also be documented in the subject’s medical 
records.
∀
The original copy of the signed ICF will be retained at the study site.
∀
A copy of the ICF and any other written information must be provided to the subject or 
the subject’s legally acceptable representative.
∀
If the ICF is revised, the revised ICF must have received the IRB's approval/favorable 
opinion in advance of its use. Subjects must be informed of the changes to the ICF 
and must re-consent to the most current version during their participation in the study.
The subject or the subject’s legally acceptable representative should be informed in a 
timely manner if new information becomes available that may be relevant to the 
subject’s willingness to continue participation in the study. The communication of this 
information should be documented.
∀
The investigator is also responsible for asking the subject if the subject has a primary 
care physician and if the subject agrees to have his/her primary care physician 
informed of the subject’s participation in the clinical study unless it is a local 
requirement. The investigator shall then inform the primary care physician. If the 
subject agrees to such notification, the investigator is to inform the subject’s primary 
care physician of the subject’s participation in the clinical study. If the subject does not 
have a primary care physician and the investigator will be acting in that capacity, the 
investigator is to document such in the subject’s medical records.
9.4
Financing and Insurance
9.4.1
Contractual and Financial Details
The investigator (and/or, as appropriate, the hospital administrative representative) and 
Amgen, or its designee, will sign a clinical study agreement prior to the start of the study, 
outlining overall Amgen, or its designee, and investigator responsibilities in relation to the 
study. The contract should describe whether costs for pharmacy, laboratory, and other 
protocol-required services are being paid directly or indirectly.
9.4.2
Insurance, Indemnity, and Compensation
Amgen will maintain an appropriate clinical study insurance policy. Any arrangements for 
compensation to subjects for injury or illness that arises in the study are described in the 


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Compensation for Injury section of the Informed Consent that is available as a separate 
document.
9.4.3
Financial Disclosure
Investigators and sub-investigators will provide Amgen with sufficient, accurate financial 
information as requested to allow Amgen to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.
10
Records Management
All clinical study information should be collected, handled, and stored in a way that allows its 
accurate reporting, interpretation, and verification. This principle applies to all records 
referenced in this protocol, irrespective of the type of media used.
An eCRF will be used to store and transmit subject information. The eCRF must be reviewed 
and electronically signed and dated by the investigator on an ongoing basis throughout the 
study. The investigator is responsible for verifying that the data entries are accurate and 
correct by signing the eCRF.
Access to the eCRF will be strictly password protected and limited to personnel directly 
participating in the study. Data should be entered into the eCRF completely by authorized site 
personnel (e.g., investigators and the study coordinators). The eCRF must be completed as 
soon as possible after any subject evaluation or communication. If data are to be changed 
due to erroneous input or other reason, an electronic audit trail will track these changes. The 
eCRFs and computers that store them must be accessible to study monitors and other 
regulatory auditors. Changes to the eCRF will be electronically tracked.
During each study visit, the investigator will maintain progress notes in the subject’s medical 
records to document all significant observations. At a minimum, these notes are to contain:
∀The date of the visit and the corresponding day or visit in the study schedule.
∀General condition and status remarks by the subject, including any significant medical 
findings. The severity, frequency, duration, and resolution of any reported AE, and the 
investigator's assessment as to whether or not the reported AE is related to the IP.
∀Changes (including dosages) in concomitant medications/therapies or procedures.
∀A general reference to the procedures completed.
∀The signature or initials of all physicians making an entry in the medical record (progress 
notes).


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In addition, any contact with the subject by telephone or other means that provides significant 
clinical information should be documented in the medical record (progress notes), as 
described above.
Information from medical records (progress notes) and other source documents should be 
promptly entered into the appropriate section of the eCRF.
Changes to information in medical records (progress notes) and other source documents are 
to be initialed and dated on the day the change is made by the investigator (or designee). If 
the reason for the change is not apparent, a brief explanation for the change is to be written 
adjacent to the change.
The ICON data management department will write a data management plan, which will be 
finalized prior to performing any data validation.
10.1 Source Documentation
Source documents contain the results of original observations and activities of a clinical 
investigation. They are the original records in which raw data are first collected. Source 
documents include, but are not limited to, medical records (progress notes), computer 
printouts, screening logs, and drug dispensing/accountability logs, etc.
The investigator/site personnel should maintain adequate and accurate source documents 
and study records that include all pertinent observations on each of the study site’s study 
subjects. Source data should be attributable, legible, contemporaneous, original, accurate, 
and complete. Changes to source data should be traceable, should not obscure the original 
entry, and should be explained if necessary (e.g., through an audit trail).
All source documents from this study are to be maintained by the investigator and made 
available for inspection by authorized persons. The investigator will provide direct access to 
source documents/data for study-related monitoring, audits, IRB review, and regulatory 
inspections. Amgen should verify that each subject has consented, in writing, to direct access 
to his/her original medical records for study-related monitoring, audit, IRB review, and 
regulatory inspection. The original signed ICF for each subject shall be filed with records kept 
by the investigator and a copy shall be given to the subject.
10.2 Case Report Form Completion and Data Management
The file structure and format for the eCRF will be provided by Amgen or its representative and 
should be handled in accordance with the instructions provided.
The eCRF must be reviewed and electronically signed and dated by the investigator.
Changes to the eCRF will be electronically tracked.


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Data will be entered/loaded into a validated electronic database using a clinical data 
management system. Computerized data cleaning checks will be used in addition to manual 
review to check for discrepancies and to ensure consistency of the data.
10.3 Study Files and Record Retention
All data derived from the study will remain the property of Amgen. Amgen assumes 
accountability for actions delegated to other individuals, e.g., the CRO.
Records must be retained in accordance with the current ICH Guidelines on GCP. All essential 
study documents, including records of subjects, source documents, eCRFs, and the IP
inventory, must be kept on file.
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region, or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of ABP 938. However, essential documents may be 
retained for a longer period if required by the applicable regulatory requirements or by 
agreement with Amgen. Amgen is responsible for informing the investigator when these 
documents need no longer be retained.
The investigator is not to dispose of any records relevant to this study without written 
permission from Amgen and is to provide Amgen the opportunity to collect such records. The 
investigator shall take responsibility for maintaining adequate and accurate hard copy source 
documents of all observations and data generated during this study. Such documentation is 
subject to inspection by Amgen, its representatives, and regulatory authorities.
If an investigator moves, withdraws from a study, or retires, the responsibility for maintaining 
the records may be transferred to another person who will accept responsibility. Notice of 
transfer must be made to and agreed by Amgen.
11
Auditing and Monitoring
Auditing
Amgen or its representative may conduct audits at the sites including, but not limited to, drug 
supply, presence of required documents, the informed consent process, and comparison of 
eCRFs with source documents. All medical records (progress notes) must be available for the 
audit. The investigator must agree to participate with audits conducted at a convenient time 
in a reasonable manner.
Government regulatory authorities may also inspect the site during or after the study. The 
investigator (or designee) should contact Amgen/CRO immediately if this occurs.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
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The purpose of an audit is to assess whether ethics, regulatory, and quality requirements are 
being fulfilled.
Monitoring
Sponsor-assigned monitors will conduct regular site visits at the site for the purpose of 
monitoring various aspects of the study, such as assessing subject enrollment, compliance 
with protocol procedures, completeness and accuracy of data entered into the eCRFs, 
verification of eCRF data against original source documents, and occurrence of AEs. The 
investigator must agree to sponsor-authorized personnel having direct access to the clinical 
(or associated) files and clinical study supplies (dispensing and storage areas) to ensure 
compliance with applicable regulations, and the investigator will assist with Amgen’s
monitoring activities.
Quality control will occur at each stage of data handling to ensure that all data are reliable and 
have been processed correctly. Amgen should ensure oversight of any study-related duties 
and functions carried out on its behalf, including study-related duties and functions that are 
subcontracted to another party by Amgen’s contracted CRO(s).
The eCRFs should be completed in a timely manner and on an ongoing basis to allow regular 
review by the study monitor.
Details describing the strategy, responsibilities, and requirements of the study monitoring are 
provided in the clinical management plan.
11.1 Risk and Quality Tolerance Limits
Perceived risks and quality tolerance limits (QTLs) will be identified and documented before 
the start of the study.
Amgen will review risk control measures periodically to ascertain whether the implemented 
quality management activities remain effective and relevant. The quality management 
approach and any important deviations from the predefined QTLs (and remedial actions 
adopted) will be described in the clinical study report.
11.2 Protocol Adherence and Deviations
The investigator and site personnel should conduct the study in compliance with the protocol 
and should use continuous vigilance to identify and report protocol deviations.
A protocol deviation is any change, divergence, or departure from the study design or 
procedures defined in the protocol that may be on the part of the investigator, site personnel, 
or the subject.


Sponsor Name: Amgen Inc.
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Important protocol deviations are a subset of protocol deviations that may significantly impact 
the completeness, accuracy, and/or reliability of the study data or that may significantly affect 
a subject's rights, safety, or well-being. For example, important protocol deviations may 
include enrolling subjects in violation of key eligibility criteria designed to ensure a specific 
subject population or failing to collect data necessary to interpret primary endpoints, as this 
may compromise the scientific value of the study.
The investigator should not implement any deviation from the protocol without agreement from 
Amgen and prior review and approval from the IRB of an amendment, except where 
necessary to eliminate an immediate hazard to a study subject, or when the change involves 
only logistical or administrative aspects of the study, such as a change in a monitor or 
telephone number.
In the event of an important protocol deviation, the investigator will discuss the deviation with 
Amgen’s medical monitor and will come to an agreement as to whether the subject should be 
withdrawn from the study due to the important protocol deviation.
12
Amendments
Protocol modifications, except those intended to reduce immediate risk to study subjects, may 
be made only by Amgen. A protocol change intended to eliminate an apparent immediate 
hazard to subjects should be implemented immediately.
Any permanent change to the protocol must be handled as a protocol amendment. The written 
amendment must be submitted to the IRB, and the investigator must await approval before 
implementing the changes. Amgen will submit protocol amendments to the appropriate 
regulatory authorities for approval.
The current version of the ICF will require similar modification if the IRB, investigator, and/or 
sponsor, judge the amendment to the protocol to substantially change the study design and/or 
increase the potential risk to the subject and/or impact the subject's involvement as a study 
subject. In such cases, the ICF will be renewed for enrolled subjects before their continued 
participation in the study.
13
Study Report and Publications
Amgen is responsible for preparing and providing the appropriate regulatory authorities with 
the CSR according to the applicable regulatory requirements. Amgen should ensure that the 
CSR meets the standards of the ICH Guideline for Structure and Content of Clinical Study 
Reports (ICH E3).
To coordinate dissemination of data from this study, Amgen may facilitate the formation of a 
publication committee consisting of several investigators and appropriate Amgen staff, the 
governance and responsibilities of which are set forth in a Publication Charter. The committee 


Sponsor Name: Amgen Inc.
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is expected to solicit input and assistance from other investigators and to collaborate with 
authors and Amgen staff, as appropriate, as defined in the Publication Charter. Membership 
on the committee (both for investigators and Amgen staff) does not guarantee authorship. The 
criteria described below are to be met for every publication.
Authorship of any publications resulting from this study will be determined on the basis of the 
Uniform Requirement for Manuscripts Submitted to Biomedical Journals International 
Committee of Medical Journal Editors Recommendations for the Conduct of Reporting, 
Editing, and Publications of Scholarly Work in Medical Journals, which states: Authorship 
credit is to be based on: (1) substantial contributions to conception and design, acquisition of 
data, or analysis and interpretation of data; (2) drafting the article or revising it critically for 
important intellectual content; (3) final approval of the version to be published; and (4) 
agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Authors need to meet conditions 1, 2, 3, and 4.
When a large, multi-site group has conducted the work, the group is to identify the individuals 
who accept direct responsibility for the manuscript. These individuals must fully meet the 
criteria for authorship defined above. Acquisition of funding, collection of data, or general 
supervision of the research group, alone, does not justify authorship. All persons designated 
as authors must qualify for authorship, and all those who qualify are to be listed. Each author 
must have participated sufficiently in the work to take public responsibility for appropriate 
portions of the content. All publications (e.g., manuscripts, abstracts, oral/slide presentations, 
book chapters) based on this study must be submitted to Amgen for review. The Clinical Trial 
Agreement among the institution, investigator, and Amgen will detail the procedures for, and 
timing of, Amgen’s review of publications.
14
Study Start and Termination
The study start date is the date on which the first subject provides informed consent.
The end of the study date is the date when the last subject has completed the assessments 
for the end of study visit.
If the study concludes prior to the end of study date originally planned in the protocol (i.e., 
early termination of the study), then the end of study will be the date when the last subject is 
assessed or receives an intervention for evaluation in the study (i.e., last subject last visit).
Both Amgen and the investigator reserve the right to terminate the study or the participation 
in the study at an investigator’s site at any time. In terminating the study, Amgen and the 
investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.


Sponsor Name: Amgen Inc.
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If the study is prematurely terminated or suspended for any reason, Amgen/investigators/site 
personnel should promptly inform the study subjects and should assure appropriate therapy 
and follow-up for the subjects. Where required by the applicable regulatory requirements, the 
IRB should be informed promptly and be provided with a detailed written explanation of the 
termination or suspension.
If the investigator terminates or suspends a study without prior agreement of Amgen, the 
investigator should inform the site personnel. The investigator/site personnel should promptly 
inform Amgen and the IRB. The investigator/site personnel should also provide Amgen and 
the IRB a detailed written explanation of the termination or suspension.
15
Confidentiality
All information generated in this study is considered confidential and must not be disclosed to 
any person or entity not directly involved with the study unless prior written consent is gained 
from Amgen. However, authorized regulatory officials, IRB personnel, Amgen and its 
authorized representatives are allowed full access to the records.
All study subjects must be informed that their personal study-related data will be used by 
Amgen in accordance with local data protection law. The level of disclosure must also be 
explained to the subject, who will be required to give consent for their data to be used as 
described in the ICF. The subjects must be informed that their medical records may be 
examined by auditors or other authorized personnel appointed by Amgen, by appropriate IRB 
members, and by inspectors from regulatory authorities.
Identification of subjects and eCRFs shall be by unique subject identification numbers (such 
as screening or randomization number only). All personal identifiers according to applicable 
regulations (e.g., name, phone number) must be redacted permanently by the study site 
personnel and replaced with the subject’s unique identification number in all records and data 
before transfer to Amgen (or designee).
All personal details will be treated as confidential by the investigator and staff at ICON.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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16
References
1. Campochiaro PA. Ocular neovascularization. J Mol Med (Berl). 2013;91(3):311-21.
2. Ho VY, Yeh S, Olsen TW, Bergstrom CS, Yan J, Cribbs BE, et al. Short-term outcomes 
of aflibercept for neovascular age-related macular degeneration in eyes previously 
treated with other vascular endothelial growth factor inhibitors. Am J Ophthalmol. 
2013;156(1):23-8 e2.
3. Nishikawa K, Oishi A, Hata M, Miyake M, Ooto S, Yamashiro K, et al. Four-Year 
Outcome of Aflibercept for Neovascular Age-Related Macular Degeneration and 
polypoidal choroidal vasculopathy. Scientific reports. 2019;9(1):3620.
4. Eylea®. United States Prescribing Information. August 2022.
5. Eylea®. Summary of Product Characteristics. March 2022.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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17
Appendices
17.1 Appendix I - Study Administrative Structure
Sponsor:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 
Phone: +1 (805) 447-1000
Sponsor’s Medical Expert:
, MD, PhD
Executive Medical Director
Amgen Inc.
Phone: 
Sponsor’s Project Manager:
Senior Manager, Study Management
Amgen Inc.
Phone: 
Medical Monitor:
Safety Lead
Amgen Inc.
Phone: 
CRO:
ICON Clinical Research
South County Dublin Business Park,
Leopardstown, Dublin 18, D18X5R3
Ireland
Phone: +353-1-2912000
Fax: +353-1-2476260
ABP 938 Manufacturer:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 
Phone: +1 (805) 447-1000
ABP 938 Distributor:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 
Phone: +1 (805) 447-1000
A log of the name and title of the investigators who are responsible for conducting the study, 
and the address and telephone numbers of the study sites will be maintained.


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Protocol Number: 20210034
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Sponsor Name: Amgen Inc.
Protocol Number: 20210034
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17.2 Appendix II - Clinical Laboratory Tests
A urine pregnancy test will be performed for female subjects of childbearing potential at a local 
laboratory at the screening visit.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
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17.3 Appendix III - Contraceptive Guidance and Collection of Pregnancy and 
Lactation Information
Study-specific contraception requirements for male and female subjects of childbearing 
potential are outlined in Section 4.2.
Male and female subjects of child bearing potential must receive pregnancy prevention 
counseling and be advised of the risk to the fetus if they become pregnant or father a child
during the study.
Definition of Females of Childbearing Potential
A female is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile.
Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Females In The Following Categories Are Not Considered Females Of Childbearing 
Potential:
∀
Premenopausal female with one of the following criteria met:
o Documented hysterectomy.
o Documented bilateral salpingectomy.
o Documented bilateral oophorectomy.
Note: Site personnel documentation from the following sources is acceptable: 1) review 
of subject’s medical records; 2) subject’s medical examination; or 3) subject’s medical 
history interview.
∀
Premenarchal female.
∀
Post-menopausal female as defined in the following:
o A post-menopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle-stimulating hormone (FSH) level in the 
post-menopausal range may be used to confirm a post-menopausal state in women 
not using hormonal contraception or hormonal replacement therapy (HRT). However, 
in the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient.
o Females on HRT and whose menopausal status is in doubt will be required to use 1 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of post-menopausal status before study enrollment.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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Contraception Methods for Female Subjects
Highly Effective Contraceptive Methods
Note: Failure rate of < 1% per year when used consistently and correctly.
∀
Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation (oral, intravaginal, or transdermal).
∀
Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable, implantable).
∀
Intrauterine device.
∀
Intrauterine hormonal-releasing system.
∀
Bilateral tubal ligation/occlusion.
∀
Vasectomized partner (provided that the partner is the sole sexual partner of the 
female subject of childbearing potential and that the vasectomized partner has 
received medical assessment of the surgical success).
∀
Sexual abstinence (defined as refraining from heterosexual intercourse during the
entire period of risk associated with the study treatments; the reliability of sexual 
abstinence must be evaluated in relation to the duration of the study and the preferred 
and usual lifestyle of the subject).
or
Acceptable Methods Of Effective Contraception
∀Combined (estrogen and progestogen containing) or progestogen-only hormonal methods 
given by oral, intravaginal, transdermal, injectable, or implantable route).
∀Intrauterine device.
∀Intrauterine hormonal-releasing system.
∀Bilateral tubal ligation/occlusion.
∀Vasectomized partner (provided that the partner is the sole sexual partner of the female
subject of childbearing potential and that the vasectomized partner has received medical 
assessment of the surgical success).
∀Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the study treatments; the reliability of sexual abstinence 
must be evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the subject).


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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∀Male or female condom with or without spermicide.
∀Cap, diaphragm or sponge with spermicide.
∀Double barrier method: the male uses a condom and the female may choose either a cap, 
diaphragm, or sponge with spermicide (a female condom is not an option due to the risk 
of tearing when both partners use a condom).
Contraception Methods for Male Subjects
∀Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the IP; the reliability of sexual abstinence must be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the subject).
∀Use a condom while on-study and for 3 months after IP administration.
The female partner should consider using an acceptable method of effective contraception 
such as: hormonal, intrauterine device, intrauterine hormonal-releasing system, female barrier 
method (diaphragm, cap, sponge).
Note: If the male’s sole female partner is of non-childbearing potential or has had a bilateral 
tubal ligation/occlusion, he is not required to use additional forms of contraception during the 
study.
Unacceptable Methods of Birth Control for [Male and] Female Subjects
Birth control methods that are considered unacceptable in clinical studies include:
∀
Periodic abstinence (calendar, symptothermal, post-ovulation methods).
∀
Withdrawal (coitus interruptus).
∀
Spermicides only.
∀
Lactational amenorrhea method.
Collection of Pregnancy Information
Female Subjects Who Become Pregnant
∀
The investigator will collect pregnancy information on any female subject who 
becomes pregnant during the study until the end of study visit.
∀
Information will be collected on the Pregnancy Notification Form. The form must be 
submitted to Amgen or its designee within 24 hours of learning of a subject’s 
pregnancy.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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Note: Sites are not required to provide any information on the Pregnancy Notification 
Form that violates the country or regions local privacy laws.
∀
After obtaining the female subject’s signed authorization for release of pregnancy and 
infant health information, the investigator will collect pregnancy and infant health 
information and complete the pregnancy questionnaire for any female subject who 
becomes pregnant while in the study. This information will be forwarded to Amgen or 
its designee. Generally, infant follow-up will be conducted up to 12 months after the 
birth of the child (if applicable).
∀
Any termination of pregnancy will be reported to Amgen or its designee, regardless of 
fetal status (presence or absence of anomalies) or indication for procedure.
∀
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or report of a congenital anomaly or developmental delay, fetal death, or 
suspected adverse reactions in the neonate will be reported as an AE or SAE. Note 
that an elective termination with no information on a fetal congenital malformation or 
maternal complication is generally not considered an AE, but still must be reported to 
Amgen or its designee as a pregnancy exposure case.
∀
If the outcome of the pregnancy meets a criterion for immediate classification as a 
SAE (e.g., female subject experiences a spontaneous abortion, stillbirth, or neonatal 
death or there is a fetal or neonatal congenital anomaly) the investigator will report the 
event as a SAE.
∀
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to Amgen 
or its designee. While the investigator is not obligated to actively seek this information 
in former study subjects, he or she may learn of a SAE through spontaneous reporting.
Male Subjects With Partners Who Become Pregnant Or Were Pregnant At The Time Of 
Enrollment
∀
In the event a male subject fathers a child during the study, the information will be 
recorded on the Pregnancy Notification Form. The form must be submitted to Amgen 
or its designee within 24 hours of the site’s awareness of the pregnancy.
Note: Sites are not required to provide any information on the Pregnancy Notification 
Form that violates the country or regions local privacy laws.
∀
The investigator will attempt to obtain a signed authorization for release of pregnancy 
and infant health information directly from the pregnant female partner to obtain 
additional pregnancy information.


Sponsor Name: Amgen Inc.
Protocol Number: 20210034
Version and Date: Version 1.0, 19 Oct 2022
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∀
After obtaining the female partner’s signed authorization for release of pregnancy and 
infant health information, the investigator will collect pregnancy outcome and infant 
health information on the pregnant partner and her baby and complete the pregnancy
questionnaires. This information will be forwarded to Amgen or its designee.
∀
Generally, infant follow-up will be conducted up to 12 months after the birth of the child 
(if applicable).
∀
Any termination of the pregnancy will be reported to Amgen or its designee regardless 
of fetal status (presence or absence of anomalies) or indication for procedure.
Collection of Lactation Information
∀
The investigator will collect lactation information on any female subject who 
breastfeeds during the study through end of study visit.
∀
Information will be recorded on the Lactation Notification Form (see below) and 
submitted to Amgen or its designee within 24 hours of the investigator’s knowledge of 
event.
With the female subject’s signed authorization for release of mother and infant health 
information, the investigator will collect mother and infant health information and 
complete the lactation questionnaire on any female subject who breastfeeds while in 
the study.


Amgen Proprietary - Confidential
Pregnancy Notification Form
Report to Amgen Safety at: US FAX: +1-888-814-8653 or EMAIL: svc-ags-in-us@amgen.com
1. Case Administrative Information
Protocol/Study Number: ABP 938 Protocol#: 20210034
Study Design:
Interventional
Observational (If Observational:
Prospective
Retrospective)
2. Contact Information
Investigator Name
_
Site #
Phone (
)
_
Fax (_    _)
Email
Institution
Address 
3. Subject Information
Subject ID #
_
Subject Gender:
Female
Male
Subject age (at onset):       (in years)
4. Amgen Product Exposure
Amgen Product
Dose at time of 
conception
Frequency
Route
Start Date
           
ABP 938
mm
/dd
/yyyy
Was the Amgen product (or study drug) discontinued?
Yes
No
If yes, provide product (or study drug) stop date: mm 
/dd
/yyyy
Did the subject withdraw from the study?
Yes
No
5. Pregnancy Information
Pregnant female’s last menstrual period (LMP)
mm
/ dd______/ yyyy
Unknown
N/A
Estimated date of delivery   mm
/ dd
_/ yyyy
If N/A, date of termination (actual or planned) mm
/ dd _/ yyyy
Has the pregnant female already delivered?
Yes
No
Unknown
N/A
If yes, provide date of delivery: mm 
/ dd
/ yyyy
Was the infant healthy?
Yes
No
Unknown
N/A
If any Adverse Event was experienced by the infant, provide brief details:
Form Completed by:
Print Name: 
Title: 
Signature: 
Date: 
FORM-115199                                                                                       Version 1.0                                                                         Effective Date: 24-Sept-2018


Amgen Proprietary - Confidential
Lactation Notification Form
Report to Amgen Safety at: US FAX: +1-888-814-8653 or EMAIL: svc-ags-in-us@amgen.com
1. Case Administrative Information
Protocol/Study Number: ABP 938 Protocol#: 20210034
Study Design:
Interventional
Observational (If Observational:
Prospective
Retrospective)
2. Contact Information
Investigator Name
Site #
Phone (
)
Fax (
)
Email
Institution
Address 
3. Subject Information
Subject ID #
Subject age (at onset):       (in years)
4. Amgen Product Exposure
Amgen Product
Dose at time of 
breast feeding
Frequency
Route
Start Date
ABP 938
mm
/dd
/yyyy
Was the Amgen product (or study drug) discontinued?
Yes
No
If yes, provide product (or study drug) stop date: mm 
/dd
/yyyy
Did the subject withdraw from the study?
Yes
No
5. Breast Feeding Information
Did the mother breastfeed or provide the infant with pumped breast milk while actively taking an Amgen product?
Yes
No
If No, provide stop date: mm
/dd
/yyyy
Infant date of birth: mm
/dd
/yyyy
Infant gender:
Female
Male
Is the infant healthy?
Yes
No
Unknown
N/A
If any Adverse Event was experienced by the mother or the infant, provide brief details:
  Form Completed by:
Print Name: 
Title: 
Signature:  
Date: 
FORM-115201          
Version 1.0
   Effective Date: 24-Sept-2018

SAP_001.pdf: 
16.1.9 
Documentation of Statistical Methods  
16.1.9.1 
Statistical Analysis Plan 
Statistical Analysis Plan Version 
Statistical Analysis Plan Date 
Version 1.0 
19 Oct 2022 
Page 1 of 35
Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 1
CONFIDENTIAL 


oeG>ID 
Statistical Analysis Plan (SAP) 
Protocol Title: 
An Open Label, Two-Arm Study in Subjects with Chorioretinal 
Vascular Disease to Evaluate ABP 938 and Aflibercept (Eylea®) in a 
Prefilled Syringe 
Protocol Number: 
20210034 
Protocol Version, Date 
Version 1.0, 19 Oct 2022 
ICON ID: 
0302/2363 
Document Version, Date: 
Version 1.0, 17 Jan 2022 
Prepared by: 
ICON Clinical Research Services 
On behalf of: 
Amgen Inc. 
One Amgen Center Drive 
Thousand Oaks, CA 91320-1799 
Statistical Analysis Plan 
Version: Vl.0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02Nersion 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 1 of33 
Page 2 of 35
Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 2
CONFIDENTIAL 
NCT number: NCT05704725
This NCT number has been applied to the document
for purposes of posting on clinicaltrials.gov


oeG>ID 
Statistical Analysis Plan (SAP) 
Confidentiality statement: 
The information provided in this document is strictly confidential. 
The recipients of the SAP must not disclose the confidential information 
contained within this document or any related information to other persons 
without the permission of the sponsor. 
In addition, the recipients of the SAP must keep this confidential document in a 
controlled environment which prevents unauthorized access to the document. 
Statistical Analysis Plan 
Version: Vl.0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02Nersion 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 2 of33 
Page 3 of 35
Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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oeG>ID 
Statistical Analysis Plan (SAP) 
SIGNATURE PAGE 
P
ared at ICON Clinical Research by:
18 Jan 2023 18:09:58 UTC (Z)
18-JAN-2023
REASON: I approve this document 
a6abd90c-91c0-41ae-aac1-8456384a198d 
, Senior Biostatistician 
Reviewed at ICON Clinical Research by: 
18 Jan 2023 18:39:32 UTC (Z)
REASON: I approve this document 
71 c58482-18a2-4a72-9c38-4eb08379d037 
, Senior Biostatistician 
Approved at Amgen, Inc. by: 
18 Jan 2023 16:55:52 UTC (Z) 
REASON: I approve this document 
22hb4740-0153-4t5c-hc16-hdce65c2f77c 
, Senior Manager, Biostatistics, Biosimilars 
Date 
(DD 
YYYY) 
01/18/2023 
Date 
(DD 
YYYY) 
01/18/2023 
Date 
(DD 
YYYY) 
Statistical Analysis Plan 
Version: Vl.0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02Nersion 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Mmm 
Mmm 
Mmm 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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oeG>ID 
Statistical Analysis Plan (SAP) 
18 Jan 2023 17: 11:42 UTC (Z) 
REASON: I approve this document 
826fd546-1d0c-45b2-a29e-f7bba6b52b22 
 MD, PhD, Global Development Lead, 
Biosimilars 
18Jan2023 
Date 
(DD 
YYYY) 
Statistical Analysis Plan 
Version: Vl.0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02Nersion 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Mmm 
Page 4 of33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 5
CONFIDENTIAL 


oeG)CD 
Statistical Analysis Plan (SAP) 
REVISION HISTORY 
Version/Date 
Version 1.0/ 
17-JAN-2023
Statistical Analysis Plan 
Version name 
20210034-SAP-
Final Vl.0 17-
-
-
JAN-2023 
Section 
NIA 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02Nersion 3.0/Effective: 16 December 2019 
Changes implemented 
NIA 
(Ref. BST004-SOP) 
Version: VI .0, Date: 17-JAN-2023 
Page 5 of33 
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Page 6 of 35
Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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CONFIDENTIAL 


Statistical Analysis Plan (SAP) 
TABLE OF CONTENTS 
SIGNATURE PAGE ............................................................................................................. 4 
REVISION HISTORY .......................................................................................................... 6 
TABLE OF CONTENTS ...................................................................................................... 7 
LIST OF ABBREVIATIONS ............................................................................................... 9 
1 
INTRODUCTION ......................................................................................................... 11 
2 STUDY OBJECTIVES ................................................................................................. 12 
2.1 
Primary Objective(s) ............................................................................................. 12
2.2 Secondary Objective(s) ......................................................................................... 12 
3 STUDY DESIGN .......................................................................................................... 13 
3.1 
General Study Design ........................................................................................... 13 
3.2 
Study Eye .............................................................................................................. 14 
3.3 
Randomization and Masking ................................................................................ 14 
3.4 
Study Treatments and Assessments ...................................................................... 14 
4 STUDY ENDPOINTS ................................................................................................... 16 
4.1 Primary Endpoint(s) ............................................................................................. 16 
4.2 Secondary Endpoint(s) ......................................................................................... 16 
5 
SAMPLE SIZE AND POWER ..................................................................................... 17 
6 ANALYSIS POPULATIONS ....................................................................................... 1 8 
6.1 Full Analysis Set (FAS) ........................................................................................ 18 
6.2 
Safety Analysis Set.. ............................................................................................. 18 
6.3 
Protocol DeviationsNiolations and Exclusions from Analysis Sets .................... 18 
7 Statistical Considerations and analysis .......................................................................... 19 
7 .1 
Derived Variables ................................................................................................. 19 
7 .2 Handling of Missing Data and Outliers ................................................................ 19 
7 .2.1 
Missing Data Analysis Methods ............................................................... 19 
7 .2.2 Handling of Missing or Incomplete Dates ................................................ 19 
8 STATISTICAL METHODS .......................................................................................... 22 
8.1 General Statistical Conventions ............................................................................ 22 
8.2 
Disposition ............................................................................................................ 23 
8.2.1 
Summary of Study Reporting Period ........................................................ 23 
8.2.2 
Subject Disposition ................................................................................... 23 
8.2.3 
Summary of Analysis Sets ........................................................................ 23 
8.3 Protocol Deviations .............................................................................................. 24 
8.4 
Demographics, Baseline Characteristics, and Randomization Stratification ....... 24 
8.4.1 
Demographics and Baseline Disease Characteristics ............................... 24 
8.4.2 
Summary of Randomization Stratification ............................................... 24 
8.4.3 
Medical History ........................................................................................ 24 
8.4.4 
Prior and Concomitant Medications ......................................................... 24 
8.5 
Primary Endpoint Analysis ................................................................................... 25 
8.5.1 Analysis Methods ..................................................................................... 25 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29·81b1-4ff9•ab3b-fe25a6ed0615 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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Statistical Analysis Plan (SAP) 
8.5.1.1 Multiplicity ............................................................................................... 25 
8.5.1.2 Treatment by center interaction analysis (multi-center study) ................. 25 
8.5.2 Analysis of Primary Endpoint(s) .............................................................. 25 
8.6 Secondary Endpoint(s) Analyses .......................................................................... 26 
8. 7 Safety Analyses .................................................................................................... 26 
8.7.1 
Adverse Events ......................................................................................... 26 
8. 7.2 
Intraocular Pressure .................................................................................. 27 
8.7.3 
Slit-lamp Biomicroscopy .......................................................................... 27 
8.7.4 
Indirect Ophthalmoscopy ......................................................................... 28 
8.8 Other Endpoints .................................................................................................... 28 
8.8.1 
Best Corrected Visual Acuity (Early Treatment Diabetic Retinopathy 
Study) ........................................................................................................ 28 
8.8.2 
Spectral Domain - Ocular Coherence Tomography ................................. 28 
8.9 Subgroup Analysis ................................................................................................ 29 
8 .10 Interim Analysis ................................................................................................... 30 
9 CHANGES TO PLANNED ANALYSIS FROM STUDY PROTOCOL ..................... 31 
10 REFERENCES .............................................................................................................. 32 
11 APPENDICES ............................................................................................................... 33 
Appendix 1 - Event oflnterest (EOI) ........................................................................... 33 
Appendix 2 - Definition of INTRA OCULAR INFLAMMATION and VITREOUS 
HAEMORRHAGE ............................................................................................... 34 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29·81b1-4ff9•ab3b-fe25a6ed0615 
Page 7 of33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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Statistical Analysis Plan (SAP) 
LIST OF ABBREVIATIONS 
The following abbreviations will be used within this Statistical Analysis Plan (SAP). 
Abbreviation 
special term 
AE 
AMD 
BCVA 
CI 
CRF 
CSR 
CTMS 
CVD 
DBL 
DME 
DR 
eCRF 
EOI 
ICH 
IMP 
IOP 
IP 
IRT 
IVT 
IXRS 
MedDRA 
PD 
PFS 
PT 
RVO 
Ql 
Q3 
or Explanation 
Adverse Event 
Age-Related Macular Degeneration 
Best Corrected Visual Acuity 
Confidence Interval 
Case Report Form 
Clinical Study Report 
Clinical Trials Management System 
Chorioretinal Vascular Disease 
Database Lock 
Diabetic Macular Edema 
Diabetic Retinopathy 
Electronic Case Report Form 
Events oflnterest 
International Conference on Harmonisation 
Investigational Medicinal Product 
Intraocular Pressure 
Investigational Product 
Interactive Response Technology 
Intravitreal 
Interactive Voice/Web Response System 
Medical Dictionary for Regulatory Activities 
Protocol Deviations 
Prefilled Syringe 
Preferred Term 
Retinal Vein Occlusion 
Lower Quartile 
Upper Quartile 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 8 of33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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CONFIDENTIAL 


SAE 
SAS 
SAP 
SD 
SD-OCT 
soc 
SOP 
TEAE 
TE-SAE 
TFLs 
Statistical Analysis Plan (SAP) 
Serious Adverse Event 
Statistical Analysis System 
Statistical Analysis Plan 
Standard Deviation 
Spectral Domain-Optical Coherence Tomography 
System Organ Class 
Standard Operating Procedure 
Treatment-Emergent Adverse Event 
Treatment-Emergent Serious Adverse Events 
Tables, Figures and Listings 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 9 of33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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Statistical Analysis Plan (SAP) 
1 
INTRODUCTION 
The purpose of this SAP is to provide detailed descriptions of the statistical methods, data derivations 
and data displays for the final analysis for study protocol 20210034 "An Open Label, Two-Arm 
Study in Subjects with Chorioretinal Vascular Disease to Evaluate ABP 938 and Aflibercept (Eylea®) 
in a Prefilled Syringe" dated 19 Oct 2022. The table of contents and templates for the Table, Figures, 
Listings (TFLs) will be produced in a separate document. 
Any deviations from this SAP will be described and justified in the Clinical Study Report (CSR). 
The preparation of this SAP has been based on International Conference on Harmonization (ICH) 
E9 and E3 guidelines. This SAP will be finalized prior to first patient randomized to maintain trial 
integrity in accordance with ICON standard operating procedures (SOP). SAP amendments will not 
be permitted after the first subject has been randomized. 
All data analyses and generation of TFLs will be performed using Statistical Analysis System (SAS) 
9.4® or higher. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 10 of33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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CONFIDENTIAL 


Statistical Analysis Plan (SAP) 
2 
STUDY OBJECTIVES 
2.1 
Primary Objective(s) 
The primary objective for this study is to assess the ability of retina specialists to successfully 
administer, via an intravitreal (IVT) injection, a 2 mg dose of ABP 938, using the ABP 938 Prefilled 
Syringe (PFS), compared to a 2 mg dose of aflibercept using the aflibercept PFS. 
2.2 
Secondary Objective(s) 
The secondary objective is to assess the safety of ABP 938 administered to subjects with 
Chorioretinal Vascular Disease (CVD) via an IVT injection, using the ABP 938 PFS compared to 
aflibercept administered using the aflibercept PFS. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 11 of33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 12
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Statistical Analysis Plan (SAP) 
3 
STUDY DESIGN 
3.1 
General Study Design 
This is an open label, two-arm, randomized, multi-site study within the US in adult subjects with 
CVD. Approximately 48 adult male or female subjects will be randomized in a ratio of 2: 1 to receive 
either a single IVT injection of ABP 938 in a PFS or a single injection of aflibercept in a PFS. 
Randomization will be stratified by retina specialist. 
The study population will include men or women with treatrnent-nai"ve or previously treated 
neovascular Age-Related Macular Degeneration (AMD), Diabetic Macular Edema (DME), macular 
edema following Retinal Vein Occlusion (RVO), or Diabetic Retinopathy (DR), in whom treatment 
with aflibercept is indicated. 
The study duration for each subject will be approximately 28 days (± 7 days) excluding screening 
and the study will end for subjects when they complete the end of study visit assessments. 
The study design is outlined in Figure 1, and the visit schedule and planned assessments at each visit 
are detailed in Table 1. 
No interim analyses are planned. 
Figure 1: Study Flow Chart 
s 
C 
R 
E 
E 
N 
I 
N 
G 
R 
A 
N 
D 
0 
M 
I 
z 
A 
T 
I 
0 
N 
ABP 938 (40 mg/mL) 
Single 2 mg/0.05ml IVT dose using prefilled syringe 
n - 32 
Aflibercept (40 mg/mL) 
Single 2 mg/0.05ml IVT dose using prefilled syringe 
n - 16 
28 (± 7) Days 
E 
N 
D 
0 
F 
s 
T 
u 
D 
y 
Day -1 
Baseline (Injection) 
Day 1 
Safety Follow Up 
Week 4 
IVT = intravitreal; mg = milligram; mL = milliliter; n = number of subjects. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 201 9  
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 12 of 33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 13
CONFIDENTIAL 


Statistical Analysis Plan (SAP) 
3.2 
Study Eye 
Only one eye is selected as the study eye by retina specialists. The study eye selection recorded in 
the eCRFs will be used for all statistical analyses. 
3.3 
Randomization and Masking 
Randomization will be performed through a centralized IXRS. On Day 1, eligible subjects will be 
assigned to ABP 938 or aflibercept in a 2: 1 ratio. Each subject will receive a unique randomization 
number when he/she is assigned treatment. Subjects will be allocated to treatment according to the 
randomization code. Randomization will be stratified by retina specialist. 
Investigators, site staff, and study teams will not be masked to treatment assignments. However, final 
live randomization lists will not be released to study teams until the database has been locked and 
approval of release is obtained from the Sponsor by ICON. Additionally, dry run statistical outputs 
generated prior to database lock in preparation for final analysis will be restricted to the ICON and 
Amgen statistical and programming teams. 
3.4 
Study Treatments and Assessments 
The study consists of a screening visit (Day -1 ), a baseline visit (Day 1) and an end of study visit 
(Day 28 ± 7 days). 
At the screening visit (Day -1), the investigator will obtain signed informed consent from the subject 
before any study procedures or assessments are performed. Once subject eligibility is confirmed the 
subject will be enrolled into the study. At this visit, the subject will undergo ocular safety procedures 
including the Best Corrected Visual Acuity (BCV A) scale, intraocular pressure (IOP), slit-lamp 
biomicroscopy, indirect ophthalmoscopy, and spectral domain-optical coherence tomography 
(SD-OCT). 
At the baseline visit (Day 1 ), the subject will be randomized to receive a single IVT injection of 
either ABP 938 or aflibercept (open label) in a PFS administered by a retina specialist. Only one eye 
will be selected as the study eye. IOP will be measured, and indirect ophthalmoscopy will be 
performed before and after investigational product (IP) administration. The screening and baseline 
visit may be combined into one visit (Day 1). 
At the end of study visit (Day 28 ± 7 days), the ocular safety procedures performed at the screening 
visit will be repeated. 
Adverse events (AEs) will be collected from the signing of the informed consent form (ICF) until 
the end of study visit. 
The method of assigning subjects to treatment is discussed in section 3.3 of this SAP. 
A detailed description of procedures and assessments to be conducted during this study 1s 
summarized in the Scheduled of Study Assessments in Table 1 below. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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Statistical Analysis Plan (SAP) 
Table 1: Schedule of Assessments 
Baseline 
End of Studyb 
Study Procedure 
Screening 
(Randomization 
and Injection) 
(± 7 days) 
Day -1 
Day 1 a 
Day 28 
Informed Consent 
X 
Medical and Ophthalmic History 
X 
Demographic Data 
X 
Concomitant Medications 
X 
X 
X 
Adverse Events c 
X 
X 
X 
BCVA by ETDRS d 
X 
X 
Slit-Lamp Biomicroscopy d 
X 
X 
lntraocular Pressure (IOP) d 
X 
x e  
X 
Indirect Ophthalmoscopy d 
X 
xr 
X 
SD-OCT d 
X 
X 
Urine Pregnancy g 
X 
Randomization 
X 
IVT Injection of Study Medication (ABP 938 or 
X 
aflibercept) 
BCVA = Best Corrected Visual Acuity; ETDRS = Early Treatment Diabetic Retinopathy Study; 
IVT = lntravitreal; IOP = lntraocular pressure; SD-OCT = Spectral Domain-Optical Coherence Tomography 
a The screening and baseline visits may be combined on Day 1 .  
b I n  the event of premature discontinuation, the subject should complete the assessments indicated at the 
end of study visit, whenever possible. 
c Adverse events will be collected from the signing of the informed consent form until the end of study visit. 
d All ophthalmic safety assessments should be performed on the study eye only. 
e IOP will be measured pre-dose (prior to dilation) and 1 5-60 minutes after IP administration. 
1 Indirect ophthalmoscopy will be performed pre-dose and after IP administration.
g Required for females of childbearing potential. Test will be performed by local laboratory. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 15
CONFIDENTIAL 


Statistical Analysis Plan (SAP) 
4 
STUDY ENDPOINTS 
4.1 
Primary Endpoint(s) 
The primary endpoint for the study is the proportion of IVT injections successfully administered to 
subjects with CVD by retina specialists, utilizing the ABP 938 PFS or aflibercept PFS. 
4.2 
Secondary Endpoint(s) 
The secondary endpoint for the study is the incidence of ocular AEs and serious adverse events 
(SAEs) in the study eye, and non-ocular SAEs until the end of study visit (Day 28 visit). 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 16
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Statistical Analysis Plan (SAP) 
5 
SAMPLE SIZE AND POWER 
For this study, no prospective calculations of statistical power have been made. 
It is planned to enroll approximately 48 adult male or female subjects into the study, with a minimum 
of 32 subjects in the ABP 938 PFS arm and a minimum of 16 subjects in the aflibercept PFS arm, 
randomized in a ratio of 2: 1. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 16 of33 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 17
CONFIDENTIAL 


Statistical Analysis Plan (SAP) 
6 
ANALYSIS POPULATIONS 
6.1 
Full Analysis Set (FAS) 
The FAS will include all randomized subjects and will be analyzed according to randomized 
treatment. This analysis set will be used for summaries of the primary endpoint. 
6.2 
Safety Analysis Set 
The Safety Analysis Set will include all randomized subjects who receive the IP and will be analyzed 
according to the actual treatment received. This analysis set will be used for summaries of safety 
data. 
6.3 
Protocol DeviationsNiolations and Exclusions from Analysis Sets 
Protocol deviations will be collected and recorded during the trial. However, important protocol 
deviations will not be a cause for subject exclusion from any analysis sets. Protocol deviations will 
be summarized in accordance with section 8.3 of this SAP. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 18
CONFIDENTIAL 


Statistical Analysis Plan (SAP) 
7 
STATISTICAL CONSIDERATIONS AND ANALYSIS 
7.1 
Derived Variables 
The below table provides the list of derived variables for demographic and baseline characteristics, 
duration derivations, and baseline derivations applicable for this study. 
Table 2: Derived Variables 
Variables 
Formula 
Derivation of Duration 
Study day at any visit 
Date of interest - date of first dose of study drug. One day is 
added if this difference is > 0 
Baseline Derivations 
Baseline 
The baseline value lS defined as the last non-m1ssmg 
measurement before IP administration 
Change from baseline 
Post-baseline value - Baseline value 
7.2 
Handling of Missing Data and Outliers 
Missing data will not be imputed for the primary and secondary endpoints with the exception of 
missing or incomplete dates as specified in section 7.2.2. 
7.2.1 
Missing Data Analysis Methods 
All analyses will be carried out with observed data only. 
7.2.2 Handling of Missing or Incomplete Dates 
If dates are missing or incomplete for an AE (including deaths) or concomitant medication, the 
following algorithm will be used for imputation: 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
Page 19
CONFIDENTIAL 


Statistical Analysis Plan (SAP) 
Table 3: Imputation Rules for Partial or Missing Start Dates 
Stop Date 
Complete: 
yyyymmdd 
<1st 
2::l't 
Start Date 
dose 
dose 
= 1st dose 
1 
Partial: 
yyvvmm 
2 
yyyymm 
'f 1st dose 
2 
yyvvmm 
= 1st dose 
1 
Partial: 
YYVV 
3 
yyyy 
'f 1st dose 
3 
YYVV 
Missing 
4 
1 
1 = Impute as the date of first dose 
2 = Impute as the first of the month 
3 = Impute as January 1 of the year 
4 = Impute as January 1 of the stop year 
Partial: yyyymm 
<1st dose 
2::1 st dose 
yyyymm 
yyyymm 
n/a 
1 
2 
2 
1 
3 
3 
4 
1 
Partial: yyyy 
2::l't 
<1st dose 
dose 
vvvv 
vvvv 
n/a 
1 
2 
2 
n/a 
1 
3 
3 
4 
1 
m1ssmg 
1 
2 
1 
3 
1 
Note: If the start date imputation leads to a start date that is after the stop date, then there is a data 
error and do not impute the start date. 
Imputation rules for partial or missing stop dates: 
1. Initial imputation
a.
For partial stop date "mmyyyy", impute the last of the month.
b.
For partial stop date "yyyy", impute December 31 of the year.
c. For completely missing stop date, do not impute.
2.
If the stop date imputation leads to a stop date that is after the death date, then impute the
stop date as the death date.
3.
If the stop date imputation leads to a stop date that is before the start date, then there is a data
error and do not impute the stop date.
Imputation rules for partial or missing death dates: 
4.
If death year and month are available but day is missing:
a.
If "mmyyyy" for last contact date = "mmyyyy" for death date, set death date to the
day after the last contact date.
b.
If "mmyyyy" for last contact date < "mmyyyy" for death date, set death date to the
first day of the death month.
c.
If "mmyyyy" for last contact date > "mmyyyy" for death date, data error and do not
impute.
5.
If both month and day are missing for death date or a death date is totally missing, set death
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
Page 19 of33 
Page 20 of 35
Product:  ABP 938 
Clinical Study Report:  20210034 
Date:  14 June 2023 
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Statistical Analysis Plan (SAP) 
date to the day after the last contact date. 
The imputed dates will be used to assess whether AEs should be considered as treatment­
emergent and if medications should be included in the safety summaries as prior or concomitant, 
however the original, partial dates will be included in data listings. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
8 
STATISTICAL METHODS 
8.1 
General Statistical Conventions 
Continuous variables will be summarized using descriptive statistics, including number of subjects 
(n), mean, median, standard deviation (SD), first and third quartiles, minimum and maximum. 
For categorical variables, summaries will include counts of subjects and percentages. Percentages 
will be rounded to one decimal place. 
Two-sided 95% confidence intervals (CI) will be provided when relevant. 
For summary purposes, all summaries will be presented by treatment group unless otherwise 
specified. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
8.2 
Disposition 
8.2.1 
Summary of Study Reporting Period 
A summary of key dates for the study will be reported including: 
•
First subject emollment
•
Last subject emollment
•
Last subject end of IP
•
Last subject end of study
•
Data cut-off date
8.2.2 
Subject Disposition 
Subject disposition information will be summarized by treatment group and for all subjects. The 
number of subjects and percentage of subjects who were randomized, who were dosed, who 
completed the study and who discontinued from the study will be presented. The primary reason for 
study discontinuation will also be tabulated. COVID-19 related discontinuations will be summarized 
as well. Separate summaries will be generated using the FAS and Safety Analysis Set. 
A listing of discontinued subjects will be produced. 
8.2.3 
Summary of Analysis Sets 
A separate summary of analysis sets will be produced using all screened subjects. The number of 
total screened subjects and randomized subjects by treatment group and overall will be summarized. 
Additionally, the number and percentage of subjects in each analysis set (FAS and Safety Analysis 
Set) will also be tabulated. The number and percentage of subjects excluded from each analysis set 
will be presented with the reasons for exclusion. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
8.3 
Protocol Deviations 
Protocol deviations (PD) data will be entered into the Clinical Trials Management System (CTMS). 
The study team will conduct reviews of the PD data from CTMS. All PDs will be categorized as 
important or not important prior to the database lock and release of final live randomization lists. 
Based on the PD data entered CTMS, a summary of important PDs will be tabulated using number 
and percentage of subjects with important PDs by category and deviation type, by randomized 
treatment group and for all subjects using the FAS. A summary table of COVID related PDs will 
also be tabulated in a similar manner. Subject listings of subjects with important PDs and COVID-
19 related PDs will be provided. 
8.4 
Demographics, Baseline Characteristics, and Randomization Stratification 
8.4.1 
Demographics and Baseline Disease Characteristics 
Age at baseline will be summarized using continuous descriptive statistics. Race, ethnicity, and sex, 
will be summarized using categorical descriptive statistics. 
Any subjects that select more than one race will be summarized as "Multiple". The multiple racial 
combinations selected will be summarized under this "Multiple" category. 
Baseline variables of BCV A, IOP, and SD-OCT will be summarized by descriptive statistics in the 
same way as continuous demographic variables. 
Separate summaries will be generated for the FAS and Safety Analysis Set. 
8.4.2 Summary of Randomization Stratification 
The count and percentage of subjects randomized under each retina specialist (randomization 
stratum) will be summarized using the FAS population. Subjects randomized under the incorrect 
retina specialist will be summarized as well. 
8.4.3 Medical History 
Summaries of unresolved medical history will be presented by system organ class (SOC) and 
preferred term (PT) using the most current version of Medical Dictionary for Regulatory Activities 
(MedDRA) at the time of the final analysis by treatment group and overall using FAS population. 
8.4.4 Prior and Concomitant Medications 
Medications used in this study will be coded by using the current version of the World Health 
Organization Drug Dictionary at the time of the final analysis. 
Prior medications: are defined as those that were stopped at or within 30 days prior to the baseline 
visit. 
Concomitant medications: are defined as those that are ongoing at the time of IP administration and 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
during the follow-up period. 
Ocular study eye, ocular fellow eye, and non-ocular concomitant medications will be summarized 
descriptively using frequency tables by preferred name by treatment group and overall using the 
Safety Analysis Set. 
Details for imputing missing or partial start and/or stop dates of medication are described in 
section 7.2.2. 
8.5 
Primary Endpoint Analysis 
8.5.1 
Analysis Methods 
8.5.1.1 Multiplicity 
No formal statistical hypothesis testing will be conducted as part of this SAP. As such, type I error 
control will be not applicable. 
8.5.1.2 Treatment by center interaction analysis (multi-center study) 
Treatment by center interaction analyses will not be conducted as part of this SAP. 
8.5.2 Analysis of Primary Endpoint(s) 
The primary endpoint of the number of successful IP injections with the PFS will be summarized 
using the FAS with observed data only. Successful injections for the purpose of the analysis of the 
primary endpoint will be defined by the following response recorded by the retina specialists in the 
Investigational Product Administration eCRF for each subject: 
Did the prefilled syringe allow as a safe and effective administration of the prescribed dose? 
(Yes/No) 
The number and percentage of injections successfully administered utilizing the PFS will be provided 
descriptively by randomized treatment group. For each retina specialist, the number and percentage 
of successful IP injections will be summarized. The estimated success rate for each treatment group 
will be calculated by the average of each retina specialists' individual success rate. The variance of 
this estimator will be calculated as: 
V 
( ) _ If=1CPi - p) 2 
ar p -
K(K - l) 
where Pi is the proportion of successful IVT injections administered for the i-th retina specialist and 
p is the average of proportions of successfully administered IVT injections across all retina 
specialists, K is the total number of retina specialists. T-distribution with (K - 1) degrees of freedom 
will be used to calculate the corresponding two-sided 95% CI. 
Should any treatment group have 100% successful IP injections, then exact Clopper-Pearson 95% 
Cls will be presented for both treatment groups instead of Cis based on the t-distribution. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
8.6 
Secondary Endpoint(s) Analyses 
The secondary endpoints of ocular AEs in the study eye, SAEs in the study eye and non-ocular SAEs 
will be summarized as described in section 8. 7.1 using the Safety Analysis Set. 
8. 7 
Safety Analyses
Safety analyses will be conducted on the Safety Analysis Set according to actual treatment received 
and will be performed for all safety variables specified below. 
8.7.1 Adverse Events 
Only TEAEs will be summarized. TEAEs are any AE with onset after IP administration. AEs that 
occur on the day of IP dosing will be categorized as TEAEs if the event is indicated as not starting 
before first dose of IP per recorded responses in the Adverse Event eCRF. 
All AEs will be classified by Primary SOC and PT according to the most current version of MedDRA. 
The severity of each TEAE will be graded per Common Terminology Criteria for Adverse Events 
(CTCAE) v5.0 criteria. 
In summaries by SOC and PT, TEAEs will be sorted by decreasing frequency by SOC and PTs within 
each SOC according to ABP 938. In summaries by PT, TEAEs will be sorted by decreasing frequency 
according to ABP 938. 
Counting of TEAEs will be by subject, and subjects will be counted only once within each SOC or 
PT. For tables categorized by severity, subjects with multiple events within a SOC or PT will be 
counted under the category of their most severe event within that SOC or PT. 
Details for imputing missing or partial start dates of AEs are described in section 7.2.2 of this SAP. 
An overall summary table of TEAEs will be presented which will include the number and percentage 
of subjects with at least one of the following events: 
•
ocular TEAEs in the study eye,
•
non-ocular TEAEs,
•
ocular TE-SAEs in the study eye,
•
non-ocular TE-SAEs,
•
CTCAE grade >= 3 TEAEs,
•
fatal TEAEs, 
•
COVID-19 TEAEs,
•
TEAEs leading to discontinuation of study,
•
IP related TEAEs,
•
study procedure related TEAEs,
•
device related TEAEs, and
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
•
treatment-emergent Events oflnterest (EOis).
The EOis to be summarized are as defined in Appendix 1 - Events oflnterest. 
Separate AE summary tables will include the following: 
•
Ocular TEAEs in the Study Eye by PT 
•
Non-Ocular TEAEs by PT 
•
Ocular TE-SAEs in the Study Eye by PT
•
Non-Ocular TE-SAEs by PT
•
Ocular TEAEs in the Study Eye by SOC, PT, and Maximum CTCAE Grade
•
Non-Ocular TEAEs by SOC, PT, and Maximum CTCAE Grade
•
Treatment-Emergent Intraocular Inflammation AEs by PT
•
Treatment-Emergent Vitreous Haemorrhage AEs by PT
•
TE-SAEs Occurring on or After Presumed Start Date of COVID-19 Infection by PT
•
Treatment-Emergent COVID-19 AEs by PT 
•
Overall Summary of Treatment-Emergent EOis
•
Treatment-Emergent Endophthalmitis Events by PT
•
Treatment-Emergent Increase in Intraocular Pressure Events by PT
•
Treatment-Emergent Retinal Detachment Events by PT
•
Treatment-Emergent Thromboembolic Events by PT
•
TEAEs Resulting in Study Discontinuation by PT
The TEAEs of Intraocular Inflammation and Vitreous Haemorrhage are as defined in Appendix 2. 
Subject listings of TE-SAEs and TE-SAEs occurring on or after positive COVID-19 infection in 
subjects diagnosed with COVID-19 will be generated. 
8.7.2 lntraocular Pressure 
Visit values and changes from baseline for IOP (mm Hg) will be summarized by actual treatment 
group at each visit and time point scheduled during treatment period using continuous descriptive 
statistics. Only the study eye will be summarized. 
8. 7 .3 
Slit-lamp Bio microscopy
Visit values for slit-lamp biomicroscopy will be summarized by each region assessed and by actual 
treatment group at each visit and time point scheduled during treatment period using categorical 
descriptive statistics. Only the study eye will be summarized. 
Separate summaries will be generated for shifts from baseline to the end of study visit using the study 
eye only. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
8. 7 .4 
Indirect Ophthalmoscopy
Visit values for indirect ophthalmoscopy will be summarized by each region assessed and by actual 
treatment group at each visit and time point scheduled during treatment period using categorical 
descriptive statistics. Only the study eye will be summarized. 
Separate summaries will be generated for shifts from baseline to each post-baseline assessment using 
the study eye only. 
8.8 
Other Endpoints 
Other endpoints will be summarized using the FAS. 
8.8.1 
Best Corrected Visual Acuity (Early Treatment Diabetic Retinopathy Study) 
Visit values and changes from baseline for BCV A score will be summarized by randomized 
treatment group at each visit scheduled during treatment period using continuous descriptive 
statistics. Only the study eye will be summarized. 
8.8.2 
Spectral Domain - Ocular Coherence Tomography 
Visit values and changes from baseline for SD-OCT score (µm) will be summarized by randomized 
treatment group at each visit and time point scheduled during treatment period using continuous 
descriptive statistics. Only the study eye will be summarized. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
8.9 
Subgroup Analysis 
No pre-specified subgroup analyses will be conducted as part of this SAP. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
8.10 Interim Analysis 
No planned interim analysis will be conducted as part of this SAP. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
9 
CHANGES TO PLANNED ANALYSIS FROM STUDY 
PROTOCOL 
There are no changes to planned statistical analyses indicated in the protocol. 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
10 
REFERENCES 
1. 
ICH Topic E3: Structure and Content of Clinical Study Reports (CPMP/ICH/137/95-
adopted December 1995).
2. 
ICH Topic E9: Statistical Principles for Clinical Trials (CPMP/ICH/363/96 - adopted March
1998).
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
11 
APPENDICES 
Appendix 1 - Event of Interest (EOI) 
Event of Interest (EOI) 
ENDOPHTHALMITIS 
INCREASE IN INTRAOCULAR 
PRESSURE 
RETINAL DETACHMENT 
THROMBOEMBOLIC EVENTS 
MedDRA Terms or Search Strategy 
Any of the following preferred term: 
Endophthalmitis 
Candida endophthalmitis 
Mycotic endophthalmitis 
Eye infection 
Eye infection bacterial 
Eye infection fungal 
Eye infection chlamydia! 
Eye infection staphylococcal 
Eye infection intraocular 
Any of the following preferred term: 
Intraocular pressure increased 
Ocular hypertension 
Angle closure glaucoma 
Borderline glaucoma 
Glaucoma 
Glaucoma traumatic 
Normal tension glaucoma 
Open angle glaucoma 
Phacolytic glaucoma 
Pseudophakic glaucoma 
Uveitic glaucoma 
Glaucomatous optic disc atrophy 
Any of the following preferred term: 
Retinal tear 
Retinal detachment 
Embolic and Thrombotic events SMQ (Narrow) 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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Statistical Analysis Plan (SAP) 
Appendix 2 - Definition of INTRAOCULAR INFLAMMATION and VITREOUS 
HAEMORRHAGE 
Event 
MedDRA Terms 
INTRA OCULAR INFLAMMATION 
Any of the following preferred term: 
Anterior chamber cell 
Anterior chamber flare 
Anterior chamber inflammation 
Aqueous fibrin 
Autoimmune uveitis 
Chorioretinitis 
Choroiditis 
Cyclitis 
Eye inflammation 
Hypopyon 
Uveitis 
Iridocyclitis 
Iritis 
Non-infectious endophthalmitis 
Ocular vasculitis 
Pseudoendophthalmitis 
Retinal vasculitis 
Retinitis 
Vitreal cells 
Vitritis 
VITREOUS HAEMORRHAGE 
Any of the following preferred term: 
Vitreous haemorrhage 
Vitreous haematoma 
Statistical Analysis Plan 
Version: VI .0, Date: l 7-JAN-2023 
Protocol Number: 20210034 
Confidential General and Administrative 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019 
(Ref. BST004-SOP) 
DocUUID: e2994b29-81b1-4ff9-ab3b-fe25a6ed0615 
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16.1.9.2 
Statistical Methods and Analysis Output 
Not applicable 
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