Clinical trial NCT04270747
Conditions: Neovascular (Wet) Age-related Macular Degeneration (AMD)
Sponsor: Amgen
Start date: 2020-06-22; Completion date: 2023-01-30
Enrollment: 576 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the efficacy and safety of ABP 938 versus Aflibercept (Eylea®) in the treatment of neovascular age-related macular degeneration. Subjects will be randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) administered by intravitreal (IVT) injection.

Detailed description:
Approximately 566 subjects will be randomized in approximately 126 global sites.

This study consists of a screening period of up to 4 weeks, after which subjects will receive investigational product for 48 weeks, followed by a safety follow-up period to week 52, for a total study duration of up to 56 weeks.

Subjects will be randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) administered by IVT injection.

At week 8, subjects will be assessed for the primary endpoint. The primary endpoint is the change in Best Corrected Visual Acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline to week 8, in order to assess the efficacy of ABP 938 compared to aflibercept.

Subjects will then be re-randomized at week 16 in a masked fashion such that:

* Subjects initially randomized to ABP 938 (Treatment Group A) will continue to receive ABP 938 by IVT injection every 8 weeks from week 16 until week 48
* Subjects initially randomized to aflibercept (Treatment Group B) will be re-randomized in a 1:1 ratio to either continue on aflibercept (Treatment Group B1) or transition to ABP 938 (Treatment Group B2) by IVT injection every 8 weeks from week 16 until week 48

Arms: arm 1: Subjects will receive 2 mg (0.05 mL) of ABP 938 by intravitreal (IVT) injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, and week 8) and every 8 weeks from week 16 until week 48. arm 2: Subjects will receive 2 mg (0.05 mL) of aflibercept (Treatment Group B) by IVT injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, and week 8). Subjects will be re-randomized to receive aflibercept by IVT injection every 8 weeks from week 16 until week 48. arm 3: Subjects will receive 2 mg (0.05 mL) of aflibercept (Treatment Group B) by IVT injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, and week 8). Subjects will be re-randomized to receive ABP 938 by IVT injection every 8 weeks from week 16 until week 48
Interventions: intervention 1: ABP 938 intervention 2: Aflibercept
Intervention descriptions: intervention 1: Subject will receive ABP 938 2 mg (0.05 mL) IVT injection every 4 weeks for the first 3 doses, followed by once every 8 weeks intervention 2: Subject will receive aflibercept 2 mg (0.05 mL) IVT injection every 4 weeks for the first 3 doses, followed by once every 8 weeks

Protocol documents:
Prot_000.pdf: 
Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
Page 1 of 88 
Confidential 
CLINICAL STUDY PROTOCOL 
Title: 
A Randomized, Double-masked, Phase 3 Study of ABP 938 
Efficacy and Safety Compared to Aflibercept (Eylea®) in 
Subjects with Neovascular Age-related Macular 
Degeneration  
Protocol number: 
20170542 
Study phase:  
Phase 3 
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 USA 91320 
Contract research 
organization:  
Parexel International (IRL) Limited 
Protocol version and 
date:  
Version 4.0, 16 May 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)/Independent Ethics 
Committee(s) under the condition that they keep it confidential. 
NCT Number: NCT04270747
This NCT number has been applied to the document
for purposes of posting on Clinicaltrials.gov




Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022 
Page 3 of 88
PROTOCOL SIGNATURE PAGE - CONTRACT RESEARCH ORGANIZATION (CRO) 
This protocol has been reviewed and approved by the representative(s) listed below. Any 
modification of the protocol must be agreed upon by the sponsor and the investigator and 
must be documented in writing. 
CRO representative(s): 
Print Name 
Title 
Date (DD Month YYYY) 
Confidential 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
Page 4 of 88 
Confidential 
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)/Independent Ethics 
Committee (IEC), 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 (or a legally authorized representative) 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 (ICH) guidelines on Good Clinical Practice (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 me (including, if 
applicable, my spouse [or legal partner] and dependent children) and my subinvestigators 
(including, if applicable, their spouses [or legal partners] and dependent children) at the start 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
Page 5 of 88 
Confidential 
of the study and for up to 1 year after the study is completed, if there are changes that affect 
my financial disclosure status. 
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 (DD Month YYYY) 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
Page 6 of 88 
Confidential 
SERIOUS ADVERSE EVENT CONTACT INFORMATION 
Serious adverse event information will be recorded in the electronic data capture (EDC) 
system and transmitted to Amgen within 24 hours following the investigator’s knowledge of 
the event.  If the EDC system is not functional, the serious adverse event can be reported by 
faxing a completed paper Serious Adverse Event Form or by direct telephone 
communication with Parexel at the numbers provided below.  The event must be updated 
electronically in the EDC system by the clinical study center once the EDC function 
resumes. 
Global reporting of SAEs (except Japan): 
Phone (Safety line): +1 (781) 434-5010  
NorthAmerica_Medical@parexel.com
Japan (Safety line): +81 3 6888 5377   


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
Page 7 of 88 
Confidential 
PROTOCOL AMENDMENT 3 (16 MAY 2022) 
Amendment rationale 
In accordance with the International Council for Harmonisation (ICH) E9 (R1) 
addendum, the protocol is amended to specify the primary estimand of the study and 
to update the statistical section of the protocol in order to meet the regulation 
obligation for the USA Food and Drug Administration. 
All content updates to the existing text in this protocol amendment are illustrated 
throughout in BOLD font and presented in this protocol summary. 
Changes from the protocol version 3.0 to protocol version 4.0 

Footnotes “b, d, g, j” of Table 1 Schedule of Activities have been updated. 

Objectives/Endpoints/Estimand in the Protocol Summary has been updated to 
include the information of primary estimand. 

Statistical methods in the Protocol Summary has been updated. 

Section 2 Study Objectives, Endpoints, and Estimand has been updated to 
include the information of primary estimand. 

Section 8.5.1 Primary Endpoint/Estimand has been updated to include the 
analysis of primary estimand. 

Section 8.5.10 Handling of Missing Values has been updated to further clarify 
the analysis of missing data. 

Section 17.1 Sponsor’s medical expert and clinical research organization’s 
medical monitor information have been updated. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
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PROTOCOL SUMMARY 
Protocol number:  20170542 
Protocol title:  A Randomized, Double-masked, Phase 3 Study of ABP 938 Efficacy and 
Safety Compared to Aflibercept (Eylea®) in Subjects with Neovascular Age-related Macular 
Degeneration 
Sponsor:  Amgen, Inc
Study phase:  Phase 3 
Indication:  Neovascular Age-related Macular Degeneration
Study centers:  Approximately 126 global sites 
Objectives/Endpoints/Estimand: 
Objectives 
Endpoints 
Primary 
Primary efficacy endpoint 
To assess the efficacy of ABP 938 
compared to aflibercept. 
Change from baseline in best corrected 
visual acuity (BCVA) as measured by Early 
Treatment Diabetic Retinopathy Study 
(ETDRS) letter score at week 8 
Secondary efficacy endpoints 
Proportion of subjects who maintained vision 
at week 52, where a subject was classified 
as maintaining vision if he/she lost fewer 
than 15 letters in ETDRS letter score 
compared to baseline  
Change from baseline in BCVA as measured 
by ETDRS letter score over the study 
duration  
Proportion of subjects who gained at least 
10 letters of vision at week 8 and proportion 
of subjects who gained at least 15 letters of 
vision at week 52 as compared to baseline 
Change from baseline in choroidal 
neovascularization (CNV) area as measured 
by fluorescein angiography (FA) and central 
subfield thickness (CST) as measured by 
spectral domain optical coherence 
tomography (SD-OCT) over the study 
duration   


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
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Secondary 
To assess the safety and immunogenicity of 
ABP 938 compared to aflibercept. 
Treatment-emergent adverse events, 
adverse events of interest (EOIs), and 
serious adverse events 
Incidence of antidrug antibodies (ADA) 
Primary estimand: 
The primary estimand is the difference in change from baseline in BCVA at week 8 
between the ABP 938 group and the aflibercept group in subjects with neovascular (wet) 
age-related macular degeneration (AMD) who are randomized, regardless of missing or 
discontinuing investigational product administration to the study eye, or use of 
additional medications for AMD in the study eye prior to observing BCVA at week 8. 
Study design: This is a randomized, double-masked, active controlled multiregional clinical 
study in adult subjects with neovascular (wet) AMD.  Approximately 566 subjects (including at 
least 30 subjects from East Asia) will be randomized in a masked 1:1 ratio to receive 2 mg 
(0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) 
administered by intravitreal (IVT) injection every 4 weeks for the first 3 doses (ie, baseline/day 
1, week 4, and week 8).  Randomization will be stratified by geographic region and disease 
severity (baseline BCVA < 64 letters vs. ≥ 64 letters). 
At week 8, subjects will be assessed for the primary endpoint (BCVA change from baseline as 
measured by ETDRS).  Subjects will then be re-randomized at week 16 in a masked fashion 
such that: 
 
Subjects initially randomized to ABP 938 (Treatment Group A) will continue to receive 
ABP 938 by IVT injection every 8 weeks from week 16 until week 48 
 
Subjects initially randomized to aflibercept (Treatment Group B) will be re-randomized in a 
1:1 ratio to either continue on aflibercept (Treatment Group B1) or transition to ABP 938 
(Treatment Group B2) by IVT injection every 8 weeks from week 16 until week 48 
Re-randomization will be stratified using the same factors as the initial randomization.  
Subjects who are unable to complete the week 16 visit within the visit window will not be 
re-randomized, will be discontinued from the study, and will be asked to return to complete an 
end-of-study (EOS) visit within 28 days from determining that the subject will discontinue from 
the study.  An EOS visit will be conducted at week 52 for subjects that complete the study.   
The primary analysis for the study is planned when all subjects reach week 24 or terminate 
early.  This analysis will comprise at least 24 weeks of efficacy, safety, and immunogenicity 
data.  The final analysis is planned when all enrolled subjects complete the week 52 visit or 
terminate early.  An external, independent data monitoring committee will evaluate the safety 
data throughout the study. 
For subjects receiving neovascular (wet) AMD treatment in the fellow eye during the study, 
sites must request an additional box of investigational product.  
Approximately 32 subjects will be consented and enrolled into a pharmacokinetic (PK) 
substudy.  These subjects will have a PK sample collected predose (within 60 minutes before 
day 1 dose) and postdose (approximately 24 hours after day 1 dose), with an allowable window 
-6 hours to +24 hours (ie, 18 hours to 48 hours after day 1 dose) and postdose at week 8 
(approximately 24 hours after week 8 dose), with an allowable time window of -6 hours to 
+24 hours (ie, 18 hours to 48 hours postdose). 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
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If it is anticipated that the fellow eye will need to be treated prior to the week 8 postdose PK 
sample, then the subject should not be enrolled into the PK substudy.  If an enrolled PK 
substudy subject develops a requirement for fellow eye treatment prior to week 8 postdose PK 
sample, no further PK samples will be collected.  
If the need for treating the fellow eye is identified at the week 8 visit, then the fellow eye must 
be treated after the week 8 postdose PK sample has been drawn for those subjects included in 
the PK substudy. 
Study procedures: Efficacy procedures will include BCVA, recorded using ETDRS charts, 
FA, and SD-OCT.  Safety procedures will include assessment of adverse events, clinical 
laboratory tests, vital signs, indirect ophthalmoscopy, slit-lamp test, and intraocular pressure.
Study duration: After a screening period of up to 4 weeks, subjects will receive 
investigational product for 48 weeks, followed by a safety follow-up period to week 52, for a 
total study duration of up to 56 weeks.  The start of the study will be the date on which the first 
subject is randomized to the study, and the end of the study will be the last subject’s last 
assessment.   
Planned number of subjects:  Approximately 566 subjects (including at least 30 subjects 
from East Asia) will be randomized in a 1:1 ratio to receive ABP 938 (Treatment Group A) or 
aflibercept (Treatment Group B).  The total sample size will provide approximately 90% power 
to demonstrate equivalence at a 2-sided significance level of 0.025 with an equivalence margin 
of (-3.9, 3.9) on the primary efficacy endpoint of BCVA change from baseline at week 8, 
assuming a true mean difference of 0 in the primary endpoint between the 2 groups, a 
standard deviation of 12.5 letters, and a 2% dropout by week 8.  In addition, the number of 
East Asian subjects (ie, at least 30) was chosen to enable an assessment of the treatment 
difference within East Asian subjects with reasonable accuracy and precision, while ensuring 
the study recruitment is feasible and can be completed in a timely manner.   
Target population: 
Both eyes will be assessed at the screening visit for eligibility, and only 1 eye will be selected 
from each subject as the study eye.  In case both eyes meet the eligibility criteria, the study 
eye will be the one with the worst BCVA.  All images will be sent to central imaging vendor for 
confirming eligibility. 
INCLUSION CRITERIA:  
1. Subjects or their legally authorized representative must sign an Institutional Review 
Board/Independent Ethics Committee approved informed consent form before any study-
specific procedures 
2. Men or women ≥ 50 years old 
3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by 
central imaging vendor before randomization) 
4. Active, treatment naïve subfoveal CNV lesions secondary to neovascular (wet) AMD 
including juxtafoveal lesions that affect the fovea as confirmed with SD-OCT, FA and/or FP 
in the study eye (confirmed by central imaging vendor before randomization) 
5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 
6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV 
in the study eye (confirmed by central imaging vendor before randomization) 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
Page 11 of 88 
Confidential 
7. Central retinal thickness of > 270 µm in the study eye as measured by the machine 
calculated average thickness in the ETDRS central 1 mm subfield (CST) by SD-OCT at 
screening (confirmed by central imaging vendor before randomization) 
EXCLUSION CRITERIA: 
Eye Related 
Subjects are excluded if they meet any of the following criteria in the study eye:
1. Total lesion size > 12 disc areas (30.5 mm2, including blood, scars, and neovascularization) 
in the study eye (confirmed by central imaging vendor before randomization) 
2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in 
the study eye (confirmed by central imaging vendor before randomization) 
3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by 
central imaging vendor before randomization) 
4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye 
(confirmed by central imaging vendor before randomization)
5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 
6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 
8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis 
syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye 
(confirmed by central imaging vendor before randomization with the exception of the 
refractive error and axial length which is to be assessed by the investigator) 
7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal 
laser photocoagulation) in the study eye 
8. History of retinal detachment in the study eye 
9. Any history of macular hole of stage 2 and above in the study eye 
10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant 
epiretinal membrane (confirmed by central imaging vendor before randomization) in the 
study eye
11. Any intraocular or periocular surgery within 3 months before randomization on the study 
eye, except lid surgery, which may not have taken place within 4 weeks before 
randomization, as long as it is unlikely to interfere with the injection 
12. Prior trabeculectomy or other filtration surgery in the study eye 
13. Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with 
antiglaucoma medication) in the study eye 
14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred 
as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 
15. Previous therapeutic radiation in the region of the study eye 
16. History of corneal transplant or corneal dystrophy in the study eye 
17. Significant media opacities, including cataract, which might interfere with visual acuity or 
assessment of safety, in the study eye 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
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18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye 
that, in the opinion of the investigator, requires planned medical or surgical intervention 
during the study or increases the risk to the subject beyond what is expected from standard 
procedures of intraocular injection, or which otherwise may interfere with the injection 
procedure or with evaluation of efficacy or safety 
Subjects are excluded if they meet any of the following criteria in either eye: 
19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any 
other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed 
by central imaging vendor before randomization) 
20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 
2 weeks before randomization  
21. Active scleritis or episcleritis or presence of scleromalacia  
Other Medical Conditions 
22. Active extraocular infection or history of extraocular infections as follows: 
a. any active infection for which systemic anti-infectives were used within 4 weeks before 
randomization  
b. recurrent or chronic infections or other active infection that, in the opinion of the 
investigator, might cause this study to be detrimental to the subject 
23. Acute coronary event or stroke within 3 months before randomization 
24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, 
hypertension, cardiovascular disease including moderate to severe heart failure (New York 
Heart Association class III/IV), renal disease, or liver disease  
25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or 
basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 
Washouts and Nonpermitted Treatments
26. Any prior ocular or systemic treatment, including another investigational product or surgery 
for neovascular (wet) AMD (including anti-vascular endothelial growth factor [VEGF] 
therapy) in the study eye, except dietary supplements or vitamins 
27. Any ocular or systemic treatment including another investigational product or surgery for 
neovascular (wet) AMD (including anti-VEGF therapy) in the fellow eye, within 30 days 
before randomization, except dietary supplements or vitamins  
28. Prior systemic anti-VEGF treatment as follows: 
a. Investigational or approved anti-VEGF therapy systemically within 3 months before 
randomization 
b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at 
any time 
29. Any IVT therapy, including adrenocorticotropic hormone, in the study or fellow eye, or 
intramuscular or intravenous corticosteroids within 4 weeks before randomization.  The use 
of long-acting steroids, either systemically or intraocularly, in the 3 months before 
randomization 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
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30. Currently receiving treatment with another investigational device or study drug, or less than 
30 days or 5 half-lives (whichever is longer) since ending treatment on another 
investigational device or drug study(ies).  Other investigational procedures while 
participating in this study are excluded 
General
31. For women:  pregnant or breast feeding, or planning to become pregnant while enrolled in 
the study and for 3 months after the last dose of investigational product 
32. Sexually active subjects and their partners who are of childbearing potential (ie, neither 
surgically sterile nor postmenopausal) and not agreeing to use adequate contraception (eg, 
true abstinence, sterilization, birth control pills, Depo Provera injections, contraceptive 
implants, or other effective methods) while on study and for 3 months after the last dose of 
study drug.  Male subjects must agree not to donate sperm during study and for 3 months 
following treatment with test article or until the scheduled end of the study (whichever is 
longer) 
33. Allergy or hypersensitivity to investigational product, to any of the excipients of ABP 938 or 
aflibercept, or to other study-related procedures/medications (eg, anesthesia, antiseptic, 
fluorescein dye) 
34. History or evidence of any other clinically significant disorder, condition, or disease (with 
the exception of those outlined above) that, in the opinion of the investigator or Amgen 
physician, if consulted, would pose a risk to subject safety or interfere with the study 
evaluation, procedures, or completion 
35. Subject likely to not be available to complete all protocol-required study visits or 
procedures, and/or to comply with all required study procedures (eg, Clinical Outcome 
Assessments) to the best of the subject and investigator’s knowledge  
Test product: 
Name: ABP 938 
Dose:  2 mg (0.05 mL) every 4 weeks for the first 3 doses, followed by 2 mg (0.05 mL) once 
every 8 weeks. 
Mode of administration: IVT injection 
Reference Product: 
Name: aflibercept  
Dose:  2 mg (0.05 mL) every 4 weeks for the first 3 doses, followed by 2 mg (0.05 mL) once 
every 8 weeks. 
Mode of administration: IVT injection 
Statistical methods:  The primary analysis of primary and secondary efficacy endpoints will 
be based on the Full Analysis Set (FAS), consisting of all randomized subjects, based on the 
treatment the subject is randomized to.   
The primary estimand is the difference in change from baseline in BCVA at week 8 
between the ABP 938 group and the aflibercept group in subjects with neovascular (wet) 
AMD who are randomized, regardless of missing or discontinuing investigational 
product administration to the study eye, or use of additional medications for AMD in the 
study eye prior to observing BCVA at week 8. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
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Clinical equivalence will be evaluated by comparing the 95% confidence interval (CI) of the 
treatment difference between ABP 938 and aflibercept in the primary endpoint, change from 
baseline in BCVA at week 8, with an equivalence margin of (-3.9, 3.9) letters.  The least 
squares (LS) mean difference between the 2 treatment groups and the corresponding 95% CI 
will be estimated using an analysis of covariance (ANCOVA) model for the week 8 BCVA 
change from baseline adjusted for region and baseline BCVA.  Consistency in treatment 
effects between the East Asian subjects and the overall population will be evaluated by 
descriptive summaries and/or graphical displays. 
The intercurrent events will be handled using a treatment policy strategy.  The value of 
BCVA at week 8 (if observed) will be used regardless of whether an intercurrent event 
occurs.  Missing BCVA value at week 8 is assumed to be missing completely at random 
(MCAR) for the primary analysis for the primary estimand based on observed data using 
the FAS.  Sensitivity analyses will be conducted to evaluate the robustness of the result 
to potential departure from the MCAR assumption. 
Secondary efficacy endpoints will be analyzed descriptively.  BCVA, CNV, and CST changes 
from baseline will be summarized by visit.  The LS mean differences and 95% CIs will be 
estimated using ANCOVA models similar to that used for the primary endpoint.  Generalized 
linear models with identity link will be utilized to obtain the point estimate and 95% CIs for 
treatment differences in proportions of subjects gaining ≥ 10 letters at week 8, maintaining 
vision at week 52, and gaining ≥ 15 letters at week 52.   
Sensitivity analyses will be performed on the primary and key secondary efficacy endpoints in 
the Per Protocol Analysis Set.  The Per Protocol Analysis Set is a subset of FAS, which 
includes subjects who have completed dosing at day 1 and week 4 and have completed BCVA 
assessment at week 8 without experiencing a protocol deviation that may affect their 
evaluation for the primary endpoint of the study. 
Safety will be assessed descriptively in the Safety Analysis Set, including all treated subjects 
who received at least 1 dose of investigational product.  Subject level safety data and safety 
data for the study eye will be summarized descriptively and separately for day 1 through 
week 8, day 1 through week 16, week 16 through the EOS visit, and day 1 through the EOS 
visit, based on actual treatment received in the study eye.  The summaries for day 1 through 
week 8 and day 1 through week 16 will be presented by treatment (ABP 938 vs. aflibercept).  
The summaries for week 16 through the EOS visit and day 1 through the EOS visit will be 
presented by treatment sequence (ABP 938/ABP 938 vs. aflibercept/aflibercept vs. 
aflibercept/ABP 938) for subjects who are re-randomized and treated post re-randomization.  
For the subset of subjects who also have the fellow eye treated with the investigational 
product, their safety data collected for the fellow eye from the first investigational product 
treatment of the fellow eye to the EOS visit will be summarized similarly, and summaries will be 
based on the actual treatment received in the fellow eye.  All reported adverse events will be 
assigned the system organ class and preferred term according to the Medical Dictionary for 
Regulatory Activities dictionary as of the time of analysis and graded by Common Terminology 
Criteria for Adverse Events version 4.03.  The number and percent of subjects reporting 
treatment-emergent adverse events (all, serious, and fatal) and EOIs will be tabulated.  
Laboratory data, vital signs, and ophthalmoscopic assessments will be summarized by visit.  
The number and percent of subjects developing ADAs will be tabulated by visit.   
Pharmacokinetic concentration data from the PK substudy will be summarized descriptively by 
visit for the PK Analysis Set, consisting of subjects in the PK substudy who receive at least 
1 dose of investigational product between day 1 and week 8 (inclusive) and who have at least 
1 reported serum concentration of ABP 938 or aflibercept. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
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Statistical hypothesis:  ABP 938 is equivalent to aflibercept in the treatment of neovascular 
(wet) AMD.
Protocol version and date: Version 4.0, 16 May 2022


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
 
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Figure 1 
Study Schematic 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
 
Page 17 of 88
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Table 1 
Schedule of Activities 
Screening
Baseline
Week 
( 3 days) 
Week 
( 5 days)
End of Studyl
( 5 days)
day 1 (week 0) 
4 
8 
16l
24 
32 
40 
48 
52 
Clinical Assessments 
Informed Consent 
X 
Medical/treatment history 
X 
Physical examination 
X 
X 
X 
   Height and weight 
X 
Vital signs 
X 
X 
X 
X 
X 
ECG 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
Xa
X 
X 
X 
X 
X 
X 
X 
X 
X 
Treatment 
Randomization 
X 
X 
ABP 938/afliberceptb
X 
X 
X 
X 
X 
X 
X 
X 
Disease Assessment 
Indirect ophthalmoscopyc,d
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Slit-lampd,e
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IOPd,f
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BCVA using ETDRS chart 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fluorescein angiography (FA) 
X 
X 
X 
X 
X 
Fundus Photography (FP) 
X 
X 
X 
X 
X 
Spectral domain optical coherence tomography 
(SD-OCT) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
Serum chemistry 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
PT, aPTT, and INR 
X 
PK samples (substudy subjects only)g 
Xh
Xi
Anti-drug antibodiesj
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
Pregnancyk
X 
X 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 4.0, 16 May 2022
 
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ADA = antidrug antibody; BCVA = best corrected visual acuity; ECG = electrocardiogram; ETDRS = Early Treatment Diabetic Retinopathy 
Study; INR = international normalized ratio; IOP = intraocular pressure; PK = pharmacokinetics; PT = prothrombin time; aPTT = activated 
partial thromboplastin time 
a 
Only serious adverse events are reported during the screening period. 
b 
ABP 938/aflibercept will be administered after all other procedures are completed for each visit (except for postdose slit-lamp 
examination and postdose IOP), ensuring that the study eye is administered first, then the fellow eye.  If the subject presents with an 
infection at the dosing visit(s), the administration of investigational product may be delayed (up to 3 days for weeks 4 and 8, and up to 
5 days for doses thereafter).  In the case of delayed or missed dose for any reason, subsequent doses should be administered according 
to the original schedule (ie, at the planned timepoint relative to first dose). 
c 
Examination of the retina of the study eye to be performed with pupil dilation.  Predose on treatment days. 
d 
Procedure will be performed for the fellow eye on the day of investigational product administration to the fellow eye, including the EOS 
visit (if the fellow eye is dosed). 
e 
Predose (on the day of injection) and postdose (within 60 minutes) slit-lamp examination to be performed with pupil dilation on treatment 
days.  Single, postdilation examination on other days. 
f 
IOP should be measured predose (on the day of injection) and postinjection (at minimum 15 minutes and no longer than 60 minutes) on 
treatment days.  Single examination on other days. 
g
For subjects who have consented for the PK substudy only:  approximately 32 subjects who have consented for the PK sub study will 
have PK samples collected at the timepoints noted.  If it is anticipated that the fellow eye will need to be treated prior to the week 
8postdose PK sample, then the subject should not be enrolled into the PK substudy.  If an enrolled PK substudy subject develops a need
for treatment of the fellow eye prior to the week 8 postdose PK sample, no further PK samples will be collected.  If the need for treating 
the fellow eye is identified at the week 8 visit, then the fellow eye must be treated after the week 8 postdose PK sample has been drawn 
for those subjects included in the PK substudy.
h 
This measurement will be taken predose (within 60 minutes before day 1 dose) and postdose (approximately 24 hours after the day 1 
dose), with an allowable window of: -6 hours to +24 hours (ie, 18 hours to 48 hours after day 1 dose). 
i 
PK sample collection window 1 day after week 8 dose:  -6 hours to +24 hours (ie, 18 hours to 48 hours after week 8 dose).  Details will be 
provided in an Investigator Laboratory Manual.   
j 
ADA samples should be taken within 3 hours prior to administration of investigational product into either eye at the study visits noted in 
schedule above.  Details will be provided in an Investigator Laboratory Manual. 
k 
Required for females of childbearing potential.  Serum pregnancy test will be done at screening by the central laboratory.  A urine 
pregnancy test will be performed locally.  Additional local urine pregnancy tests should be done as per local requirements as needed. 
l 
Subjects who are unable to complete the week 16 visit within the visit window will not be re-randomized and will be discontinued from the 
study.  For subjects who discontinue from the study or terminate study early, perform all the end-of-study procedures scheduled for 
week 52 within 28 days from determining that the subject will discontinue from the study.  


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ..................................................................................... 1
PROTOCOL SIGNATURE PAGE – SPONSOR ............................................................. 2
PROTOCOL SIGNATURE PAGE – CONTRACT RESEARCH ORGANIZATION 
(CRO)....................................................................................................................... 3
PROTOCOL SIGNATURE PAGE – INVESTIGATOR ..................................................... 4
SERIOUS ADVERSE EVENT CONTACT INFORMATION ............................................. 6
PROTOCOL AMENDMENT 3 (16 MAY 2022) ................................................................ 7
PROTOCOL SUMMARY ................................................................................................ 8
TABLE OF CONTENTS ................................................................................................ 19
LIST OF TABLES ......................................................................................................... 22
LIST OF FIGURES ....................................................................................................... 22
LIST OF ABBREVIATIONS .......................................................................................... 23
1
INTRODUCTION AND RATIONALE ..................................................................... 25
1.1
Background...................................................................................................... 25
1.1.1
Amgen Investigational Product ABP 938 Background ............................ 25
1.1.2
Non-Amgen Investigational Product Aflibercept ..................................... 26
1.2
Study Rationale ............................................................................................... 27
1.3
Benefit/Risk Assessment ................................................................................ 28
2
STUDY OBJECTIVES, ENDPOINTS, AND ESTIMAND ........................................ 29
3
STUDY PLAN ........................................................................................................ 30
3.1
Overall Study Design and Plan ....................................................................... 30
3.2
Discussion of Study Design ........................................................................... 31
3.3
End of Study .................................................................................................... 32
3.3.1
End-of-Study Definition ............................................................................. 32
3.3.2
Study Duration for Subjects ...................................................................... 32
4
STUDY POPULATION ........................................................................................... 32
4.1
Inclusion Criteria ............................................................................................. 32
4.2
Exclusion Criteria ............................................................................................ 33
4.3
Subject Enrollment .......................................................................................... 37
4.4
Screen Failures ................................................................................................ 38
4.5
Premature Discontinuation ............................................................................. 38
4.5.1
Premature Discontinuation of Investigational Product ........................... 38
4.5.2
Premature Discontinuation from the Study ............................................. 39
4.5.3
Lost to Follow-up ....................................................................................... 40
5
DESCRIPTION OF STUDY ASSESSMENTS ........................................................ 41
5.1
Demographics and Other Screening Assessments ...................................... 41
5.1.1
Informed Consent ...................................................................................... 41
5.1.2
Medical History .......................................................................................... 41
5.1.3
Demographics ............................................................................................ 41
5.1.4
Disease-Specific Medical History ............................................................. 41
5.2
Efficacy Assessments ..................................................................................... 42
5.2.1
Best Corrected Visual Acuity .................................................................... 42
5.2.2
Fluorescein Angiography .......................................................................... 42
5.2.3
Spectral Domain Optical Coherence Tomography .................................. 42
5.2.4
Fundus photography ................................................................................. 43


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Protocol Number: 20170542 
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5.3
Safety Assessments ........................................................................................ 43
5.3.1
Adverse Events .......................................................................................... 43
5.3.2
Clinical Laboratory Evaluations ................................................................ 43
5.3.3
Slit-Lamp Examination .............................................................................. 44
5.3.4
Indirect Ophthalmoscopy .......................................................................... 44
5.3.5
Intraocular Pressure .................................................................................. 45
5.3.6
Pregnancy .................................................................................................. 45
5.3.7
12-lead Electrocardiogram ........................................................................ 46
5.3.8
Vital Signs .................................................................................................. 46
5.3.9
Physical Examination ................................................................................ 46
5.4
Pharmacokinetics ............................................................................................ 47
5.5
Antidrug Antibodies ........................................................................................ 47
6
TREATMENTS ....................................................................................................... 48
6.1
Investigational Product(s) ............................................................................... 48
6.1.1
Description of Investigational Product(s) ................................................ 48
6.1.2
Preparation, Handling, and Storage ......................................................... 48
6.1.3
Packaging, Labeling, and Shipment ......................................................... 48
6.1.4
Product Complaints ................................................................................... 49
6.1.5
Excluded Treatments, Medical Devices, and/or Procedures During 
Study Period ............................................................................................... 49
6.2
Masking ............................................................................................................ 49
6.3
Method of Assigning Treatment ..................................................................... 50
6.4
Dose and Administration ................................................................................ 51
6.4.1
Dose Modification ...................................................................................... 51
6.4.2
Intervention After the End of the Study .................................................... 51
6.5
Treatment of the Fellow Eye ........................................................................... 52
6.6
Precautions and/or Lifestyle Considerations ................................................ 52
6.6.1
Coronavirus Disease 2019 Considerations .............................................. 53
6.7
Prior and Concomitant Therapy ..................................................................... 53
6.7.1
Prior Treatment .......................................................................................... 53
6.7.2
Concomitant Treatments (Medications and Therapies) .......................... 53
6.7.3
Prohibited Concomitant Medications ....................................................... 53
6.7.4
Other Concomitant Medications and Treatments .................................... 53
6.8
Compliance ...................................................................................................... 54
6.9
Accountability .................................................................................................. 54
7
ADVERSE EVENTS ............................................................................................... 55
7.1
Definitions ........................................................................................................ 55
7.1.1
Adverse Events .......................................................................................... 55
7.1.1.1
Events Meeting the Adverse Event Definition .................................... 55
7.1.1.2
Events NOT Meeting the Adverse Event Definition ........................... 56
7.1.2
Serious Adverse Events ............................................................................ 56
7.1.3
Clinical Laboratory Abnormalities and Other Abnormal Assessments . 58
7.1.4
Events of Interest ....................................................................................... 58
7.2
Assessment of Adverse Events ...................................................................... 58
7.2.1
Severity ....................................................................................................... 58
7.2.2
Causality ..................................................................................................... 59
7.3
Documenting and Reporting Adverse Events ............................................... 59


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7.4
Reporting of Serious Adverse Events ............................................................ 61
7.4.1
Regulatory Reporting Requirements for Serious Adverse Events ......... 62
7.5
Reporting of Serious Adverse Event After the Protocol-required 
Reporting Period ............................................................................................. 62
7.6
Method of Detecting Adverse Events and Serious Adverse Events ............ 63
7.7
Adverse Event and Serious Adverse Event Follow-up ................................. 63
8
STATISTICS .......................................................................................................... 64
8.1
General Procedures ......................................................................................... 64
8.2
Analysis Populations ...................................................................................... 64
8.3
Sample Size...................................................................................................... 65
8.4
Planned Analyses ............................................................................................ 65
8.5
Statistical Methods .......................................................................................... 66
8.5.1
Primary Endpoint/Estimand ...................................................................... 66
8.5.2
Secondary Endpoint(s) .............................................................................. 66
8.5.3
Safety Endpoint(s) ..................................................................................... 67
8.5.4
Demographic and Baseline Characteristics ............................................. 68
8.5.5
Exposure to Investigational Product ........................................................ 68
8.5.6
Exposure to Concomitant Medications .................................................... 68
8.5.7
Pharmacokinetic Endpoints ...................................................................... 68
8.5.8
Immunogenicity Endpoints ....................................................................... 68
8.5.9
Subgroup Analyses and Covariates ......................................................... 69
8.5.10
Handling of Missing Values....................................................................... 69
9
ETHICS AND RESPONSIBILITIES ....................................................................... 69
9.1
Good Clinical Practice ..................................................................................... 69
9.2
Institutional Review Board/Independent Ethics Committee ......................... 70
9.3
Informed Consent ............................................................................................ 71
9.4
Data Monitoring Committee ............................................................................ 72
9.5
Financing and Insurance ................................................................................. 73
9.5.1
Contractual and Financial Details ............................................................. 73
9.5.2
Insurance, Indemnity, and Compensation ............................................... 73
9.5.3
Financial Disclosure .................................................................................. 73
10
RECORDS MANAGEMENT .................................................................................. 73
10.1
Source Documentation.................................................................................... 75
10.2
Case Report Form Completion and Data Management ................................. 75
10.3
Study Files and Record Retention .................................................................. 76
11
AUDITING AND MONITORING ............................................................................. 76
11.1
Risk and Quality Tolerance Limits ................................................................. 77
11.2
Protocol Adherence and Deviations............................................................... 77
12
AMENDMENTS ..................................................................................................... 78
13
STUDY REPORT AND PUBLICATIONS ............................................................... 79
14
STUDY START AND TERMINATION .................................................................... 80
15
CONFIDENTIALITY ............................................................................................... 80
16
REFERENCES ....................................................................................................... 81
17
APPENDICES ........................................................................................................ 83
17.1
Appendix I – Study Administrative Structure ................................................ 83
17.2
Appendix II - Contraceptive Guidance and Collection of Pregnancy and 
Lactation Information ...................................................................................... 84


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
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LIST OF TABLES 
Table 1
Schedule of Activities .......................................................................... 17
Table 2
Investigational Product (ABP 938) ...................................................... 48
Table 3
Reference Product (Aflibercept) ......................................................... 48
LIST OF FIGURES 
Figure 1
Study Schematic .................................................................................. 16


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
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LIST OF ABBREVIATIONS 
ADA 
antidrug antibody 
ADR 
adverse drug reactions 
AMD 
age-related macular degeneration 
ANCOVA 
analysis of covariance 
aPTT 
activated partial thromboplastin time 
BCVA 
best corrected visual acuity 
CFR 
Code of Federal Regulations 
CI  
confidence interval 
CNV 
choroidal neovascularization 
COVID-19 
coronavirus disease 2019 
CRF 
case report form  
CRO 
contract research organization 
CRT 
central retinal thickness 
CSR 
clinical study report 
CST 
central subfield thickness 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMC 
data monitoring committee 
DME 
diabetic macular edema 
DR 
diabetic retinopathy 
ECG 
electrocardiogram 
EDC 
electronic data capture 
EOI 
event of interest 
EOS 
end-of-study 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FA 
fluorescein angiography 
FAS 
Full Analysis Set 
Fc 
fragment crystallizable 
FDA 
Food and Drug Administration 
FP 
Fundus Photography 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practices 


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HIPAA 
Health Insurance Portability and Accountability Act 
HRT 
hormonal replacement therapy 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonisation  
IEC 
independent ethics committee 
IOP 
intraocular pressure 
IRB 
institutional review board 
IVT 
intravitreal 
IXRS 
Interactive Web/Voice Response System 
LS 
least squares 
MCAR 
missing completely at random 
OCT 
optical coherence tomography 
PK 
pharmacokinetic(s) 
PlGF 
placental growth factor 
PT 
prothrombin time  
QTL 
quality tolerance limit 
RVO 
retinal vein occlusion 
SAP 
Statistical Analysis Plan 
SD-OCT 
spectral domain optical coherence tomography 
TMF 
trial master file 
VEGF 
vascular endothelial growth factor 
VEGFR 
vascular endothelial growth factor receptor 
WBC 
white blood cell 
YAG 
yttrium aluminum garnet 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
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1 
Introduction and Rationale 
1.1 
Background 
Age-related macular degeneration (AMD) is the leading cause of irreversible central vision 
loss and blindness in individuals older than 50 years in developed countries (1).  It is 
generally painless and leads to the gradual impairment of vision, but it can sometimes cause 
a rapid reduction in vision.  The prevalence of AMD is higher among white individuals and 
increases with age.  Prevalence is approximately 1% among white individuals in their 50s 
and increases to 15% among those in their 80s (2). 
AMD is a disease spectrum with early and later stages and can be divided into 2 categories.  
The non-neovascular (‘dry’) AMD is the most common form and accounts for about 80% of 
AMD cases.  The most severe vision loss occurs in the neovascular (or wet) form of AMD, 
and it is responsible for nearly 90% of the severe central visual acuity loss from neovascular 
(wet) AMD (2).  Early treatments, such as laser ablation (3) and photodynamic therapy with 
verteporfin (4), slowed severe vision loss but rarely resulted in stabilization or improvement.  
Neovascular (wet) AMD appears to be driven by choroidal neovascularization (CNV), which 
results in retinal swelling and edema (5), and the vesicular abnormality is regulated by 
vascular endothelial growth factor (VEGF).  Inhibition of VEGF can lead to visual 
improvement, and intravitreal (IVT) anti-VEGF therapy is the current gold standard for 
treatment.  The current primary treatments for neovascular (wet) AMD are a humanized, 
monoclonal, anti-VEGF antibody antigen binding fragment (FAB), ranibizumab (Lucentis®) 
and a recombinant, high-affinity human VEGF receptor (VEGFR), aflibercept (Eylea®).  
1.1.1 
Amgen Investigational Product ABP 938 Background 
Amgen is developing ABP 938 as a biosimilar candidate to Eylea® (aflibercept).  In the US, 
aflibercept is approved for IVT administration in the treatment of neovascular (wet) AMD, 
macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), and 
diabetic retinopathy (DR) in patients with DME (6).  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 CNV (7).   


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ABP 938 has the same amino acid sequence, dosage form, route of administration, and 
product strength as aflibercept, but it will have a different formulation containing compendial 
excipients at final drug product concentrations approved for IVT administration. 
ABP 938 and aflibercept belong to the pharmacologic class of VEGF inhibitors.  Like 
aflibercept, ABP 938 is a recombinant fusion protein consisting of portions of human 
VEGFRs 1 and 2 extracellular domains fused to the fragment crystallizable (Fc) portion of 
human immunoglobulin isotype class G subclass 1 monoclonal antibody.  ABP 938 and 
aflibercept are produced by recombinant DNA technology in mammalian Chinese hamster 
ovary cell expression systems and purified by processes that include specific viral 
inactivation and filtration steps.  The mechanism of action across indications involves the 
protein molecule acting as a soluble decoy receptor that binds VEGF type A (VEGF-A) and 
placental growth factor (PlGF), and to a lesser extent VEGF type B (VEGF-B), with higher 
affinity than their native receptors, and thereby inhibits binding and activation of VEGFR-1 
and VEGFR-2.   
The totality of evidence available to date from an ongoing analytical program suggests that 
ABP 938 is analytically similar to aflibercept with respect to identity, general properties, 
primary and higher order structure, carbohydrate structure, purity and impurity profile, and 
biological activity.   
A detailed description of the chemical and nonclinical data of ABP 938 is provided in the 
Investigator’s Brochure (IB). 
ABP 938 has not been tested in humans to date.  Based on the demonstration of analytical 
and nonclinical similarity of ABP 938 and aflibercept, the clinical efficacy and safety 
information for aflibercept as described in the product labeling for Eylea® (Eylea® USPI [6], 
Eylea® SmPC [7]) are considered relevant to predicting the effects of ABP 938 in humans 
(Section 1.1.2).   
1.1.2 
Non-Amgen Investigational Product Aflibercept 
As described above for ABP 938, aflibercept acts as a soluble decoy receptor that binds 
VEGF-A and PlGF, and to a lesser extent VEGF-B, with higher affinity than their native 
receptors, and thereby inhibits binding and activation of VEGFR-1 and VEGFR-2 (6). 


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Systemic drug exposure following IVT administration of aflibercept is negligible. In patients 
with neovascular (wet) AMD, following IVT administration of aflibercept at 2 mg per eye, the 
free aflibercept plasma concentrations were undetectable 2 weeks post-dosing in all 
patients.  After a 2 mg aflibercept IVT administration to patients, the mean peak 
concentration of free aflibercept is more than 100-fold lower than the concentration of 
aflibercept required to half maximally bind systemic VEGF.  Consistent with this, no 
systemic effects (eg, changes in blood pressure) were observed after IVT aflibercept 
administration to patients (6,8,9).   
When aflibercept was administered to subjects with neovascular (wet) AMD in clinical 
studies, anatomic measures of disease activity improved similarly in all treatment groups 
from baseline to week 52; when administered to subjects with RVO and DME, reductions in 
mean retinal thickness were observed at week 24 compared to baseline and at weeks 52 
and 100 compared to baseline, respectively (6).   
Adverse events reflected in the warnings and precautions section of the product labeling for 
aflibercept that may be serious include endophthalmitis and retinal detachment, increase in 
intraocular pressure (IOP), potential for immunogenicity, arterial thromboembolic events 
(including nonfatal stroke, nonfatal myocardial infarction, or vascular death [including deaths 
of unknown cause]), traumatic cataract, cataract, vitreous haemorrhage, vitreous 
detachment, intraocular inflammation, hypersensitivity, conjunctival hemorrhage, visual 
acuity reduced, eye pain, and vitreous floaters (6,7).   
1.2 
Study Rationale 
In the US, EU, and much of the world, laws, regulations, and guidance have been put in 
place to increase availability of biological treatments by developing and licensing biosimilar 
products (10,11,12,13,14).  A biosimilar product, generally, is highly similar to a licensed 
biologic reference product, and there are no clinically meaningful differences between the 
biosimilar and reference products in terms of safety, purity, and potency.  Biosimilarity is 
demonstrated by the totality of the evidence, including analytical, nonclinical, and clinical 
evidence.  The analytical similarity of ABP 938 and aflibercept is summarized in more detail 
in the IB. 


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Given the biochemical and nonclinical similarity of ABP 938 to aflibercept, a human study to 
fully establish biosimilarity is warranted.  Because pharmacokinetic (PK) exposure following 
IVT administration is negligible and not informative as a demonstration of similarity, a PK 
similarity study will not be performed, but a PK substudy of the current study will be 
performed to assess the similar minimal systemic exposure of ABP 938 and aflibercept, and 
thereby support a demonstration of no clinically meaningful differences between ABP 938 
and aflibercept. 
The current study is designed to demonstrate the clinical similarity between ABP 938 and 
aflibercept in terms of efficacy, safety, and immunogenicity for subjects with neovascular 
(wet) AMD (10,11,12,13,14).  In addition, subjects will be recruited in East Asia to assess 
consistency of results between the East Asian subgroup and the overall study population. 
1.3 
Benefit/Risk Assessment 
ABP 938 is expected to be biosimilar to aflibercept.  The risks and benefits of ABP 938 are 
therefore expected to be the same as those of aflibercept, as specified in the product 
labeling and summarized in Section 1.1.2.  All subjects in this study will receive an active 
treatment.   
More detailed information about the expected benefits, risks, and reasonably expected 
adverse events of ABP 938 can be found in the IB. 
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 neovascular (wet) AMD. 
A risk assessment will be performed on an ongoing basis to evaluate the potential impact of 
coronavirus disease 2019 (COVID-19) on subjects.  Risk mitigation measures, including 
COVID-19 related precautions and procedures (including severe acute respiratory syndrome 
coronavirus 2 [SARS-CoV-2] testing/screening) will be implemented based on the prevailing 
situation during study conduct, at the investigator’s discretion and in accordance with local 
and institutional guidelines, as applicable. 


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2 
Study Objectives, Endpoints, and Estimand 
Objectives 
Endpoints 
Primary 
Primary efficacy endpoint 
To assess the efficacy of ABP 938 compared 
to aflibercept. 
Change from baseline in best corrected visual 
acuity (BCVA) as measured by Early 
Treatment Diabetic Retinopathy Study 
(ETDRS) letter score at week 8 
Secondary efficacy endpoints 
Proportion of subjects who maintained vision 
at week 52, where a subject was classified as 
maintaining vision if he/she lost fewer than 
15 letters in ETDRS letter score compared to 
baseline  
Change from baseline in BCVA as measured 
by ETDRS letter score over the study duration 
Proportion of subjects who gained at least 
10 letters of vision at week 8 and proportion of 
subjects who gained at least 15 letters of 
vision at week 52 as compared to baseline 
Change from baseline in CNV area as 
measured by fluorescein angiography (FA) 
and central subfield thickness (CST) as 
measured by spectral domain optical 
coherence tomography (SD-OCT) over the 
study duration   
Secondary 
To assess the safety and immunogenicity of 
ABP 938 compared to aflibercept. 
Treatment-emergent adverse events, adverse 
events of interest (EOIs), and serious adverse 
events 
Incidence of antidrug antibodies (ADAs) 
Primary estimand: 
The primary estimand is the difference in change from baseline in BCVA at week 8 
between the ABP 938 group and the aflibercept group in subjects with neovascular 
(wet) AMD who are randomized, regardless of missing or discontinuing 
investigational product administration to the study eye, or use of additional 
medications for AMD in the study eye prior to observing BCVA at week 8. 


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3 
Study Plan 
3.1 
Overall Study Design and Plan 
This is a randomized, double-masked, active controlled multiregional clinical study in adult 
subjects with neovascular (wet) AMD.  Approximately 566 subjects (including at least 
30 subjects from East Asia) will be randomized in a masked 1:1 ratio to receive 2 mg 
(0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) 
administered by IVT injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, 
and week 8).  Randomization will be stratified by geographic region and disease severity 
(baseline BCVA < 64 letters vs. ≥ 64 letters). 
At week 8, subjects will be assessed for the primary endpoint (BCVA change from baseline 
as measured by ETDRS).  Subjects will then be re-randomized at week 16 in a masked 
fashion such that: 
 
Subjects initially randomized to ABP 938 (Treatment Group A) will continue to receive 
ABP 938 by IVT injection every 8 weeks from week 16 until week 48 
 
Subjects initially randomized to aflibercept (Treatment Group B) will be re-randomized in 
a 1:1 ratio to either continue on aflibercept (Treatment Group B1) or transition to 
ABP 938 (Treatment Group B2) by IVT injection every 8 weeks from week 16 until 
week 48 
Re-randomization will be stratified using the same factors as the initial randomization.   
Subjects who are unable to complete the week 16 visit within the visit window will not be 
re-randomized, will be discontinued from the study, and will be asked to return to complete 
an end-of-study (EOS) visit within 28 days from determining that the subject will discontinue 
from the study.  An EOS visit will be conducted at week 52 for subjects that complete the 
study.  The study design and treatment schema are presented in Figure 1.  
The primary analysis for the study is planned when all subjects reach week 24 or terminate 
early.  This analysis will comprise at least 24 weeks of efficacy, safety, and immunogenicity 
data.  The final analysis is planned when all enrolled subjects complete the week 52 visit or 
terminate early.  An external, independent data monitoring committee (DMC) will evaluate 
the safety data throughout the study. 


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For subjects receiving neovascular (wet) AMD treatment in the fellow eye during the study, 
sites must request an additional box of investigational product.  Refer to Section 6.5.  
Approximately 32 subjects will be consented and enrolled into a PK substudy.  These 
subjects will have a PK sample collected predose (within 60 minutes before day 1 dose) and 
postdose (approximately 24 hours after day 1 dose), with an allowable window -6 hours to 
+24 hours (ie, 18 hours to 48 hours after day 1 dose) and postdose at week 8 
(approximately 24 hours after week 8 dose), with an allowable time window of -6 hours to 
+24 hours (ie, 18 hours to 48 hours postdose). 
If it is anticipated that the fellow eye will need to be treated prior to the week 8 postdose PK 
sample, then the subject should not be enrolled into the PK substudy.  If an enrolled PK 
substudy subject develops a requirement for fellow eye treatment prior to week 8 postdose 
PK sample, no further PK samples will be collected.  
If the need for treating the fellow eye is identified at the week 8 visit, then the fellow eye 
must be treated after the week 8 postdose PK sample has been drawn for those subjects 
included in the PK substudy.  
3.2 
Discussion of Study Design 
This study is randomized and double-masked to prevent bias in treatment allocation and in 
the subjective assessment of effect.  The re-randomization at week 16 will allow a masked 
evaluation of the effects of a single transition from aflibercept to ABP 938. 
All subjects will receive active treatment in accordance with the approved aflibercept product 
labeling.  The population is selected to be sensitive enough to detect any clinical differences 
between ABP 938 and aflibercept.  The efficacy measures were selected to make a 
meaningful comparison of the effects and are similar to those in the aflibercept product 
labeling.  The safety measures are standard and well understood and include 
ophthalmologic assessments and the assessment of ADAs, as this is protein product. 


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3.3 
End of Study 
3.3.1 
End-of-Study Definition 
If the study concludes prior to the primary completion date originally planned in the protocol 
(ie, early termination of the study), then the primary completion will be the date when the last 
subject is assessed or receives an intervention for evaluation in the study (ie, last subject 
last visit). 
In this study, the primary endpoint is assessed at week 8, and subjects will remain on 
treatment for up to 48 weeks for assessment of safety and secondary endpoints.  The 
primary completion date will be the date when the last subject is assessed for week 8 visit or 
terminates early.  The primary analysis will be performed when all subjects reach week 24 
or terminate early.  The final analysis will be performed when all subjects complete the 
week 52 visit or terminate early. 
End of Study:  The EOS date is defined as the date when the last subject across all centers 
is assessed or receives an intervention for evaluation in the study (ie, last subject last visit). 
3.3.2 
Study Duration for Subjects 
The study consists of a screening period of up to 4 weeks, a treatment period of 48 weeks, 
followed by a safety follow-up period through week 52, for a total study duration of up to 
56 weeks.   
4 
Study Population 
Both eyes will be assessed at the screening visit for eligibility, and only 1 eye will be 
selected from each subject as the study eye.  In case both eyes meet the eligibility criteria, 
the study eye will be the one with the worst BCVA.  All images will be sent to central imaging 
vendor for confirming eligibility. 
4.1 
Inclusion Criteria 
The following inclusion criteria must be met for a subject to be eligible for inclusion in the 
study: 


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1. Subjects or their legally authorized representative must sign an Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) 
before any study-specific procedures 
2. Men or women ≥ 50 years old 
3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by 
central imaging vendor before randomization)  
4. Active, treatment naïve subfoveal CNV lesions secondary to neovascular (wet) AMD 
including juxtafoveal lesions that affect the fovea as confirmed with SD-OCT, FA and/or
FP in the study eye (confirmed by central imaging vendor before randomization) 
5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 
6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active 
CNV in the study eye (confirmed by central imaging vendor before randomization) 
7. Central retinal thickness (CRT) of > 270 µm in the study eye as measured by the 
machine, calculated average thickness in the ETDRS central 1 mm subfield (CST) by 
SD-OCT at screening (confirmed by central imaging vendor before randomization) 
4.2 
Exclusion Criteria 
A subject who meets any of the following exclusion criteria will not be eligible for inclusion in 
the study: 
EYE RELATED 
Subjects are excluded if they meet any of the following criteria in the study eye: 
1. Total lesion size > 12 disc areas (30.5 mm2, including blood, scars, and 
neovascularization) in the study eye (confirmed by central imaging vendor before 
randomization) 
2.  Active CNV area (classic plus occult components) that is < 50% of the total lesion area 
in the study eye (confirmed by central imaging vendor before randomization) 
3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by 
central imaging vendor before randomization) 


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4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye 
(confirmed by central imaging vendor before randomization) 
5. History of any vitreous hemorrhage within 4 weeks before randomization in the study 
eye 
6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 
8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis 
syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye 
(confirmed by central imaging vendor before randomization with the exception of the 
refractive error and axial length which is to be assessed by the investigator) 
7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal 
laser photocoagulation) in the study eye 
8. History of retinal detachment in the study eye 
9. Any history of macular hole of stage 2 and above in the study eye 
10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant 
epiretinal membrane (confirmed by central imaging vendor before randomization) in the 
study eye 
11. Any intraocular or periocular surgery within 3 months before randomization on the study 
eye, except lid surgery, which may not have taken place within 4 weeks before 
randomization, as long as it is unlikely to interfere with the injection 
12. Prior trabeculectomy or other filtration surgery in the study eye 
13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite 
treatment with antiglaucoma medication) in the study eye 
14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred 
as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 
15. Previous therapeutic radiation in the region of the study eye 
16. History of corneal transplant or corneal dystrophy in the study eye 


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17. Significant media opacities, including cataract, which might interfere with visual acuity or 
assessment of safety, in the study eye 
18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye 
that, in the opinion of the investigator, requires planned medical or surgical intervention 
during the study or increases the risk to the subject beyond what is expected from 
standard procedures of intraocular injection, or which otherwise may interfere with the 
injection procedure or with evaluation of efficacy or safety 
Subjects are excluded if they meet any of the following criteria in either eye: 
19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or 
any other vascular disease affecting the retina, other than neovascular (wet) AMD 
(confirmed by central imaging vendor before randomization) 
20. Active intraocular inflammation or active or suspected ocular or periocular infection, 
within 2 weeks before randomization  
21. Active scleritis or episcleritis or presence of scleromalacia  
Other Medical Conditions 
22. Active extraocular infection or history of extraocular infections as follows: 
a. any active infection for which systemic anti-infectives were used within 4 weeks 
before randomization  
b. recurrent or chronic infections or other active infection that, in the opinion of the 
investigator, might cause this study to be detrimental to the subject 
23. Acute coronary event or stroke within 3 months before randomization 
24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, 
hypertension, cardiovascular disease including moderate to severe heart failure (New 
York Heart Association class III/IV), renal disease, or liver disease  
25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous 
or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 


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Washouts and Nonpermitted Treatments
26. Any prior ocular or systemic treatment, including another investigational product or 
surgery for neovascular (wet) AMD (including anti-vascular endothelial growth factor 
[VEGF] therapy) in the study eye, except dietary supplements or vitamins 
27. Any ocular or systemic treatment including another investigational product or surgery for 
neovascular (wet) AMD (including anti-VEGF therapy) in the fellow eye, within 30 days 
before randomization, except dietary supplements or vitamins  
28. Prior systemic anti-VEGF treatment as follows: 
a. Investigational or approved anti-VEGF therapy systemically within 3 months before 
randomization 
b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at 
any time 
29. Any IVT therapy, including adrenocorticotropic hormone, in the study or fellow eye, or 
intramuscular or intravenous corticosteroids within 4 weeks before randomization.  The 
use of long-acting steroids, either systemically or intraocularly, in the 3 months before 
randomization 
30. Currently receiving treatment with another investigational device or study drug, or less 
than 30 days or 5 half-lives (whichever is longer) since ending treatment on another 
investigational device or drug study(ies).  Other investigational procedures while 
participating in this study are excluded 
General
31. For women:  pregnant or breast feeding, or planning to become pregnant while enrolled 
in the study and for 3 months after the last dose of investigational product 
32. Sexually active subjects and their partners who are of childbearing potential (ie, neither 
surgically sterile nor postmenopausal) and not agreeing to use adequate contraception 
(eg, true abstinence, sterilization, birth control pills, Depo Provera injections, 
contraceptive implants, or other effective methods) while on study and for 3 months after 
the last dose of study drug.  Male subjects must agree not to donate sperm during study 


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and for 3 months following treatment with test article or until the scheduled end of the 
study (whichever is longer) 
33. Allergy or hypersensitivity to investigational product, to any of the excipients of ABP 938 
or aflibercept, or to other study-related procedures/medications (eg, anesthesia, 
antiseptic, fluorescein dye) 
34. History or evidence of any other clinically significant disorder, condition, or disease (with 
the exception of those outlined above) that, in the opinion of the investigator or Amgen 
physician, if consulted, would pose a risk to subject safety or interfere with the study 
evaluation, procedures, or completion 
35. Subject likely to not be available to complete all protocol-required study visits or 
procedures, and/or to comply with all required study procedures (eg, Clinical Outcome 
Assessments) to the best of the subject and investigator’s knowledge  
4.3 
Subject Enrollment 
Before subjects begin participation in any study-specific activities/procedures, Amgen 
requires a copy of the site’s written IRB/IEC approval of the protocol, ICF, and all other 
subject information and/or recruitment material. 
The subject or his/her legally authorized representative must personally sign and date the 
IRB/IEC and Amgen approved ICF before commencement of study specific procedures. 
A subject is considered enrolled when the investigator decides that the subject has met all 
eligibility criteria and has been randomized in the Interactive Web/Voice Response System 
(IXRS).  The investigator is to document this eligibility decision and date in the subject’s 
medical record. 
Each subject will have a unique subject identification number obtained from the IXRS.  This 
will be assigned at the screening visit.  The unique 11-digit subject identification will be 
assigned in sequential order for each site in the format “542XXXXX###,” where 
“542XXXXX” refers to the site number and “###” refers to the sequential subject ordering as 
each subject at a site is entered into the IXRS (eg, 54212345001).  This 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 investigator will keep a record (the subject 


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screening log) that includes limited information (such as date of screening) about the 
potential candidates for subjects who entered screening.   
If a subject withdraws from study participation, his/her unique identification number(s) 
cannot be re-used for another subject. 
The subject identification number must remain constant throughout the entire clinical study; 
it must not be changed after initial assignment, including if a subject is rescreened.  This 
number will not necessarily be the same as the randomization number assigned for the 
study. 
4.4 
Screen Failures 
If a subject has not met all eligibility criteria at the end of the screening period, the subject 
will be registered as a screen fail.  Laboratory assessments used to determine subject 
eligibility may be repeated during the screening period before the subject is considered a 
screen failure.  Screen failed subjects may be rescreened up to 2 times at the investigator’s 
discretion (ie, a total of 3 screens including initial screening).  If screening procedures 
cannot be completed within 28 days before day 1, the subject will be considered a screen 
failure but may be eligible for rescreening.  The subject will retain the same subject 
identification number provided at initial screening.  These subjects can be rescreened under 
the same ICF if rescreening and randomization occurs within 30 days of initial consent date.  
If it is longer than 30 days from the initial consent, the subject will need to be re-consented. 
4.5 
Premature Discontinuation 
Subjects have the right to withdraw from investigational product, protocol procedures, or the 
study completely 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 Product 
Subjects (or a legally authorized representative) can decline to continue receiving 
investigational product or procedures at any time during the study but continue participation 
in the study.  If this occurs, the investigator is to discuss with the subject the appropriate 
processes for discontinuation from investigational product and must discuss with the subject 


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the possibilities for continuation of the Schedule of Activities (see Table 1) including different 
options of follow-up (eg, 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, adverse events, and must document 
this decision in the subject’s medical records.  Subjects who have discontinued 
investigational product and/or other protocol-required therapies or procedures should not be 
automatically removed from the study.  Whenever safe and feasible, it is recommended that 
these subjects remain on study to ensure safety surveillance and/or collection of efficacy 
data, where possible. 
Reasons for early removal from protocol-required investigational product(s) or procedural 
assessments may include any of the following: 
 
Decision by sponsor 
 
Lost to follow-up 
 
Death 
 
Adverse event 
 
Subject request 
 
Protocol deviation 
 
Noncompliance 
 
Pregnancy 
Subjects who are unable to complete the week 16 visit within the visit window will not be re-
randomized, will be discontinued from the study, and will be asked to return to complete an 
EOS visit within 28 days from determining that the subject will discontinue from the study.   
4.5.2 
Premature Discontinuation from the Study 
Participation in the study is strictly voluntary.  A subject (or a legally authorized 
representative) 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:  
 
Violation of the protocol 


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 
Requirement for alternative therapy or alternative dosing schedule (eg, subjects who 
require treatment every 4 weeks) per the investigator’s determination 
 
Severe adverse events or serious adverse events 
 
Any other reason relating to the subject's safety or integrity of the study data 
 
Noncompliance with study procedures 
If a subject is withdrawn from the study, the Clinical Research Associate will be informed 
immediately.  Withdrawal of consent for a study means that the subject does not wish to 
receive further protocol-required therapies or procedures, and the subject does not wish to 
or is unable to continue further study participation.  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.  The investigator is to discuss with the subject 
appropriate procedures for withdrawal from the study, and must document the subject’s 
decision to withdraw in the subject’s medical records.   
If a subject withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the study center study records 
and notify the sponsor or designee. 
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 EOS visit within 28 days 
from determining that the subject will discontinue from the study; see Table 1. 
Subjects who prematurely discontinue from the study cannot subsequently rejoin the study. 
For details on the discontinuation of study centers 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 center. 
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 


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 
The study center 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. 
 
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, 3 telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the subject 
notes. 
 
Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
5 
Description of Study Assessments 
A full Schedule of Activities is presented in Table 1. 
5.1 
Demographics and Other Screening Assessments 
Safety assessments that are also part of the screening assessments are described in 
Section 5.3. 
5.1.1 
Informed Consent 
All subjects or their legally authorized representative must sign and personally date the 
IRB/IEC approved ICF before any study-specific procedures are performed. 
5.1.2 
Medical History 
Medical history, including any ongoing illnesses, will be recorded in the case report form 
(CRF), with the start date and stop date (if applicable) of the illness/condition. 
5.1.3 
Demographics 
Demographic data, including (where permitted), date of birth/age, sex, race, and ethnicity 
will be collected. 
5.1.4 
Disease-Specific Medical History 
Neovascular (wet) AMD history will be collected. 


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5.2 
Efficacy Assessments 
5.2.1 
Best Corrected Visual Acuity 
The BCVA will be recorded using ETDRS charts at screening and each visit (for the study 
eye) thereafter as described in the Study Manual.  Whenever possible, postbaseline 
assessments will be performed by the same assessor that performed the baseline 
assessment. 
5.2.2 
Fluorescein Angiography 
Fluorescein angiography will be taken using a standardized protocol approved by the central 
reading center at the visits specified in the Schedule of Activities (Table 1). 
Study sites and imaging personnel will be certified by the central reading center for 
fluorescein angiography.  All imaging assessments should be done on central reading 
center certified equipment and by a central reading center certified technician.  All post 
baseline assessments should be done on the same equipment that was used for the 
baseline assessment. 
All images will be sent to central imaging vendor.  See imaging manual for more information. 
5.2.3 
Spectral Domain Optical Coherence Tomography 
SD-OCT parameters will be obtained of the posterior pole per standard protocols approved 
by the central reading center.  The CST is defined as the average thickness in the ETDRS 
central 1 mm diameter subfield (the central subfield). 
Study sites and imaging personnel will be certified by the central reading center for SD-OCT 
scans.  All imaging assessments should be done on central reading center certified 
equipment and by a central reading center certified technician.  All post baseline 
assessments should be done on the same equipment that was used for the baseline 
assessment. 
All images will be sent to central imaging vendor.  See imaging manual for more information. 


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5.2.4 
Fundus photography 
Fundus photography evaluates vascular and structural changes in the eye by capturing 
images of posterior pole of eye (fundus).  The central and peripheral retina, optic disc and 
macula will be examined.  Fundus photography will be taken using a standardized protocol 
approved by the central reading center at the visits specified in the Schedule of Activities
(Table 1). 
Study sites and imaging personnel will be certified by the central reading center for fundus 
photography.  All imaging assessments should be done on central reading center certified 
equipment and by a central reading center certified technician.  All post baseline 
assessments should be done on the same equipment that was used for the baseline 
assessment. 
All images will be sent to central imaging vendor.  See imaging manual for more information. 
5.3 
Safety Assessments 
5.3.1 
Adverse Events 
Adverse events are defined in Section 7.1.1.  Adverse events will be followed, recorded, and 
reported in line with the procedures described in Section 7.3.  
5.3.2 
Clinical Laboratory Evaluations 
With the exception of urine pregnancy test, all laboratory assessments will be performed by 
a central laboratory.  Blood and urine samples will be collected at the times indicated in 
Table 1.  At visits when investigational product is administered, clinical laboratory samples 
will be collected before investigational product administration. 
The following parameters will be assessed:  
Hematology:  hemoglobin, hematocrit, red blood cells, platelets, total white blood cell 
(WBC) count, differential WBC count, and absolute neutrophil count 
Biochemistry:  albumin, alkaline phosphatase, alanine aminotransferase, amylase, 
aspartate aminotransferase, calcium, creatinine, gamma glutamyltransferase, glucose, 
lipase, potassium, sodium, and total bilirubin 


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Coagulation:  international normalized ratio, prothrombin time (PT), activated partial 
thromboplastin time (aPTT) 
Urinalysis:  pH, specific gravity, creatinine, glucose, bilirubin, blood, and protein 
A serum pregnancy test will be performed at screening by the central laboratory.  A urine 
pregnancy test will be performed locally.  Additional local urine pregnancy tests should be 
done as per local requirements as needed. 
Refer to the Investigator Laboratory Manual for details regarding the collection, processing, 
and shipping of the blood and urine samples. 
The investigator must review the laboratory report as described in Section 7.1.3. 
Any blood samples (eg, PK, immunogenicity) collected according to the Schedule of 
Activities (Table 1) can be analyzed for any of the tests outlined in the protocol and for any 
tests necessary to minimize risks to study subjects.  This includes testing to ensure 
analytical methods produce reliable and valid data throughout the course of the study.  This 
can also include, but is not limited to, investigation of unexpected results, incurred sample 
reanalysis, and analyses for method transfer and comparability. 
5.3.3 
Slit-Lamp Examination 
Slit-lamp biomicroscopy will be used to examine eye structures for both eyes during 
screening and the study eye at each study visit.  At screening, slit-lamp examinations will be 
performed according to local standard of care.  On days of investigational product 
administration, slit-lamp examinations will be done before investigational product is 
administered and again within 60 minutes after investigational product administration; both 
examinations will be performed postdilation.  If a subject receives investigational product in 
the fellow eye, that eye will also be examined at all study visits, including end of study.  
Slit-lamp examinations will include lids, conjunctiva, cornea, anterior chamber, iris, pupil, 
lens, and anterior vitreous, and will be performed according to local standards.   
5.3.4 
Indirect Ophthalmoscopy 
Indirect ophthalmoscopy will be used to examine the retina of both eyes during screening 
and the study eye at each subsequent study visit, and will be performed with pupil dilation.  


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At visits when investigational product is administered, indirect ophthalmoscopy will be 
performed before investigational product administration.  If a subject receives investigational 
product in the fellow eye, that eye will also be examined at all study visits, including end of 
study.  Indirect ophthalmology will include retina vessels, macula, fovea, periphery, optic 
nerve, and vitreous, and will be performed according to local standards.   
5.3.5 
Intraocular Pressure 
IOP will be measured for both eyes during screening and the study eye at each study visit.  
IOP will be measured according to the standard procedure at each site.  At visits when 
investigational product is administered, IOP will be measured before investigational product 
is administered and again at minimum 15 minutes and no longer than 60 minutes after 
investigational product administration.  If a subject receives investigational product in the 
fellow eye, that eye will also be examined at all study visits, including end of study.
The examiner will measure IOP and record results in mmHg with 1 decimal place (eg, 24.0).  
The method of IOP measurement used must remain consistent throughout the study and 
must be calibrated for accuracy according to manufacturer’s instructions throughout the 
study. 
5.3.6 
Pregnancy 
Details of all pregnancies and/or lactation in female subjects and female partners of male 
subjects that occur after the start of study treatment and until 3 months after the last IVT 
injection will be collected.  
If a pregnancy is reported, the investigator is to inform Amgen within 24 hours of learning of 
the pregnancy and/or lactation and is to follow the procedures outlined in Section 17.2.  
Amgen or its designee will follow-up with the investigator regarding additional information 
that may be requested. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Section 17.2. 


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5.3.7 
12-lead Electrocardiogram 
Electrocardiograms (ECGs) will be read locally at screening.  Computerized 12-lead ECG 
recordings will be obtained after the subject has been supine for 5 minutes.  Each lead will 
be recorded for at least 3 to 5 beats at a speed of 25 mm/sec paper speed and 10 mm/mV 
amplitude.  At a minimum, heart rate, P-wave, PR-interval, QRS-wave, QT-interval, and 
corrected QT-intervals (msec) will be recorded from the 12-lead ECG.  A copy of the ECGs 
will be retained at the study center.  For the purposes of screening, the investigator or a 
designee will evaluate whether the ECG is normal or abnormal and whether it is clinically 
acceptable for inclusion, if abnormal. 
5.3.8 
Vital Signs 
Vital signs will be measured in a semi-supine or sitting position after 5 minutes’ rest and will 
include temperature, systolic and diastolic blood pressure, pulse, and respiratory rate.  Vital 
signs should be assessed in the same position (either semi-supine or sitting position) 
throughout the study.
5.3.9 
Physical Examination 
Subjects will undergo complete and brief physical examinations, as indicated in the 
Schedule of Activities (Table 1).  Physical examination findings will be recorded.  
Physical examinations will be performed by a physician and will include examination of the 
following: general appearance, head, ears, eyes, nose, throat, neck, skin, cardiovascular 
system, respiratory system, abdominal system, and nervous system.  For each body 
system, an assessment of normal or abnormal will be recorded.  Clinically relevant changes 
from baseline will be reported as adverse events. 
Body weight and height will be measured and recorded as indicated in Table 1.  The subject 
should be dressed in light clothing, without shoes or jacket.   
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.  Any new abnormalities or worsening of existing abnormalities should be reported 
as adverse events, as appropriate (see Section 7). 


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5.4 
Pharmacokinetics 
PK will be assessed only in a subset of approximately 32 subjects who consent to 
participate in the PK substudy.  PK samples will be collected predose (within 60 minutes 
before day 1 dose) and postdose (approximately 24 hours after day 1 dose), with an 
allowable window -6 hours to +24 hours (ie, 18 hours to 48 hours after day 1 dose) and 
postdose at week 8 (approximately 24 hours after week 8 dose) with an allowable time 
window of -6 hours to +24 hours (ie, 18 hours to 48 hours postdose). 
If it is anticipated that the fellow eye will need to be treated prior to the week 8 postdose PK 
sample, then the subject should not be enrolled into the PK substudy.  If an enrolled PK 
substudy subject develops a requirement for fellow eye treatment prior to week 8 postdose 
PK sample, no further PK samples will be collected.  
If the need for treating the fellow eye is identified at the week 8 visit, then the fellow eye 
must be treated after the week 8 postdose PK sample has been drawn for those subjects 
included in the PK substudy. Instructions for the collection and handling of biological 
samples will be provided in the Investigator Laboratory Manual.  The actual date and time of 
collection of each sample will be recorded.  
5.5 
Antidrug Antibodies 
Blood samples for ADA assessments will be collected at the time points indicated in Table 1.  
ADA samples should be taken within 3 hours prior to administration of investigational 
product into either eye at the study visits.  Samples that have been tested for positive 
binding antibodies may be further assessed for neutralizing antibodies. Additional blood 
samples may be obtained to rule out ADAs during the study. 
The detection and characterization of antibodies to ABP 938 will be performed using a 
validated assay method by the sponsor or under the supervision of the sponsor.   


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6 
Treatments 
6.1 
Investigational Product(s) 
6.1.1 
Description of Investigational Product(s)  
Table 2 
Investigational Product (ABP 938) 
Name: 
ABP 938  
Dose(s):  
2 mg (0.05 mL) administered every 4 weeks for the first 3 doses, 
followed by 2 mg (0.05 mL) once every 8 weeks 
Mode of administration: 
IVT injection 
Table 3 
Reference Product (Aflibercept) 
Name: 
aflibercept (Eylea®) 
Dose(s):  
2 mg (0.05 mL) administered every 4 weeks for the first 3 doses, 
followed by 2 mg (0.05 mL) once every 8 weeks 
Mode of administration: 
IVT injection 
6.1.2 
Preparation, Handling, and Storage 
Refer to the Investigator Manual Clinical Trial Supply for full details regarding the 
preparation of ABP 938 and aflibercept. 
The investigator (or designee) is responsible for the safe and proper storage of 
investigational product at the study center.  ABP 938 and aflibercept will be stored under 
controlled conditions according to the storage requirements described on the labels and in 
the Investigator Manual Clinical Trial Supply. 
6.1.3 
Packaging, Labeling, and Shipment 
ABP 938 and aflibercept will be packaged and labeled in accordance with all applicable 
regulatory requirements and Good Manufacturing Practice guidelines. 
ABP 938 and aflibercept will be shipped and stored under controlled conditions according to 
the storage requirements. 


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Refer to the Investigator Manual Clinical Trial Supply for full details for packaging, labeling, 
and shipment of the investigational product. 
6.1.4 
Product Complaints 
A product complaint is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug(s) or device(s) after it is released for distribution to market or clinic by 
either Amgen or by distributors and partners for whom Amgen manufactures the material. 
Any product complaint(s) associated with an ABP 938 or aflibercept supplied by Amgen are 
to be reported according to the instructions provided in the Investigator Manual Clinical Trial 
Supply. 
6.1.5 
Excluded Treatments, Medical Devices, and/or Procedures During Study 
Period 
Any nonstudy intraocular treatments, including macular photocoagulation or photodynamic 
therapy, long-acting intramuscular or intravenous corticosteroids (Exclusion Criterion 29) are 
prohibited.  Nonstudy aflibercept and ziv-aflibercept and any nonstudy intraocular or 
systemic anti-VEGF therapy are prohibited.  Any experimental (biological or nonbiological) 
therapy (within or outside of a clinical study), except for the study drug, for subjects are 
prohibited.  Subjects requiring these treatments will discontinue study treatment.   
6.2 
Masking 
The study is double-masked; therefore, the investigators, study personnel, and the study 
subjects will remain masked to treatment allocation. 
Randomization data will be kept strictly confidential, accessible only to authorized staff and 
the independent DMC until the time of unmasking.  Authorized staff includes the 
randomization statistician, who will store the master randomization list in a secure system, 
an unmasked statistician, and unmasked programmers, who will provide the independent 
DMC with unmasked data for review, as and when required, in accordance with the 
procedures described in the DMC charter.  All authorized unmasked staff must be 
documented.  Personnel unmasked for the primary analysis will not be subsequently 
involved in study management. 


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ABP 938 and aflibercept will be coded and labeled in a manner that protects masking.  The 
coding system will permit rapid identification of the product (in case of medical 
emergencies), that does not permit undetectable breaking of the mask. 
Unmasking is only allowed in the case of an emergency, when knowledge of the 
investigational product is essential for the clinical management of the subject.  The 
investigator must make every effort to contact the sponsor or designee’s medical monitor 
prior to breaking the masking and must contact the sponsor or designee within 1 working 
day after the event, without revealing to the sponsor (or contract research organization 
[CRO]) the results of the code break, except to the designated global patient safety 
representative.   
Emergency unmasking will be organized through the IXRS.  The investigator must record 
the date of unmasking and the reason.  All breaks of the masking must be adequately 
documented. 
If a serious adverse event is reported, the designated global patient safety representative 
may unmask the treatment assignment for the individual subject through IXRS in order to 
meet regulatory reporting requirements. 
6.3 
Method of Assigning Treatment 
Once the subject has met the criteria for enrollment and the investigator has determined that 
the subject is eligible, the subject will be randomized within the IXRS. 
Randomization will be performed through a centralized IXRS.  Eligible subjects will be 
assigned to ABP 938 or aflibercept in a 1:1 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.  The randomization will be stratified by 
geographic region and disease severity (baseline BCVA < 64 letters vs. ≥ 64 letters). 
At week 8, subjects will be assessed for the primary endpoint (BCVA change from baseline).  
Subjects will then be re-randomized at week 16 in a masked fashion such that: 
 
Subjects initially randomized to ABP 938 (Treatment Group A) will continue to receive 
ABP 938 by IVT injection every 8 weeks from week 16 until week 48 


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 
Subjects initially randomized to aflibercept (Treatment Group B) will be re-randomized in 
a 1:1 ratio to either continue on aflibercept (Treatment Group B1) or transition to 
ABP 938 (Treatment Group B2) by IVT injection every 8 weeks from week 16 until 
week 48 
Re-randomization will be stratified using the same factors as the initial randomization.  Each 
subject will receive a second randomization number when he/she is re-randomized. 
6.4 
Dose and Administration 
Investigational product will be administered to the study eye at the times indicated in Table 1
via IVT by the Investigator (or qualified designee) under aseptic conditions and in 
accordance with the Eylea® product labeling.  Anesthesia/analgesia and any other 
medication used for investigational product administration will be recorded in the CRF. 
6.4.1 
Dose Modification 
No dose modifications are permitted during the study.  However, investigational product 
dose(s) may be withheld if clinically necessary, in accordance with the current product 
labeling for Eylea® (eg, in case of rhegmatogenous retinal detachment, stage 3 or 4 macular 
hole, a subretinal hemorrhage involving the center of the fovea, or other reason per the 
product labeling).  
If the subject presents with an infection at the dosing visit(s), the administration of 
investigational product may be delayed (up to 3 days for weeks 4 and 8, and up to 5 days 
for doses thereafter).   
In the case of delayed or missed dose for any reason, subsequent doses should be 
administered according to the original schedule (ie, at the planned timepoint relative to first 
dose) investigational product dose(s). 
6.4.2 
Intervention After the End of the Study 
After completing dosing with investigational product at week 48 and the follow-up visit at 
week 52, subjects will have completed the study.  ABP 938 or aflibercept (Eylea®) will not be 
provided for poststudy use. 


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6.5 
Treatment of the Fellow Eye 
The treatment of the fellow eye is allowed starting at baseline (day 1) if needed.  
For subjects receiving neovascular (wet) AMD treatment in the fellow eye during the study, 
sites must request an additional box of investigational product from the IXRS to be 
dispensed for the fellow eye.  The treatment dispensed for the fellow eye via the IXRS will 
be the same treatment type as the treatment received by the study eye.  Other anti-VEGF 
treatments and investigational products (except for this study’s investigational product) in 
the fellow eye are prohibited during the study. 
Those subjects needing fellow eye treatment at Day 1 or week 4 should follow the same 
dosing schedule of the study eye (every 4 weeks ± 3 days). 
Those subjects needing fellow eye treatment at week 8, 16, 24, 32, 40 and 48 should follow 
the same dosing schedule of the study eye (every 8 weeks ± 5 days).  
If it is anticipated that the fellow eye will need to be treated prior to the week 8 postdose PK 
sample, then the subject should not be enrolled into the PK substudy.  If an enrolled PK 
substudy subject develops a requirement for fellow eye treatment prior to week 8 postdose 
PK sample, no further PK samples will be collected.  
If the need for treating the fellow eye is identified at the week 8 visit, then the fellow eye 
must be treated after the week 8 postdose PK sample has been drawn for those subjects 
included in the PK substudy.  
Safety assessments should be performed for the fellow eye at the fellow eye dosing days 
and at the end of study visit.  Safety assessments include indirect ophthalmoscopy [assess 
predose only], slit-lamp [pre- and postdose], and intraocular pressure [pre- and postdose]), 
and the fellow eye should be monitored for safety events.  Investigational product dosing 
data and safety data from the fellow eye administration should be captured in the CRF.  
6.6 
Precautions and/or Lifestyle Considerations 
There are no lifestyle considerations (such as dietary or physical activity restrictions) for this 
study other than required contraception as listed in the inclusion/exclusion criteria 
(Section 4). 


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6.6.1 
Coronavirus Disease 2019 Considerations 
Study centers and subjects will follow local and institutional guidelines, as applicable, for the 
prevention of COVID-19 infection.  In the event that a subject experiences any 
signs/symptoms of COVID-19, the subject should promptly notify the investigator. 
6.7 
Prior and Concomitant Therapy 
6.7.1 
Prior Treatment 
Prior neovascular (wet) AMD therapies 1 month before randomization will be collected. 
Prior non-neovascular (wet) AMD therapies that were being taken/used from 28 days prior 
to randomization will also be collected. 
6.7.2 
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 listed in 
Section 6.1.5. 
All medication (including vaccines, over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) taken from 28 days before randomization until the end of the 
follow-up period/ end of study will be recorded in the appropriate section of the CRF.   
The medical monitor should be contacted if there are any questions regarding prior or 
concomitant medication or procedures. 
6.7.3 
Prohibited Concomitant Medications 
See Section 6.1.5. 
6.7.4 
Other Concomitant Medications and Treatments 
Any other treatment (not explicitly excluded) considered necessary for the subject’s welfare 
may be given at the discretion of the investigator.  Administration of concomitant 
medications must be recorded.  


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All subjects who discontinue the investigational product should be offered alternative 
treatment if applicable.  Treatment should be given according to normal clinical practice, 
after an EOS visit. 
6.8 
Compliance 
Investigational product will be administered by the investigator or study center personnel, 
under medical supervision.  The date and time of each dose administered in the clinic will be 
recorded in the source documents and in the CRF.  Treatment compliance will be assured 
by the reconciliation of all investigational product supplies and the site source documents by 
the Clinical Research Associate. 
6.9 
Accountability 
The investigational product must not be used for any purpose other than that defined in this 
protocol.  All supplies of investigational product will be accounted for in accordance with 
Good Clinical Practices (GCP).  Guidance and information on preparation, handling, 
storage, accountability, destruction, or return of the investigational product during the study 
are provided in the Investigator Manual Clinical Trial Supply.  
The pharmacist or (designee) should maintain accurate records of all investigational product 
supplies received during the study.  These records should include the dates and amounts of 
investigational product that were received at the study center, dispensed, and destroyed or 
returned to the sponsor (or designee).  The records should include dates, quantities, 
batch/serial numbers, expiration dates (if applicable), and the unique code numbers 
assigned to the investigational product and study subjects.  If errors or damage in the 
investigational product shipments occur, the investigator should contact the sponsor (or its 
designee) immediately.  Copies of the investigational product accountability records will be 
provided by each investigator for inclusion in the trial master file (TMF).  The Clinical
Research Associate will periodically check the supplies of investigational product held by the 
investigator or pharmacist to verify accountability of the investigational product used. 
The investigator (or designee) will administer the investigational product only to the 
identified subjects in this study, according to the procedures described in this study protocol.  
Details of investigational product administered to subjects will be recorded in the CRF.  


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Investigators should maintain records that document adequately that the subjects were 
provided the doses specified by the protocol and reconcile all investigational product 
received from the sponsor (or designee). 
After the end of the study, all unused investigational product and all medication containers 
should be returned to the sponsor (or designee) for destruction or destroyed at the study 
center (if approved by the sponsor or designee).  In either instance, complete 
documentation will be returned to the sponsor (or designee).  The investigational product 
resupply will be managed by the IXRS. 
7 
Adverse Events 
7.1 
Definitions 
7.1.1 
Adverse Events 
An adverse event is any untoward medical occurrence in a clinical trial subject.  The event 
does not necessarily have a causal relationship with the investigational product.  An adverse 
event can therefore be an unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) 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 adverse event definition are as follows: 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram, radiological scans, vital signs 
measurements), including those that worsen from baseline, that are considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease). 
 
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 drug-drug interaction. 
 
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 an 
adverse event/serious adverse event unless it is an intentional overdose taken with 


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possible suicidal/self-harming intent.  Such overdoses are to be reported regardless of 
sequelae. 
 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an adverse event or serious adverse event.  Such instances will be captured 
in the efficacy assessments.  However, the signs, symptoms, and/or clinical sequelae 
resulting from lack of efficacy will be reported as adverse event or serious adverse event 
if they fulfill the definition of an adverse event or serious adverse event. 
7.1.1.2 
Events NOT Meeting the Adverse Event Definition 
Events not meeting the adverse event definition include: 
 
Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that leads 
to the procedure is the adverse event. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
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. 
 
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 adverse event 
7.1.2 
Serious Adverse Events 
A serious adverse event is defined as any untoward medical occurrence that meets at least 
1 of the following serious criteria: 
 
Results in death (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:  the term “life-threatening” in the definition of “seriousness” refers to 
an event in which the subject was at risk of death at the time of the event.  It does 
not refer to an event, which hypothetically might have caused death, if it were more 


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severe.  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 adverse event or suspected adverse 
reaction that, had it occurred in a more severe form, might have caused death. 
Hospitalization:  In general, hospitalization signifies that the subject has been 
detained (usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in the 
physician's office or outpatient setting.  Complications that occur during 
hospitalization are an adverse event.  If a complication prolongs hospitalization or 
fulfills any other serious criteria, the event is serious.  When in doubt as to whether 
“hospitalization” occurred or was necessary, the adverse event should be considered 
serious.  Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an adverse event.  
Disability/incapacity:  The term disability means a substantial disruption of a person’s 
ability to conduct 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 (eg, 
sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
Other medically important serious event:  Medical or scientific judgment is to be 
exercised in deciding whether serious adverse event reporting is appropriate in other 
situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or 
may require medical or surgical intervention to prevent 1 of the other outcomes listed 
in the above definition.  These events are typically to be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 


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7.1.3 
Clinical Laboratory Abnormalities and Other Abnormal Assessments 
The investigator is responsible for reviewing all laboratory test results, including review of 
laboratory test results prior to subject randomization and reviewing subsequent laboratory 
test results throughout the study.  The investigator will determine whether an abnormal 
value in an individual study subject represents a clinically significant change from the 
subject’s baseline values.  Laboratory abnormalities without clinical significance (based on 
the investigator's judgment) should not be recorded as adverse events or serious adverse 
events.  However, laboratory abnormalities (eg, clinical chemistry, hematology, and 
urinalysis abnormalities) that require medical or surgical intervention or lead to 
investigational product interruption, modification, or discontinuation must be recorded as an 
adverse event or serious adverse event, as applicable.  Where applicable, clinical sequelae 
(not the laboratory abnormality) are to be recorded as the adverse event.  In addition, 
laboratory or other abnormal assessments (eg, in ECGs, vital signs) that are associated with 
signs and/or symptoms must be recorded as an adverse event or serious adverse event if 
they meet the definition of an adverse event or serious adverse event as described in 
Sections 7.1.1 and 7.1.2.  If the laboratory abnormality is part of a syndrome, record the 
syndrome or diagnosis (eg, anemia), not the laboratory result (eg, decreased hemoglobin). 
7.1.4 
Events of Interest 
The 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 adverse event report that qualifies to 
be expedited as part of regulatory reporting rules for investigational products.  
7.2 
Assessment of Adverse Events 
7.2.1 
Severity 
The investigator will make an assessment of severity for each adverse event and serious 
adverse event reported during the study.  The assessment of severity will be based on: 
The Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm


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7.2.2 
Causality 
The investigator is obligated to assess the relationship between investigational product and 
each occurrence of each adverse event/serious adverse event. 
Relatedness means that there are facts or reasons to support a relationship between 
investigational product and the event. 
The investigator will use 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 in his/her assessment. 
For each adverse event/serious adverse event, the investigator must document in the 
medical notes that he/she has reviewed the adverse event/serious adverse event and has 
provided an assessment of causality. 
There may be situations in which a serious adverse event 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 serious adverse event data. 
The investigator may change his/her opinion of causality in light of follow-up information and 
send a serious adverse event follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
7.3 
Documenting and Reporting Adverse Events 
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur from the time of randomization through the 
EOS visit are recorded in subject’s medical records as well as the applicable CRF Adverse 
Event Summary page.  The adverse event grading scale to be used for this study will be the 
CTCAE version 4.03, as described in Section 7.2.1. 


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The investigator must assign the following adverse event attributes: 
 
Adverse event diagnosis or syndrome(s), if known (if not known, signs or symptoms) 
 
Dates of onset and resolution 
 
Severity (National Cancer Institute CTCAE version 4.03) 
 
Assessment of relatedness to investigational product, other protocol-required therapies 
or devices 
 
Action taken 
The investigator’s clinical judgment is used to determine whether a subject is to be removed 
from treatment due to an adverse event.  A subject, or subject’s legal guardian, can also 
voluntarily withdraw from treatment due to an adverse event.  If the subject withdraws 
consent, the subject is encouraged to undergo, at a minimum, an EOS assessment. 
It is the investigator’s responsibility to review all documentation (eg, hospital notes, 
laboratory reports, and diagnostic reports) related to an adverse event.  Wherever possible, 
the investigator’s diagnosis, not the individual signs and symptoms, will be documented as 
the adverse event. 
It is not acceptable for the investigator to send photocopies of the subject’s medical records 
to sponsor or responsible CRO in lieu of completion of the CRF 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 
masked on the copies of the medical records before submission to sponsor or responsible 
CRO. 
Investigators are not obligated to actively seek adverse events or serious adverse events 
after the subject’s conclusion of study participation.  However, if the investigator learns of 
any serious adverse event, 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 
investigational product or study participation, the investigator must promptly notify the 
sponsor. 


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7.4 
Reporting of Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by the 
investigator or reported by the subject that occur after signing of the ICF through the EOS 
visit are reported using the applicable CRF Adverse Event Summary page.  
All serious adverse event must be collected, recorded and transmitted to Amgen, or its 
designee, within 24 hours following the investigator’s knowledge of the event.  
The investigator will submit any updated serious adverse event data to the sponsor or 
designee within 24 hours of it being available. 
The criteria for grade 4 in the CTCAE grading scale differs from the regulatory criteria for 
serious adverse events.  It is left to the investigator’s judgment to report these grade 4 
abnormalities as serious adverse events. 
If the electronic data capture (EDC) system is not functional, the serious adverse event can 
be reported by faxing a completed paper Serious Adverse Event Form or by direct 
telephone communication with Parexel at the numbers provided below.  The event must be 
updated electronically in the EDC system by the clinical study center once the EDC function 
resumes. 
Global reporting of SAEs (except Japan): 
Phone (Safety line): +1 (781) 434-5010  
NorthAmerica_Medical@parexel.com
Japan (Safety line): +81 3 6888 5377  
After the study is completed at a given center, the EDC system will be taken off-line to 
prevent the entry of new data or changes to existing data.  If a center receives a report of a 
new serious adverse event from a study subject or receives updated data on a previously 
reported serious adverse event after the EDC has been taken off-line, then the center can 
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7.4.1 
Regulatory Reporting Requirements for Serious Adverse Events 
If a subject is permanently withdrawn from protocol-required therapies because of a serious 
adverse event, this information must be submitted to Amgen, or its designee. 
Prompt notification by the investigator to the sponsor (or designee) of serious adverse 
events 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.  
The sponsor (or designee) 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.  The sponsor (or designee) will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, IRBs/IECs, and 
investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and sponsor (or designee) policy and 
forwarded to investigators as necessary. 
An investigator who receives an individual safety report describing a serious adverse event 
or other specific safety information (eg, summary or listing of serious adverse events) from 
the sponsor (or designee) will file it along with the IB and will notify the IRB/IEC, if 
appropriate according to local requirements. 
To comply with worldwide reporting regulations for serious adverse events, the treatment 
assignment of subjects who develop serious, unexpected, and related adverse events may 
be unmasked by Amgen or designee before submission to regulatory authorities.  Aggregate 
analyses may also be unblinded by the Safety Assessment Team, as appropriate.  
Investigators will receive notification of related serious adverse events reports sent to 
regulatory authorities in accordance with local requirements. 
7.5 
Reporting of Serious Adverse Event After the Protocol-required Reporting 
Period 
There is no requirement to monitor study subjects for serious adverse events following the 
protocol-required reporting period or after the end of the study.  However, these serious 
adverse events can be reported to Amgen.  Per local requirements in some countries, 


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investigators are required to report serious adverse events that they become aware of after 
the end of the study.  If serious adverse events are reported, the investigator is to report 
them to Amgen within 24 hours following the investigator’s knowledge of the event. 
Serious adverse events reported outside of the protocol-required reporting period will be 
captured within the safety database as clinical study cases and handled accordingly based 
on relationship to investigational product. 
7.6 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious 
adverse events.  Open-ended and nonleading verbal questioning of the subject is the 
preferred method to inquire about adverse event occurrence.  
7.7 
Adverse Event and Serious Adverse Event Follow-up 
During the study the adverse events and serious adverse events should be followed 
proactively by the investigator at subsequent visits/contact.  All adverse events and serious 
adverse events will be followed until resolution, stabilization, 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 ongoing adverse events and serious adverse events should be 
evaluated for resolution.  All new or updated information for previously reported serious 
adverse events must be sent to Amgen within 24 hours following knowledge of the new 
information.  New or updated information will be recorded in the originally completed 
Adverse Event CRF.  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.  Information provided about the serious adverse event must be 
consistent with that recorded on the Adverse Event CRF. 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Amgen to 
elucidate the nature and/or causality of the adverse event or serious adverse event as fully 
as possible.  This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 


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If a subject is permanently withdrawn from protocol-required therapies because of a serious 
adverse event, this information must be submitted to Amgen.  If a subject dies during 
participation in the study, the investigator will provide Amgen with a copy of any 
post-mortem findings including histopathology if available. 
8 
Statistics 
8.1 
General Procedures 
All personnel involved with the analysis of the study will remain masked until database lock 
and identification of protocol deviations for the primary analysis.  Personnel unmasked for 
the primary analysis will not be further involved in the management of the study.  Analyses 
will be performed using SAS® version 9.4 or higher (SAS Institute, Cary, NC, US) by the 
sponsor or its representatives. 
The SAP will be approved prior to lock of the study database and unmasking of the study 
data for the primary analysis.  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, median, minimum, and maximum) will be provided 
for continuous variables, and counts and percentages will be presented for categorical 
variables.  Confidence intervals (CIs) may also be provided (when specified). 
In general, baseline is defined as the last non-missing measurement/procedure before or on 
the date of first administration of investigational product. 
8.2 
Analysis Populations 
The Full Analysis Set (FAS) will include all randomized subjects based on the treatment the 
subject is randomized to (regardless of actual treatment received).  This analysis set will be 
the primary set used for analyses/summaries of the primary efficacy endpoint, as well as for 
all secondary efficacy endpoints. 
The Safety Analysis Set will include all subjects who receive at least 1 dose of 
investigational product and will be analyzed according to actual treatment received.  This 
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The Per Protocol Analysis Set will include all subjects in the FAS who have completed 
dosing at day 1 and week 4 and have completed BCVA assessment at week 8 without 
experiencing a protocol deviation that may affect their evaluation for the primary endpoint of 
the study.  Important protocol deviations that could affect the primary endpoint will be 
defined and agreed upon before unmasking.  The analysis set will be analyzed according to 
actual treatment received in the study eye.  This analysis set will be used for sensitivity 
analyses for the primary and key secondary efficacy endpoints. 
The PK Analysis Set will include all subjects enrolled in the PK substudy who receive at 
least 1 dose of investigational product between day 1 and week 8 (inclusive) and who have 
at least 1 reported serum concentration of ABP 938 or aflibercept.  The analysis set will be 
analyzed according to the actual treatment received in the study eye. 
8.3 
Sample Size 
Approximately 566 subjects (including at least 30 subjects from East Asia) will be 
randomized in a 1:1 ratio initially to receive ABP 938 (Treatment Group A) or aflibercept 
(Treatment Group B).  The total sample size will provide approximately 90% power to 
demonstrate equivalence at a 2-sided significance level of 0.025 with an equivalence margin 
of (-3.9, 3.9) on the primary efficacy endpoint of BCVA change from baseline at week 8, 
assuming a true mean difference of 0 in the primary endpoint between the 2 groups, a 
standard deviation of 12.5 letters, and a 2% dropout by week 8.  In addition, the number of 
East Asian subjects (ie, at least 30) was chosen to enable an assessment of the treatment 
difference within East Asian subjects with reasonable accuracy and precision, while 
ensuring the study recruitment is feasible and can be completed in a timely manner.   
8.4 
Planned Analyses 
The primary analysis of the study will be performed after all enrolled subjects reach week 24 
or terminate early.  The final analysis will be performed when all enrolled subjects complete 
the week 52 visit or terminate early.  


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8.5 
Statistical Methods 
8.5.1 
Primary Endpoint/Estimand 
Primary Estimand 
The primary estimand is the difference in change from baseline in BCVA at week 8 
between the ABP 938 group and the aflibercept group in subjects with neovascular 
(wet) AMD who are randomized, regardless of missing or discontinuing 
investigational product administration to the study eye, or use of additional 
medications for AMD in the study eye prior to observing BCVA at week 8.  
Clinical equivalence will be evaluated using the FAS by comparing the 95% CI of the 
treatment difference between ABP 938 and aflibercept in the primary endpoint, change from 
baseline in BCVA at week 8, with an equivalence margin of (-3.9, 3.9) letters.  The least 
squares (LS) mean difference between the 2 treatment groups and the corresponding 95% 
CI will be estimated using an analysis of covariance (ANCOVA) model for the week 8 BCVA 
change from baseline adjusted for region and baseline BCVA.  Consistency in treatment 
effects between the East Asian subjects and the overall population will be evaluated by 
descriptive summaries and/or graphical displays. 
The intercurrent events will be handled using a treatment policy strategy.  The value 
of BCVA at week 8 (if observed) will be used regardless of whether an intercurrent 
event occurs.  Missing BCVA value at week 8 is assumed to be missing completely at 
random (MCAR) for the primary analysis for the primary estimand based on observed 
data using the FAS.  Sensitivity analyses will be performed in the Per Protocol Analysis 
Set.  Sensitivity analyses will be conducted to evaluate the robustness of the result to 
potential departure from the MCAR assumption (see Section 8.5.10). 
8.5.2 
Secondary Endpoint(s) 
Secondary efficacy endpoints will be analyzed descriptively.  BCVA, CNV, and CST 
changes from baseline will be summarized by visit.  The LS mean differences and 95% CIs 
will be estimated using ANCOVA models similar to that used for the primary endpoint.  
Generalized linear models with identity link will be utilized to obtain the point estimate and 
95% CIs for treatment differences in the following secondary endpoints: proportions of 


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subjects gaining ≥ 10 letters at week 8, maintaining vision at week 52, and gaining 
≥ 15 letters at week 52.   
Sensitivity analyses for the proportion of subjects who gained at least 10 letters of vision at 
week 8, CNV changes from baseline at week 8, and CST change from baseline at week 8 
will be performed in the Per Protocol Analysis Set. 
8.5.3 
Safety Endpoint(s) 
Safety analyses will focus on treatment-emergent adverse events.  Treatment-emergent 
adverse events are defined as those that begin or increase in severity or frequency at or 
after the time of first treatment to the EOS visit. 
Safety will be assessed descriptively in the Safety Analysis Set.  Subject level safety data 
and safety data for the study eye will be summarized descriptively and separately for day 1 
through week 8, day 1 through week 16, week 16 through the EOS visit, and day 1 through 
the EOS visit, based on actual treatment received in the study eye.  The summaries for 
day 1 through week 8 and day 1 through week 16 will be presented by treatment (ABP 938 
vs. aflibercept).  The summaries for week 16 through the EOS visit and day 1 through the 
EOS visit will be presented by treatment sequence (ABP 938/ABP 938 vs. 
aflibercept/aflibercept vs. aflibercept/ABP 938) for subjects who are re-randomized and 
treated post re-randomization.  For the subset of subjects who also have the fellow eye 
treated with the investigational product, their safety data collected for the fellow eye from the 
first investigational product treatment of the fellow eye to the EOS visit will be summarized 
similarly, and summaries will be based on the actual treatment received in the fellow eye.  
All reported adverse events will be assigned the system organ class and preferred term 
according to the Medical Dictionary for Regulatory Activities as of the time of the primary 
analysis and assessed for severity by CTCAE version 4.03.  The number and percent of 
subjects reporting treatment-emergent adverse events (all, serious, and fatal) and EOIs will 
be tabulated.   
Laboratory data (hematology, serum chemistry, and urinalysis) will be converted to Système 
International units for reporting and processing purposes.  Absolute values and changes 
from baseline by visit will be presented descriptively.   


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Vital signs and ophthalmoscopic assessments (indirect ophthalmoscopy, slit-lamp 
examinations, and IOP) will be presented by visit descriptively. 
8.5.4 
Demographic and Baseline Characteristics 
Demographic characteristics (including age, sex, ethnicity, and race) and baseline 
characteristics (including height, weight, body mass index, and disease characteristics) will 
be presented by assigned treatment descriptively. 
8.5.5 
Exposure to Investigational Product 
Exposure to ABP 938/aflibercept will be summarized descriptively at the subject level and 
separately for study eyes and fellow eyes for the different reporting periods specified for the 
safety analyses in Section 8.5.3. 
8.5.6 
Exposure to Concomitant Medications 
Prior and concomitant medications will be coded using the latest available World Health 
Organization Drug Dictionary as of the time of the primary analysis and summarized 
descriptively. 
8.5.7 
Pharmacokinetic Endpoints 
Serum ABP 938 and aflibercept concentrations from the PK substudy will be summarized 
descriptively for the PK Analysis Set by treatment for each sampling time point.   
8.5.8 
Immunogenicity Endpoints 
The number and percentage of subjects developing ADAs will be tabulated by visit and by 
actual treatment received in the study eye for the different reporting periods specified for the 
safety analyses in Section 8.5.3.  Only subjects who were re-randomized, and treated post 
re-randomization, and had a result post re-randomization will be included in the analyses for 
week 16 through the EOS visit.  Subjects who were not re-randomized or were not treated 
post re-randomization will be excluded from the analyses for week 16 through the EOS visit 
and day 1 through the EOS visit. 


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8.5.9 
Subgroup Analyses and Covariates 
Consistency in treatment effects between the East Asian subjects and overall population will 
be evaluated descriptively by summaries and/or graphical displays. 
Geographic regions and baseline BCVA letters, will be included in statistical models for the 
efficacy analyses as covariates.  Additionally, subgroup analyses for efficacy endpoints may 
include geographic region and baseline BCVA category. 
Full details of the subgroup analyses and covariates will be prespecified in the SAP. 
8.5.10 
Handling of Missing Values 
For both the primary and secondary efficacy endpoints, the primary analysis will be 
based on observed data using the FAS; missing values will not be imputed.  As a 
sensitivity analysis, missing data will be imputed by the last observation carried 
forward for the primary endpoint and non-response imputation for the binary 
secondary endpoints.  A repeated-measures analysis for change from baseline in 
BCVA from day 1 through week 8 will also be performed assuming the data are 
missing at random.  In addition, for the primary endpoint, tipping point analyses will 
be performed to explore the sensitivity of the results based on different assumptions 
for the missing data.  Additional details are provided in the SAP. 
Subjects who prematurely discontinue the study will be evaluated based on the data 
collected at each visit attended.  Data collected during the withdrawal visit will be used as an 
EOS assessment for these subjects.  
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 International Council on Harmonisation (ICH) Good Clinical Practice (GCP) Harmonised 
Tripartite Guideline E6 (R1)/Integrated Addendum E6 (R2); US Food and Drug 
Administration (FDA) Code of Federal Regulations (CFR) (Title 21 Parts 50, 56, 312), 
requirements for the conduct of clinical studies as provided in the EU Directive 2001/20/EC; 


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the general guidelines indicated in the Declaration of Helsinki; and all applicable laws and 
regulatory requirements. 
9.2 
Institutional Review Board/Independent Ethics Committee 
Before initiating a study, the investigator/institution must have written and dated 
approval/favorable opinion from the IRBs/IECs for the study protocol/amendment(s), written 
ICF, any ICF updates, subject recruitment procedures (eg, advertisements), and any written 
information to be provided to subjects and a statement from the IRBs/IECs 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/IEC. 
A copy of the written approval of the protocol and ICF must be received by Amgen or 
designee before recruitment of subjects into the study and shipment of Amgen 
investigational product. 
Amgen may amend the protocol at any time.  The IRB/IEC approval(s) must identify the 
protocol version as well as the documents reviewed.  Any amendments to the protocol will 
require IRB/IEC 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: 
 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
 
Notifying the IRB/IEC of serious adverse events or other significant safety findings, 
including adverse drug reactions (ADRs) that are both serious and unexpected, as 
required by IRB/IEC procedures 
 
Providing oversight of the conduct of the study at the study center 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/IEC approval/renewal throughout the duration of the study.  
Copies of the investigator’s reports and the IRB/IEC continuance of approval must be 
sent to Amgen or designee 


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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.  Prior to the beginning of the study, the 
investigator should have the IRB/IEC's written approval/favorable opinion of the written ICF 
and any other written information to be provided to subjects. 
 
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 authorized 
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 authorized 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/IEC or study center. 
 
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 authorized representative, and 
by the person who conducted the informed consent discussion. 
 
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 center. 
 
A copy of the ICF and any other written information must be provided to the subject or 
the subject’s legally authorized representative. 
 
If the ICF is revised, the revised ICF must have received the IRB/IEC's 
approval/favorable opinion in advance of its use.  Subjects or legally authorized 
representative 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 authorized 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 


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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 record. 
If a subject is unable to read or if a legally authorized representative is unable to read, an 
impartial witness should be present during the entire informed consent discussion.  The 
witness should sign and personally date the ICF after: 
 
The written ICF and any other written information to be provided to subjects is read and 
explained to the subject or the subject’s legally authorized representative 
 
The subject or the subject’s legally authorized representative has orally consented to the 
subject’s participation in the study 
 
The subject or the subject’s legally authorized representative has signed and personally 
dated the ICF, if they are capable of doing so 
By signing the ICF, the witness attests that the information in the ICF and any other written 
information was accurately explained to, and apparently understood by, the subject or the 
subject's legally authorized representative, and that informed consent was freely given by 
the subject or the subject’s legally authorized representative. 
9.4 
Data Monitoring Committee 
A DMC will be formed with members consisting of individuals external to Amgen and the 
CRO chosen for their expertise in neovascular (wet) AMD.  Members of the DMC will 
include, at a minimum, physicians and statistician(s).  The primary role of this independent 
DMC will be to monitor safety data.  
The DMC will review unmasked safety data at regular intervals beginning after 
approximately the first 16 subjects complete 2 doses (day 1 and week 4) of investigational 
product and approximately every 6-8 months thereafter, as outlined in the DMC charter.  
In addition, the DMC will communicate any major safety concerns and recommendations 
regarding study modification or termination to Amgen senior management at any time during 
the conduct of the study.  
Records of all meetings will be maintained by the CRO in a restricted, unmasked location for 
the duration of the study.  Records of all meetings will be transferred and stored in the study 


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TMF at the conclusion of the study.  Selected Amgen, or its designee, staff may serve as 
liaisons with the DMC, but will not be voting members.  Personnel at Amgen or its designee 
involved in preparation or review of DMC unmasked materials will not be otherwise involved 
in the study.  Details regarding the DMC will be provided in the DMC charter. 
9.5 
Financing and Insurance 
9.5.1 
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.   
9.5.2 
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 
Compensation for Injury section of the Informed Consent that is available as a separate 
document. 
9.5.3 
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor or designee with sufficient, 
accurate financial information as requested to allow the sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate regulatory 
authorities.   
10 Records Management 
All clinical study information should be recorded, 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. 
A CRF will be used to store and transmit subject information.  The CRF must be reviewed 
and electronically signed and dated by the investigator on an ongoing basis throughout the 


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study.  The investigator is responsible for verifying that the data entries are accurate and 
correct by signing the CRF. 
Access to the CRF will be strictly password protected and limited to personnel directly 
participating in the study.  Data should be entered into the CRF completely by authorized 
site personnel (eg, investigators and the study coordinator).  The CRF 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 CRFs and computers that store them must be accessible to Clinical
Research Associates and other regulatory auditors.  Changes to the CRF will be 
electronically tracked. 
During each study visit, a physician participating in the study 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 adverse 
event, and the investigator's assessment as to whether or not the reported adverse 
event is related to investigational product 
 
Changes (including dosages) in concomitant medications/therapies (including 
over-the-counter medications and vitamins or dietary supplements) 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) 
In addition, any contact with the subject by telephone or other means that provides 
significant clinical information is to also be documented in the medical record (progress 
notes), as described above. 
Information from the medical records (progress notes) and other source documents is to be 
promptly entered into the appropriate section of the CRF. 
Changes to information in the medical record (progress notes) and other source documents 
are to be initialed and dated on the day the change is made by the investigator (or 


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designee).  If the reason for the change is not apparent, a brief explanation for the change is 
to be written adjacent to the change.  Changes to the CRF will be electronically tracked. 
The CRO 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 recorded.  Source 
documents include, but are not limited to, medical records (progress notes), ECG and 
computer printouts, screening logs, completed scales, and recorded data from automated 
instruments. 
The investigator/site personnel should maintain adequate and accurate source documents 
and study records that include all pertinent observations on each of the study center’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 (eg, 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/IEC review, and regulatory 
inspections.  The sponsor should verify that each subject has consented, in writing, to direct 
access to his/her original medical records for study-related monitoring, audit, IRB/IEC 
review, and regulatory inspection. 
10.2 
Case Report Form Completion and Data Management 
The file structure and format for the CRF will be provided by the sponsor or its 
representative and should be handled in accordance with the instructions provided. 
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. 


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10.3 
Study Files and Record Retention 
All data derived from the study will remain the property of the sponsor.  The sponsor 
assumes accountability for actions delegated to other individuals, eg, 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, CRFs, and the 
investigational product 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 the sponsor.  The sponsor 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 the sponsor and is to provide the sponsor the opportunity to collect such 
records.  The investigator shall take responsibility for maintaining adequate and accurate 
source documents of all observations and data generated during this study.  Such 
documentation is subject to inspection by the sponsor, 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 the sponsor. 
11 Auditing and Monitoring 
Sponsor-assigned Clinical Research Associates will conduct regular monitoring of the 
investigational facilities 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 CRFs, verification of CRF data against original source 
documents, and occurrence of adverse events.  The investigator must agree to 
sponsor-authorized personnel having direct access to the clinical (or associated) files and 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
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clinical study supplies (dispensing and storage areas) to ensure compliance with applicable 
regulations, and the investigator will assist with the sponsor’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.  The sponsor 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 the sponsor’s contracted CRO(s). 
The CRFs should be completed in a timely manner and on an ongoing basis to allow regular 
review by the Clinical Research Associate. 
Details describing the strategy, responsibilities, and requirements of the study monitoring 
are provided in the Study Monitoring Plan.   
The purpose of an audit is to assess whether ethics, regulatory, and quality requirements 
are being fulfilled.  The sponsor or its representative may conduct audits at the investigative 
centers including, but not limited to, drug supply, presence of required documents, the 
informed consent process, and comparison of CRFs with source documents.  Government 
regulatory authorities may also inspect the investigator during or after the study.  The 
investigator (or designee) should contact the sponsor/CRO immediately if this occurs.  All 
medical records (progress notes) must be available for audit.  The investigator must agree 
to participate with audits conducted at a convenient time in a reasonable manner. 
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. 
The sponsor and CRO 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 (CSR). 
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. 


Sponsor Name: Amgen, Inc 
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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. 
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 the sponsor and prior review and approval from the IRB/IEC 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 the sponsor’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 the sponsor.   
Any permanent change to the protocol must be handled as a protocol amendment.  The 
written amendment must be submitted to the IRB/IEC, and the investigator must await 
approval before implementing the changes.  The sponsor or designee will submit protocol 
amendments to the appropriate regulatory authorities for approval. 
The current version of the ICF will require similar modification if the IRB/IEC, 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. 


Sponsor Name: Amgen, Inc 
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13 Study Report and Publications 
This study will be registered on ClinicalTrials.gov in accordance with applicable laws and 
publication policy, and may also be registered on other publicly accessible websites as 
necessary.  The results of the study will be posted for public disclosure within 12 months of 
study completion. 
The sponsor or designee is responsible for preparing and providing the appropriate 
regulatory authorities with the CSR according to the applicable regulatory requirements.  
The sponsor 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 
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, multicenter 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 (eg, manuscripts, abstracts, oral/slide 
presentations, book chapters) based on this study must be submitted to Amgen for review.  


Sponsor Name: Amgen, Inc 
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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 is randomized to study. 
The EOS date is defined as the date when the last subject across all centers is assessed or 
receives an intervention for evaluation in the study (ie, last subject visit) or has withdrawn 
prematurely, as applicable. 
The sponsor reserves the right to terminate the study or the participation in the study at an 
investigator’s center at any time.  In terminating the study, the sponsor and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests. 
If the study is prematurely terminated or suspended for any reason, the 
sponsor/investigator/site personnel should promptly inform the study subjects and should 
ensure appropriate therapy and follow-up for the subjects.  Where required by the applicable 
regulatory requirements, the IRB/IEC should be informed promptly and be provided with 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 the sponsor.  However, authorized regulatory officials, IRB/IEC personnel, the 
sponsor, and the sponsor’s 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 the 
sponsor or designee 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 the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
Page 81 of 88 
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Identification of subjects and CRFs shall be by unique subject identification numbers (such 
as subject identification number or randomization number only).  All personal identifiers 
according to applicable regulations (eg, name, phone number) must be redacted 
permanently by the study center personnel and replaced with the subject’s unique 
identification number in all records and data before transfer to the sponsor (or designee). 
All personal details will be treated as confidential by the investigator and staff at the CRO. 
16 References 
1. 
Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, 
Mariotti SP.  Global data on visual impairment in the year 2002.  Bull World Health 
Organ. 2004 Nov;82(11):844-51.  
2. 
Congdon NC, Friedman DS, Lietman T.  Important causes of visual impairment in 
the world today.  JAMA. 2003; 290:2057-60. 
3. 
Macular Photocoagulation Study Group.  Laser photocoagulation of subfoveal 
neovascular lesions of age-related macular degeneration.  Updated findings from 
two clinical trials.  Arch Ophthalmol. 1993; 111:1200-9. 
4. 
Treatment of Age-related Macular Degeneration Study Group (TAP Study Group).  
Photodynamic therapy of subfoveal choroidal neovascularization in age-related 
macular degeneration with verteporfin: one-year results of 2 randomized clinical 
trials.  Arch Ophthalmol. 1999; 117:1329-45. 
5. 
Yancopoulos GD.  Clinical application of therapies targeting VEGF.  Cell. 2010; 
143:13-6. 
6. 
Eylea® USPI.  Regeron, Tarrytown, NY USA.  May 2019. 
7. 
Eylea® SmPC.  Bayer AG, 51368 Leverkusen Germany.  July 2019. 
8. 
EMA.  Eylea® European Public Assessment Report, EMA/481361/2018.  
9. 
BLA 125387 Clinical Pharmacology and Biopharmaceutics Review.  CDER, 2018. 
10. 
EMA.  Guideline on similar biological medicinal products.  CHMP/437/04 Rev 1, 
2014. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
Page 82 of 88 
Confidential 
11. 
EMA.  Guideline on similar biological medicinal products containing biotechnology-
derived proteins as active substance:  Quality issues.  
EMA/CHMP/BWP/247713/2005 Rev 1. 2012.  
12. 
EMA.  Guideline on similar biological medicinal products containing biotechnology-
derived proteins as active substance:  Non-clinical and clinical issues.  
EMEA/CHMP/BMWP/42832/2005, Rev 1. 2014. 
13. 
US FDA.  Guidance for Industry:  Scientific considerations in demonstrating 
biosimilarity to a reference product.  April 2015a, US FDA. 
14. 
US FDA.  Guidance for Industry:  Quality considerations in demonstrating 
biosimilarity to a reference protein product.  April 2015b, US FDA. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
Page 83 of 88 
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17 Appendices 
17.1 
Appendix I – Study Administrative Structure 
Sponsor: 
Amgen, Inc 
One Amgen Center Drive 
Thousand Oaks, CA USA 91320
Sponsor’s medical 
expert 
, MD, MPH 
Vice President, Global Development-Biosimilars
Amgen, Inc 
CRO’s medical 
monitor: 
, MD 
Associate Medical Director 
Parexel International (IRL) Limited 
, MD 
Medical Director 
Parexel International (IRL) Limited 
 MD 
Associate Medical Director 
Parexel International (IRL) Limited 
CRO: 
Parexel International (IRL) Limited 
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 centers will be maintained. 
The names and addresses of any other laboratories involved in the study will be provided in 
the Investigator Laboratory Manual. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
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17.2 
Appendix II - Contraceptive Guidance and Collection of Pregnancy and 
Lactation Information 
Male subjects and female subjects of childbearing potential must receive pregnancy 
prevention counseling and be advised of the risk to the fetus if they become pregnant or 
father a child during treatment and for 3 months after the last dose of protocol-required 
therapies. 
Definition of Females of Childbearing Potential 
A female is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile.  Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
Females in the following categories are not considered female of childbearing potential: 
 
Premenopausal female with 1 of the following: 
○ Documented hysterectomy; 
○ Documented bilateral salpingectomy; or 
○ 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 
 
Postmenopausal female 
○ A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  A high follicle-stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal 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. 
○ Females on HRT and whose menopausal status is in doubt will be required to use 1 
of the nonhormonal highly effective contraception methods if they wish to continue 
their HRT during the study.  Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
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Contraception Methods for Female Subjects 
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 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) 
 
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 protocol-required therapies; 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 during treatment and for an additional 3 months after the last dose of 
investigational product 
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 [a female condom is not an option because there is 
a risk of tearing when both partners use a condom]). 


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Note:  If the male’s sole female partner is of nonchildbearing 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, postovulation methods) 
 
Withdrawal (coitus interruptus) 
 
Spermicides only 
 
Lactational amenorrhea method 
Collection of Pregnancy Information 
Female Subjects Who Become Pregnant 
 
Investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking protocol-required therapies through 3 months after the last dose of 
investigational product. 
 
Information will be recorded 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.  
(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 taking protocol-required therapies through 3 months after the 
last dose of investigational product.  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 adverse event or serious adverse 
event, 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 
adverse event or serious adverse event.  Note that an elective termination with no 
information on a fetal congenital malformation or maternal complication is generally not 
considered an adverse event, but still must be reported to Amgen or its designee as a 
pregnancy exposure case. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
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 
If the outcome of the pregnancy meets a criterion for immediate classification as a 
serious adverse event (eg, 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 serious adverse event. 
 
Any serious adverse event occurring as a result of a poststudy 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 serious adverse event 
through spontaneous reporting.  
 
Any female subject who becomes pregnant while participating will discontinue study 
treatment. 
Male Subjects With Partners Who Become Pregnant  
 
In the event a male subject fathers a child during treatment, and for an additional 
3 months after the last dose of investigational product, 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 center’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. 
 
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 
 
Investigator will collect lactation information on any female subject who breastfeeds 
while taking protocol-required therapies through 3 months after the last dose of 
investigational product. 
 
Information will be recorded on the Lactation Notification Form and submitted to Amgen 
or its designee within 24 hours of the investigator’s knowledge of event. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Version and Date: Version 4.0, 16 May 2022
Page 88 of 88 
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 
Study treatment will be discontinued if female subject breastfeeds during the study as 
described in Exclusion Criterion 31. 
 
With the female subjects 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 taking 
protocol-required therapies through 3 months after discontinuing protocol-required 
therapies. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 3.0, 23 March 2021 
Page 7 of 88 
 
 
Confidential 
 
 
PROTOCOL AMENDMENT 2 (23 MARCH 2021) 
Amendment rationale 
The protocol is being amended to adjust the assessments in the protocol based on 
site and regulatory feedback. 
All content updates to the existing text in this protocol amendment are illustrated 
throughout in BOLD font and presented in this protocol summary. 
Changes to the protocol version 2.0 
• 
Japan (Safety line) Telephone number has been updated. 
• 
Number of global sites has been updated in the Synopsis. 
• 
Footnotes “b, d, e, g, j, I, k” of Table 1 Schedule of Activities have been 
updated. 
• 
Section 1.1.2 Non-Amgen Investigational Product (Aflibercept) has been 
updated to include additional adverse events reflected in the warnings and 
precautions section of the product labeling. 
• 
Section 1.3 Benefit/ Risk Assessment has been updated to include a COVID-19 
risk assessment.  
• 
Section 2 Study Objective and Endpoints, one of the secondary efficacy 
endpoints has been updated. 
• 
Section 3.1, Section 4.5.1, and Footnote “l” of Table 1 Schedule of Activities 
have been updated to include language with regards to the week 16 visit to 
ensure it is clear that a visit outside of the window is not allowed in. 
• 
Section 3.1 Study Design has been updated to include information on 
PK substudy/on treatment of the fellow eye. 
• 
Section 3.3.1 End-of-Study Definition, the definition of the primary completion 
date has been updated.  


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 3.0, 23 March 2021 
Page 8 of 88 
 
 
Confidential 
 
 
• 
Section 4.1 Inclusion Criteria and Section 4.2 Exclusion Criteria have been 
updated. 
• 
Sections 4.3, 4.5.1, 4.5.2 and throughout have been updated to mention a 
legally authorized representative (previously referred to as legally acceptable 
representative). 
• 
Sections 5.2.2, 5.2.3, 5.3.3, 5.3.4 and 5.3.5 have been updated to provide 
information on study visits. 
• 
Section 5.3.2 Clinical Laboratory Evaluations has been updated to include 
information on additional local urine pregnancy tests. 
• 
Section 5.3.8 Vital Signs has been updated. 
• 
Section 5.4 Pharmacokinetics has been updated with information related to 
PK substudy. 
• 
Section 5.5 Antidrug antibodies has been updated. 
• 
Section 6.1.5 Excluded Treatments, Medical Devices, and/or Procedures during 
Study Period has been updated. 
• 
Section 6.5 Treatment of the Fellow Eye has been updated. 
• 
Section 6.6.1, a new section, Coronavirus Disease 2019 Considerations has 
been included.  
• 
Section 6.7.1 Prior Treatment has been updated; to confirm that prior 
neovascular (wet) AMD therapies will now be collected 1 month before 
randomization. 
• 
Section 8.5.8 Immunogenicity Endpoints has been updated. 
• 
Section 7.4 Reporting of Serious Adverse Events has been updated with new a 
Japan Safety line. 
• 
Section 8.5.8 Immunogenicity Endpoints has been updated. 


Sponsor Name: Amgen, Inc 
Protocol Number: 20170542 
Protocol Version and Date: Version 3.0, 23 March 2021 
Page 9 of 88 
 
 
Confidential 
 
 
• 
Section 11 Auditing and Monitoring has been updated based on remote 
monitoring visits.  


Sponsor Name: Amgen, Inc 
 
Protocol Number: 20170542 
 
Protocol Version and Date: Version 2.0, 18 October 2019
Page 7 of 84
 
 
 
 
 
 
Confidential 
 
 
 
 
 
PROTOCOL AMENDMENT 1 (OCTOBER 2019) 
Amendment rationale 
The protocol is being amended to adjust the assessments in the protocol based on 
site feedback. 
Changes to the protocol version 1.0 
 
Number of study centers has been updated to 116. 
 
Section 4.1 Inclusion Criteria and section 4.2 Exclusion Criteria have been 
updated. 
 
Neovascular AMD has been updated to neovascular (wet) AMD for 
consistency. 
 
Section 5.2 Efficacy Assessments has been updated. 
 
Section 5.2.4 Fundus photography has been added as an efficacy assessment. 
 
Table 1 Schedule of Activities has been updated to reflect changes. 
Approved 
 
 

SAP_001.pdf: 
Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
Page 1 of 41 
CONFIDENTIAL 
 US Specific Statistical Analysis Plan 
Protocol Title: 
A Randomized, Double-masked, Phase 3 Study of 
ABP 938 Efficacy and Safety Compared to 
Aflibercept (Eylea®) in Subjects with Neovascular 
Age-related Macular Degeneration 
Short Protocol Title: 
NA 
Protocol Number: 
20170542 
NCT Number: 
NA 
Authors: 
, M.S. 
Sponsor: 
Amgen, Inc 
One Amgen Center Drive 
Thousand Oaks, CA USA 91320 
SAP Date: 
Document Version 
Date 
Original – US (v2.0) 
 26 May 2022 
NCT Number: NCT04270747
This NCT number has been applied to the document for 
purposes of posting on Clinicaltrials.gov


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
Page 2 of 41 
CONFIDENTIAL  
 
 
Version Number 
Date 
(DDMMMYYYY) 
Summary of Changes,  
including rationale for changes 
Original – US (v1.0) 
09SEP2019 
NA 
v2.0 
26May2022 
Major updates: 
1. add primary estimand of the study 
to meet regulation obligation per 
protocol amendment 3. (section 
9.5.1) 
2. update the analysis method in 
section 9.5.2.1-9.5.2.3 to use 
stratified Newcombe confidence 
limits (with Mantel-Haenszel 
weights) due to potential non-
convergence in the original 
statistical model. 
3. update ADA windows to align with 
DMC agreed approach (section 
5.1) and add Treatment boosted 
ADA definition (section 9.6.8). 
4. add COVID-19 related information 
in disposition, exposure, AEs and 
IPD sections (section 5.3, 9.2, 9.3, 
9.6.2, 9.6.9) based on release of 
Amgen standard COVID-19 shells. 
5. Add detailed search strategies for 
event of interest (EOI) in Appendix 
1 and analyses of Intraocular 
inflammation and vitreous 
hemorrhage and an Appendix 2 
(section 9.6.1). 
6. add “Subjects with Fellow Eye 
treated prior to week 8 (Y/N)” into 
sensitivity analysis and A 
subgroup analysis: The "Analysis 
of Change from Baseline in Best 
Corrected Visual Acuity at Week 8 
by Subgroup" based on the 
protocol amendment 2 fellow eye 
related updates.  
7. update covariate section to 
exclude CNV and CST from 
subgroup analysis. (section 4.1) 
since CNV and CST do not have a 
clear cutoff to define disease 
severity and subgroup analysis 
cannot be performed. 
Minor editorial changes:  
1. Update List of Abbreviations, text 
in secondary efficacy endpoint, 
study design section, study period, 
ADA section and add fellow eye in 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
Page 3 of 41 
CONFIDENTIAL  
 
 
the through week 8 period 
definition per Protocol Amendment 
2.  
2. Update NRI wording and total IP 
exposure duration and add text to 
show that how imaging 
assessments (CNV area size and 
CST values) are processed in 
database (section 5.1). Clarify 
definition of “TEAE post week 16”, 
and “AEs leading to 
discontinuation from IP/study” in 
alignment with the final AE CRF 
and TEAE for Fellow eye (section 
5.3) and change Duration of 
disease algorithm to be in Weeks. 
(section 9.4). 
 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
Page 4 of 41 
CONFIDENTIAL  
 
 
SPONSOR SIGNATURE PAGE 
 
 
Approved by:  
_________________________ 
 
_______________ 
, MD, MPH                              Date 
 
 
VP Global Development    
Amgen, Inc. 
 
 
 
Approved by:  
_________________________ 
 
_______________ 
, MS                                                Date 
 
 
Biostatistics  
Amgen, Inc. 
 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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Table of Contents 
Table of Contents ................................................................................................... 5 
1. 
Introduction ........................................................................................................... 10 
2. 
Objectives, Endpoints and Hypotheses ................................................................. 10 
2.1 
Objectives and Endpoints .......................................................................... 10 
2.2 
Hypotheses and/or Estimations ................................................................. 11 
3. 
Study Overview .................................................................................................... 11 
3.1 
Study Design ............................................................................................. 11 
3.2 
Sample Size .............................................................................................. 14 
4. 
Covariates and Subgroups ................................................................................... 14 
4.1 
Planned Covariates ................................................................................... 14 
4.2 
Subgroups ................................................................................................. 15 
5. 
Definitions ............................................................................................................. 15 
5.1 
General ..................................................................................................... 15 
Actual Treatment Received ....................................................................... 15 
Baseline 15 
Change from Baseline ............................................................................... 16 
Concomitant and Prior Medication ............................................................ 16 
End of Study (EOS) Date .......................................................................... 16 
First Dose Date ......................................................................................... 16 
Last Dose Date ......................................................................................... 16 
Last observation carried forward (LOCF) .................................................. 17 
Non Responder Imputation (NRI) .............................................................. 17 
Disease Duration ....................................................................................... 17 
Study Day 1 .............................................................................................. 17 
Study Day ................................................................................................. 17 
Study Randomization ................................................................................ 18 
Study Period ............................................................................................. 18 
Study Analysis Visit ................................................................................... 20 
Total IP Exposure Duration ....................................................................... 21 
5.2 
Efficacy ..................................................................................................... 22 
Maintaining Vision ..................................................................................... 22 
CNV Area Size and CST ........................................................................... 22 
5.3 
Safety ........................................................................................................ 22 
AE Leading to Discontinuation from IP/Study ............................................ 22 
COVID-19 AEs .......................................................................................... 22 
Event of Interest (EOI)............................................................................... 22 
Treatment-emergent Adverse Event .......................................................... 22 
6. 
Analysis Sets ........................................................................................................ 23 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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6.1 
Full Analysis Set........................................................................................ 23 
6.2 
Safety Analysis Set ................................................................................... 23 
6.3 
Per Protocol Set(s) .................................................................................... 23 
6.4 
Pharmacokinetic (PK) Analysis Set ........................................................... 23 
7. 
Planned Analyses ................................................................................................. 24 
7.1 
Interim Analysis and Early Stopping Guidelines ........................................ 24 
7.2 
Primary Analysis ....................................................................................... 24 
7.3 
Final Analysis ............................................................................................ 24 
8. 
Data Screening and Acceptance ........................................................................... 24 
8.1 
General Principles ..................................................................................... 24 
8.2 
Data Handling and Electronic Transfer of Data ......................................... 24 
8.3 
Handling of Missing and Incomplete Data ................................................. 25 
Imputation for Partial or Missing Dates ...................................................... 25 
8.4 
Validation of Statistical Analyses ............................................................... 26 
9. 
Statistical Methods of Analysis.............................................................................. 26 
9.1 
General Considerations ............................................................................. 26 
9.2 
Subject Accountability ............................................................................... 27 
9.3 
Important and COVID-19 Related Protocol Deviations .............................. 27 
9.4 
Demographic and Baseline Characteristics ............................................... 28 
9.5 
Efficacy Analyses ...................................................................................... 29 
9.5.1 
Analyses of Primary Efficacy Endpoint/Estimand ....................... 29 
9.5.1.1 
Primary Analysis ..................................................... 29 
9.5.1.2 
Sensitivity Analyses................................................. 30 
9.5.2 
Analyses of Secondary Efficacy Endpoint(s).............................. 31 
9.5.2.1 
Proportion of subjects who maintained 
vision at week 52 ..................................................... 31 
9.5.2.2 
Proportion of subjects who gained ≥ 15 
letters at week 52 .................................................... 32 
9.5.2.3 
Proportion of subjects who gained ≥ 10 
letters at week 8 ...................................................... 32 
9.5.2.4 
Change from baseline in BCVA over the 
study duration.......................................................... 32 
9.5.2.5 
Change from baseline in CNV area size 
and CST over the study duration ............................. 32 
9.5.3 
Analyses of Exploratory Efficacy Endpoint(s) ............................. 32 
9.6 
Safety Analyses ........................................................................................ 33 
9.6.1 
Adverse Events ......................................................................... 33 
9.6.2 
Deaths and Serious Adverse Events ......................................... 35 
9.6.3 
Laboratory Test Results ............................................................ 36 
9.6.4 
Vital Signs ................................................................................. 36 
9.6.5 
Intraocular Pressure .................................................................. 36 
9.6.6 
Slit-Lamp Examination and Indirect Ophthalmoscopy ................ 37 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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9.6.7 
Physical Examinations ............................................................... 37 
9.6.8 
Immunogenicity ......................................................................... 37 
9.6.9 
Exposure to Investigational Product .......................................... 38 
9.6.10 
Prior and Concomitant Medications ........................................... 38 
9.7 
Other Analyses ......................................................................................... 38 
9.7.1 
Analyses of Pharmacokinetic Endpoints .................................... 38 
9.7.2 
Analyses of Clinical Outcome Assessments .............................. 38 
9.7.3 
Analyses of Health Economic Endpoints ................................... 38 
9.7.4 
Analyses of Biomarker Endpoints .............................................. 38 
10. 
Changes From Protocol-specified Analyses.......................................................... 39 
11. 
Literature Citations / References ........................................................................... 39 
Appendix 1 List of Events of Interest and the Associated SMQ and EOI 
Searching Strategies ............................................................................................ 40 
Appendix 2 Search strategy of INTRAOCULAR INFLAMMATION and 
VITREOUS HAEMORRHAGE .............................................................................. 41 
 
List of Table 
Table 1: Calculation of the Duration of wet AMD ........................................................... 17 
Table 2:  Imputation Rules for Partial or Missing Start Dates ......................................... 25 
 
 
 
List of Figures 
Figure 1 
Study Schematic ..................................................................................... 13 
 
 
 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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List of Abbreviations and Definition of Terms 
 
Abbreviation or Term 
Definition/Explanation 
ADA 
antidrug antibody 
AE 
adverse event 
ALT 
alanine aminotransferase 
AMD 
age-related macular degeneration 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
BCVA 
best corrected visual acuity 
CDISC 
standard Clinical Data Interchange Standards Consortium  
CI  
confidence interval 
CNV 
choroidal neovascularization 
COVID-19 
Coronavirus Disease 2019 
CRF 
case report form  
CRO 
contract research organization 
CSR 
clinical study report 
CST 
central subfield thickness 
CTCAE 
Common terminology Criteria for Adverse Events 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
EDC 
electronic data capture 
EOI 
event of interest 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA 
fluorescein angiography 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
ICH 
International Council on Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
IOP 
intraocular pressure 
IP 
investigational product 
IRB 
institutional review board 
IV 
intravenous 
IVT 
intravitreal 
IXRS 
Interactive Web/Voice Response System 
MCAR 
missing completely at random 
MedDRA 
Medical Dictionary for Regulatory Activities 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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NCI 
National Cancer Institute  
OCT 
optical coherence tomography 
PK 
pharmacokinetic(s) 
PP 
per protocol 
PT 
preferred term  
SAP 
statistical analysis plan 
SDTM 
Standard Data Tabulation Model 
SD-OCT 
spectral domain optical coherence tomography 
TEAE 
treatment-emergent adverse event 
WBC 
white blood cell 
 


Product:  ABP 938  
Protocol Number:  20170542 
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1. 
Introduction 
The purpose of this US-specific Statistical Analysis Plan (SAP) is to provide details of 
the statistical analyses that have been outlined within the protocol for ABP 938 study 
20170542 (version 4.0, dated 16May2022) and the additional analyses to support the 
BLA submission in the US. The scope of this plan includes the primary analysis and the 
final analysis that are planned and will be executed by the designated contract research 
organization (CRO), Parexel International. 
2. 
Objectives, Endpoints and Hypotheses 
2.1 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
Primary efficacy endpoint 
To assess the efficacy of ABP 938 compared 
to aflibercept. 
Change from baseline in best corrected visual 
acuity (BCVA) as measured by Early 
Treatment Diabetic Retinopathy Study 
(ETDRS) letter score at week 8 
 
Secondary efficacy endpoints 
 
Proportion of subjects who maintained vision 
at week 52, where a subject was classified as 
maintaining vision if he/she lost fewer than 
15 letters in ETDRS letter score compared to 
baseline  
 
Change from baseline in BCVA as measured 
by ETDRS letter score over the study duration  
 
Proportion of subjects who gained at least 
10 letters of vision at week 8 and proportion of 
subjects who gained at least 15 letters of 
vision at week 52 as compared to baseline 
 
Change from baseline in choroidal 
neovascularization (CNV) area size as 
measured by fluorescein angiography (FA) 
and central subfield thickness (CST) as 
measured by spectral domain optical 
coherence tomography (SD-OCT) over the 
study duration   
Secondary 
To assess the safety and immunogenicity of 
ABP 938 compared to aflibercept. 
Treatment-emergent adverse events, adverse 
events of interest (EOIs), and serious adverse 
events 
 
Incidence of antidrug antibodies (ADAs) 
Primary estimand: 
The primary estimand is the difference in change from baseline in BCVA at week 8 
between the ABP 938 group and the aflibercept group in subjects with neovascular (wet) 
age-related macular degeneration (AMD) who are randomized, regardless of missing or 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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CONFIDENTIAL  
 
 
discontinuing investigational product administration to the study eye, or use of additional 
medications for AMD in the study eye prior to observing BCVA at week 8. 
2.2 
Hypotheses and/or Estimations 
The study will assess the hypothesis that there are no clinically meaningful differences 
between ABP 938 and aflibercept treatment arms in the primary efficacy endpoint: BCVA 
change from baseline at week 8. For the marketing application globally, this primary 
efficacy endpoint will be evaluated by comparing the 2-sided 95% Confidence Interval 
(CI) of the mean difference between ABP 938 and aflibercept arms with an equivalence 
margin of (-3.9, 3.9).  For the BLA submission in the US, the primary endpoint will be 
evaluated by comparing the 2-sided 90% CI (rounded to the nearest integer) with an 
equivalence margin of (-3, 3).  
3. 
Study Overview 
3.1 
Study Design 
This is a randomized, double-masked, active controlled multiregional clinical study in 
adult subjects with neovascular Age-related Macular Degeneration (wet AMD).  
Approximately 566 subjects (including at least 30 subjects from East Asia) will be 
randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 
(Treatment Group A) or aflibercept (Treatment Group B) administered by intravitreal 
(IVT) injection every 4 weeks for the first 3 doses (i.e., baseline/day 1, week 4, and week 
8).  Randomization will be stratified by geographic region and disease severity (baseline 
BCVA < 64 letters vs. ≥ 64 letters). 
At week 8, subjects will be assessed for the primary endpoint (BCVA change from 
baseline as measured by ETDRS).  Subjects will then be re-randomized at week 16 in a 
masked fashion such that: 
• 
Subjects initially randomized to ABP 938 (Treatment Group A) will continue to 
receive ABP 938 by IVT injection every 8 weeks from week 16 until week 48 
• 
Subjects initially randomized to aflibercept (Treatment Group B) will be re-
randomized in a 1:1 ratio to either continue on aflibercept (Treatment Group B1) 
or transition to ABP 938 (Treatment Group B2) by IVT injection every 8 weeks 
from week 16 until week 48 
Re-randomization will be stratified using the same factors as the initial randomization.   
Subjects who are unable to complete the week 16 visit within the visit window will not be 
re-randomized, will be discontinued from the study, and will be asked to return to 


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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complete an end-of-study (EOS) visit within 28 days from determining that the subject 
will discontinue from the study.  An end-of-study visit will be conducted at week 52 for 
subjects that complete the study.  The study design and treatment schema are 
presented in Figure 1. 
The primary analysis for the study is planned when all subjects reach week 24 or 
terminate early.  This analysis will comprise at least 24 weeks of efficacy, safety, and 
immunogenicity data.  The final analysis is planned when all enrolled subjects complete 
the week 52 visit or terminates early.  An external, independent data monitoring 
committee (DMC) will evaluate the safety data throughout the study. 
The treatment of the fellow eye is allowed starting at baseline (day 1) if needed.  
Approximately 32 subjects will be consented and enrolled into a Pharmacokinetic (PK) 
substudy.  These subjects will have a PK sample collected predose (within 60 minutes 
before day 1 dose) and postdose at day 1 (approximately 24 hours after day 1 dose), 
with an allowable window -6 hours to +24 hours (ie, 18 hours to 48 hours after day 1 
dose) and postdose at week 8 (approximately 24 hours after week 8 dose), with an 
allowable time window of -6 hours to +24 hours (ie, 18 hours to 48 hours postdose). 
If it is anticipated that the fellow eye will need to be treated prior to the week 8 postdose 
PK sample, then the subject should not be enrolled into the PK substudy. If an enrolled 
PK substudy subject develops a requirement for fellow eye treatment prior to week 8 
postdose PK sample, no further PK samples will be collected.  
If the need for treating the fellow eye is identified at the week 8 visit, then the fellow eye 
must be treated after the week 8 postdose PK sample has been drawn for those 
subjects included in the PK substudy.  


Product:  ABP 938  
Protocol Number:  20170542 
Date:  26 May 2022 
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Figure 1 
Study Schematic 
Week 52
Treatment Group A:
ABP 938 2mg 
(every 4 weeks) 
3 doses (Day 1, W4, W8)
N 283
Treatment Group B:
Aflibercept 2mg 
(every 4 weeks) 
3 doses (Day 1, W4, W8)
N 283
Treatment Group A (N283):
ABP 938 2mg 
(every 8 weeks) 
5 doses (W16, W24, W32, W40, W48)
Treatment Group B1 (N 141):
Aflibercept 2mg 
(every 8 weeks) 
5 doses (W16, W24, W32, W40, W48)
S
C
R
E
E
N
I
N
G
R
A
N
D
O
M
I
Z
A
T
I
O
N
Treatment Group B2 (N 141):
ABP 938 2mg 
(every 8 weeks) 
5 doses (W16, W24, W32, W40, W48)
E
N
D
O
F
S
T
U
D
Y
Day 1
≤ 4 weeks
Last Dose: Week 48
Week 16
Primary Analysis: Week 24
R
E
-
R
A
N
D
O
M
I
Z
E
Week 8*
*Primary Endpoint assessment will be performed at Week 8.  
 


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Protocol Number:  20170542 
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3.2 
Sample Size 
Approximately 566 subjects (including at least 30 East Asian subjects) will be 
randomized in a 1:1 ratio initially to receive ABP 938 (Treatment Group A) or aflibercept 
(Treatment Group B).  The total sample size will provide > 90% power to demonstrate 
equivalence at a 2-sided significance level of 0.025 with an equivalence margin of (-3.9, 
3.9) (global) on the primary efficacy endpoint BCVA change from baseline at week 8, 
assuming a true mean difference of 0 in the primary endpoint between the 2 groups, a 
standard deviation of 12.5 letters, and a 2% dropout by week 8.  It will also provide 
approximately 90% power (with rounding of CI) to demonstrate equivalence at a 2-sided 
significance level of 0.05 with a margin of (-3, 3) (US). In addition, the number of East 
Asian subjects (i.e., at least 30) was chosen to enable an assessment of the treatment 
difference within East Asian subjects with reasonable accuracy and precision, while 
ensuring the study recruitment is feasible and can be completed in a timely manner.   
4. 
Covariates and Subgroups 
4.1 
Planned Covariates 
Unless stated otherwise, the following stratification factors will be adjusted as covariates 
in models or will be used to examine treatment effect in subgroups: 
• 
Geographic region (East Asia, Europe, North America) 
• 
Disease severity (baseline BCVA < 64 letters vs. ≥ 64 letters). 
In addition, the following covariates may be used for further exploration in subgroups or 
as covariates: 
• 
Age (< 65 years vs. ≥ 65 years) 
• 
Race (White vs. Non-White) 
• 
Gender 
• 
CNV area size (excluding from subgroups) 
• 
CST (excluding from subgroups) 
• 
Subjects with Fellow Eye treated prior to week 8 (Y/N) 
• 
Baseline BCVA measurement (continuous)  
Covariate values may be discordant if collected via CRF and IXRS. Analyses that are 
intended to evaluate the treatment effect and include stratification variables as 
covariates in the model will be based on the CRF stratification values, regardless of the 


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subject’s IXRS stratification values, to provide unbiased estimates of the effects of 
treatment and stratification variables without loss of efficiency (Ke et al, 2017). 
4.2 
Subgroups 
Please refer to Section 4.1. 
For subgroup analyses where the subgroup factor is a stratification variable, an analysis 
similar to the primary analysis (except the inclusion of the subgroup factor) should be 
done for each subgroup defined by the CRF values of the subgroup factor. 
5. 
Definitions 
5.1 
General 
Actual Treatment Received 
The actual treatment received on an eye level (separately for the study eye and the 
fellow eye) is the IP treatment the eye actually received, regardless of what the subject 
was randomized to.  For each of the “through week 8”, “through week 16”, and “post 
week 16” study periods (see definition of Study Period later in this section), if an eye 
received both ABP 938 and aflibercept, the actual treatment received will be based on 
the majority of the IP treatment the eye received during that study period. In the case of 
a tie, the actual treatment received will be assigned to ABP 938. For the “entire study” 
study period, the actual treatment sequence for subjects who were re-randomized and 
treated post re-randomization will be defined based on the actual treatments received 
during the “through week 16” and “post week 16” study periods.  
The actual treatment received on a subject level will be set to be same as the actual 
treatment received for the study eye. 
Baseline 
Unless stated otherwise, the baseline at the subject level (aka study baseline) is defined 
as the last non-missing assessment taken prior to the first dose of IP the subject 
received (see definition of first dose date for the subject later in this section). In cases 
where baseline assessments are taken on the same day as the first dose of IP, and 
either no times are reported or the IP and assessment times are the same, it will be 
assumed that these assessments are taken prior to IP being administered. For subjects 
who are randomized but not dosed after the randomization, the baseline is defined as 
the last non-missing assessment prior to or on the date of randomization.   


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The baselines at the eye level for study eyes and fellow eyes are defined according to 
the first dose date of the respective eye (see definitions of the first dose date for the 
study eye and the fellow eye later in this section). 
Change from Baseline 
Change from baseline at the subject level or eye level is defined as (value at post-
baseline visit – value at baseline), where subject or eye level post-baseline and baseline 
values are used, respectively.  Refer to definitions of baseline for the subjects, study 
eyes, and fellow eyes above.  
Concomitant and Prior Medication 
Prior medications are defined as medications with a stop date prior to first dose of IP the 
subject received (see definition of first dose date for the subject). Concomitant 
medications are defined as any medications ongoing at the start of IP treatment for the 
subject or with a start date on or after the first dose date.  
End of Study (EOS) Date 
The EOS date is the date recorded on the End of Study page of the CRF. 
First Dose Date   
• 
First Dose Date for the Study Eye 
 It is defined as the date on which the study eye is administered the first dose of IP.  
• 
First Dose Date for the Fellow Eye 
 It is defined as the date on which the fellow eye is administered the first dose of IP.  
• 
First Dose Date for the Subject 
It is defined as the date the subject received the first dose of IP (i.e., earlier of the first 
dose dates of study eye and fellow eye). According to the protocol, it is expected to be 
the same as the first dose date for the study eye.  
Last Dose Date   
• 
Last Dose Date for the Study Eye 
 It is defined as the date on which the study eye is administered the last dose of IP.  
• 
Last Dose Date for the Fellow Eye 
 It is defined as the date on which the fellow eye is administered the last dose of IP.  
• 
Last Dose Date for the Subject 
 It is defined as the later of last dose date for the study eye and the fellow eye.  


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Protocol Number:  20170542 
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Last observation carried forward (LOCF)   
A method of imputation where missing post-baseline data will be imputed by carrying 
forward the last non-missing post-baseline value for that endpoint.  Baseline values will 
not be carried forward. 
Non Responder Imputation (NRI) 
A method of imputation where subject with missing post-baseline value of a binary 
endpoint will be imputed as a non-responder, regardless of the reasons for missing data.  
Disease Duration 
The disease duration is the number of weeks from the date of diagnosis of wet AMD to 
the date of randomization, which will be derived based on the table below. No imputation 
will be done for disease diagnosis date, but to avoid disease duration of zero, 1 month 
(or 4.34524 weeks) may be added. 
Table 1: Calculation of the Duration of wet AMD 
Observed 
portion  
Missing 
portion  
Formula to Calculate Duration  
Year, Month, 
Day 
 
(Date of Randomization – Date of wet AMD Diagnosis + 
1)/365.25 
Year, Month  
Day  
[Year(Date of Randomization)-Year(Date of wet AMD 
Diagnosis)]+ [Month(Date of Randomization)-
Month(Date of wet AMD Diagnosis)]/12* 
Year 
Month, 
Day 
[Year(Date of Randomization)-Year(Date of wet AMD 
Diagnosis)] *  
     *if the duration equals 0, add 1 month or 4.34524 weeks. 
 
Study Day 1 
Study day 1 is defined as the first day of IP the subject received (see definition of first 
dose date for the subject). For subjects who are randomized but not dosed after 
randomization, study day 1 is defined as the date of study randomization.  
Study Day 
Study day is defined as the number of days from Study Day 1. 
• 
Before Study Day 1: Study Day = (Date of assessment – Date of Study Day 1) 
• 
On or After Study Day 1: Study Day = (Date of assessment – Date of Study Day 1)+1 
Therefore, the day prior to Study Day 1 is -1.  
 


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Study Randomization 
Study randomization is defined as when subject initially receives a random treatment 
allocation via the IXRS system.   
Study Period 
Study periods are defined separately for subjects, study eyes, and fellow eyes. 
 
At a subject level:   
• 
Through Week 8: 
It is defined as the time period from the first dose of IP the subject received (see 
definition of first dose date for the subject) to the week 8 dose date (earlier of the dosing 
dates of the study eye and fellow eye) for subjects who have received week 8 dose, or to 
the EOS visit for subjects discontinued the study prior to week 8 visit, or to Study Day 64  
for subjects who have never received week 8 dose but remained on study. According to 
the protocol, the treatment of the fellow eye is allowed starting at baseline (day 1) if 
needed. Subjects are classified according to their randomized treatment at study 
randomization (aka initial randomized treatment) (ABP 938 or aflibercept) for efficacy 
analysis. Subjects are classified according to their treatment actually received at the 
subject level (ABP 938 or aflibercept) for safety and immunogenicity analysis. 
• 
Through Week 16: 
It is defined as the time period from the first dose of IP the subject received (see 
definition of first dose date for the subject) to the 1st dose (earlier of the dosing dates for 
study eye and fellow eye) post re-randomization for re-randomized and treated subjects, 
or to the EOS visit for subjects not re-randomized or for subjects who were re-
randomized but not treated post re-randomization. For subjects that are ongoing (i.e. 
EOS visit not available), the analysis data cutoff date will be used. Subjects are 
classified according to their randomized treatment (ABP 938 or aflibercept) for efficacy 
analyses. Subjects are classified according to their treatment actually received at the 
subject level (ABP 938 or aflibercept) for safety and immunogenicity analyses.     
• 
Post Week 16  
It is defined as the time period from the first dose (earlier of the dosing dates for study 
eye and fellow eye) post re-randomization to the EOS visit or analysis data cutoff date, 
whichever is earlier. Subjects are classified according to their full treatment sequence: 
ABP 938/ABP 938, aflibercept/aflibercept, or aflibercept/ABP 938. Planned treatment 


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sequence will be used for efficacy analysis and actual treatment sequence at the subject 
level will be used for safety and immunogenicity analyses.   
• 
Entire Study  
It is defined as the time period throughout the study from the first dose of IP the subject 
received (see definition of first dose date for the subject) to the EOS visit or analysis 
data cutoff date, whichever is earlier. Subjects are classified according to their full 
treatment sequence: ABP 938/ABP 938, aflibercept/aflibercept, or aflibercept/ABP 938. 
Planned treatment sequence will be used for efficacy analysis and actual treatment 
sequence at the subject level will be used for safety and immunogenicity analyses.   
At an eye level: 
The study periods for the study eye and fellow eye are defined based on the first dose 
and last dose dates of the respective eye. Efficacy analyses will be performed only for 
the study eye and will be based on the randomized treatment or treatment sequence for 
the study eye. Safety analyses for study eyes and fellow eyes will be based on actual 
treatment or treatment sequence received in the respective eye (see the definition of 
actual treatment in section 5.1). 
• 
Through Week 8: 
It is defined as the time period from the first dose of IP of the study eye (fellow eye) to 
the week 8 dose date of the study eye (fellow eye) for subjects who have received week 
8 dose to the study eye (fellow eye), or to the EOS visit for subjects discontinued the 
study prior to week 8 visit, or to Study Day 64 for subjects who have never received 
week 8 dose for the study eye (fellow eye) but remained on study.  Study eyes (fellow 
eye) are classified according to treatment actually received by the study eyes (fellow 
eyes) (ABP 938 or aflibercept) for safety analyses.   
• 
Through Week 16: 
It is defined as the time period from the first dose of IP of the study eye (fellow eye) to 
the first dose of IP of the study eye (fellow eye) post re-randomization for re-randomized 
and treated subjects or to the EOS visit or for subjects not re-randomized or for subjects 
who were re-randomized but not treated post re-randomization.  For subjects that are 
ongoing (i.e. EOS visit not available), the analysis data cutoff date will be used. Study 
eyes (fellow eyes) are classified by the treatment the study eyes (fellow eyes) actually 
received (ABP 938 or aflibercept) for safety analyses.      
• 
Post Week 16  


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It is defined as the time period from the first dose of IP of the study eye (fellow eye) post 
re-randomization to the EOS visit or analysis data cutoff date, whichever is earlier. Study 
eyes (fellow eyes) are classified according to their full treatment sequence as received 
(ABP 938/ABP 938, aflibercept/aflibercept, or aflibercept/ABP 938) for safety analyses   
• 
Entire Study  
It is defined as the time period throughout the study from the first dose of IP of the study 
eye (fellow eye) to the subject’s EOS visit or analysis data cutoff date, whichever is 
earlier. Study eyes (fellow eyes) are classified according to their full treatment sequence 
as received (ABP 938/ABP 938, aflibercept/aflibercept, or aflibercept/ABP 938) for safety 
analyses.     
Study Analysis Visit 
Since the actual visit for a subject may not exactly coincide with their scheduled visit 
date, the actual visit date is mapped to the study analysis visit as follows. The actual visit 
date is allowed to fall within a specified interval of the target day; this avoids the 
existence of gaps between weeks. 
If more than one actual visit (including the unscheduled visits) falls within the same 
defined window, the visit closest to the target day with non-missing data will be 
considered for analysis. If two actual visit dates are at the same distance from the target 
day, the later visit with non-missing data will be considered for analysis.  
For efficacy, intraocular pressure, indirect ophthalmoscopy, slit-lamp: 
 
Study Analysis Visit  
Target Day  
Study Day  
Interval (days) 
Baseline 
1  
≤1  
NA  
Week 4 
29 
22-36 
15 
Week 8 
57 
50-64 
15 
Week 16 
113 
86 – 141 
56 
Week 24 
169 
142 – 197 
56 
Week 32 
225 
198 – 253 
56 
Week 40 
281 
254 - 309 
56 
Week 48 
337 
310 - 351 
42 
Week 52 
365 
≥352 
NA 
                 
For vital signs, safety laboratory a (including serum chemistry, hematology, 
urinalysis)   
Study Analysis Visit  
Target Day  
Study Day  
Interval (days) 
Baselineb 
1  
≤1  
NA  
Week 8 
57 
50-64 
15 
Week 16 
113 
86 – 141 
56 


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Week 52 
365 
≥352 
NA 
                 a Laboratory parameters will only be included at the visits where it is scheduled for 
assessment in the output tables. 
b If a subject has laboratory measurements on the same day as the first dose date but at 
a time after the first dose of IP is administered, the lab measurements will not be defined 
as baseline, but as week 8 measurements.  
The rules above for selecting a visit from multiple ones within the same visit window are 
not applicable to retest values of lab data. If the lab measurement is a retest, the retest 
value will be chosen. 
For ADA: 
 
Study Analysis Visit  
Target Day  
Study Day  
Baseline 
1  
≤1  
by Week 8 
57 
≤64 
by Week 16 
113 
≤141 
by Week 24 
169 
≤197 
by Week 40 
281 
≤309 
by Week 52 
365 
NA 
 
For PK substudy: 
Nominal visits will be used for PK analysis and analysis windows are not defined for PK 
visits. 
Total IP Exposure Duration 
The total IP exposure duration for the subject (in days) for each study period (through 
week 8, through week 16, post week 16, and entire study) will be derived as: the period 
end date for the subject – the period start date for the subject +1.  
The total IP exposure duration for the study eye (in days) for each study period (through 
week 8, through week 16, post week 16, and entire study) will be derived as: the period 
end date for the study eye – the period start date for the study eye +1. 
The total IP exposure duration for the fellow eye (in days) for each study period (through 
week 8, through week 16, post week 16, and entire study) will be derived as: the period 
end date for the fellow eye – the period start date for the fellow eye+1. 
The definitions for each study period at the subject level and eye level are defined in 
section 5.1. 


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5.2 
Efficacy 
Maintaining Vision  
A subject is classified as maintaining vision if he/she loses fewer than 15 letters in 
ETDRS letter score, assessed on the study eyes, compared to baseline.  
CNV Area Size and CST 
For imaging assessments, when three readers are used, the median value is used for 
analysis. When two readers are used, the mean value is used for analysis. When only 
one reader is used then that value is used for analysis. 
5.3 
Safety 
AE Leading to Discontinuation from IP/Study 
AEs leading to discontinuation from IP/study are those with an action taken with 
Investigational Medicinal Product indicating “drug withdrawn” or Other action taken of 
“study discontinued”. 
COVID-19 AEs 
COVID-19 AEs will be flagged based on the COVID-19 standardized query (SMQ) of the 
current MedDRA version at the time of the primary analysis. 
Event of Interest (EOI) 
An EOI is defined as a noteworthy event for a particular product or class of products that 
a sponsor may wish to monitor carefully. It could be serious or non-serious and could 
include events that might be potential precursors or prodromes for more serious medical 
conditions in susceptible individuals (Council for International Organizations of Medical 
Sciences [CIOMS] VI, 2005). The EOIs for this study will include:  
• 
Endophthalmitis 
• 
Retinal Detachment 
• 
Increase in Intraocular Pressure 
• 
Thromboembolic events 
The detailed search strategies for the EOIs are included in Appendix 1.    
Treatment-emergent Adverse Event  
A treatment-emergent AE (TEAE) for subjects, study eye, and fellow eye is defined for 
each study periods, when applicable. 
A treatment-emergent AE (TEAE) for a given study period is defined as an AE that 
begins in the respective study period (see definition of Study Period in section 5.1).    


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If the AE starts on the same day as the first dose of IP then the flag indicating whether 
the AE started prior to the first dose on the adverse event CRF page will be used. For re-
randomized and treated subjects, an AE that starts on the same day as the first dose 
post re-randomization will be considered as a TEAE post week 16. 
Ocular AEs that occur in the fellow eye prior to fellow eye treatment are considered 
treatment-emergent at the subject level but will not be considered treatment-emergent 
for fellow eye. 
6. 
Analysis Sets 
6.1 
Full Analysis Set 
The Full Analysis Set (FAS) will include all randomized subjects.  It will be analyzed 
according to randomized treatment (regardless of actual treatment received).  This 
analysis set will be the primary set used for analyses/summaries of the primary efficacy 
endpoint, as well as for all secondary efficacy endpoints. 
6.2 
Safety Analysis Set 
The Safety Analysis Set will include all subjects who receive at least one dose of IP. It 
will be analyzed according to actual treatment received.  This analysis set will be used 
for summaries of safety data as well as immunogenicity data.    
6.3 
Per Protocol Set(s) 
The Per protocol (PP) Analysis Set will include all subjects in the FAS who have 
completed dosing at day 1 and week 4 and have completed BCVA assessment at week 
8 without experiencing an important protocol deviation that may affect their evaluation for 
the primary endpoint of the study. Important protocol deviations that could affect the 
primary endpoint will be defined and agreed upon before unmasking for the primary 
analysis. This analysis set will be used for sensitivity analyses for the primary and key 
secondary efficacy endpoints.  Analyses will be based on actual treatment the subject 
received in the study eye (see definition of actual treatment received at the study eye 
level in section 5.1). 
6.4 
Pharmacokinetic (PK) Analysis Set 
The PK Analysis Set will include all subjects enrolled in the PK substudy who receive at 
least one dose of IP between day 1 and week 8 (inclusive) and who have at least 1 
reported serum concentration of ABP 938 or aflibercept. The analysis set will be 
analyzed according to actual treatment the subject received in the study eye (see 
definition of actual treatment received at the study eye level in section 5.1). 


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7. 
Planned Analyses 
7.1 
Interim Analysis and Early Stopping Guidelines 
No interim analyses are planned for this study. 
7.2 
Primary Analysis 
The primary analysis (PA) for the study will be performed after all subjects reach week 
24 or terminate early, and the analysis will comprise at least 24 weeks of efficacy, safety, 
and immunogenicity data. 
All data collected by the time of data cut will be included in the PA. An independent 
unmasked team who are not involved in the operations of the study after PA database 
lock will perform the PA. 
7.3 
Final Analysis 
The final analysis will be performed at the end of study after all enrolled subjects have 
completed week 52 visit (or early terminated from the study). 
8. 
Data Screening and Acceptance 
8.1 
General Principles 
The objective of the data screening is to assess the quantity, quality, and statistical 
characteristics of the data relative to the requirements of the planned analyses. 
Data screening process will be documented in a data management plan by Parexel and 
agreed by Amgen.  In addition to the data screening built into the Parexel Data 
Management Plan, the programming of analysis datasets, tables, figures and listings 
(TFL) provides additional data screening.  
When the database has been declared to be complete and accurate, the database will 
be locked.  Database lock will follow the standard operating procedure(s) at Parexel. 
8.2 
Data Handling and Electronic Transfer of Data 
Clinical data will be entered in RAVE database and exported as SAS® version 9.4 or 
higher datasets. Converted datasets will be created using SAS® and following standard 
Clinical Data Interchange Standards Consortium Standard Data Tabulation Model 
(CDISC SDTM, version 1.4, Implementation Guide version v3.2) conventions.  Analysis 
datasets will be created using SAS® and following CDISC Analysis Data Model (ADaM, 
version 2.1, Implementation Guide 1.1) standards. 
Medical history and AEs will be coded using the current version of MedDRA at the time 
of the primary analysis to assign a system organ class (SOC) and preferred term (PT) to 
each event. Adverse events and abnormal laboratory results considered as AEs are 


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assigned a toxicity grade according to National Cancer Institute (NCI-US) Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.03. Prior and concomitant 
medications will be coded using the current version of the World Health Organization 
Drug Dictionary (WHO-DD) at the time of the primary analysis. 
8.3 
Handling of Missing and Incomplete Data 
For both the primary and secondary efficacy endpoints, the primary analysis will be 
based on observed data and FAS; missing values will not be imputed. As a sensitivity 
analysis, missing data will be imputed by LOCF for the primary endpoint and NRI for the 
binary secondary endpoints.  In addition, for the primary endpoint, tipping point analyses 
and a repeated-measures analysis will be performed to explore the sensitivity of the 
results based on different assumptions for the missing data.  
Missing safety and PK endpoints will not be imputed. 
Imputation for Partial or Missing Dates 
If dates are missing or incomplete for an AE (including deaths) or concomitant 
medication, the following algorithm will be used for imputation:  
Table 2:  Imputation Rules for Partial or Missing Start Dates 
Start Date 
Stop Date 
Complete: 
yyyymmdd 
Partial: yyyymm 
Partial: yyyy 
Missing 
<1st 
dose 
≥1st 
dose 
<1st 
dose 
yyyymm 
≥1st dose 
yyyymm 
<1st 
dose 
yyyy 
≥1st 
dose 
yyyy 
Partial: 
yyyym
m 
= 1st 
dose 
yyyymm 
2 
1 
n/a 
1 
n/a 
1 
1 
≠ 1st 
dose 
yyyymm 
2 
2 
2 
2 
2 
2 
Partial: 
yyyy 
= 1st 
dose 
yyyy 
3 
1 
3 
1 
n/a 
1 
1 
≠ 1st 
dose 
yyyy 
3 
3 
3 
3 
3 
Missing 
4 
1 
4 
1 
4 
1 
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 


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4 = Impute as January 1 of the stop year 
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 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. 
8.4 
Validation of Statistical Analyses 
All report outputs will be produced/All statistical analyses will be performed using SAS® 
version 9.4 or a higher version in a secure and validated environment. 
Programs will be developed and maintained and output will be verified in accordance 
with current standard operating procedures at Parexel.  The validation process is 
repeated any time TFLs are re-delivered with different data.  Execution of this validation 
process is documented throughout the study. The entire set of TFLs will be checked for 
completeness, accuracy prior to its delivery to Amgen. 
9. 
Statistical Methods of Analysis 
9.1 
General Considerations 
All statistical analyses will be performed using SAS® (Version 9.4 or higher). 
Unless otherwise specified, descriptive data summaries will be tabulated by treatment 
for all endpoints. Categorical data will be summarized using number of subjects, 


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frequency and percentages of subjects falling into each category, with the denominator 
for percentages being the number of subjects in the analysis sets for each treatment 
group, unless otherwise noted. Percentages will be rounded to one decimal place except 
for 100%, which will have no decimal place. 
All continuous variables will be summarized using mean, standard deviation, median, 
minimum, maximum, 25th percentile (Q1), 75th percentile (Q3), and number of subjects 
with observations. The mean, median, Q1, and Q3 will be presented to one decimal 
place greater than the original data, standard deviation will be to two decimal places 
greater than the original data, and the minimum and maximum will have the same 
number of decimal places as the original data.  
Confidence intervals (CIs) may also be provided (when specified). 
 
For any of the summaries that are to be done by visit, the derived analysis study visit as 
defined in Section 5.1 will be used for analysis unless otherwise noted. 
9.2 
Subject Accountability 
The following information will be summarized for subject disposition and accountability: 
• 
Number of subjects randomized at the initial randomization (2 treatment groups) 
and re-randomization (3 treatment sequences) by geographic region, country, 
and site. 
• 
Subject disposition before and after re-randomization (including number of 
subjects who were randomized, treated with ABP 938/aflibercept in study eye 
and fellow eye, completed IP in study eye, discontinued IP in study eye and 
fellow eye with reason of discontinuation, completed study and discontinued 
study with reason of discontinuation) for each of the analysis sets defined in 
Section 6. Note that discontinued IP and discontinued study due to COVID-19 
related reasons will be further summarized by Adverse Event or “Other”. 
• 
Number of screened subjects and number of subjects in each analysis set by 
initial randomized treatment, and reasons for exclusion from each analysis set. 
• 
Randomization list of subjects and their actual versus randomized and/or re-
randomized treatment groups for all randomized subjects. 
9.3 
Important and COVID-19 Related Protocol Deviations 
Important Protocol Deviations (IPDs) data will be identified and recorded. The study 
team will conduct on-going reviews of the IPD data throughout the study and the 


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resulting set of subjects to be included in the PP analysis set. The PP analysis set must 
be finalized prior to database lock of each analysis. 
A summary of incidence of IPDs will be tabulated using number and percentage of 
subjects by deviation type (including COVID-19 related) and initial randomized treatment 
through week 16 and by initial/re-randomized treatment through entire study. In addition, 
a summary of incidence of any eligibility related PDs (regardless of important or not 
important) will be tabulated using number and percentage of subjects by deviation type 
and initial randomized treatment. Listings of subjects with IPDs will be provided to 
support these summary tables (with a flag indicating whether the deviation leads to 
exclusion from the PP analysis set, and another flag indicating if COVID-19 related in all 
listings). A subject listing with eligibility criteria deviations will also be provided. 
Furthermore, all COVID-19 related protocol deviations (PD) will be summarized by 
COVID-19 related deviation type for the FAS through week 16 and entire study. Listings 
of subjects with COVID-19 related PDs will be provided to support these summary 
tables.  
9.4 
Demographic and Baseline Characteristics 
The following demographics and baseline characteristics will be summarized by 
treatment for the FAS, PP analysis set, and safety analysis set and by treatment 
sequence for the subset of subjects in the FAS who are re-randomized and for the 
subset of subjects in the safety analysis set who are re-randomized and treated post re-
randomization:  
• 
age (in years, at time of signing informed consent) and age category (< 65 vs ≥ 
65),  
• 
race,  
• 
sex,  
• 
ethnicity,  
• 
height,  
• 
weight,  
• 
body mass index (BMI),  
• 
geographic region,  
• 
duration of disease (in weeks),  
• 
baseline BCVA group (≤ 64 vs > 64 letters), 
• 
BCVA ETDRS letter score,  
• 
CNV area size, 


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• 
CST  
 
9.5 
Efficacy Analyses 
Efficacy analyses will be performed for the study eye and will be based on the 
randomized treatment or treatment sequence for the study eye. 
9.5.1 
Analyses of Primary Efficacy Endpoint/Estimand 
The primary estimand is the difference in change from baseline in BCVA at week 8 
between the ABP 938 group and the aflibercept group in subjects with neovascular (wet) 
AMD who are randomized, regardless of missing or discontinuing investigational product 
administration to the study eye, or use of additional medications for AMD in the study 
eye prior to observing BCVA at week 8. 
The intercurrent events will be handled using a treatment policy strategy. The value of 
BCVA at week 8 (if observed) will be used regardless of whether an intercurrent event 
occurs.  Missing BCVA value at week 8 is assumed to be missing completely at random 
(MCAR) for the primary analysis for the primary estimand based on observed data using 
the FAS.   
The primary efficacy endpoint is change from baseline in BCVA as measured by ETDRS 
letter score at week 8. 
9.5.1.1 
Primary Analysis  
The primary analysis will be performed using the FAS based on randomized treatment 
and observed data. 
Analysis will assess the hypothesis that there are no clinically meaningful differences 
between ABP 938 and aflibercept treatment arms in BCVA change from baseline at 
week 8. The clinical similarity will be evaluated by comparing the 2-sided 95% CI of the 
change from baseline at week 8 of BCVA between ABP 938 and aflibercept arms with 
an equivalence margin of (-3.9, 3.9) (global).  If the 2-sided 95% CI is within the pre-
specified global equivalence margin (-3.9, 3.9), then it is declared that ABP 938 and 
aflibercept is clinically similar per global criteria. For the US BLA submission, the clinical 
similarity will be evaluated by comparing the 2-sided 90% CI (rounding to the nearest 
integers) of the change from baseline at week 8 of BCVA between ABP 938 and 
aflibercept arms with an equivalence margin of (-3, 3). The point estimate of the mean 
difference in change from baseline in BCVA at week 8 between ABP 938 and aflibercept 
and its corresponding 2-sided 90% and 95% confidence intervals will be obtained from 


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an ANCOVA model with treatment, region and baseline BCVA measurement as 
covariates.  Regions with small number of subjects in them will be combined.   
9.5.1.2 
Sensitivity Analyses 
To assess the robustness of the primary analysis result, the ANCOVA analysis 
described above will be repeated using the PP analysis set based on observed cases 
and using FAS analysis set based on LOCF imputation. 
In addition, a repeated-measures analysis for day 1 through week 8 period based on 
FAS analysis set will be performed as a sensitivity analysis. Besides the stratification 
factor of region, the baseline BCVA value, visit, treatment, and treatment-by-visit 
interaction will be included in the model, with visit as a categorical variable. The point 
estimate of the mean difference in change from baseline in BCVA at week 8 between 
ABP 938 and aflibercept and its corresponding 2-sided 90% and 95% confidence 
intervals will be obtained. The mixed model repeated measures analysis will be 
implemented using PROC MIXED and a compound symmetry covariance structure in 
SAS.   
Another sensitivity analysis based on FAS will be done to explore the impact of the 
baseline covariates in section 9.4 on BCVA change from baseline at week 8 in addition 
to the stratification factor of region and the baseline BCVA value. A stepwise model 
selection (with <0.25 p-value to enter the model and <0.1 to stay in the model) will be fit 
using PROC GLM and will be used to determine if any of the covariates have significant 
impact on the outcome variable. The final ANCOVA model will be fit using PROC GLM 
and will maintain treatment, the stratification factor region, the baseline BCVA value, and 
the covariates identified by the stepwise model.  
In addition, the mean difference in the BCVA change from baseline at week 8 between 
the two group will be examined in the subgroups as defined by the covariates in Section 
4.1. These additional explorations will be performed on the FAS by using the ANCOVA 
analysis. The 90% CI and 95% CIs of difference in mean change from baseline of BCVA 
across these subgroups will be displayed by forest plots.  
The rate of missing BCVA at week 8 will be tabulated with reasons, such as missing 
baseline, outside of the defined week 8 analysis time frame and discontinued from the 
study early prior to week 8 (i.e. prior to day 50). 
Tipping point analyses will be performed using FAS to explore the sensitivity of results to 
violations in assumptions about the missing data (i.e., to various missing not-at-random 


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assumptions). Assumptions (tipping point) under which the 90% CI or 95% CI no longer 
rules out unacceptable differences in efficacy as determined by BCVA change from 
baseline at week 8 between ABP 938 and aflibercept will be identified.  
In this analysis, all the observed data will be included as non-missing, regardless of 
adherence to treatment or use of prohibited medication. The analysis will be performed 
using a general three-step approach: 
(1) Multiple imputation will be done using PROC MI to generate multiple (e.g., 10) 
imputed datasets by imputing missing data assuming monotone missing pattern and that 
subjects with missing data have, on average, worse or better efficacy compared to those 
who have values. The mean difference between the (unobserved) missing values and 
observed values (refer to as shift) can vary independently for the different treatment 
groups. 
(2) Each of these imputed datasets (which contains identical values of non-missing data 
but different values imputed for missing data) is analyzed using standard SAS 
procedure, e.g., PROC GLM, PROC GENMOD, etc. 
(3) Results from all imputed datasets are then combined together for overall inference 
using PROC MIANALYZE.  
For BCVA change from baseline at week 8, seven equally spaced shifts (-6 to 6 by 2) for 
the BCVA change from baseline for subjects with missing data will be explored.  
9.5.2 
Analyses of Secondary Efficacy Endpoint(s) 
Analyses for secondary efficacy endpoints will be provided by visit from Day 1 to EOS. In 
general, treatment comparison of interest for time points prior to re-randomization (week 
16 included) include the comparison between treatment ABP 938 and aflibercept; 
treatment comparison of interest for time points after re-randomization include the 
comparison between treatment sequence ABP 938/ABP 938 and aflibercept/aflibercept 
and the comparison between treatment sequence aflibercept/ABP 938 and 
aflibercept/aflibercept. Analysis strata with small number of subjects in them will be 
combined. 
9.5.2.1 
Proportion of subjects who maintained vision at week 52  
The analyses of proportion of subjects who maintained vision are descriptive and will be 
based on observed cases and FAS.  


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The number and percent of subjects who maintained vision at week 52 with the 
associated 95% CI will be summarized by initial/re-randomization treatment sequence. 
In addition, treatment risk difference and the corresponding 90% and 95% CI will be 
estimated using  the stratified Newcombe confidence limits (with Mantel-Haenszel 
weights) adjusting for stratification factors. In addition, the above analyses for proportion 
of subjects who maintained vision will be repeated using NRI for FAS. 
9.5.2.2 
Proportion of subjects who gained ≥ 15 letters at week 52  
The analyses of proportion of subjects who gained ≥ 15 letters will be performed per the 
analyses for the proportion of subjects who maintained vision at week 52 (as described 
in section 9.5.2.1). 
9.5.2.3 
Proportion of subjects who gained ≥ 10 letters at week 8  
The analyses of proportion of subjects who gained ≥ 10 letters will be performed per the 
analyses for the proportion of subjects who maintained vision at week 52 (as described 
in section 9.5.2.1).  The analysis will be repeated using PP analysis set.  
9.5.2.4 
Change from baseline in BCVA over the study duration 
For time period from Day 1 to EOS, change from baseline in BCVA as measured by 
ETDRS letter score at each visit will be analyzed using the same ANCOVA model for 
primary analysis as described in section 9.5.1.1 for the FAS and observed cases. 
The BCVA change from baseline will be plotted by treatment and visit for the FAS with 
mean and 95% CI. 
9.5.2.5 
Change from baseline in CNV area size and CST over the study 
duration 
The analyses of CNV area size and CST are descriptive. For time period from Day 1 to 
EOS, change from baseline in CNV area size and CST at each visit will be analyzed 
using an ANCOVA model with baseline CNV area size or CST measurement and 
stratification factors as covariates for the FAS and observed cases.  Treatment 
difference and 90% and 95% CI will be estimated. 
9.5.3 
Analyses of Exploratory Efficacy Endpoint(s) 
The number and percent of subjects who maintained vision at each visit along with the 
associated 95% CIs will be summarized and plotted by initial randomized treatment for 
all subjects in the FAS through week 16 and by initial/re-randomization treatment 
sequence for re-randomized subjects post week 16 through EOS using the observed 
data. 


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Proportion of subjects who gained ≥ 10 letters and ≥ 15 letters at each visit will be 
summarized similarly.   
9.6 
Safety Analyses 
All safety analyses will be performed on the safety analysis set based on actual 
treatment received (see definitions of actual treatment in Section 5.1).  
Subject level and study eye level safety summaries will be provided separately as 
follows:  
• 
through week 8 period for the actual treatment groups: ABP 938 and aflibercept. 
• 
through week 16 period for the actual treatment groups: ABP 938 and aflibercept. 
• 
post week 16 period for the actual treatment sequence: aflibercept/aflibercept 
and aflibercept/ABP 938, and ABP 938/ABP 938. 
• 
entire study period for the actual treatment sequence: aflibercept/aflibercept and 
aflibercept/ABP 938, and ABP 938/ABP 938.  
The definitions for each study period at subject level and for the study eye are provided 
in Section 5.1. 
For the subset of subjects who also have the fellow eye treated with the IP, their safety 
data collected for the fellow eye from the first IP treatment of the fellow eye to the EOS 
visit will be summarized similarly.  Summaries will be based on the actual treatment 
received in the fellow eye (see definition in Section 5.1). 
9.6.1 
Adverse Events 
All reported AEs will be coded to the appropriate SOC and PT according to the most 
current version of MedDRA at the time of the primary analysis, and the severity of each 
AE will be graded by the investigator per CTCAE v4.03 criteria. 
At the subject level: 
For summary of AEs at the subject level, the following AE summaries, (a) through (h), 
will be provided by treatment for each study period of through week 8, through week 16, 
and post week 16.   In addition, summaries (a) and (c) will be provided for the entire 
study period. 
(a) overall summary of treatment-emergent AEs, 
(b) treatment-emergent AEs by SOC, PT, and maximum severity grade, 
(c) treatment-emergent AEs by SOC and PT, 


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(d) overall summary of treatment-emergent EOIs, 
(e) treatment-emergent AEs by PT, 
(f) grade 3 or higher treatment-emergent AEs by PT, 
(g) treatment-emergent AEs leading to discontinuation from IP/study by PT, 
(h) treatment-emergent EOIs by PT, 
(i) treatment-emergent COVID-19 AEs by PT, 
 
Counting of AEs will be by subject, and subjects will be counted only once within each 
SOC or PT by study period. For tables categorized by severity, subjects with multiple 
events within a particular SOC or preferred term will be counted under the category of 
their most severe event with that SOC or preferred term.  
AEs tabulated by preferred term will be presented in descending order of frequency in 
the ABP 938 arm or the ABP 938/ABP 938 arm when appropriate. 
The risk difference and 95% CI of each EOI through week 8, through week 16 and post 
week 16 will be calculated on the safety analysis set using Wald asymptotic confidence 
limits or exact confidence limits (Farrington-Manning score) if the number of subjects 
with EOIs for any treatment is less than 25.  Forest plots will be created to summarize 
the variability in risk difference across the EOIs. 
Listings of treatment-emergent EOIs from day 1 through the EOS visit will be provided.  
At the eye level: 
For summary of AEs of study eyes or fellow eyes, the following summaries will be 
provided by treatment for through week 8, through week 16, and by treatment sequence 
post week 16.(refer to definitions of study period in Section Error! Reference source 
not found.):  
• 
overall summary of ocular treatment-emergent AEs, including serious AE 
summary by serious criteria, 
• 
treatment-emergent ocular AEs by SOC, PT, and maximum severity grade, 
• 
treatment-emergent ocular AEs by SOC and PT, 
• 
treatment-emergent Ocular AE Leading to Discontinuation From IP or Study 
by PT, 
• 
treatment-emergent intraocular inflammation Events by PT, 
• 
treatment-emergent vitreous hemorrhage Events by PT.   


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Searching strategies of AEs intraocular inflammation and vitreous hemorrhage are 
specified in Appendix 2 Search strategy of INTRAOCULAR INFLAMMATION and 
VITREOUS HAEMORRHAGE.For the entire study period, the following summaries will 
be provided. 
• 
overall summary of ocular treatment-emergent AEs, including serious AE 
summary by serious criteria, 
• 
treatment-emergent ocular AEs by SOC and PT, 
 
Counting of AEs will be by respective eye within subject and will be counted only once 
within each SOC or PT by study period.  For tables categorized by severity, study eyes 
or fellow eyes with multiple events within a particular SOC or preferred term will be 
counted under the category of their most severe event with that SOC or preferred term 
for the respective eyes.  
In addition, a listing of ocular AEs for study eyes and fellow eyes from day 1 through the 
EOS visit will be provided.   
9.6.2 Deaths and Serious Adverse Events 
Summaries of serious treatment-emergent AE will be provided for subjects, study eyes 
and fellow eyes by study periods, except for the entire study period.  Death summary will 
only be provided at the subject level by study periods, except for the entire study period. 
At the subject level:  
Subject incidence of the following will be tabulated for study period: through week 8, 
through week 16, and post week 16: 
(j) serious treatment-emergent AEs by SOC and PT, 
(k) serious treatment-emergent AEs by PT,  
(l) treatment-emergent fatal AEs by PT. 
(m) serious treatment-emergent AEs occurring on or after presumed start date of 
COVID-19 infection by PT. 
Summaries will be sorted in descending order of frequency in the ABP 938 arm or ABP 
938/ABP938, when applicable. 
Refer to counting AE for the subject level analysis in section 9.6.1.   


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A listing of treatment-emergent serious AEs and a listing of treatment-emergent serious 
AEs occurring on or after presumed start date of COVID-19 infection from day 1 through 
EOS visit will be provided.   
At the eye level: 
Treatment-emergent serious AEs by treatment groups and by PT will be summarized for 
study period: through week 8, through week 16, post week 16 for the study eyes and 
fellow eyes. (refer to counting AE for the eye level analysis in section 9.6.1).   
9.6.3 
Laboratory Test Results 
Laboratory data (hematology, serum chemistry, and urinalysis) will be converted to 
Système International units for reporting and processing purposes.  Absolute values and 
changes from baseline by visit will be presented descriptively for each study period 
except for through week 8 period (refer to study period definition in section 5.1). Shift 
tables of the worst on-study laboratory toxicity based on CTCAE grading relative to 
baseline will be presented by study period.  There is no re-baseline for post week 16 
analyses.    
The shift tables will take into account all post-baseline (schedule and unscheduled) 
laboratory results in the determination of the worst on-study laboratory toxicity. In 
addition, subject incidence tables of grade ≥ 3 laboratory toxicities will be provided. 
Standard ranges will be used for the laboratory analysis. 
Lab assessments will be grouped for summary as follows: 
Hematology:  hemoglobin, hematocrit, red blood cells, platelets, total white blood cell 
(WBC) count, differential WBC count, and absolute neutrophil count 
Biochemistry:  albumin, alkaline phosphatase, alanine aminotransferase (ALT), 
amylase, aspartate aminotransferase (AST), calcium, creatinine, gamma 
glutamyltransferase, glucose, lipase, potassium, sodium, and total bilirubin 
Urinalysis:  pH, specific gravity, creatinine, glucose, bilirubin, blood, and protein 
9.6.4 
Vital Signs 
Observed and change from baseline for each vital sign parameter will be summarized 
descriptively by visit for study periods: through week 16, post week 16, and the entire 
study (refer to study period definition in section 5.1 and treatment group/sequence 
specified for subject level safety summary in section 9.6).    


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9.6.5 
Intraocular Pressure 
Observed and change from baseline for intraocular pressure for the study eyes and 
fellow eyes will be summarized by visit and time point for the following study periods: 
through week 16, post week 16, and the entire study (refer to study period definition in 
section 5.1 and treatment group/sequence specified for eye level safety summary in 
section 9.6).   
9.6.6 
Slit-Lamp Examination and Indirect Ophthalmoscopy 
Abnormal slit-lamp biomicroscopy and indirect ophthalmoscopy results for the study 
eyes and fellow eyes will be summarized by visit and time point for study periods: 
through week 16, post week 16, and entire study (refer to study period definition in 
section 5.1 and treatment group/sequence specified for eye level safety summary in 
section 9.6).  
9.6.7 
Physical Examinations 
None. 
9.6.8 
Immunogenicity 
The number and percentage of subjects developing binding ADAs will be tabulated by 
visit and actual treatment received at a subject level (refer to definition of actual 
treatment received in section 5.1).   
Developing antibody incidence through week 16 and through EOS is defined as the 
number of subjects with a negative or no antibody result at baseline and a positive 
antibody result at a post-baseline visit divided by the number of subjects with a binding 
negative or no result at baseline and at least one post baseline result within the 
respective study period. Treatment boosted ADA is defined as total number and 
percentage of subjects with a positive immunoassay result at baseline and at least 1 
post-baseline immunoassay result that is ≥4x magnitude of baseline result. A transient 
antibody result is defined as a positive post-baseline result with a negative result at the 
subject’s last visit tested within the respective study period.  
Developing antibody incidence in the post week 16 period is evaluated among subjects 
who were re-randomized and treated post re-randomization.  It is defined as number of 
subjects who had a positive result post re-randomization, had never tested positive (i.e., 
negative or no results) through week 16, and tested negative at the last visit prior to 
receiving IP post re-randomization by the number of subjects who had at least a result 
post re-randomization, had never tested positive (i.e., negative or no results) through 


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week 16, and tested negative at the last visit prior to receiving treatment post re-
randomization.  
 
9.6.9 
Exposure to Investigational Product 
IP exposure (ABP 938 or aflibercept) will be tabulated separately for subject, the study 
eye and the fellow eye using the safety analysis set and according to the actual 
treatment received. Summary statistics will be provided for the total number of doses 
administered, total dose received, and total duration of IP exposure by the different study 
periods specified for the safety analyses in section 9.6.1. For study eyes and fellow 
eyes, the number of subjects who missed at least one dose of IP due to COVID-19 
related reasons will be summarized by number of doses not administered. In addition, 
the number of subjects with at least one dose not administered will be summarized by 
reason and also by relatedness to COVID-19. 
A subject listing of each administered lot number(s) for IP and a listing of unique 
manufacturing lot numbers used in the study will be provided separately for subject, the 
study eye and the fellow eye. 
9.6.10 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the current version of the World 
Health Organization-Drug Dictionary (WHO-DD) and will be summarized by preferred 
name. The prior medications will be summarized by initial treatment the subject 
received. The concomitant medications will be summarized for the different study 
periods specified for the safety analyses in section 9.6.1 using safety analysis set.  
The number and percentage of subjects using each medication will be displayed by 
treatment arm. Subjects taking more than one medication in the same preferred name 
will be counted once for the number of subjects taking that preferred name.  
9.7 
Other Analyses 
9.7.1 
Analyses of Pharmacokinetic Endpoints 
Serum ABP 938 and aflibercept concentrations from the PK substudy will be 
summarized descriptively by treatment for each sampling time point for PK analysis set.   
9.7.2 
Analyses of Clinical Outcome Assessments 
None. 
9.7.3 
Analyses of Health Economic Endpoints 
None. 


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9.7.4 
Analyses of Biomarker Endpoints 
None. 
10. 
Changes From Protocol-specified Analyses 
There are no changes to the protocol-specified analyses. 
11. 
Literature Citations / References 
1. 
Ke C, Wang J, Zhang C, Jiang Q, Snapinn S. On errors in stratified 
randomization. Statistics in Biopharmaceutical Research 2017; 9 (2): 225-33. 
2. 
US FDA.  Guidance for Industry:  Scientific considerations in demonstrating 
biosimilarity to a reference product.  April 2015a, US FDA. 


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Appendix 1 List of Events of Interest and the Associated SMQ and EOI Searching 
Strategies 
Event of Interest (EOI) 
MedDRA Terms or Search Strategy 
ENDOPHTHALMITIS 
Any of the following preferred term: 
Endophthalmitis 
Candida endophthalmitis 
Mycotic endophthalmitis 
Eye infection  
Eye infection bacterial 
Eye infection fungal 
Eye infection chlamydial 
Eye infection staphylococcal 
Eye infection intraocular 
INCREASE IN INTRAOCULAR 
PRESSURE  
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 
RETINAL DETACHMENT 
Any of the following preferred term: 
Retinal tear 
Retinal detachment 
 
THROMBOEMBOLIC EVENTS 
Embolic and Thrombotic events SMQ (Narrow) 
 


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Appendix 2 Search strategy of INTRAOCULAR INFLAMMATION and VITREOUS 
HAEMORRHAGE 
 
Event 
MedDRA Terms  
INTRAOCULAR 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