XEN-45 Gel Stent Versus Trabeculectomy in Glaucoma: Gold-Standard Pathway Study (GPS)
Phase: PHASE4
Conditions: Glaucoma
Sponsor: Allergan

CLINICAL STUDY PROTOCOL
XEN-45 Gel Stent Versus Trabeculectomy in Glaucoma: Gold-standard 
Pathway Study (GPS)
Protocol Number:
CMO-US-EYE-0600
EudraCT Number:
Not Applicable
ClinicalTrials.gov Number:
NCT03654885
Syneos Health Study Number:
1013549
Study Product:
XEN-45 Gel Stent (XEN)
Phase:
Postmarketing study
Sponsor:
Allergan (North America)
2525 Dupont Drive
Irvine, CA 92612
United States
Contract Research Organization: Syneos Health
1030 Sync Street
Morrisville, NC 27560
United States
Protocol Date:
21 Mar 2019
Protocol Version:
Version 2.0
CONFIDENTIAL
This protocol may not be reproduced or communicated to a third party without the 
written permission of Allergan.
NCT03654885

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 2 of 63
CONFIDENTIAL
1
PROTOCOL APPROVAL SIGNATURES
Not applicable. Allergan uses an electronic approval system.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 3 of 63
CONFIDENTIAL
2
STUDY PERSONNEL
Sponsor Personnel 
Project Manager
Name:
Title:
, CMO Clinical Trial Manager
Address:
Allergan plc
2525 Dupont Drive
Irvine, CA 92623
United States
Telephone No.:
Statistician
Name:
Title:
, Global Medical Operations Biostatistics
Address:
Allergan
5 Giralda Farms
Madison, NJ 07940 
United States
Telephone No.:
Contract Research Organization Personnel
Medical Monitor  
Name:
Title:
Address:
Syneos Health
Encino Trace Building II, Suite 200
5707 Southwest Parkway
Austin, TX 78735 
United States
Telephone No.:
Direct 
Mobile

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 4 of 63
CONFIDENTIAL
3
SYNOPSIS
Protocol Number:
CMO-US-EYE-0600
Title:
XEN-45 Gel Stent Versus Trabeculectomy in Glaucoma: Gold-standard Pathway Study (GPS)
Study Product:
XEN-45 Gel Stent (XEN)
Study Centers:
Approximately 25 to 40 sites in the United States
Phase:
Postmarketing
Objective:
To compare the effectiveness and safety of XEN to trabeculectomy in subjects with glaucoma refractory 
to topical medical therapy defined as intraocular pressure (IOP) not at target on 1 or more topical 
medications.
Study Design:
Multicenter, randomized, parallel-group, prospective, open-label
Number of Subjects: 
Eyes of approximately 285 subjects (1 eye per subject) will be randomized to have approximately 
256 study eyes complete the study.
Treatment:
XEN or Trabeculectomy
Study Duration:
12 months per participating study eye
Study Methodology:
This study will include subjects with glaucoma poorly controlled on topical therapy who are candidates 
for a subconjunctival drainage procedure. Subjects will be screened for enrollment and eligible candidates 
will be approached to ascertain interest in study participation. Subjects will be randomized at a ratio of 
2:1, resulting in approximately 190 eyes being implanted with XEN and approximately 95 eyes receiving
trabeculectomy. A randomized study design was chosen because it prevents selection bias in treatment 
assignments and produces comparable groups.
Study Population:
Inclusion Criteria
To be eligible for study entry subjects must satisfy all the following criteria in the study eye (only 1 eye 
will be allowed in the study):
1.
0DOHRUIHPDOHVXEMHFWVDJHV\HDUV
2.
Able to provide signed written informed consent
3.
Glaucoma in which the IOP is not controlled on current topical IOP-lowering glaucoma 
medication
4.
Best-corrected baseline Snellen visual acuity of 20/100 or better 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 5 of 63
CONFIDENTIAL
5.
Visual field mean deviation no worse than -18.0 dB (with no dense paracentral scotomas, eg,
>18 dB total deviation on 1 or more of the 4 paracentral points)
6.
0HGLFDWHG,2315 mm +JDQG44 mm Hg on at least 1 topical IOP-lowering medication
7.
Subjects not anticipated to require any other ocular surgery (eg, cataract surgery) in either eye up 
to 3 months from the time of inclusion 
8.
Area of healthy, free, and mobile conjunctiva in the target area, ie, superior bulbar conjunctiva
9.
Visible trabecular meshwork with 6KDIIHUDQJOHJUDGH2 in the target area or, in eyes with prior 
failed angle surgery, an open angle in the target area 
10.
Preoperative laser trabeculoplasty is allowed 3 or more months prior to randomization 
11. 
Failed ab-interno canal or suprachoroidal microinvasive glaucoma surgery (MIGS) procedures 
(such as iStent®, gonioscopy-assisted transluminal trabeculotomy [GATT], ab-interno canaloplasty 
[ABiC™], Kahook Dual Blade goniotomy, etc) are allowed 3 or more months before enrollment,
with the exception of CyPass® Micro-Stents, which are not allowed. Ab-interno ablative 
procedures (such as endoscopic cyclophotocoagulation [ECP]) are also allowed 3 or more months 
before enrollment.
Exclusion Criteria
Subjects will be excluded from the study if one or more of the following criteria are applicable in the 
study eye:
1.
Subject has active neovascular, uveitic, or angle-recession glaucoma or any glaucoma associated 
with vascular disorders 
2.
Subject has had prior ab-externo incisional glaucoma surgery (such as trabeculectomy, 
viscocanalostomy, canaloplasty, tube shunts of any type, collagen implants, etc.), conjunctival 
filtering surgery (such as XEN), transscleral cycloablative procedures (such as 
cyclophotocoagulation, micropulse cyclophotocoagulation, cryotherapy, ultrasonic circular 
cyclocoagulation [UC3], etc) or prior major conjunctival surgery (ie, scleral buckle)
3.
Clinically significant inflammation or infection within 30 days before the Preoperative Visit (eg,
blepharitis, conjunctivitis, severe ocular surface disease, keratitis, uveitis, herpes simplex 
infection)
4.
Presence of conjunctival scarring or prior conjunctival surgery or other conjunctival pathologies 
(eg, pterygium) in the target area
5.
History of corneal surgery, corneal opacities, or corneal disease that could impact 
assessments/surgical outcomes in the study
6.
&HQWUDOFRUQHDOWKLFNQHVV ȝPRU620 ȝP
7.
Subjects on systemic carbonic anhydrase inhibitors (eg, Diamox® [acetazolamide] and Neptazane®
[methazolamide]) at Baseline Qualifying Visit
8. 
Vitreous present in the anterior chamber
9.
Aphakia
10.
Subject has had prior intraocular VXUJHU\LQHLWKHUH\HZLWKLQ3 months before the Preoperative
Visit (including phacoemulsification)
11.
History of complicated cataract surgery with visual impairment, vitreous loss, anterior chamber 
intraocular lens (ACIOL), sutured intraocular lens (IOL), scleral fixated IOL or cystoid macular 
edema (CME), dislocated IOL
12.
Presence of intraocular silicone oil
13.
Active diabetic retinopathy, proliferative retinopathy, choroidal neovascularization, branch retinal 
vein occlusion, central retinal vein occlusion, geographic atrophy, or other ophthalmic disease or 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 6 of 63
CONFIDENTIAL
disorder that could confound study results or impaired episcleral venous drainage (eg, Sturge-
Weber or nanophthalmos, Axenfeld-Rieger, iridocorneal endothelial [ICE] syndrome, etc)
14.
Known or suspected allergy or sensitivity to drugs required for the protocol (including anesthesia), 
or any of the device components (eg, bovine or porcine products, or glutaraldehyde)
15.
Pregnant or nursing women and those planning a pregnancy during the study period
16.
Participation in another drug or device clinical trial that concludes within 30 days before the 
Preoperative Visit or that starts at any time during this study
Primary Effectiveness Endpoint:
Percentage of sXEMHFWVDFKLHYLQJPHDQ,23UHGXFWLRQIURPbaseline at Month 12 on the same or 
fewer number of topical IOP-lowering medications, without clinical hypotony, loss of vision to count 
fingers, or a secondary glaucoma surgical intervention.
Secondary Endpoints:
Effectiveness:
x
Mean and changes in mean IOP and number of topical IOP-lowering medications from 
preoperative baseline over time 
x
Change from baseline (medicated) in mean IOP and mean number of topical IOP-lowering 
medications at Month 12
x
Proportion of eyes achieving specific IOP targets (18 mm Hg, 17 mm Hg, 16 mm Hg,
15 mm Hg, 14 mm Hg, 13 mm Hg, and 12 mm Hg at Month 12)
x
Proportion of eyes achieving specific percentage IOP lower targets from baseline (25% to 50% 
in 5% increments)
x
3URSRUWLRQRIH\HVDFKLHYLQJIOP reductions and specific IOP targets detailed above on 
same or lower number of topical IOP-lowering medications at Month 12
x
Mean and changes in mean IOP and number of topical IOP-lowering medications from 
preoperative baseline over time in eyes with medicated EDVHOLQH,23PP+J
x
Needling rates; number of needlings per eye; outcomes post needling, including mean IOP and 
number of medications measured by proportion of eyes achieving >20% reduction at Month 12
on same or fewer topical IOP-lowering medications, and number of subjects not using any 
topical IOP-lowering medications; and antifibrotic use during needling
Complete and qualified success:
x
Complete success (IOP 8 mm Hg, with 20% or greater IOP lowering from medicated baseline 
on no topical medications) at Month 12 (eyes with clinical hypotony will be excluded)
x
Qualified success (IOP 8 mmHg with 20% or greater IOP lowering from medicated baseline 
with topical medications) at Month 12 (eyes with clinical hypotony will be excluded)
x
Medication-free eyes, mean IOP in this cohort, and proportion of eyes at specific IOPs 
(18 mm Hg, 17 mm Hg, 16 mm Hg, 15 mm Hg, 14 mm Hg, 13 mm Hg, and 12 mm Hg 
at Month 12)
x
Proportion of eyes achieving specific percentage IOP lower targets from baseline (25% to 50% 
in 5% increments) with medication-free eyes. 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 7 of 63
CONFIDENTIAL
Intraoperative adjunctive antifibrotic therapy administered: 
x
Compound/product, mode of administration, dose and concentration, timing of adjunctive agent 
(surgery day and pre- and postsurgical procedure/implantation)
Visual parameters recovery post surgery:
x
Best corrected visual acuity (BCVA) with current glasses (preoperative and postoperative Day 1, 
Weeks 1 and 2, and Months 1, 3, 6, 9, and 12)
x
Manifest refraction (baseline and postoperative Months 1, 3, 6, and 12)
x
Surgically induced astigmatism (autorefractor reading [preoperative and postoperative Months 1, 
6, and 12] and, at selected sites, topography [preoperative and postoperative Week 1 and 
Months 1 and 12])
x
Optical biometry (anterior chamber depth and keratometric values [preoperative and 
postoperative Day 1 and Week 2]) at selected sites.
Other:
x
Bleb morphology (anterior segment optical coherence tomography [AS-OCT] and slit lamp 
photography at selected sites).
Safety:
x
Clinical hypotony defined as vision reduction (2 lines or more) related to macular changes 
consistent with hypotony maculopathy (macular folds), optic disc edema, and/or serous 
choroidal detachments because of low IOP
x
Eyes with IOP 6 mm Hg or less at any time point and relevant clinical assessment (vision 
reduction [2 lines or more] related to macular changes consistent with hypotony maculopathy
[macular folds], optic disc edema, anterior chamber status, and/or serous choroidal detachments 
because of low IOP) of these eyes at those time points
x
Adverse events (AEs) including specific intraoperative and postoperative events of interest
x
BCVA, pachymetry, visual field
x
AE including serious AEs (SAEs)
x
Adverse device effects (ADEs) including serious ADEs (SADEs)
Patient-reported Outcomes:
x
Patient-reported Outcomes (PRO)
Sample Size:
The trial is intended to demonstrate that XEN is comparable to trabeculectomy in terms of treatment 
success rate. The sample size calculation is based on an equivalence test.
To control Type-I error rate at 5% and to attain 80% power for demonstrating that the difference is within 
the equivalence limit of 18%, about 256 study eyes will be needed for the study with a randomization 
ratio of 2:1 for the XEN arm: trabeculectomy arm. Allowing a 10% dropout rate for the first year, 
approximately 285 study eyes (190 for the XEN arm and 95 for the trabeculectomy arm) will need to be 
recruited for the study.
Statistical Analysis:
Four analysis populations will be used:
x
Enrolled population: all study eyes for which the subject has signed the ICF

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 8 of 63
CONFIDENTIAL
x
Intent-to-treat (ITT) population: all enrolled eyes randomized to study glaucoma surgery (XEN 
or trabeculectomy)
x
Modified Intent-to-treat (mITT) population: eyes in the ITT population that receive study 
glaucoma surgery and have no major protocol deviations
x
Safety population: all enrolled eyes that undergo study glaucoma surgery, whether surgery is 
completed or aborted, and have follow-up visits or evaluations
The ITT population will be the primary effectiveness analysis population; some effectiveness analyses 
will also be run with the mITT population. All safety analyses will be run with the Safety population.
Descriptive statistics (such as mean, SD, minimum, median, and maximum) will be presented for each 
continuous variable. Categorical variables will be displayed using frequency counts and percentages.
7KHQXPEHUDQGSURSRUWLRQRIVXEMHFWVDFKLHYLQJPHDQ,23UHGXFWLRQIURPEDVHOLQHDW0RQWK
on the same or fewer number of topical IOP-lowering medications, without clinical hypotony, loss of 
vision to count fingers, or a secondary glaucoma surgical intervention will be tabulated with 95% CI 
calculated by using the normal approximation method. The difference of the proportions will be estimated 
and the 95% CI of the difference will also be calculated with the method of normal approximation. The 
2 treatment arms will be claimed as equivalent if the 95% CI of the differences is within the -18% to 18% 
interval. The least squares mean change from baseline in IOP and the least squares mean difference 
between the 2 treatment groups will be estimated using the analysis of covariance (ANCOVA) model or 
the mixed-effect model repeat measurement (MMRM) model. The proportion and the 95% CI of
complete success and qualified success will be calculated with normal approximation. All reported 
treatment-emergent AEs and all safety measures collected will be tabulated by counts and percentages.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 9 of 63
CONFIDENTIAL
4
TABLE OF CONTENTS
1 
Protocol Approval Signatures......................................................................... 2 
2 
Study Personnel................................................................................................ 3 
3 
Synopsis............................................................................................................. 4 
4 
Table of Contents.............................................................................................. 9 
5 
List of Abbreviations and Definition of Terms............................................ 12 
6 
Introduction .................................................................................................... 14 
6.1 
Overview of Glaucoma................................................................................... 14 
6.2 
XEN Gel Stent................................................................................................. 16 
6.2.1 
Device Description.......................................................................... 16 
6.2.2 
Clinical Experience ......................................................................... 16 
7 
Study Objectives............................................................................................. 17 
7.1 
Primary Endpoint........................................................................................... 17 
7.2 
Secondary Endpoints ..................................................................................... 17 
7.3 
Exploratory Objective.................................................................................... 19 
8 
Investigational Plan........................................................................................ 20 
8.1 
Overall Study Design and Plan: Description ............................................... 20 
8.1.1 
Study Design ................................................................................... 20 
8.1.2 
Schedule of Assessments................................................................. 20 
8.2 
Discussion of Study Design............................................................................ 23 
8.2.1 
Study Design ................................................................................... 23 
8.2.2 
Quality Management and Risk Evaluation...................................... 23 
8.3 
Selection of Study Population........................................................................ 24 
8.3.1 
Number of Planned Subjects........................................................... 24 
8.3.2 
Inclusion Criteria............................................................................. 25 
8.3.3 
Exclusion Criteria............................................................................ 25 
8.3.4 
Removal of Subjects from Therapy or Assessments....................... 27 
8.4 
Investigated in Protocol ................................................................................. 28 
8.4.1 
Study Product and Procedures......................................................... 28 
8.4.1.1 
XEN................................................................................................. 28 
8.4.1.2 
Comparator – Trabeculectomy........................................................ 28 
8.4.2 
Packaging and Labeling .................................................................. 28 
8.4.3 
Device Complaint Reporting........................................................... 28 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 10 of 63
CONFIDENTIAL
8.4.4 
Method of Assigning Subjects to Treatment Groups...................... 28 
8.4.5 
Prior and Concomitant Therapy ...................................................... 29 
9 
Timing of Study Procedures.......................................................................... 30 
9.1 
Pretreatment Visits......................................................................................... 30 
9.1.1 
Baseline Qualifying Visit................................................................ 30 
9.1.2 
Preoperative Visit (Visit 1).............................................................. 30 
9.1.3 
Operative Visit (Visit 2).................................................................. 30 
9.2 
Postoperative Visits ........................................................................................ 30 
9.2.1 
Day 1 (Visit 3)................................................................................. 30 
9.2.2 
Week 1 (Visit 4) .............................................................................. 31 
9.2.3 
Week 2 (Visit 5) .............................................................................. 31 
9.2.4 
Month 1 (Visit 6)............................................................................. 31 
9.2.5 
Month 3 (Visit 7)............................................................................. 31 
9.2.6 
Month 6 (Visit 8)............................................................................. 31 
9.2.7 
Month 9 (Visit 9)............................................................................. 31 
9.2.8 
Month 12 (Visit 10)......................................................................... 31 
9.2.9 
Early Withdrawal Visit.................................................................... 31 
9.3 
Duration of Study........................................................................................... 31 
9.4 
Pregnancy........................................................................................................ 32 
10 
Effectiveness and Safety Variables ............................................................... 33 
10.1 Effectiveness and Safety Measurements Assessed....................................... 33 
10.1.1 
Effectiveness Variables ................................................................... 33 
10.1.1.1 
Intraocular Pressure......................................................................... 33 
10.1.1.2 Topical IOP-lowering Medication................................................... 33 
10.1.1.3 Patient-reported Outcomes.............................................................. 33 
10.1.2 
Safety Analysis................................................................................ 34 
10.1.2.1 Adverse Events................................................................................ 34 
10.2 Data Safety Monitoring Board...................................................................... 40 
10.2.1 
Appropriateness of Measurements .................................................. 40 
11 
Statistical Methods ......................................................................................... 41 
11.1.1 
Datasets or Populations Analyzed................................................... 41 
11.1.2 
Demographic and Other Baseline Characteristics........................... 41 
11.1.3 
Effectiveness Variables and Statistical Analyses............................ 41 
11.1.4 
Safety Variables .............................................................................. 42 
11.1.5 
Interim Analyses.............................................................................. 42 
11.1.6 
Handling of Missing Data ............................................................... 42 
11.2 Determination of Sample Size ....................................................................... 43 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 11 of 63
CONFIDENTIAL
11.3 Protocol Deviations......................................................................................... 43 
12 
Quality Assurance and Quality Control....................................................... 44 
12.1 Audit and Inspection...................................................................................... 44 
12.2 Monitoring ...................................................................................................... 44 
12.3 Data Management and Coding ..................................................................... 44 
12.4 Quality Management and Risk Evaluation.................................................. 45 
13 
Records and Supplies..................................................................................... 46 
13.1 Device Accountability..................................................................................... 46 
13.2 Financing and Insurance ............................................................................... 46 
14 
Ethics ............................................................................................................... 47 
14.1 Independent Ethics Committee or Institutional Review Board................. 47 
14.2 Regulatory Authorities................................................................................... 47 
14.3 Ethical Conduct of the Study ........................................................................ 47 
14.4 Informed Consent........................................................................................... 47 
14.5 Subject Confidentiality .................................................................................. 48 
15 
Reporting and Publication, Including Archiving........................................ 49 
16 
References ....................................................................................................... 50 
17 
Appendices ...................................................................................................... 53 
17.1 The SHPC-18 Questionnaire......................................................................... 53 
17.2 Postsurgical Question on Resumption of Activities and Daily 
Routine
......................................................................................................... 57 
17.3 Work Productivity and Activity Impairment Questionnaire..................... 58 
17.4 Protocol Revision History.............................................................................. 60 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 12 of 63
CONFIDENTIAL
5
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
LIST OF ABBREVIATIONS
ABiC
ab-interno canaloplasty
ACIOL
anterior chamber intraocular lens
ADE
adverse device effect
AE
adverse event
ANCOVA
analysis of covariance
AS-OCT
anterior segment optical coherence tomography
BCVA
best corrected visual acuity
CAI
carbonic anhydrase inhibitors
CIGTS
Collaborative Initial Glaucoma Treatment Study
CME
cystoid macular edema
CRO
contract research organization
eCRF
electronic case report form
EDC
electronic data capture
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
Food and Drug Administration
GATT
gonioscopy-assisted transluminal trabeculotomy
GCP
Good Clinical Practice
GPS
Gold-standard Pathway Study
HIPAA
Health Insurance Portability and Accountability Act
ICE
iridocorneal endothelial
ICF
informed consent form
ICH
International Council on Harmonisation
IEC
independent ethics committee
IOP
intraocular pressure 
IOL
intraocular lens
IRB
institutional review board
ITT
intent-to-treat
MedDRA
Medical Dictionary for Regulatory Activities
MIGS
microinvasive glaucoma surgery
mITT
modified intent-to-treat
MMRM
mixed-effect model repeat measurement
MTMT
maximal tolerated medical therapy
n
number of subjects with an observation
N
number of subjects in the dataset or population
PACG
primary angle-closure glaucoma
POAG
primary open-angle glaucoma
PRO
patient-reported outcomes
RTSM
Randomization and Trial Supply Management
SADE
serious adverse device effect
SAE
serious adverse event
SAP
statistical analysis plan
SHPC-18
Symptom and Health Problem Checklist (18 items)
SLT
selective laser trabeculoplasty
SOP
standard operating procedure
UC3
ultrasonic circular cyclocoagulation
WHO
World Health Organization

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 13 of 63
CONFIDENTIAL
WPAI
Work Productivity and Activity Impairment
XEN
XEN-45 Gel Stent

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 14 of 63
CONFIDENTIAL
6
INTRODUCTION
6.1
Overview of Glaucoma
Glaucoma is the leading cause of irreversible vision loss worldwide. Although several 
eye conditions are variants of glaucoma, the most common types of glaucoma are 
primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). 
Asia accounts for a disproportionate number of PACG cases, whereas the prevalence of 
POAG is more evenly distributed throughout the world (Quigley 1996).
The goal in the treatment of glaucoma is to prevent further loss of functional vision 
during the remainder of a patient’s life and to avoid an adverse impact on the patient’s 
quality of life (AAO Glaucoma PPP Panel 2015).
There are many known risk factors for glaucoma including age, ethnicity, and family 
history. Intraocular pressure (IOP) is the only modifiable risk factor that is currently 
available to arrest visual field loss and reduction of IOP has been shown to reduce the 
risk of glaucomatous visual field loss in many landmark trials.
The prevention of glaucomatous loss of vision is mainly achieved by lowering the eye 
pressure to a threshold that is deemed to be safe for the ganglion cells given the current 
amount of damage in the optic nerve head (ie, target IOP).
There are many approaches to lower IOP including pharmacotherapy (topical and 
systemic), laser therapy, and surgery. Topical medications are often the first line of 
treatment, especially in early disease along with selective laser trabeculoplasty (SLT).
Most patients require multiple medications to lower IOP to target (AAO Glaucoma PPP
Panel 2015).
Traditional incisional glaucoma surgery results in robust IOP lowering; however, the 
accompanying side effects often preclude use earlier in the treatment paradigm. 
Trabeculectomy is the gold standard and currently the most commonly used drainage 
procedure, but complications are a major problem. Early and late complications include 
bleb leak, excessive drainage, flat anterior chamber, filtration failure, clinical hypotony, 
symptomatic blebs, bleb encapsulation, filtration failure, hyphema, choroidal effusion, 
suprachoroidal hemorrhage, and bleb infection (Gedde et al. 2007). Complications 
associated with drainage surgeries can have serious consequences and require careful 
management to prevent further problems. The bleb is currently the cornerstone of 
trabeculectomy drainage surgery, but the trabeculectomy bleb is also fragile and 
susceptible to scarring (Azuara-Blanco and Katz 1998). Another subconjunctival 
surgical approach includes the Ex-PRESS® miniature glaucoma implant (Alcon 
Laboratories Inc., Fort Worth, TX), which is a biocompatible, nonvalved stainless steel 
tube. The Ex-PRESS is currently implanted using a procedure like standard 
trabeculectomy, and includes creation of a sclera flap and a conjunctival filtration bleb, 
but no peripheral iridectomy is required when implanting the Ex-PRESS (Moisseiev et 
al. 2015).

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 15 of 63
CONFIDENTIAL
Trabeculectomy and tube shunt surgeries have an important role in glaucoma 
management, offering the ability to achieve IOP lowering independent of patients’ 
compliance in appropriate candidates. Tube shunts are being increasingly used in the 
surgical management of glaucoma. The Ahmed glaucoma valve and the Baerveldt 
implant represent the most commonly used tube shunts. The Ahmed valve has a valve 
mechanism to prevent postoperative hypotony and shallow anterior chambers, whereas
the Baerveldt implants provide a greater surface area in the end plate for aqueous 
reabsorption, providing better IOP control and a reduced need for glaucoma medication 
over the long term (Gedde et al. 2010, Wang et al. 2016). All the above procedures,
performed using an ab-externo approach, achieve lowering of IOP via drainage of 
aqueous from the anterior chamber to the subconjunctival space (Gedde et al. 2012).
However, each of these procedures is associated with a lengthy and variable 
recuperation and prolonged time to visual recovery. In some instances, there is 
associated loss of best corrected visual acuity (BCVA) and significant risk of short- and 
long-term complications, including hypotony, choroidal effusion, cataract, and flat or 
shallow anterior chamber, as well as valve-related complications, such as tube blockage, 
erosion, and endothelial cell loss (Gedde et al. 2012, Shaarawy et al. 2004, Rulli et al.
2013, Vijaya et al. 2011).
An alternative option to the more invasive traditional surgeries described above, in the 
form of microinvasive glaucoma surgery (MIGS) devices, are now available that have
an improved safety profile and recovery compared with trabeculectomy and tube shunts
(Saheb and Ahmed 2012). There are several devices fitting the definition of MIGS
including XEN-45 Gel Stent (XEN); they can be categorized by their intended 
mechanism of action, ie, they may improve outflow by targeting the trabecular 
meshwork or the supraciliary space (Caprioli et al. 2015). Unlike canal-based and 
supraciliary MIGS devices, XEN facilitates subconjunctival drainage like the gold-
standard surgical option trabeculectomy to provide robust IOP lowering from a 
medicated baseline (Vera et al. 2018, Mansouri et al. 2018, Hengerer et al. 2017).
Topical therapy is often the first line intervention for IOP lowering in open-angle 
glaucoma. Although the standard practice is to prescribe a second IOP-lowering 
medication when the first drug has lowered a patient’s IOP, but not to an optimal level, 
the efficacy seen with monotherapy may not translate into similar efficacy when a 
medication is used adjunctively. Additionally, the side effects of multiple medications 
need to be considered for patient quality of life (Fechtner and Singh 2001). 
To quantify the IOP reduction after surgery in clinical trials versus topical IOP-lowering 
medications, a consistent definition of the baseline, or reference IOP is necessary. For 
practical purposes, the highest challenge for a trial is the maximal tolerated medical 
therapy (MTMT) of IOP-lowering medications because that level would be considered 
the best that those drugs can achieve (Shaarawy et al. 2004). To determine the MTMT 
for glaucoma and the amount of medication an eye can tolerate, patients may need to 
endure severe adverse effects before advancing to surgery. In contrast, in clinical 
practice, the goal is optimal medical therapy, in which the practitioner uses the least 
amount of medicine to achieve the desired goal with the least adverse effects. In 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 16 of 63
CONFIDENTIAL
standard clinical practice, ophthalmologists prescribe at least 2 glaucoma medications 
before suggesting surgical intervention to a patient. After treatment failure with the 
second, and certainly after the third medication is added, it is unlikely that additional 
agents will improve the outcome (Fechtner and Singh 2001).
6.2
XEN Gel Stent
6.2.1
Device Description
A MIGS drainage device implanted via an ab-interno approach that facilitates drainage 
of aqueous from the anterior chamber to the subconjunctival space (XEN-45; Allergan, 
Irvine, CA) has recently been approved in the United States for use in the surgical 
management of glaucoma. This device, which can be used as a standalone procedure, 
offers the potential to achieve IOP lowering that is comparable to trabeculectomy, but
with less tissue manipulation (Schlenker et al. 2017, Reitsamer 2016).
The device, which is implanted using a handheld disposable injector, is constructed 
from porcine-derived gelatin that is formed into a tube and cross-linked with 
glutaraldehyde, thus allowing it to expand and remain flexible when hydrated. The 
expansion of the tube’s outer diameter, when in contact with fluid, also aids in retention 
of the gel stent in its intended location after surgical implantation, which helps minimize 
many of the issues associated with other materials, such as migration, erosion, and
corneal endothelial damage (Aref and Varma 2012). The gel stent was designed using 
principles established by the Hagen–Poiseuille equation, whereby outflow resistance to 
the fluid increases linearly in proportion to the length of the tube, and decreases to the 
fourth power of the diameter of the tube lumen. In sum, a longer and thinner tube 
provides greater resistance than a shorter and wider tube (Sheybani et al. 2015).
The XEN Gel Stent, XEN-45, or XEN Gel Implant (XEN) is indicated for the 
management of refractory glaucomas, including cases in which previous surgical 
treatment has failed, cases of POAG, and cases of pseudoexfoliative or pigmentary 
glaucoma with open angles that are unresponsive to MTMT.
6.2.2
Clinical Experience
XEN is the first ab-interno minimally invasive procedure that creates a new pathway for 
aqueous flow from the anterior chamber to the subconjunctival space. Clinical studies 
have shown XEN is effective at reducing IOP with fewer complications as compared 
with those published for trabeculectomy studies (Schlenker et al. 2017, Mansouri et al. 
2018, Hengerer et al. 2017, DeGregorio et al. 2018, Grover et al. 2017).

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 17 of 63
CONFIDENTIAL
7
STUDY OBJECTIVES
To compare the effectiveness and safety of XEN to trabeculectomy in subjects with 
glaucoma refractory to topical medical therapy defined as intraocular pressure (IOP) not 
at target on 1 or more topical medications.
7.1
Primary Endpoint
3HUFHQWDJHRIVXEMHFWVDFKLHYLQJPHDQ,23UHGXFWLRQIURm baseline at Month 12 
on the same or fewer number of topical IOP-lowering medications, without clinical 
hypotony, loss of vision to count fingers, or secondary glaucoma surgical intervention.
7.2
Secondary Endpoints
Effectiveness:
x
Mean and changes in mean IOP and number of topical IOP-lowering 
medications from preoperative baseline over time
x
Change from baseline (medicated) in mean IOP and mean number of topical 
IOP-lowering medications at Month 12
x
3URSRUWLRQRIH\HVDFKLHYLQJVSHFLILF,23WDUJHWVPP +J mm Hg, 
 mm +JPP +JPP +JPP Hg, and PP Hg at 
Month 12)
x
Proportion of eyes achieving specific percentage IOP lower targets from 
EDVHOLQH% to 50% in 5% increments)
x
3URSRUWLRQRIH\HVDFKLHYLQJ,23UHGXFWLRQVDQGVSHFLILF,23WDUJHWV
detailed above on same or lower number of topical IOP-lowering medications at 
Month 12 
x
Mean and changes in mean IOP and number of topical IOP-lowering 
medications from preoperative baseline over time in eyes with medicated 
EDVHOLQH,23 mm Hg
x
Needling rates; number of needlings per eye; outcomes post needling, including 
mean IOP and number of medications measured by proportion of eyes achieving 
>20% reduction at Month 12 on same or fewer topical IOP-lowering 
medications, and number of subjects not using any topical IOP-lowering 
medications; and antifibrotic use during needling.
Complete and qualified success:
x
&RPSOHWHVXFFHVV,23 mm Hg, with 20% or greater IOP lowering from 
medicated baseline on no topical medications) at Month 12 (eyes with clinical 
hypotony will be excluded)
x
4XDOLILHGVXFFHVV,23 mm Hg with 20% or greater IOP lowering from 
medicated baseline with topical medications) at Month 12 (eyes with clinical 
hypotony will be excluded)

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 18 of 63
CONFIDENTIAL
x
Medication-free eyes, mean IOP in this cohort, and proportion of eyes at specific 
IOPs (18 mm Hg, 17 mm Hg, 16 mm Hg, 15 mm Hg, 14 mm Hg, 
13 mm Hg, and 12 mm Hg at Month 12) 
x
Proportion of eyes achieving specific percentage IOP lower targets from 
EDVHOLQH% to 50% in 5% increments) with medication-free eyes. 
Intraoperative adjunctive antifibrotic therapy administered: 
x
Compound/product, mode of administration, dose and concentration, timing of 
adjunctive agent (surgery day and pre- and postsurgical procedure/implantation).
Visual parameters recovery post surgery:
x
BCVA with current glasses (preoperative and postoperative Day 1; Weeks 1 and
2; and Months 1, 3, 6, 9, and 12) 
x
Manifest refraction (baseline and postoperative Months 1, 3, 6, and 12)
x
Surgically induced astigmatism (autorefractor reading [preoperative and 
postoperative Months 1, 6, and 12] and, at selected sites, topography 
[preoperative and postoperative Week 1, and Months 1 and 12])
x
Optical biometry (anterior chamber depth and keratometric values) at 
preoperative and postoperative Day 1 and Week 2 at selected sites.
Other:
x
Bleb morphology (anterior segment optical coherence tomography [AS-OCT]
and slit lamp photography at selected sites).
Safety:
x
Clinical hypotony defined as vision reduction (2 lines or more) related to 
macular changes consistent with hypotony maculopathy (macular folds), optic 
disc edema, and/or serous choroidal detachments because of low IOP
x
Eyes with IOP 6 mm Hg or less at any time point and relevant clinical 
assessment (vision reduction [2 lines or more] related to macular changes 
consistent with hypotony maculopathy [macular folds], optic disc edema, 
anterior chamber status, and/or serous choroidal detachments because of low 
IOP) of these eyes at those time points 
x
Adverse events (AEs) including specific intraoperative and postoperative events 
of interest
x
BCVA, pachymetry, visual field 
x
AEs including serious AEs (SAEs)
x
Adverse device effects (ADEs) including serious ADEs (SADEs)
Patient-reported Outcomes:
x
Patient-reported Outcomes (PRO)

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 19 of 63
CONFIDENTIAL
7.3
Exploratory Objective
Not applicable.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 20 of 63
CONFIDENTIAL
8
INVESTIGATIONAL PLAN
8.1
Overall Study Design and Plan: Description
This is a multicenter, randomized, parallel-group, prospective, open-label clinical trial 
to compare the ability of XEN and trabeculectomy to reduce IOP and reduce the number
of topical IOP-lowering medications in subjects with IOP that is poorly controlled on 
topical therapy.
Subjects will be randomized 2:1, resulting in approximately 190 eyes being implanted 
with XEN and approximately 95 eyes receiving trabeculectomy. Subjects will be 
screened for enrollment, and eligible candidates will be approached to ascertain interest 
in study participation. Duration of participation in the study will be approximately 
12 months. The study design is depicted in Figure 8-1.
If both eyes of a subject meet the study entry criteria, the study eye will be selected by 
the investigator.
8.1.1
Study Design
Figure 8-1 Flow Chart of the Study
8.1.2
Schedule of Assessments
The schedule of planned study assessments is shown in Table 8.1.
Randomized 2:1
N=285
XEN
N=190
Trabeculectomy 
N=95
Screened
N=318
Note: These numbers are approximate. 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 22 of 63
CONFIDENTIAL
Procedure / Data to be Recorded
Baseline
Qualifying
Visita
Preoperative
Visit 1a
Operative
Postoperative Visits (visit window; time since Day 0)
Visit 2
Day 0
Visit 3
Day 1
(6-48 h)
Visit 4
Week 1
(3-10 d)
Visit 5
Week 2
(11-20 d)
Visit 6
Month 1
(3-8 wk)
Visit 7
Month 3
(9-17 wk)
Visit 8
Month 6
(18-32 wk)
Visit 9
Month 9
(33-47 wk)
Visit 10
Month 12
(48-60 wk)
Record Needling and Laser Suture
Lysis, and Antifibrotic Treatments
X
X
X
X
X
X
X
X
Adverse Events Assessment
X
Xh
X
X
X
X
X
X
X
X
AS-OCT = anterior segment optical coherence tomography; BCVA = Best corrected visual acuity; d = day; h = hour; HIPAA = Health Insurance Portability and 
Accountability Act; IOP = intraocular pressure; PRO = patient reported outcome; SHPC-18 = Symptom and Health Problem Checklist; wk = week; WPAI = Work 
Productivity and Activity Impairment
a The Baseline Qualifying Visit and the Preoperative Visit may be done on the same day if there are no changes in preoperative IOP medications. The Preoperative Visit may 
be repeated to complete all procedures, if needed. The visit window for Preoperative Visit 1 (including any repeated visits) is up to 4 weeks before study glaucoma 
VXUJHU\LQWKHVWXG\H\HDQG3 months since previous intraocular surgery in either eye.
b This is the medicated baseline IOP value. This should be performed at approximately the same time at each visit whenever possible. Subject has taken IOP medication.
c BCVA should be performed using a Snellen chart with glasses.
d Performed at Baseline Qualifying Visit and then at other times at the investigator´s discretion
e Can use valid results up to 3 months prior to screening
f At selected sites only
g Patient questionnaires should be self-administered prior to any clinical assessments.
h Refers to intraoperative events or surgical complications

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 23 of 63
CONFIDENTIAL
8.2
Discussion of Study Design
8.2.1
Study Design
Subjects will be randomized at a ratio of 2:1, resulting in approximately 190 eyes being
implanted with XEN and approximately 95 eyes receiving trabeculectomy. A
randomized study design was chosen because it prevents selection bias in treatment 
assignments and produces comparable groups. This study will include subjects 
presenting with glaucoma poorly controlled on topical therapy who are candidates for a 
subconjunctival drainage procedure. Subjects will be screened for enrollment and 
eligible candidates will be approached to ascertain interest in study participation. 
Subjects can be enrolled into one of the following groups:
Group 1: XEN implanted (XEN group)
Group 2: Trabeculectomy (Trab group).
All inclusion/exclusion criteria, effectiveness endpoints, success rate determinations,
and follow-up examinations will be identical for both groups.
At baseline, subjects with glaucoma not at target IOP when using at least 1 topical IOP-
lowering medication will be screened for eligibility to participate in the study. After the 
subject is determined to be eligible for participation in the study and is enrolled, the 
physician may stop the previously prescribed medications 1 to 4 weeks before surgery 
and begin preoperative medications (eg, steroids, antibiotics, artificial tears, oral 
carbonic anhydrase inhibitors [CAIs]) to prepare the ocular surface before surgery. The 
detection and treatment of comorbid conditions, particularly diseases of the ocular 
surface disease (dry eye) and blepharitis, can help reduce eye inflammation (Baudouin 
2012). Stopping or reducing IOP-lowering medications and replacing them, if 
necessary, with oral acetazolamide prior to surgery may be considered along with use of 
topical steroids and preservative-free lubricants to reduce ocular surface inflammation
and improve the likelihood of successful implantation (Vera et al. 2018). 
Subjects will undergo at least 1 preoperative visit (and more as needed), and then be 
scheduled for XEN gel stent implantation or trabeculectomy. Subjects will be examined 
postoperatively at the following timepoints: Day 1; Weeks 1 and 2; and Months 1,
Month 3, Month 6, Month 9, and Month 12.
8.2.2
Quality Management and Risk Evaluation
As noted in XEN’s Directions for Use the complications that may occur in conjunction 
with the use of XEN include, but are not limited to, the following: choroidal effusion, 
hyphema, hypotony, implant migration, implant exposure, wound leak, need for 
secondary surgical intervention and other known complications of intraocular surgery 
(eg, flat or shallow chamber, corneal edema, endophthalmitis).

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 24 of 63
CONFIDENTIAL
The risk profile for XEN has been established based on the review of all applicable 
safety data. These complications include adverse reaction to implant material, infection, 
implant failure, device malfunction, hypotony, flat anterior chamber (central lens, 
corneal touch), endophthalmitis, and ocular injury (inadvertent perforation of the sclera, 
hyphema, inadvertent loss of vitreous, choroidal hemorrhage or effusion, bleeding, 
device wound dehiscence). Risks involved in the procedure include persistent 
inflammation, corneal complications, retinal complications, choroidal complications, 
visual acuity loss (loss of 2 Snellen lines or more), chronic pain, unplanned secondary 
surgical intervention, loss of eye, and infection.
XEN is currently contraindicated under the following circumstances or conditions: 
angle-closure glaucoma, previous glaucoma shunt/valve in the target quadrant, presence 
of conjunctival scarring, prior conjunctival surgery or other conjunctival pathologies 
(eg, pterygium) in the target quadrant, active inflammation (eg, blepharitis, 
conjunctivitis, keratitis, uveitis), active iris neovascularization or neovascularization of 
the iris within 6 months of the surgical date, anterior chamber intraocular lens (ACIOL),
presence of intraocular silicone oil, vitreous present in the anterior chamber. The 
exclusion criteria of this trial are in accordance with the contraindications for the device 
(see Section 8.3.3).
The risks associated with the use of XEN are considered reasonable in comparison with
the anticipated benefits to subjects. XEN poses an acceptable level of risk for its 
intended use.
The risks associated with the gold-standard subconjunctival filtering procedure 
trabeculectomy have been well studied and include choroidal effusion, shallow/flat
anterior chamber, wound leak, hyphema, dysesthesia, encapsulated bleb, and persistent 
corneal edema (Gedde et al. 2007).
8.3
Selection of Study Population
8.3.1
Number of Planned Subjects 
This study will include subjects with glaucoma poorly controlled on topical therapy 
including those who may have had prior SLT or MIGS surgeries who meet the inclusion 
and exclusion criteria. Any questions regarding a subject’s eligibility should be 
discussed with the sponsor prior to enrollment.
This study plans to enroll subjects at approximately 25 to 40 sites in the United States.
A total of approximately 285 subjects will be included in the study: approximately 
190 subjects in the XEN arm and 95 subjects in trabeculectomy arm. One eye per 
subject will be enrolled into the study. This includes an estimated 10% dropout rate 
after screening (see Section 11.2 for the calculation of sample size).

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 25 of 63
CONFIDENTIAL
8.3.2
Inclusion Criteria
To be eligible for study entry subjects must satisfy all of the following criteria in the 
study eye (only 1 eye will be allowed in the study):
1.
0DOHRUIHPDOHVXEMHFWVDJHV\HDUV
2.
Able to provide signed written informed consent
3.
Glaucoma in which the IOP is not controlled on current topical IOP-lowering 
glaucoma medication
4.
Best-corrected baseline Snellen visual acuity of 20/100 or better 
5.
Visual field mean deviation no worse than -18.0 dB (with no dense paracentral 
scotomas, eg, >18 dB total deviation on 1 or more of the 4 paracentral points)
6.
0HGLFDWHG,2315 mm +JDQGPP Hg on at least 1 topical IOP-lowering 
medication
7.
Subjects not anticipated to require any other ocular surgery (eg, cataract surgery) 
in either eye up to 3 months from the time of inclusion 
8.
Area of healthy, free, and mobile conjunctiva in the target area, ie, superior bulbar 
conjunctiva
9.
Visible trabecular meshwork with 6KDIIHUDQJOHJUDGHLQWKHWDUJHWDUHD or, in 
eyes with prior failed angle surgery, an open angle in the target area
10.
Preoperative laser trabeculoplasty is allowed 3 or more months prior to 
randomization 
11.
Failed ab-interno canal or suprachoroidal MIGS procedures (such as i-Stent®,
gonioscopy-assisted transluminal trabeculotomy [GATT], ab-interno canaloplasty 
[ABiC™], Kahook Dual Blade goniotomy, etc) are allowed 3 or more months 
before enrollment, with the exception of CyPass® Micro-Stents, which are not 
allowed. Ab-interno ablative procedures (such as endoscopic cyclophoto-
coagulation [ECP]) are also allowed 3 or more months before enrollment.
8.3.3
Exclusion Criteria 
Subjects will be excluded from the study if 1 or more of the following criteria are 
applicable in the study eye:
1.
Subject has active neovascular, uveitic or angle-recession glaucoma or any 
glaucoma associated with vascular disorders 
2.
Subject has had prior ab-externo incisional glaucoma surgery (such as 
trabeculectomy, viscocanalostomy, canaloplasty, tube shunts of any type, collagen 
implants, etc), conjunctival filtering surgery (such as XEN), transscleral 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 26 of 63
CONFIDENTIAL
cycloablative procedures (such as cyclophotocoagulation, micropulse 
cyclophotocoagulation, cryotherapy, ultrasonic circular cyclocoagulation [UC3],
etc) or prior major conjunctival surgery (ie, scleral buckle)
3.
Clinically significant inflammation or infection within 30 days before the 
Preoperative Visit (eg, blepharitis, conjunctivitis, severe ocular surface disease, 
keratitis, uveitis, herpes simplex infection)
4.
Presence of conjunctival scarring or prior conjunctival surgery or other 
conjunctival pathologies (eg, pterygium) in the target area
5.
History of corneal surgery, corneal opacities, or corneal disease that could impact 
assessments/surgical outcomes in the study
6.
&HQWUDOFRUQHDOWKLFNQHVV ȝPRU ȝP
7.
Subjects on systemic CAIs (eg, Diamox® [acetazolamide] and Neptazane®
[methazolamide]) at Baseline Qualifying Visit
8.
Vitreous present in the anterior chamber
9.
Aphakia 
10.
6XEMHFWKDVKDGSULRULQWUDRFXODUVXUJHU\LQHLWKHUH\HZLWKLQ3 months before 
the Preoperative Visit (including phacoemulsification)
11.
History of complicated cataract surgery with: visual impairment, vitreous loss, 
ACIOL, sutured intraocular lens (IOL), scleral fixated IOL or cystoid macular 
edema (CME), dislocated IOL
12.
Presence of intraocular silicone oil
13.
Active diabetic retinopathy, proliferative retinopathy, choroidal 
neovascularization, branch retinal vein occlusion, central retinal vein occlusion, 
geographic atrophy, or other ophthalmic disease or disorder that could confound 
study results or impaired episcleral venous drainage (eg, Sturge-Weber or 
nanophthalmos, Axenfeld-Rieger, iridocorneal endothelial [ICE] syndrome, etc)
14.
Known or suspected allergy or sensitivity to drugs required for the protocol 
(including anesthesia), or any of the device components (eg, bovine or porcine 
products, or glutaraldehyde)
15.
Pregnant or nursing women and those planning a pregnancy during the study 
period
16.
Participation in another drug or device clinical trial that concludes within 30 days 
before the Preoperative Visit or that starts at any time during this study.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 27 of 63
CONFIDENTIAL
8.3.4
Removal of Subjects from Therapy or Assessments
Every attempt must be made to gather complete follow-up data for all subjects enrolled. 
Subjects who would be traveling, relocating or otherwise unavailable for the 
postoperative follow-up schedule should not be chosen for the study.
Subjects should be discontinued from the study only if irretrievably lost to follow-up for 
unavoidable reasons such as inability to locate, subject uncooperativeness, subject
illness, or subject death. A subject may also be discontinued from the study if 
complications occur during surgery and the subject does not receive XEN or undergo 
trabeculectomy. If a subject does receive XEN or undergo trabeculectomy following 
complications, then the subject should be followed up per the study protocol. Also, if 
the eye undergoes additional glaucoma surgery after the study intervention due to poor 
IOP control, it will be discontinued from the study as a failure.
In the event that a subject is discontinued from the study, the investigator shall complete 
a Subject Exit Form in the electronic data capture (EDC) system, indicating the early 
termination reason.
Subjects may withdraw their consent to continue in the study at any time. Subjects
withdrawing from the study after receiving XEN or undergoing trabeculectomy will be 
encouraged to complete the same final evaluations as subjects completing the study 
according to this protocol, particularly safety evaluations. The aim is to record data in 
the same way as for subjects who completed the study. Subjects who discontinue before 
undergoing a study surgery will not be required to return for study follow-up visits.
Reasonable efforts will be made to contact subjects who are lost to follow-up. These
efforts must be documented in the subject’s file. 
The sponsor has the right to terminate the study at any time, in case of SAEs, or if 
special circumstances concerning the study product or the company itself occur, making 
further treatment of subjects impossible. In this event, the investigator(s) will be 
informed of the reason for study termination.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 28 of 63
CONFIDENTIAL
8.4
Investigated in Protocol
8.4.1
Study Product and Procedures
8.4.1.1
XEN
XEN is manufactured by Allergan, Plc (Ireland). XEN is composed of a gelatin derived 
from porcine dermis, formed into a tube, and cross-linked with glutaraldehyde. It is 
intended to be inserted in the angle and through the sclera, connecting the anterior 
chamber to the subconjunctival space. XEN is preloaded in the XEN Injector, a single-
use mechanical delivery system. XEN is packaged with directions for use and the 
procedure to insert XEN should be carried out in line with surgical training provided by 
the manufacturer and following the standard of care at each investigative center.
8.4.1.2
Comparator – Trabeculectomy
Trabeculectomy will be performed in accordance with the standard of care at each 
investigative center with adjunctive antifibrotic therapy and including essential steps: 
conjunctival flap, scleral flap, and sclerostomy. Note: Peripheral iridectomy is not 
mandated and is left to the standard practice of the surgeon.
8.4.2
Packaging and Labeling
XEN used will be commercial supply of XEN-45 Gel Stent in the United States.
8.4.3
Device Complaint Reporting
Device complaints and malfunctions should be reported per the package insert or 
directions for use.
8.4.4
Method of Assigning Subjects to Treatment Groups
Subjects will be randomized by investigational site to a 2:1 (XEN:trabeculectomy) 
randomization schedule by the Medidata Rave RTSM (Randomization and Trial Supply 
Management) application. The randomization list will be generated by the sponsor’s 
independent Randomization Services Group using a customized validated system 
composed of a series of SAS® Macros (version 1.4). This list will be provided to the 
contract research organization’s (CRO’s) independent randomization team, who will 
upload the list into the Medidata Rave RTSM application and validate it. Upon 
completion of a randomization electronic case report form (eCRF), indicating that a
study eye meets all entry criteria, the data will be sent to the RTSM system for 
randomization. The RTSM system will then provide the surgery group assignment for 
the study eye and integrate it back into the randomization eCRF. The sponsor’s and 
CRO’s study team members, investigational site staff, and subjects will not have access 
to the randomization list.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 29 of 63
CONFIDENTIAL
8.4.5
Prior and Concomitant Therapy
Topical IOP-lowering medication may be stopped 1 to 4 weeks before surgery and re-
started according to the investigator’s recommendation. At baseline, subjects are to be 
using at least 1 topical IOP-lowering medication and, when using that medication at the 
maximum tolerated dose, their IOP is not controlled. After the subject is determined to 
be eligible for participation in the study and is enrolled, the physician may stop the 
previously prescribed medications 1 to 4 weeks before surgery and begin preoperative 
medications (eg, steroids, antibiotics, artificial tears) to prepare the ocular surface before 
surgery. The detection and treatment of comorbid conditions, particularly diseases of 
the ocular surface disease (dry eye) and blepharitis, can help reduce eye inflammation 
(Baudouin 2012). Stopping or reducing IOP-lowering medications and replacing them, 
if necessary, with oral acetazolamide prior to surgery may be considered along with use 
of topical steroids and preservative-free lubricants to reduce ocular surface 
inflammation and improve the likelihood of successful implantation (Vera et al. 2018). 
Subjects who have had prior ab-externo incisional glaucoma surgery (such as 
trabeculectomy, viscocanalostomy, canaloplasty, tube shunts of any type, collagen 
implants, etc), conjunctival filtering surgery (such as XEN), transscleral cycloablative 
procedures (such as cyclophotocoagulation, micropulse cyclophotocoagulation, 
cryotherapy, UC3, etc) or prior major conjunctival surgery (ie, scleral buckle) are not 
eligible for the study (see Section 8.3.3).
Perioperative adjunctive antifibrotic therapy should be used according to physician 
training and practice.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 30 of 63
CONFIDENTIAL
9
TIMING OF STUDY PROCEDURES
The planned study assessments are in Section 8.1.2.
Every attempt should be made to schedule the visits (specifically measurement of IOP) 
at approximately the same time of day to avoid the influence of diurnal fluctuations.
Assess IOP using Goldmann applanation tonometry. Take 2 measurements. If the first 
2 measurements differ by more than 3 mm Hg, take a third measurement. Use the 
average if 2 measurements are taken (or the median if 3 measurements are taken) to 
determine each day’s IOP.
9.1
Pretreatment Visits
9.1.1
Baseline Qualifying Visit
During the study Baseline Qualifying Visit, the procedures will be performed following 
the Schedule of Assessments (Table 8.1).
When these procedures have been performed, the next visit will be scheduled. The 
Baseline Qualifying Visit and Preoperative Visit may occur on the same day if there are 
no changes to the IOP-lowering medications prior to surgery.
9.1.2
Preoperative Visit (Visit 1)
During the study Preoperative Visit, the procedures will be performed as shown on the 
Schedule of Assessments (Table 8.1).
This visit may be repeated as necessary to complete required examinations. The visit 
window for Preoperative Visit 1 (including any repeated visits) is up to 4 weeks before 
VWXG\JODXFRPDVXUJHU\LQWKHVWXG\H\HDQG3 months since previous intraocular 
surgery in either eye. When all Visit 1 procedures have been performed, if all entry 
criteria are met, the study eye will be randomized to glaucoma surgery procedure, and 
the next visit will be scheduled.
9.1.3
Operative Visit (Visit 2)
The Operative Visit (Visit 2) will be Day 0 of the study. At this visit, glaucoma surgery 
(XEN or trabeculectomy) will be performed. Record any intraoperative complications.
9.2
Postoperative Visits
9.2.1
Day 1 (Visit 3)
The first postoperative visit will take place on study Day 1 (6-48 hours) after the 
Operative Visit. During this visit the procedures will be performed following the 
Schedule of Assessments (Table 8.1).

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 31 of 63
CONFIDENTIAL
9.2.2
Week 1 (Visit 4)
Visit 4 will take place 1 week (3-10 days) after the Operative Visit. During this visit the 
procedures will be performed following the Schedule of Assessments (Table 8.1).
9.2.3
Week 2 (Visit 5)
Visit 5 will take place 2 weeks (11-20 days) after the Operative Visit. During this visit 
the procedures will be performed following the Schedule of Assessments (Table 8.1).
9.2.4
Month 1 (Visit 6)
Visit 6 will take place 1 month (3-8 weeks) after the Operative Visit. During this visit 
the procedures will be performed following the Schedule of Assessments (Table 8.1).
9.2.5
Month 3 (Visit 7)
Visit 7 will take place 3 months (9-17 weeks) after the Operative Visit. During this visit 
the procedures will be performed following the Schedule of Assessments (Table 8.1).
9.2.6
Month 6 (Visit 8)
Visit 8 will take place 6 months (18-32 weeks) after the Operative Visit. During this 
visit the procedures will be performed following the Schedule of Assessments
(Table 8.1).
9.2.7
Month 9 (Visit 9)
Visit 9 will take place 9 months (33-47 weeks) after the Operative Visit. During this 
visit the procedures will be performed following the Schedule of Assessments
(Table 8.1).
9.2.8
Month 12 (Visit 10)
Visit 10 will take place 12 months (48-60 weeks) after the Operative Visit. During this 
visit the procedures will be performed following the Schedule of Assessments
(Table 8.1).
9.2.9
Early Withdrawal Visit
In the case of an early withdrawal, an Early Withdrawal Visit should be scheduled for 
subjects who underwent a study surgery, if possible. Procedures should be performed as 
for the Month 12, Visit 10.
9.3
Duration of Study 
The duration of study participation will be approximately 12 months.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 32 of 63
CONFIDENTIAL
9.4
Pregnancy
If a female XEN subject becomes pregnant during the study, the investigator will notify 
Allergan immediately by completing the Pregnancy Surveillance Form after the 
pregnancy is confirmed and faxing it to +1-877-605-4524 or +1-714-796-9567. Best 
practices are to be followed to ensure the welfare of the subject and the fetus. Once the 
pregnancy has reached term, the second page of the Pregnancy Surveillance Form 
concerning outcome is to be completed. The medical safety physician will contact the 
investigator to obtain information about the pregnancy outcome. The subject will 
continue to be followed up as part of the implanted population. Pregnancy by itself will 
not be considered an AE or SAE. Hospitalization for a normal delivery or elective 
abortion of a normal fetus does not constitute an SAE. However, the occurrence of an 
adverse pregnancy outcome for the mother or child may constitute an AE or SAE, and 
these are to be reported. 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 33 of 63
CONFIDENTIAL
10
EFFECTIVENESS AND SAFETY VARIABLES
10.1
Effectiveness and Safety Measurements Assessed
10.1.1
Effectiveness Variables
10.1.1.1
Intraocular Pressure
Every attempt should be made to schedule the visits at approximately the same time of 
day to avoid the influence of diurnal fluctuations on study procedures, specifically 
measurement of IOP.
Except at the Operative Visit (Visit 2), IOP will be measured at all study visits by 
standard Goldmann applanation tonometry. The readings will be recorded on the 
appropriate eCRF. The tonometer should be checked for proper calibration monthly and 
the date of calibration checking should be recorded. The eye cannot have received 
pupil-dilating medications. 
10.1.1.2
Topical IOP-lowering Medication
For endpoints evaluating the number of topical IOP-lowering medications taken by the 
subject, the following are examples of the classes of medications to be recorded: 
prostaglandin analogues, beta-adrenergic antagonists, CAIs, alpha-adrenergic agonists, 
pilocarpine, and combinations of these treatments.
10.1.1.3
Patient-reported Outcomes
The following 3 questionnaires will be completed to assess subject status.
Questionnaires will be administered to subjects on an electronic tablet at the visits 
designated in Table 8.1. Data from completed questionnaires will be imported into the 
eCRF using a validated process.
1.
Collaborative Initial Glaucoma Treatment Study (CIGTS) Symptom and
Health Problem Checklist (SHPC-18)
2.
Postsurgical question on resumption of activities and daily routine
3.
Work Productivity and Activity Impairment (WPAI): Productivity outcomes.
The SHPC-18 is an18-item questionnaire that asks subjects being treated for glaucoma 
questions about eye symptoms or problems they may experience. The questionnaire 
includes 2 domains: local eye symptoms (7 items) and visual function problems 
(11 items). The development of the SHPC-18 and validation of its 2 domains have been 
published. Each question first asks the subject if they have experienced the symptom or 
problem in the last 7 days. If the subject responds “Yes”, they are then asked how 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 34 of 63
CONFIDENTIAL
burdensome the symptom or problem was, with Likert-type response options ranging 
from “Not at all” to “A lot” (Musch et al. 2017). 
The WPAI is included because overall work productivity is significantly related to 
general health perceptions and the global measures of interference with regular activity 
(Reilly et al. 1993).
Additionally, responses to the Postsurgical Question will be collected to better 
understand differences, if any, in postoperative recovery between the 2 procedures.
These measures can be found in Appendix 17.
10.1.2
Safety Analysis
Safety analysis will be performed in both the XEN population and the population 
randomized to trabeculectomy. The numbers and percentage of subjects reporting AEs 
will be tabulated regardless of causality. AEs, ADEs, and all safety measures will be 
summarized by frequencies at each visit.
10.1.2.1
Adverse Events
Throughout the course of the study, all AEs will be monitored and reported on an AE 
eCRF, including seriousness, severity, action taken, and relationship to study treatment. 
If AEs occur, the first concern will be the safety of the study participants. Needling and 
laser suture lysis will be captured as procedures but will not be considered AEs.
All AEs and device deficiencies that occur between visits are to be recorded on the date 
of the next postoperative examination on the subject’s eCRF.
10.1.2.1.1
Definitions
The investigators will classify the AEs based on the following definitions according to 
ISO 14155 (2011).
Adverse Event
An AE is defined in accordance with ISO 14155 as any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs (including abnormal laboratory 
findings) in subjects, users or other persons, if related to the investigational medical 
device. This definition includes events related to the investigational medical device or 
comparator and events related to the procedures involved. Disease signs and symptoms 
that existed prior to the study treatment are not considered AEs unless the condition 
recurs after the participant has recovered from the pre-existing condition or the 
condition worsens in intensity or frequency during the study.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 35 of 63
CONFIDENTIAL
AEs will be monitored throughout the study beginning with the Preoperative Visit. At 
each postbaseline visit, the investigator will begin querying for AEs by asking each 
participant a general, nondirected question such as “Have you had any changes to your 
condition since your last visit?” Previous AEs and changes in therapy/concomitant 
medications are to be updated. Directed questioning and examination will then be done 
as appropriate. All reportable AEs and clinically significant abnormal laboratory 
findings will be documented on the appropriate eCRF.
Adverse Device Effect (ADE)
An ADE is defined in accordance with ISO 14155 as “an adverse event related to the 
use of an investigational medical device.” This definition includes any AEs resulting 
from insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device as 
well as any event resulting from use error (per ISO 62366) or from intentional misuse of 
the investigational medical device. 
Device Deficiency or Complaints
A device deficiency is defined in accordance with ISO 14155 as inadequacy of a 
medical device including issues with respect to its identity, quality, durability, 
reliability, safety or performance. Device deficiencies include malfunctions, use errors, 
and inadequate labeling.
If a device deficiency occurs, the investigator will notify Allergan using the eCRF.
Device deficiencies shall be documented throughout the study and appropriately 
managed by Allergan. The Clinical Trial Site will enter all the information regarding 
device deficiency into the appropriate eCRFs. Allergan shall review all device 
deficiencies and determine and document in writing whether they could have led to the
SADE. These shall be reported to the regulatory authorities and independent ethics 
committees/institutional review boards (IECs/IRBs) as required by Federal regulations.
10.1.2.1.2
Possible Adverse Events
The following is a list of AEs that can occur intraoperatively during implantation of 
XEN and/or trabeculectomy surgery. These and any other AEs that occur should be 
reported in the AE eCRF:
x
Detached Descemet’s membrane
x
Iris damage
x
Lens contact
x
Vitreous bulge or loss
x
Anterior chamber bleeding
x
Retrobulbar hemorrhage
x
Conjunctival perforation

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 36 of 63
CONFIDENTIAL
x
Conjunctival or scleral flap tearing
x
Shallow anterior chamber with peripheral iridocorneal touch
x
Flat anterior chamber with iridocorneal touch extending to the pupil
x
Device malfunction identified prior to implantation
x
Choroidal hemorrhage of effusion
The following is a list of AEs that can occur postoperatively for XEN and/or 
trabeculectomy surgery. These and any other AEs that occur should be reported in the 
AE eCRF:
x
Angle recession
x
Anterior chamber shallow with peripheral iridocorneal touch
x
Anterior chamber flat with iridocorneal touch
x
BCVA loss of 2 lines (Early Treatment Diabetic Retinopathy Study 
[ETDRS] letters)
o
GD\V
o
>30 days
o
At 12 months (persistent loss)
x
Bleb leak (without operative room or slit lamp revision)
x
Bleb leak (with operative room or slit lamp revision)
x
Blebitis (with or without anterior chamber reaction or hypopyon) 
x
Cataract formation
x
Clinically significant progression of cataract, based on an assessment by the 
investigator
x
Choroidal effusion (extending posterior to equator, without blood)
x
Choroidal effusion (obscuring disc or macula, without blood)
x
Choroidal effusion (with choroids touching in the center of the eye, without 
blood) 
x
Choroidal effusion (extending posterior to equator, with blood)
x
Choroidal effusion (obscuring disc or macula, with blood)
x
Choroidal effusion (with choroids touching in the center of the eye, with blood)
x
Choroidal effusion and/or hemorrhage occurring >30 days (persistent)
x
Chronic pain (present greater than 3 months)
x
Corneal edema grade 3 or grade 4 (>30 days postoperatively)
x
Cyclodialysis
x
Dellen
x
Device malfunction
x
Endophthalmitis
x
Fixed dilated pupil
x
Hyphema (2 mm in height [layered] at any time)
x
Hyphema (present or arising >30 days)
x
Hypotony (IOP <6 mm Hg at any time)

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 37 of 63
CONFIDENTIAL
x
Persistent hypotony (IOP <6 mm Hg at 2 visits >30 days apart) 
x
Hypotony maculopathy
x
Implant exposure
x
Implant fracture
x
Implant migration
x
Implant obstruction (complete or partial)
x
Implant repositioning requiring surgical intervention
x
Increase in cup/disc UDWLRRIXQLWV on slit lamp examination
x
,QFUHDVHLQFRUQHDOWKLFNQHVVRILQWKHpresence of corneal edema
x
IOP increase 10 mm Hg from baseline
x
Iridodialysis
x
Iritis (requiring treatment after the postoperative medication taper)
x
Loss of eye
x
Macular edema
x
Macular puckering
x
Posterior capsule opacification
x
Ptosis
x
Retinal complications
x
Secondary surgical intervention
o
Explant
o
Secondary glaucoma procedure with explant
o
Secondary glaucoma procedure
x
Significant (2-grade) worsening or a grade of moderate or severe, for any slit
lamp observation for which a standard grading scale is not available (>30 days
postoperatively)
o
Anterior chamber cells
o
Blepharitis
o
Chalazion
o
Dysesthetic bleb
o
Hyperemia
x
Significant iris injury or atrophy
x
Strabismus
x
Suture abscess or other local infection
x
Vitreous hemorrhage
x
Vitreous loss
x
Wound leak/dehiscence
Assessment of Severity
Severity is a clinical determination of the intensity of an AE. The severity assessment 
for a clinical AE will be assigned a category by the investigator as follows:

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 38 of 63
CONFIDENTIAL
Mild:
An AE that is easily tolerated by the subject, causes minimal discomfort,
may require only minimal treatment and does not interfere with everyday 
activities.
Moderate:
An AE that is sufficiently discomforting to interfere with normal 
everyday activities; intervention may be needed, but poses no significant 
or permanent risk of harm. 
Severe:
An AE that prevents normal everyday activities; treatment or other 
intervention usually needed.
If there is a change in severity of an AE, it must be recorded as a separate event.
Assessment of Causality
Relationship to a device refers to a determination of the relationship (if any) between an 
AE and the device. A causal relationship is present if the investigator determines that 
there is a reasonable possibility that the AE may have been caused by the device.
An AE could be considered procedure-related when, in the judgment of the investigator, 
it is reasonable to believe that the event is associated with the procedure, regardless of 
the relationship to the study device. Procedure-related causes that contribute to the 
occurrence of the event can be attributed to other products, surgical techniques, or 
medications required specifically for the procedure.
Every effort will be made by the investigator to assess the relationship of the AE, if any, 
to the device and/or study procedure. Causality should be assessed using the categories 
presented in the following table:
Not related:
Clinical event of which the relationship to the device and/or 
procedure can be excluded, such as if the event is incompatible time 
relationship to study procedure and/or use of the device, involves a 
body part or organ not expected to be affected by the device or
procedure, could be explained by underlying disease or other drugs or 
chemicals or is incontrovertibly not related to the study device, and is 
not due to use error. 
Unlikely:
Clinical event whose time relationship to use of the device and/or
study procedure makes a causal connection improbable, but that could 
plausibly be explained by underlying disease or other drugs or 
chemicals.
Possible:
Clinical event with a reasonable time relationship to the use of the 
device and/or study procedure, but that could also be explained by 
concurrent disease or other drugs or chemicals. Cases in which
relatedness cannot be assessed or no information has been obtained 
should also be classified as possible. 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 39 of 63
CONFIDENTIAL
Probable:
Clinical event with a reasonable time relationship to the use of the 
device and/or study procedure, and is unlikely to be attributed to 
concurrent disease or other drugs or chemicals.
Causal 
relationship:
Clinical event with plausible time relationship to the use of the device 
and/or study procedure, is a known side effect of the product category 
the device belongs to or of similar devices and procedures; follows a 
known response pattern to the medical device; involves a body-site or 
organ that the device or procedures are applied to and/or influence;
harm is due to error in use, and that cannot be explained by 
concurrent disease or other drugs or chemicals.
Follow-up of Adverse Events
All investigators should follow up subjects with AEs until the event is resolved or until, 
in the opinion of the investigator, the event is stabilized or determined to be chronic. 
Details of AE resolution must be documented in the eCRF.
10.1.2.1.3
Serious Adverse Events
Serious Adverse Event Definition
An AE is considered an SAE if it:
a) led to death,
b) led to serious deterioration in the health of the subject, that either resulted in
1) a life-threatening illness or injury, or
2) a permanent impairment of a body structure or a body function, or
3) in-patient or prolonged hospitalization, or
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function,
c) led to fetal distress, fetal death or a congenital abnormality or birth defect.
Note: Planned hospitalization for a pre-existing condition, or a procedure required by 
the protocol, without serious deterioration in health, is not considered an SAE.
Serious Adverse Device Effect (SADE)
An SADE is an adverse device effect that has resulted in any of the consequences 
characteristic of an SAE.
Reporting of Serious Adverse Events
All device- or surgery-related SAEs must be entered into the EDC system within
24 hours of being notified of the event. The sponsor will be notified by EDC system
once the SAE electronic form has been submitted.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 40 of 63
CONFIDENTIAL
The relationship of the clinical event to the devices and procedure should be reported
on the Serious Adverse Event Form for Devices and will be determined by the
investigator.
Following evaluation of each SAE, the responsible IEC/IRB will be notified as 
appropriate based on national regulations.
All SAEs that occur from the time the informed consent form (ICF) is signed through to 
their final study visit must be reported to the sponsor. In addition to entering the 
information into the EDC system, the investigator must:
x
Notify the sponsor immediately (within 24 hours) by fax using the Serious 
Adverse Event Form for Devices. The form should be sent directly to the 
sponsor at LC-Medical_Safety@allergan.com or fax to +1-877-605-4524 or 
+1-714-796-9567. The SAE report should be completed regardless of the 
amount of information available although the investigator is expected to provide 
as much information as possible.
x
Obtain and maintain in his/her files all pertinent medical records, information, 
and medical judgments from colleagues who assisted in the treatment and
follow-up of the subject.
x
Provide the sponsor with a complete, written case history (AE report form) 
which includes a statement as to whether the event was or was not related to the 
use of the investigational device or procedure.
The sponsor (or its representative) will report all SAEs associated with the use of the 
study device to the regulatory agencies (IEC/IRB, Competent Authorities) as 
appropriate according to relevant SOPs and to the national laws of the country where 
the trial is performed.
For every SAE, appropriate measures should be taken to treat/resolve and monitor the
subject. The investigator should keep Allergan closely informed of the progress as
related to the SAE. Any subjects who are withdrawn from the study due to an AE shall
still be followed up until the outcome is resolved.
10.2
Data Safety Monitoring Board
Not applicable
10.2.1
Appropriateness of Measurements
The effectiveness and safety assessments planned for this study are widely used and 
generally recognized as reliable, accurate and relevant to the disease condition.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 41 of 63
CONFIDENTIAL
11
STATISTICAL METHODS
Prior to database lock a statistical analysis plan (SAP) defining all details of analysis 
will be prepared and finalized.
11.1.1
Datasets or Populations Analyzed
The Enrolled population consists of all study eyes for which the subject has signed the 
ICF. The Enrolled population will be used to summarize disposition data.
The Intent-to-treat (ITT) population consists of all enrolled eyes randomized to study 
glaucoma surgery (XEN or trabeculectomy). The ITT population will be the primary 
analysis population for effectiveness data. Subject demographics, baseline 
characteristics, and PRO data will be analyzed using the ITT population. Subjects will 
be grouped and analyzed according to the actual surgery received.
The Modified Intent-to-treat (mITT) population consists of eyes in the ITT population 
that receive study glaucoma surgery and have no major protocol deviations, which will 
be defined in the SAP and identified prior to database lock. The mITT population will 
be used for selected effectiveness endpoints (as specified in the SAP), and will be used 
for the analyses of PRO data also.
The Safety population consists of all enrolled eyes that undergo study glaucoma 
surgery, whether surgery is completed or aborted, and have follow-up visits or 
evaluations. The Safety population will be used to analyze AEs, medical and ophthalmic 
history, and concomitant medications (ocular and systemic). Subjects will be grouped 
and analyzed according to the surgery they received.
11.1.2
Demographic and Other Baseline Characteristics
Demographic and baseline subject characteristics will be summarized. Descriptive 
statistics (such as mean, SD, minimum, median, and maximum) will be presented for 
each continuous variable. Categorical variables will be displayed using frequency 
counts and percentages.
11.1.3
Effectiveness Variables and Statistical Analyses 
Definition of Primary Effectiveness Endpoint
The primary endpoint for the study will be the percentage of subjects achievinJ
mean IOP reduction from baseline at Month 12 on the same or fewer number of topical 
IOP-lowering medications, without clinical hypotony, loss of vision to count fingers, or 
secondary glaucoma surgical intervention.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 42 of 63
CONFIDENTIAL
Definition of Secondary Effectiveness Endpoints
Effectiveness will be determined by comparing the medicated preoperative IOP with the 
postoperative IOP at Month 12, and the number of topical IOP-lowering medications at 
screening with number of topical IOP-lowering medications at Month 12. Individual 
secondary effectiveness endpoints are defined in Section 7.2.
Definition of Performance Endpoints (Device Studies)
The IOP change at all visit windows will be summarized by mean, SD, median, 
maximum, and minimum. The percentage change in IOP from baseline to Month 12
will also be summarized descriptively. When necessary, appropriate parametric or 
nonparametric analyses will be used to determine statistically significant differences.
Methods of Statistical Analysis
The number and proportion of subjects DFKLHYLQJPHDQ,23UHGXFWLRQIURP
baseline at Month 12 on the same or fewer number of topical IOP-lowering 
medications, without clinical hypotony, loss of vision to count fingers, or secondary 
glaucoma surgical intervention will be tabulated with 95% CI calculated by using the 
normal approximation method. The difference of the proportions will be estimated and 
the 95% CI of the difference will also be calculated with the method of the normal 
approximation. The 2 treatment groups will be claimed as equivalent if the 95% CI of 
the differences is within the -18% to 18% interval. The least squares mean change from 
baseline in IOP and the least squares mean difference between the 2 treatment groups
will be estimated using the analysis of covariance (ANCOVA) model or the mixed-
effect model repeat measurement (MMRM) model. The proportion and 95% CI of 
complete success and qualified success will be calculated with normal approximation.
11.1.4
Safety Variables
All reported treatment-emergent AEs (TEAEs), treatment-related TEAEs, SAEs, and all 
safety measures collected will be tabulated by counts and percentages. Adverse events 
will be summarized by presenting the number and percentage of subjects having any 
AE. Any other information collected (such as AE severity) will be tabulated and listed 
as appropriate. Pregnancy of female subjects should also be tabulated. Analyses of AEs 
and other safety variables will be described in the SAP.
11.1.5
Interim Analyses
An interim analysis may be performed.
11.1.6
Handling of Missing Data
No imputation will be performed for any missing IOP. IOP, change in IOP from

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 43 of 63
CONFIDENTIAL
baseline, percentage change in IOP from baseline, number of topical IOP-lowering 
medications used, and change in number of topical IOP-lowering medications used 
will be summarized descriptively at each scheduled visit.
11.2
Determination of Sample Size
Recent studies of XEN in treating patients with POAG have reported significantly high 
treatment success rates. Grover et al. reported 75.4% of the treated patients having 
achieved success, as defined by a >20% reduction from baseline in IOP at Month 12 on 
the same or fewer medications (Grover et al. 2017). Mansouri et al. reported 81% 
success rate at Month 12, and Tan et al. (2018) reported success rates of 87% and 92% 
at Month 12 depending on if patients were using medications (Mansouri et al. 2018, Tan 
et al. 2018). However, it should be noted that the 3 studies are based on relatively small 
sample sizes in the XEN alone arm, ranging from 21 to 61 evaluable study eyes, and a 
more conservative estimate of the success rate is about 70%. A previous study 
supported that the XEN procedure and the standard of care therapy trabeculectomy are 
comparable in terms of treatment success (Schlenker et al. 2017). Moreover, it is 
assumed that neither treatment is better or worse than the other by more than 20% in 
terms of treatment success rate. This trial is intended to demonstrate that XEN is 
comparable to trabeculectomy in terms of treatment success rate. The sample size 
calculation is based on an equivalence test.
To control Type-I error rate at 5% and to attain 80% power for demonstrating that the 
difference is within the equivalence limit of 18%, about 256 study eyes will be needed 
for the study with a randomization ratio of 2:1 for the XEN arm: trabeculectomy arm.
Allowing a 10% dropout rate for the first year, approximately 285 study eyes (190 for 
the XEN arm and 95 for the trabeculectomy arm) will need to be recruited for the study.
11.3
Protocol Deviations
Should a protocol deviation occur, the sponsor must be informed as soon as possible. 
Protocol deviations and/or violations and the reasons they occurred will be included in 
the clinical study report. Reporting of protocol deviations to the IRB/IEC and in 
accordance with applicable regulatory authority mandates is an investigator’s
responsibility.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 44 of 63
CONFIDENTIAL
12
QUALITY ASSURANCE AND QUALITY CONTROL
12.1
Audit and Inspection
Study centers and study documentation may be subject to Quality Assurance audit 
during the study or after the study has been completed by the sponsor or its nominated 
representative. In addition, inspections may be conducted by regulatory authorities at 
their discretion.
12.2
Monitoring
Subject data will be monitored remotely. Monitoring visits may be scheduled 
throughout the study, if needed. Monitoring visits will be scheduled in advance, to
ensure that the investigator has sufficient time to meet with the monitor and discuss all 
relevant findings. Subject data will be reviewed and/or audited, and all deficiencies 
corrected on site, if possible. A complete report will be made of all monitoring visits. If 
the study is terminated, a study close-out visit may be scheduled with the site if needed 
to retrieve all remaining study records.
The monitor will review the study conduct to determine compliance with the study 
protocol and GCP guidelines. The monitor will review and/or audit the electronic forms 
and source documents to ensure the accuracy and completeness of the data captured for 
the study. The monitor will review the subject ICFs to ensure that no forms were signed 
prior to the date of IEC/IRB approval of the study. The system for record-keeping will 
be reviewed.
12.3
Data Management and Coding
The CRO will be responsible for activities associated with the data management of this 
study. This will include setting up a relevant database and data transfer mechanisms, 
along with appropriate validation of data and resolution of queries. Data generated 
within this clinical study will be handled according to the relevant SOPs of the data 
management and biostatistics departments of Syneos Health.
Study centers will enter data directly into an EDC system by completing the eCRF via a 
secure internet connection. Data entered into the eCRF must be verifiable against source 
documents at the study center. Data to be recorded directly on the eCRF will be 
identified and the eCRF will be considered the source document. Any changes to the 
data entered into the EDC system will be recorded in the audit trail and will be 
compliant with FDA CFR 21 Part 11. PRO data will not require source documentation.
Medical coding will use Medical Dictionary for Regulatory Activities (MedDRA) for 
concomitant diseases and AEs, and World Health Organization (WHO) Drug Dictionary 
for medications. Secondary surgical procedures and intra- and postoperative 
complications will be captured by their specific nomenclature (not upper-level terms).

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 45 of 63
CONFIDENTIAL
Missing or inconsistent data will be queried in writing to the investigator for 
clarification. Subsequent modifications to the database will be documented.
12.4
Quality Management and Risk Evaluation
Details are provided in Section 8.2.2.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 46 of 63
CONFIDENTIAL
13
RECORDS AND SUPPLIES
13.1
Device Accountability
If devices are not supplied to the site, this section does not apply.
If devices are supplied to the site, on receipt of the study device, the investigator (or 
deputy) will conduct an inventory of the supplies and verify that study device supplies 
are received intact and in the correct amounts before completing a supplies receipt. The 
investigator will retain a copy of this receipt at the study center. The monitor may check 
the study supplies at each study center at any time during the study.
13.2
Financing and Insurance
Financing and insurance of this study will be outlined in a separate agreement between 
Syneos Health and the sponsor. The fully executed Clinical Trial Agreement covers the 
agreement between the study site and Allergan.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 47 of 63
CONFIDENTIAL
14
ETHICS
14.1
Independent Ethics Committee or Institutional Review Board
Before initiation of the study at each study center, the protocol, the ICF, other written 
material given to the subjects, and any other requested study documentation will be 
submitted to the appropriate IEC/IRB. Written approval of the study and all relevant 
study information must be obtained before the study center can be initiated. Any 
necessary extensions or renewals of IEC/IRB approval must be obtained for changes to 
the study such as amendments to the protocol, the ICF, or other study documentation. 
The written approval of the IEC/IRB together with the approved ICF must be filed in 
the study files.
The investigator will report promptly to the IEC/IRB any new information that may 
adversely affect the safety of the subjects or the conduct of the study. The investigator 
will submit written summaries of the study status to the IEC/IRB as required. On 
completion of the study, the IEC/IRB will be notified that the study has ended.
14.2
Regulatory Authorities
If required, relevant study documentation may be submitted to regulatory authorities. If 
required on completion of the study, the regulatory authorities may be provided the 
clinical study report. 
14.3
Ethical Conduct of the Study
The investigator(s) and all parties involved in this study should conduct the study in 
adherence to the ethical principles based on the Declaration of Helsinki, GCP, ICH 
guidelines, ISO 14155:2011, and the applicable national and local laws and regulatory 
requirements.
14.4
Informed Consent
The process of obtaining informed consent must be in accordance with applicable 
regulatory requirement(s) and must adhere to GCP.
The investigator is responsible for ensuring that no subject undergoes any study-related 
examination or activity before that subject has given written informed consent to 
participate in the study.
The investigator or designated personnel will inform the subject of the objectives, 
methods, anticipated benefits, and potential risks and inconveniences of the study. The 
subject should be given every opportunity to ask for clarification of any points s/he does 
not understand and, if necessary, ask for more information. At the end of the interview, 
the subject will be given ample time to consider the study. Subjects will be required to 
sign and date the ICF. After signatures are obtained, the ICF will be kept and archived 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 48 of 63
CONFIDENTIAL
by the investigator in the investigator’s study file. A signed and dated copy of the 
subject’s ICF will be provided to the subject or their authorized representative.
It should be emphasized that the subject may refuse to enter the study or to withdraw 
from the study at any time, without consequences for their further care or penalty or loss 
of benefits to which the subject is otherwise entitled. Subjects who refuse to give or who 
withdraw written informed consent should not be included or continue in the study.
If new information becomes available that may be relevant to the subject’s willingness 
to continue participation in the study, a new ICF will be approved by the IEC(s)/IRB(s) 
(and regulatory authorities, if required). The study subjects will be informed about this 
new information and reconsent will be obtained.
14.5
Subject Confidentiality
Monitors, auditors, and other authorized agents of the sponsor and/or its designee, the 
IEC(s)/IRB(s) approving this research, and the US FDA, as well as that of any other 
applicable agency(ies), will be granted direct access to the study subjects’ original 
medical records for verification of clinical study procedures and/or data, without 
violating the confidentiality of the subjects to the extent permitted by the law and 
regulations. In any presentations of the results of this study or in publications, the 
subjects’ identity will remain confidential.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 49 of 63
CONFIDENTIAL
15
REPORTING AND PUBLICATION, INCLUDING ARCHIVING
Essential documents are those documents that individually and collectively permit 
evaluation of the study and quality of the data produced. After completion of the study
(end of study defined as the date of the last visit of the last subject), all documents and 
data relating to the study will be kept in an orderly manner by the investigator in a 
secure study file. This file will be available for inspection by the sponsor or its 
representatives. Essential documents should be retained for 2 years after the study is 
closed. It is the responsibility of the sponsor to inform the study center when these 
documents no longer need to be retained. The investigator must contact the sponsor 
before destroying any study-related documentation. In addition, all subjects’ medical 
records and other source documentation will be kept for the maximum time permitted 
by the hospital, institution, or medical practice.
Data from individual study centers in this multicenter study may not be published 
separately.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 50 of 63
CONFIDENTIAL
16
REFERENCES
American Academy of Ophthalmology (AAO) Glaucoma Preferred Practice Pattern® 
(PPP) Panel. Primary open-angle glaucoma Preferred Practice Pattern. San Francisco: 
American Academy of Ophthalmology; 2006. Available from: https://www.aao.org/ 
preferred-practice-pattern/primary-open-angle-glaucoma-ppp-2015. Accessed 07 Mar 
2019.
Aref AA, Varma R. Advanced glaucoma surgery, essentials in ophthalmology.
Switzerland: Springer; 2012
Azuara-Blanco A, Katz LJ. Dysfunctional filtering blebs. Surv Ophthalmol. 
1998;43:93-126.
Baudouin C. Ocular surface and external filtration surgery: mutual relationships. Dev 
Ophthalmol. 2012;50:64-78.
Caprioli J, Kim JH, Friedman DS, Kiang T, Moster MR, Parrish RK 2nd, et al. Special 
commentary: supporting innovation for safe and effective minimally invasive glaucoma 
surgery: summary of a joint meeting of the American Glaucoma Society and the Food 
and Drug Administration, Washington, DC, February 26, 2014. Ophthalmology.
2015;122:1795-1801.
De Gregorio A, Pedrotti E, Russo L, Morselli S. Minimally invasive combined 
glaucoma and cataract surgery: clinical results of the smallest ab interno gel stent. Int
Ophthalmol. 2018 Jun;38:1129-1134.
Fechtner RD, Singh K. Maximal glaucoma therapy. J Glaucoma. 2001 Oct;10(5 Suppl 
1):S73-S75.
Gedde SJ, Herndon LW, Brandt JD, Budenz DL, Feuer WJ, Schiffman JC. Surgical 
complications in the Tube Versus Trabeculectomy Study during the first year of follow-
up. Am J Ophthalmol. 2007 Jan;143:23-31.
Gedde SJ, Heuer DK, Parrish RK 2nd; Tube Versus Trabeculectomy Study Group. 
Review of results from the Tube Versus Trabeculectomy Study. Curr Opin Ophthalmol. 
2010 Mar;21:123-128.
Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL, et al. 
Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of 
follow-up. Am J Ophthalmol. 2012 May;153:789-803.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 51 of 63
CONFIDENTIAL
Grover D, Flynn W, Bashford K, Lewis R, Duh YJ, Nangia RS, et al. Performance and 
safety of a new ab interno gelatin stent in refractory glaucoma at 12 months. Am J 
Ophthalmol. 2017;183:25-36.
Hengerer FH, Kohnen T, Mueller M, Conrad-Hengerer I. Ab interno gel implant for the 
treatment of glaucoma patients with or without prior glaucoma surgery: 1-year results. J 
Glaucoma. 2017 Dec;26:1130-1136.
Mansouri K, Guidotti J, Rao HL, Ouabas A, D'Alessandro E, Roy S, Mermoud A.
Prospective evaluation of standalone XEN Gel Implant and combined 
phacoemulsification-XEN Gel Implant surgery: 1-year results. J Glaucoma. 2018 
Feb;27:140-147.
Moisseiev E, Zunz E, Tzur R, Kurtz S, Shemesh G. Standard trabeculectomy and Ex-
PRESS Miniature Glaucoma Shunt: a comparative study and literature review. J
Glaucoma. 2015 Aug;24:410-416.
Musch DC, Tarver ME, Goren MJ, Janz NK. Development of an 18-Item measure of 
symptom burden in patients with glaucoma from the Collaborative Initial Glaucoma 
Treatment Study's Symptom and Health Problem Checklist. JAMA Ophthalmol. 2017
Dec 1;135:1345-1351.
Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol.
1996;80:389-393.
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work 
productivity and activity impairment instrument. Pharmacoeconomics. 1993;4:363-365.
Reitsamer HA. Translimbal collage implant. Aquesys XEN Gel Stent. In: Francis BA, 
Sarkisian SR, Tad JC (eds): Minimally invasive glaucoma surgery. Stuttgart: Thieme;
2016.
Rulli E, Biagioli E, Riva I, Gambirasio G, De Simone I, Floriani I, et al. Efficacy and 
safety of trabeculectomy vs nonpenetrating surgical procedures: a systematic review and 
meta-analysis. JAMA Ophthalmol. 2013 Dec;131:1573-1582.
Saheb H, Ahmed II. Micro-invasive glaucoma surgery: current perspectives and future 
directions, Curr Opin Ophthalmol. 2012;23:96-104.
Schlenker MB, Gulamhusein H, Conrad-Hengerer I, Somers A, Lenzhofer M, Stalmans 
I, et al. Efficacy, safety, and risk factors for failure of standalone ab interno gelatin 
microstent implantation versus standalone trabeculectomy. Ophthalmology. 2017 
Nov;124:1579-1588.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 52 of 63
CONFIDENTIAL
Shaarawy T, Flammer J, Haefliger IO. Reducing intraocular pressure: is surgery better 
than drugs? Eye (Lond). 2004;18:1215-1224.
Sheybani A, Reitsamer H, Ahmed II. Fluid dynamics of a novel micro-fistula implant 
for the surgical treatment of glaucoma. Invest Ophthalmol Vis Sci. 2015;56:4789-4795.
Tan SZ, Walkden A, Au L. One-year result of XEN45 implant for glaucoma: efficacy, 
safety, and postoperative management. Eye (Lond). 2018 Feb;32:324-332.
Vera V, Ahmed IIK, Stalmans I, Retisamer H. Gel stent implantation-recommendations 
for preoperative assessment, surgical technique, and postoperative management. US 
Ophthalmic Rev. 2018;11:38-46.
Vijaya L, Manish P, Ronnie G, Shantha B. Management of complications in glaucoma 
surgery. Indian J Ophthalmol. 2011 Jan;59 Suppl:S131-140.
Wang S, Gao X, Quan N. The Ahmed shunt versus the Baerveldt shunt for refractory
glaucoma: a meta-analysis. BMC Ophthalmol. 2016 Jun 8;16:83.

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 53 of 63
CONFIDENTIAL
17
APPENDICES
17.1
The SHPC-18 Questionnaire
Protocol Title:  XEN-45 Gel Stent Versus Trabeculectomy in Glaucoma:  
Gold-Standard Pathway Study (GPS) 
Site Number   XX
Subject Number  XXX   Date (DD-MMM-YYYY):      -
-
VISIT:  
Screening  
1 Day 
1 Week
2 Week  
1 Month 
3 Month 
6 Month
Below are questions about eye symptoms and vision-related problems you may be 
experiencing. Some of these questions may not apply to you, but please indicate now if
you have had any of the following symptoms or problems during the past 7 days. If you 
answer “Yes” to any of these symptoms or problems, please also answer a follow-up
question about how much these symptoms or problems bother you.
Local Eye      
Symptoms 

Have you had this symptom 
in the past 7 days?
If Yes, please rate how much you fee
the symptom is due to your 
glaucoma or its treatment 
,I“<HV”KRZPXFKKDVWKLV
SUREOHPERWKHUHG\RX"
1.   
Eye irritation 
or burning
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ප A Lot
2.    
Feeling like 
something is 
in your 
eye(s) 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
  ප A Lot
3.    
Droopy 
eyelids 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
  ප A Lot

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 54 of 63
CONFIDENTIAL
Local Eye      
Symptoms 

Have you had this symptom 
in the past 7 days?
If Yes, please rate how much you fee
the symptom is due to your 
glaucoma or its treatment 
,I“<HV”KRZPXFKKDVWKLV
SUREOHPERWKHUHG\RX"
4.    
Excessive 
tearing 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
  ප A Lot
5.    
Skin 
sensitivity 
around 
your eye(s) 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
  ප A Lot
6.    
Eye pain 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
 ප A Lot
7.    
Red eyes 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
  ප A Lot
 
9LVXDO)XQFWLRQ
3UREOHPV
Have you had this symptom 
in the past 7 days?
,I<HVSOHDVHUDWHKRZPXFK
\RXIHHOWKH V\PSWRP LVGXH
WR\RXUJODXFRPDRULWV
WUHDWPHQW
,I“<HV”KRZPXFKKDV
WKLVSUREOHPERWKHUHG
\RX"
1.    
Difficulty 
with distant 
vision 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ǹ A Lot

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 55 of 63
CONFIDENTIAL
9LVXDO)XQFWLRQ
3UREOHPV
Have you had this symptom 
in the past 7 days?
,I<HVSOHDVHUDWHKRZPXFK
\RXIHHOWKH V\PSWRP LVGXH
WR\RXUJODXFRPDRULWV
WUHDWPHQW
,I“<HV”KRZPXFKKDV
WKLVSUREOHPERWKHUHG
\RX"
2.    
Difficulty 
with near 
vision 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ǹ  A Lot
3.    
Changes in 
depth 
perception 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ǹ A Lot
4.   
Distortion in 
vision 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ǹ A Lot
5.    
Dimming of 
vision 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ǹ A Lot
6.    
Trouble 
with color 
vision 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ǹ A Lot

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 56 of 63
CONFIDENTIAL
9LVXDO)XQFWLRQ
3UREOHPV
Have you had this symptom 
in the past 7 days?
,I<HVSOHDVHUDWHKRZPXFK
\RXIHHOWKH V\PSWRP LVGXH
WR\RXUJODXFRPDRULWV
WUHDWPHQW
,I“<HV”KRZPXFKKDV
WKLVSUREOHPERWKHUHG
\RX"
7.    
Blurry 
vision 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ǹ A Lot
8.    
Difficulty 
with light 
transition 
(e.g., from 
bright to 
dark) 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes  
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ප A Lot 
9.    
Difficulty 
seeing in 
dark places 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ප A Lot 
10.  
Difficulty 
with bright 
lights 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ප A Lot 
11.  
Difficulty 
seeing when 
stepping 
down 
ǹ No 
ǹ Yes: which eye(s) is/are 
affected? 
ǹ Surgery eye 
ǹ Other eye 
ǹ Both eyes 
ǹ Entirely due 
ǹ Partially due 
ǹ Not due 
ප Not at All 
ප A Little 
ප Somewhat 
ප A Moderate Amount 
ප A Lot 
 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 57 of 63
CONFIDENTIAL
17.2
Postsurgical Question on Resumption of Activities and Daily Routine
Since your glaucoma surgery, would you consider that you have resumed your usual 
activities and daily routine?
____  Not at all ____ Somewhat   ___ Moderately so ____  Mostly  ___ Completely

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 58 of 63
CONFIDENTIAL
17.3
Work Productivity and Activity Impairment Questionnaire
Work Productivity and Activity Impairment Questionnaire:
General Health V2.0 (WPAI:GH)
The following questions ask about the effect of your health problems on your ability to 
work and perform regular activities. By health problems we mean any physical or 
emotional problem or symptom. Please fill in the blanks or circle a number, as 
indicated.
1.
Are you currently employed (working for pay)? ____  NO
____  YES
If NO, check “NO” and skip to question 6.
The next questions are about the past seven days, not including today.
2.
During the past seven days, how many hours did you miss from work because of
your health problems? Include hours you missed on sick days, times you went in 
late, left early, etc., because of your health problems. Do not include time you 
missed to participate in this study.
_____HOURS
3.
During the past seven days, how many hours did you miss from work because of 
any other reason, such as vacation, holidays, time off to participate in this study?
_____HOURS
4.
During the past seven days, how many hours did you actually work?
_____HOURS (If “0”, skip to question 6.)

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 59 of 63
CONFIDENTIAL
5.
During the past seven days, how much did your health problems affect your 
productivity while you were working?
Think about days you were limited in the amount or kind of work you could do, 
days you accomplished less than you would like, or days you could not do your 
work as carefully as usual. If health problems affected your work only a little, 
choose a low number. Choose a high number if health problems affected your 
work a great deal. 
Consider only how much health problems affected 
productivity while you were working.
Health problems 
had no effect on 
my work
Health problems 
completely 
prevented me 
from working
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
6.
During the past seven days, how much did your health problems affect your 
ability to do your regular daily activities, other than work at a job? 
By regular activities, we mean the usual activities you do, such as work around 
the house, shopping, childcare, exercising, studying, etc. Think about times you 
were limited in the amount or kind of activities you could do and times you 
accomplished less than you would like. If health problems affected your activities 
only a little, choose a low number. Choose a high number if health problems 
affected your activities a great deal. 
Consider only how much health problems affected your ability 
to do your regular daily activities, other than work at a job.
Health problems 
had no effect on 
my daily 
activities
Health problems 
completely 
prevented me 
from doing my 
daily activities
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 60 of 63
CONFIDENTIAL
17.4
Protocol Revision History
Key changes are listed below. Other changes may have included editorial revisions,
updates to the list of abbreviations and table of contents, reformatting and restyling of 
text (including the reference list and appendices), and changes in study team staff.
Specific revisions in verbatim text are shown in bold font in the changes listed below.
Version
Date
Description of Change (location)
Rationale
1.3
30 Jun 
2018
Not applicable
Original protocol
2.0
21 Mar 
2019
Added NCT number (title page)
Trial was registered on 
ClinicalTrials.gov on 31 Aug 2018
Updated name of CRO (title page, 
Section 12.3, and Section 13.2)
INC Research merged with 
inVentive Health and is now doing 
business as Syneos Health
Added description of statistical analyses 
in the Synopsis
Corrected an omission in the 
synopsis
Added objectives statement to Section 7)
Added a missing objectives 
statement that matches the one in 
the synopsis
Added a secondary effectiveness 
objective: “Mean and changes in mean 
IOP and number of topical IOP-lowering 
medications from preoperative baseline 
over time in eyes with medicated baseline 
,23 mm Hg” (Section 7.2
and Synopsis)
Adds a subgroup analysis for study 
eyes with IOP in the lower part of 
the allowed IOP range (15 to 
18 mm Hg) at preoperative baseline
Corrected timing of autorefractor 
measurements and biometry (Section 7.2
and Synopsis)
Corrected mistakes in the text of 
the protocol to match the timing of 
these procedures in Table 8.1
Clarified study duration is per study eye 
(Section 8.1 and Synopsis)
Distinguishes duration for a study
eye versus overall study duration 
(ie, all study eyes)
Investigator will select the study eye if 
both eyes meet entry criteria (Section 8.1)
Allows the investigator to make the 
decision
Clarified that 1 study eye per subject will 
be enrolled (Section 8.3.1 and Synopsis)
Clarifies that only 1 of a subject’s 
eyes will be enrolled, even if both 
eyes meet entry criteria
Added visit windows to Table 8.1;
revised postoperative visit windows in 
Sections 9.1.2 and 9.2
Provides a visit range for each 
postoperative study visit
Added randomization to Table 8.1 and the 
description of the Preoperative Visit 
(Section 9.1.2)
Specifies at which visit 
randomization occurred
Gonioscopy is required at the Baseline 
Qualifying Visit and is optional at 
Allows investigators to follow their 
standard of care for timing of 

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 61 of 63
CONFIDENTIAL
Version
Date
Description of Change (location)
Rationale
postoperative Visits 3, 4 and 10 
(Table 8.1)
postoperative gonioscopy
Removed AS-OCT at Visit 1 (Table 8.1)
Preoperative AS-OCT is not 
required.
Changed one of the listed risks of the 
XEN implantation procedure to be 
“unplanned secondary surgical 
intervention” (Section 8.2.2)
Corrected an error in the protocol 
(previously was “unplanned 
surgical re-invention”)
Increased the number of study sites to 
“approximately 25 to 40 sites”
(Section 8.3.1 and Synopsis)
Increase enrollment rate into the 
study to complete enrollment in a 
timely manner
Inclusion criterion 4. “Best-corrected 
baseline Snellen visual acuity of 20/100
or better” (Section 8.3.2 and Synopsis)
Allows inclusion of study eyes with 
poorer vision in order to improve 
enrollment rate based on 
investigator feedback
Inclusion criterion 5. “Visual field mean 
deviation no worse than -18.0 dB (with 
no dense paracentral scotomas, eg, 
>18 dB total deviation on 1 or more of 
the 4 paracentral points)” (Section 8.3.2
and Synopsis
Allows inclusion of study eyes with 
slightly more advanced visual field 
damage in order to improve 
enrollment rate based on 
investigator feedback
Inclusion criterion 6. “Medicated IOP 
15 PP+JDQGPP+Jon at least 
1 topical IOP-lowering medication”
(Section 8.3.2 and Synopsis)
Allows study eyes with lower 
medicated IOP at baseline to 
improve enrollment rate based on 
investigator feedback. Clarifies that
more than 1 IOP-lowering 
medication will be allowed.
Inclusion criterion 7. “Subjects not 
anticipated to require any other ocular 
surgery (eg, cataract surgery) in either eye 
up to 3 months from the time of 
inclusion” (Section 8.3.2 and Synopsis)
Allows inclusion of study eyes that 
may require ocular surgery during 
the 12-month study, provided the 
surgery occurs at least 3 months 
after enrollment
Inclusion criterion 9. “Visible trabecular 
PHVKZRUNZLWK6KDIIHUDQJOHJUDGHLQ
the target area or, in eyes with prior 
failed angle surgery, an open angle in 
the target area” (Section 8.3.2
and Synopsis)
Clarification that the angle is open 
in eyes that have had angle surgery,
such as GATT
Inclusion criterion 10. “Preoperative laser 
trabeculoplasty is allowed 3 or more 
months prior to randomization”
(Section 8.3.2 and Synopsis)
Corrects an error in the allowed 
period for laser trabeculoplasty

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 62 of 63
CONFIDENTIAL
Version
Date
Description of Change (location)
Rationale
Inclusion criterion 11. “Failed ab-interno 
canal or suprachoroidal microinvasive 
glaucoma surgery (MIGS) procedures 
(such as iStent®, gonioscopy-assisted 
transluminal trabeculotomy [GATT],
ab-interno canaloplasty [ABiC™],
Kahook Dual Blade goniotomy, etc) are 
allowed 3 or more months before 
enrollment, with the exception of 
CyPass® Micro-Stents, which are not 
allowed. Ab-interno ablative 
procedures (such as endoscopic 
cyclophotocoagulation [ECP]) are also 
allowed 3 or more months before 
enrollment.” (Section 8.3.2
and Synopsis)
Excludes CyPass Micro-Stents, 
which have been withdrawn from 
the market
Distinguishes ab-interno ablative 
procedures, such as ECP which is 
allowed, from transscleral 
cycloablative procedures that are 
excluded per exclusion criterion 2
Exclusion criterion 16. “Participation in 
another drug or device clinical trial that
concludes within 30 days before the 
Preoperative Visit or that starts at any 
time during this study” (Section 8.3.3
and Synopsis)
Prohibits concurrent participation 
in another drug or device clinical 
trial
Added “Subjects may withdraw their 
consent to continue in the study at any 
time.” (Section 8.3.4)
Clarifies that subjects will be free 
to withdraw consent at any time
Added “Subjects who discontinue before 
undergoing a study surgery will not be 
required to return for study follow-up 
visits” (Section 8.3.4) and updated 
Section 9.2.9 accordingly
Allows subjects who discontinue 
before glaucoma surgery to not 
return, as they will not be included 
in the safety population and no 
effectiveness data will be available
Added marketed product name (XEN-45
Gel Stent) (Section 8.4.2)
Clarified XEN implant lumen size
Added a description of the randomization 
process (Section 8.4.4)
Adds information that was missing 
from the protocol
Clarified that IOP will not be measured at 
Visit 2 (Section 10.1.1.1)
Corrected the text to 
match Table 8.1
Added that the PRO questionnaires will 
be administered using an electronic tablet, 
from which data will be imported into the 
eCRF (Section 10.1.1.3)
Clarifies that PRO data will be 
entered externally in an electronic 
tablet and then imported into the 
eCRF electronically (ie, data will 
not be entered manually into the 
PRO eCRFs)
Added “These and any other AEs that 
occur should be reported in the AE 
eCRF.” to Section 10.1.2.1.2)
Clarifies that all AEs, in addition to 
the listed possible intraoperative 
and postoperative AEs are to be 
reported in the AE eCRF

Allergan 
21 Mar 2019
CMO-US-EYE-0600
Version 2.0
Page 63 of 63
CONFIDENTIAL
Version
Date
Description of Change (location)
Rationale
Revised the worsening cataract AE to 
“Clinically significant progression of 
cataract, based on an assessment by the 
investigator” (Section 10.1.2.1.2)
Removed mention of Lens 
Opacities Classification System 
scoring because it will not be used 
in this study
Added Enrolled and mITT populations as 
analysis populations; updated definitions 
of ITT and Safety populations 
(Section 11.1.1)
Adds an Enrolled population to 
fully describe disposition of study 
eyes. Adds an analysis population 
(mITT) that excludes study eyes 
that do not undergo glaucoma 
surgery or have predefined major 
protocol deviations. Adds detail on 
which populations are used for 
study analyses.
Removed statement that all available IOP 
data will be used for calculations of 
changes from baseline, and added some 
statistical methodology (Section 11.1.3,
latter in Synopsis, too)
Selection of IOP values for change 
from baseline calculations will be 
described in the SAP, as it will be 
based on timing of IOP 
measurements relative to the visits. 
Briefly describes statistical testing 
that was missing.
Clarified that treatment-emergent AEs 
will be summarized and added details on 
some types of tabulations that are planned 
(Section 11.1.4 and Synopsis)
Clarifies that any AEs that occur 
before study surgery will not be 
included in AE summary tables. 
Cross-references the SAP for more 
details on safety analyses.
Revised “IOP, change in IOP from 
baseline, percentage change in IOP from 
baseline, number of topical IOP-
lowering medications used, and change 
in number of topical IOP-lowering
medications used will be summarized 
descriptively at each scheduled visit.”
(Section 11.1.6)
Clarified that the analysis will be of 
number of topical IOP-lowering 
medications
Deleted from the reference list those 
references not cited in the text 
(Section 16)
Corrected an error in the protocol
Increased row height in SHPC-18
questionnaire (Appendix 17.1)
Makes “Both eyes” checkboxes 
visible in all rows
Added protocol revision history 
(Appendix 17.4)
Adds a section to describe changes 
made in the protocol since the 
original version was approved
Added expansion of abbreviations and 
acronyms on first use in the synopsis and 
main text; used abbreviation/acronym 
thereafter
Standardizes use of abbreviations 
and acronyms