An Observational Multicenter Clinical Study to Provide Additional Long-Term Follow-up Beyond 60 Months for Subjects Implanted With a CyPass Micro-Stent in the COMPASS Trial
Phase: NA
Conditions: Primary Open Angle Glaucoma, Cataract
Sponsor: Alcon Research

 
 
 
 
 
An Observational Multicenter Clinical Study to Provide 
Additional Long‐Term Follow‐up Beyond 60 Months for 
Subjects Implanted with a CyPass Micro‐Stent in the 
COMPASS Trial 
 
 
STUDY ID 
GLD122‐P004 
 
 
PROTOCOL 
 
 
NCT04629521 

Page 1 of 57
Title
An Observational Multicenter Clinical Study to Provide Additional Long-
Term Follow-up Beyond 60 Months for Subjects Implanted with a CyPass 
Micro-Stent in the COMPASS Trial
Protocol Number:
GLD122-P004
Development Stage of 
Project:
N/A
Sponsor Name and 
Address:
Alcon Research, LLC and its affiliates (“Alcon”)
6201 South Freeway
Fort Worth, Texas 76134-2099
Test Product:
CyPass® Micro-Stent
Property of Alcon
Confidential
May not be used, divulged, published, or otherwise disclosed without the consent of 
Alcon
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Investigator Agreement:

I have read the clinical study described herein, recognize its confidentiality, and 
agree to conduct the described trial in compliance with Good Clinical Practice 
(GCP), the ethical principles contained within the Declaration of Helsinki, this 
protocol, all applicable regulatory authority regulations, and conditions of approval 
imposed by the reviewing IRB or regulatory authority.

I will supervise all testing of the device involving human subjects and ensure that 
the requirements relating to obtaining informed consent and IRB review and 
approval are met in accordance with applicable local and governmental regulations.

I have read and understand the appropriate use of the investigational product(s) as 
described in the protocol, current Investigator’s Brochure, product information, or 
other sources provided by the Sponsor.

I understand the potential risks and side effects of the investigational product(s).

I agree to maintain adequate and accurate records in accordance with government 
regulations and to make those records available for inspection.

I agree to comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements of the Sponsor and government 
agencies.

I agree to ensure that all associates, colleagues, and employees assisting in the 
conduct of the study are informed of their obligations in meeting the above 
commitments.
Have you ever been disqualified as an Investigator by any Regulatory Authority?
No        Yes
Have you ever been involved in a study or other research that was terminated?
No        Yes
If yes, please explain here:
Principal Investigator:
Signature
Date
Name and professional 
position:
Address:
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Table of Contents
Table of Contents .......................................................................................................................3
List of Tables..............................................................................................................................7
List of Figures............................................................................................................................8
1
GLOSSARY OF TERMS ....................................................................................................9
2
LIST OF ACRONYMS AND ABBREVIATIONS ...........................................................14
3
PROTOCOL SUMMARY.................................................................................................16
5
INTRODUCTION.............................................................................................................22
5.1
Rationale and Background ................................................................................22
5.2
Purpose of the Study..........................................................................................22
5.3
Risks and Benefits.............................................................................................22
6
STUDY OBJECTIVES......................................................................................................23
6.1
Safety Objective(s)............................................................................................23
7
INVESTIGATIONAL PLAN ............................................................................................24
7.1
Study Design .....................................................................................................24
7.2
Rationale for Study Design ...............................................................................24
7.2.1
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations........................................................................................25
7.3
Rationale for Duration of Treatment/Follow-Up...............................................25
7.4
Rationale for Choice of Control Product...........................................................25
7.5
Data Monitoring Committee..............................................................................25
7.6
Milestones..........................................................................................................25
8
STUDY POPULATION ....................................................................................................26
8.1
Inclusion Criteria...............................................................................................26
8.2
Exclusion Criteria..............................................................................................26
8.3
Rescreening of Subjects ....................................................................................26
9
TREATMENTS ADMINISTERED...................................................................................27
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9.1
Investigational Product(s)..................................................................................27
9.2
Other Medical Device or Medication Specified for Use During the Study ......28
9.3
Treatment Assignment / Randomization ...........................................................29
9.4
Treatment masking ............................................................................................29
9.5
Accountability Procedures.................................................................................29
9.6
Changes to Ocular Hypotensive Medications, Treatments/ Procedures............29
10 STUDY PROCEDURES AND ASSESSMENTS.............................................................29
10.1
Informed Consent and Screening ......................................................................29
10.2
Description of Study Procedures and Assessments...........................................30
10.2.1
Demographics....................................................................................30
10.2.2
Inclusion/Exclusion Criteria..............................................................30
10.2.3
Ocular Medical History.....................................................................30
10.2.4
Ocular Surgical History.....................................................................30
10.2.5
Ocular Hypotensive Medications: Exploratory Effectiveness 
Assessment ........................................................................................30
10.2.6
Best Corrected Visual Acuity: Safety Assessment ............................30
10.2.7
Intraocular Pressure: Exploratory Effectiveness Assessment............31
10.2.8
Pachymetry CCT: Safety Assessment ...............................................31
10.2.9
Gonioscopy: Safety Assessment........................................................31
10.2.10 UBM/OCT: Safety Assessment.........................................................31
10.2.11 Slit-Lamp Exam: Safety Assessment.................................................31
10.2.12 Visual Field........................................................................................31
10.2.13 Dilated Fundus Exam: Safety Assessment ........................................32
10.2.14 Specular Microscopy.........................................................................32
10.2.15 Adverse Event Collection: Safety Assessment..................................32
10.2.16 Device Deficiencies: Safety Assessment...........................................32
10.3
Unscheduled Visits ............................................................................................32
10.4
Discontinued Subjects .......................................................................................33
10.4.1
Screen Failures ..................................................................................33
10.4.2
Discontinuations................................................................................33
10.4.3
Schedule of Procedures and Assessments for Subjects 
Discontinued from Investigational Product.......................................33
10.5
Clinical Study Termination................................................................................34
10.5.1
Follow-Up of Subjects after Study Participation Has Ended ............34
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES ...................................................34
11.1
General Information ..........................................................................................34
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11.1.1
Postoperative Adverse Events ...........................................................35
11.1.2
Sight Threatening Adverse Events ....................................................38
11.1.3
Device Deficiencies...........................................................................39
11.2
Monitoring of Ocular Adverse Events...............................................................39
11.3
Procedures for Recording and Reporting ..........................................................40
11.3.1
Intensity and Causality Assessments.................................................41
11.4
Return Product Analysis....................................................................................42
11.5
Unmasking of the Study Information................................................................42
11.6
Follow-up of Subjects with Adverse Events .....................................................42
11.7
Pregnancy in the Clinical Study........................................................................42
12 ANALYSIS PLAN ............................................................................................................43
12.1
Subject Evaluability...........................................................................................43
12.2
Analysis Sets .....................................................................................................43
12.2.1
Enrolled .............................................................................................43
12.3
Demographic and Baseline Characteristics.......................................................43
12.4
Safety Analyses .................................................................................................43
12.4.1
Rate of Occurrence of Sight-Threatening Adverse Events (AEs).....44
12.4.1.1
Statistical Hypotheses........................................................44
12.4.1.2
Analysis Methods ..............................................................44
12.4.2
Rate of Occurrence of Ocular AEs ....................................................44
12.4.2.1
Statistical Hypotheses........................................................44
12.4.2.2
Analysis Methods ..............................................................44
12.4.3
Central and Peripheral (Nasal) ECD Measurements.........................45
12.4.3.1
Statistical Hypotheses........................................................45
12.4.3.2
Analysis Methods ..............................................................45
12.4.4
Analyses of Rate of Loss and Rate of Low ECD (ie, 
≤1000 cells/mm2)..............................................................................45
12.4.4.1
Statistical Hypotheses........................................................45
12.4.4.2
Analysis Methods ..............................................................45
12.4.5
Assessment of Stabilization of ECL..................................................46
12.4.5.1
Statistical Hypotheses........................................................46
12.4.5.2
Analysis Methods ..............................................................46
12.4.6
Corneal Sequelae Associated with ECL............................................46
12.4.6.1
Statistical Hypotheses........................................................46
12.4.6.2
Analysis Methods ..............................................................46
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12.4.7
Association between Peripheral and Central ECD Count and 
Number of Observed Rings...............................................................46
12.4.7.1
Statistical Hypotheses........................................................46
12.4.7.2
Analysis Methods ..............................................................46
12.4.8
Secondary Surgical Interventions (SSIs) to Modify the Device 
Position (eg, Repositioning, Trimming, Explanation).......................47
12.4.8.1
Statistical Hypotheses........................................................47
12.4.8.2
Analysis Methods ..............................................................47
12.4.9
Effects of SSIs on Central and Peripheral ECD ................................47
12.4.9.1
Statistical Hypotheses........................................................47
12.4.9.2
Analysis Methods ..............................................................47
12.4.10 CyPass Micro-Stent Movement and/or Malposition .........................47
12.4.10.1 Statistical Hypotheses........................................................47
12.4.10.2 Analysis Methods ..............................................................47
12.4.11 Corneal AEs (eg, Corneal Decompensation, Tube Corneal Touch, 
Corneal Edema, etc.) Caused by CyPass Micro-Stent ......................47
12.4.11.1
Statistical Hypotheses........................................................47
12.4.11.2
Analysis Methods ..............................................................48
12.4.12 Losses in Best Corrected Visual Acuity (BCVA) ≥ 10 letters ...........48
12.4.12.1 Statistical Hypotheses........................................................48
12.4.12.2 Analysis Methods ..............................................................48
12.4.13 Change in Visual Field Mean Deviation (MD) .................................48
12.4.13.1 Statistical Hypotheses........................................................48
12.4.13.2 Analysis Methods ..............................................................48
12.4.14 Change in Central Corneal Thickness ...............................................48
12.4.14.1 Statistical Hypotheses........................................................48
12.4.14.2 Analysis Methods ..............................................................49
12.4.16 Comparison of COMPASS XXT Subjects to Original COMPASS 
Subjects Implanted with CyPass .......................................................49
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12.6
Interim Analyses and Reporting........................................................................51
12.7
Handling of Missing Data .................................................................................51
12.8
Sample Size Justification...................................................................................52
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS ...............................52
13.1
Subject Confidentiality......................................................................................52
13.2
Completion of Source Documents and Case Report Forms..............................52
13.3
Data Review and Clarifications.........................................................................53
13.4
Sponsor and Monitoring Responsibilities .........................................................54
13.5
Regulatory Documentation and Records Retention ..........................................54
13.6
Quality Assurance and Quality Control.............................................................54
14 ETHICS .............................................................................................................................55
15 REFERENCES ..................................................................................................................56
15.1
References Applicable for All Clinical Studies.................................................56
15.1.1
US References Applicable for Clinical Studies.................................56
List of Tables
Table 2–1
List of Acronyms and Abbreviations Used in This Protocol ...........................14
Table 3–1
Schedule of Study Procedures and Assessments .............................................20
Table 6–1
Safety Objective(s)...........................................................................................23
Table 7-1
Study Milestones..............................................................................................25
Table 9–1
Test Product .....................................................................................................27
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List of Figures
Figure 11–1
Categorization of All Adverse Events..............................................................35
Figure 11-2
Categorization of All Serious Adverse Events.................................................35
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1
GLOSSARY OF TERMS
Names of test product(s)
Throughout this document, test product(s) will be referred to 
as CyPass or CyPass Micro-Stent
Name of Control Product(s)
N/A
Adverse Device Effect
(ADE)
Adverse event related to the use of an investigational 
medical device (test product) or control product. Note: This 
definition includes adverse events resulting from insufficient 
or inadequate instructions for use, deployment, 
implantation, installation, or operation; any malfunction; 
and use error or intentional misuse of the test product or 
control product.
Adverse Event (AE)
Any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device 
(test product). Note: For subjects, this definition includes 
events related to the test product, the control product, or the 
procedures involved. For users or other persons, this 
definition is restricted to events related to the test product.
Requirements for reporting Adverse Events in the study can 
be found in Section 11.
Anticipated Serious 
Adverse Device Effect
Serious adverse device effect which by its nature, incidence, 
severity, or outcome has been identified in the risk 
management file.
Device Deficiency
Inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Note: 
This definition includes malfunctions, use errors, and 
inadequate labeling.
Requirements for reporting Device Deficiencies in the study 
can be found in Section 11.
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Enrolled Subject
Any subject who signs an informed consent form for 
participation in the study.
Investigational Product (IP)
Is defined as a preventative (vaccine), a therapeutic (drug or 
biologic), device, diagnostic, or palliative used as a test or 
control product in a clinical trial, including a product with a 
marketing authorization when used or assembled 
(formulated or packaged) in a way different from the 
authorized form, or when used for an unauthorized 
indication, or when used to gain further information about 
the authorized form.
Malfunction
Failure of a medical device to perform in accordance with its 
intended purpose when used in accordance with the 
instructions for use or clinical investigation plan.
Non-interventional Study
A non-experimental (observational) study meeting all of the 
following conditions:

The intervention is provided according to current 
clinical practice and marketing authorization;

The assignment of a participant to a particular 
treatment strategy is not decided in advance by a 
protocol but falls within current practice; 

The decision to provide an intervention is separate 
from the decision to include the participant in the 
study; and

The diagnostic and monitoring procedures fall within 
normal clinical practice, consistent with the standard 
of care.
Interviews, questionnaires, and procedures that do not 
change or influence treatment may be considered normal 
clinical practice.
Non-serious Adverse Event
Adverse event that does not meet the criteria for a serious 
adverse event.
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Randomized Subjects
This is a single arm study; therefore, subjects will not be 
randomized.
Serious Adverse Device 
Effect (SADE)
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event.
Serious Adverse Event 
(SAE)
Adverse event that led to any of the following:

Death.

A serious deterioration in the health of the subject 
that either resulted in:
a. a life-threatening illness or injury.
Note: Life-threatening means that the 
individual was at immediate risk of death from 
the event as it occurred, ie, it does not include 
an event which hypothetically might have 
caused death had it occurred in a more severe 
form.
b. any potentially sight-threatening event or 
permanent impairment to a body structure or a 
body function.
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c. in-patient hospitalization or prolonged 
hospitalization.
Note: Planned hospitalization for a pre-
existing condition, without serious 
deterioration in health, is not considered a 
serious adverse event. In general, 
hospitalization signifies that the individual 
remained at the hospital or emergency ward 
for observation and/or treatment (usually 
involving an overnight stay) that would not 
have been appropriate in the physician's office 
or an out-patient setting. Complications that 
occur during hospitalization are adverse 
events. If a complication prolongs 
hospitalization or fulfills any other serious 
criteria, the event is serious. When in doubt as 
to whether “hospitalization” occurred, the 
event should be considered serious.
d. a medical or surgical intervention to prevent 
a) or b). 
e. any indirect harm as a consequence of 
incorrect diagnostic test results when used 
within manufacturer’s instructions for use.

Fetal distress, fetal death, or a congenital 
abnormality or birth defect.
Refer to Section 11 for additional SAEs.
Unanticipated Serious 
Adverse Device Effect
Serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in the risk 
management file.
Use Error
Act or omission of an act that results in a different medical 
device response than intended by manufacturer or expected 
by user. Note: This definition includes slips, lapses, and 
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mistakes. An unexpected physiological response of the 
subject does not in itself constitute a use error.
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2
LIST OF ACRONYMS AND ABBREVIATIONS
Table 2–1
List of Acronyms and Abbreviations Used in This Protocol
Abbreviation
Definition
AC
Anterior chamber
ADE
Adverse device effect
AE
Adverse event
BCDVA
Best corrected distance visual acuity
BCVA
Best corrected visual acuity
CCT
Central corneal thickness
C:D
Cup to disc (ratio)
CECD
Central endothelial cell density
CRF
Case report form
CyPass
CyPass Micro-Stent
dB
Decibel
ECD
Endothelial cell density
ECL
Endothelial cell loss
eCRF
Electronic case report form
EDC
Electronic data capture
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
US Food and Drug Administration
GCP
Good Clinical Practice
GPCMS
Global Product Complain Management System
ICF
Informed consent form
ICH
International Conference for Harmonization of Technical 
Requirements for Pharmaceuticals for Human Use
IEC
Independent ethics committee
IRB
Institutional review board
IP
Investigational product
ISO
International Organization for Standardization
MD
Mean deviation
mm
Millimeter
MOP
Manual of procedures
N/A
Not applicable
OCT
Optical coherence tomography
PAS
Post-approval study
POAG
Primary open angle glaucoma
SADE
Serious Adverse Device Effect
SAE
Serious adverse event
SITA
Swedish Interactive Testing Algorithm
SLE
Slit-lamp examination
SOP
Standard operating procedure
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Abbreviation
Definition
SSI
Secondary surgical intervention
UBM
Ultrasound biomicroscopy
US
United States
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3
PROTOCOL SUMMARY
Investigational 
product type
Device
Study type
Non-interventional
Investigational 
products
Test Product: CyPass Micro-Stent
The CyPass Micro-Stent is a polyimide tube with a fenestrated 
lumen. The stent has a single piece design and is 0.25” (6.35 mm) 
long. The inner diameter of the stent is 0.012” (0.30 mm) and the 
outer diameter is 0.017” (0.43 mm). The CyPass Micro-Stent is 
designed for placement in the angle of the eye, with the proximal 
end extending from the angle into the anterior chamber (AC) and 
the distal end residing in the supraciliary space.
When properly implanted, the CyPass Micro-Stent is intended to 
allow outflow of aqueous fluid from the AC, where the device 
proximal end resides, through and around the fenestrated lumen 
and distal end of the tube into the supraciliary and suprachoroidal 
space via the uveoscleral pathway.
Purpose and 
rationale
The purpose of this study is to assess long-term (10 years post-
CyPass implantation) status of the corneal endothelium in subjects
who were implanted with the CyPass Micro-Stent in the 
COMPASS trial.
Objective(s)
To assess long-term (10 years post-CyPass implantation) status of 
the corneal endothelium in subjects who were implanted with the 
CyPass Micro-Stent in the COMPASS trial.
Endpoint(s) 
Safety

Rate of occurrence of sight-threatening adverse events 
(AEs)

Rate of occurrence of ocular AEs

Central and peripheral (nasal) ECD measurements

Analyses of rate of loss and rate of low ECD (ie, 
≤1000 cells/mm2)

Assessment of stabilization of ECL

Corneal sequelae associated with ECL
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
Association between peripheral and central ECD count and 
number of observed rings

Secondary surgical interventional (SSIs) to modify the 
device position (eg, repositioning, trimming, explanation)

Effects of SSIs on central and peripheral ECD

CyPass Micro-Stent movement and/or malposition

Corneal AEs (eg, corneal decompensation, tube corneal 
touch, corneal edema, etc.) caused by CyPass Micro-Stent

Losses in Best Corrected Visual Acuity (BCVA) 
≥10 letters

Change in visual field mean deviation (MD)

Change in central corneal thickness
Assessment(s) 
Safety

Ocular medical history

Ocular surgical history

Ocular hypotensive medications

Monocular Best Corrected Distance Visual Acuity 
(BCDVA) via ETDRS

IOP

Pachymetry central corneal thickness (CCT)

Gonioscopy (with goniophotography) 

Ultrasound biomicroscopy (UBM)/Optical coherence 
tomography (OCT; if available at the site)

Slit-lamp examination

Visual field
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
Fundus examination with C:D ratio

Specular microscopy (central and peripheral [nasal] 
endothelial cell density)

Ocular adverse events (these include but are not limited to 
corneal haze/edema, device malposition, device 
explantation, device trimming, device repositioning) 
occurring since exit visit from COMPASS or COMPASS 
XT (whichever was the last study visit) will be captured as 
ocular history
Study Design
Prospective; non-interventional, non-randomized; unmasked; 
observational; single-arm; total duration of subject’s participation 
in the study is follow-up visits scheduled annually and an exit visit 
when the subject has reached 10 years post-CyPass implantation; 
duration of study is up to 4 years. For some subjects, the first visit 
will be at or after 10 years post-CyPass implantation, and therefore
the first visit may coincide with the 120-Month/Exit visit.
Because collection of ECD is not part of standard of care, 
retrospective data collection will not be attempted for visits that 
occurred prior to subject enrollment. The one exception will be 
ocular adverse events data, which will be collected for all visits, 
wherever available.
Subject population
Subjects who were implanted with a CyPass Micro-Stent in the 
COMPASS trial.
Planned number of subjects enrolled/consented: Up to 374 (total 
number implanted with a CyPass Micro-Stent in the COMPASS 
trial)
Planned number of completed subjects: Up to 374
Key inclusion 
criteria

Any subject who was implanted with a CyPass Micro-Stent 
as a participant in the COMPASS trial.
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(See Section 8.1 for a 
complete list of 
inclusion criteria)

Able to understand the requirements of the study and 
willing to follow study instructions, provide written 
informed consent, and agree to comply with all study 
requirements, including the required study follow-up visits.
Key exclusion 
criteria
(See Section 8.2 for a 
complete list of 
exclusion criteria)

Inability to comply with the protocol or required follow-up 
visit/procedures.
Data analysis and 
sample size 
justification
The analysis set for both the safety and effectiveness analyses will 
be the set of all enrolled subjects.
No hypothesis testing is planned. All study endpoints will be 
described with summary statistical appropriate to scale. No 
missing data imputation is planned.  Interim reports pertaining to 
the progress of the post-approval study will be submitted to the 
FDA for review every 6 months for the first 2 years and annually 
thereafter, starting from the date of FDA approval of the protocol, 
until study completion.
Sample size is based on the number of subjects who were 
implanted with a CyPass Micro-Stent in the COMPASS trial (374) 
and is not based on statistical power. 374 subjects were implanted 
with CyPass in the COMPASS trial. Of these, 215 volunteered to 
enroll in COMPASS XT. The total enrolled in this trial will be a 
subset of the 374 COMPASS CyPass subjects, is not restricted to 
those enrolled in COMPASS XT, and may be above or below the 
total enrolled in the COMPASS XT trial.
Key words
Prospective; non-interventional, observational, multi-center study; 
being conducted in the US only; up to 374 enrolled and up to 
374 complete annual follow-up visits; 10 years post-CyPass 
implantation
Associated materials
N/A
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Table 3–1
Schedule of Study Procedures and Assessments
Procedure
84-Month Visit
(2555±120 
days)1
96-Month Visit
(2920±120 
days)1
108-Month 
Visit
(3285±120 
days)1
120-Month 
Visit/ Exit Visit
(3650±120* 
days)1
Informed Consent2
X
X
X
X
Demographics2
X
X
X
X
Inclusion/Exclusion2
X
X
X
X
Ocular Medical History
X
X
X
X
Ocular Surgical History
X
X
X
X
Monocular BCVA (ETDRS)
X
X
X
X
Pachymetry CCT
X
X
X
X
Gonioscopy and Gonio 
photography3
X
X
X
X
UBM/OCT4
X
X
X
X
Slit-Lamp Exam
X
X
X
X
Visual Field
X
X
X
X
Fundus Exam with C:D Ratio
X
X
X
X
Specular Microscopy (central 
and peripheral ECD)
X
X
X
X
Ocular AE Assessment5
X
X
X
X
Device Deficiencies
X
X
X
X
1
Annual visits are required until 10 years post-CyPass implantation is reached. Not all visits are required for 
every subject. The number of study visits required to be completed will coincide with the number of months 
following CyPass implantation. Note: All subjects from COMPASS have surpassed the 72-month follow-up 
period. 
*For subjects who have reached the 10 years post-CyPass implantation at the time of study initiation, the 
+120-day visit window does not apply. 
2
Informed consent, demographics, and inclusion/exclusion criteria assessments are only required at the first 
study visit.
3
Gonio photography to be assessed objectively for evaluating device position.
4
Optional – if available at the site.
5
Any ocular AEs occurring since the Exit visit from COMPASS or COMPASS XT (whichever was last study 
visit) will be captured. These include but are not limited to corneal haze/edema, device malposition, device 
explantation, device trimming, and/or device repositioning.
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4
PROTOCOL AMENDMENTS
Modification of the protocol is prohibited without prior written agreement in the form of a 
protocol amendment. All amendments must be created by the Study Sponsor and must be 
approved by the IRB/IEC and global and regional Health Authorities, as applicable, prior to 
implementation except when required to mitigate immediate safety risks or when the changes 
involve only logistical or administrative revisions. 
Amendments may necessitate that the informed consent and other study-related material be 
revised. If the consent form is revised, all subjects currently enrolled in the study must sign 
the approved, revised informed consent (re-consent), as required by the IRB/IEC.
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5
INTRODUCTION
5.1
Rationale and Background
The COMPASS trial was a prospective, randomized, comparative multicenter study to assess 
the safety and effectiveness of the CyPass Micro-Stent in subjects with primary open angle 
glaucoma who were undergoing cataract surgery. In the study, a total of 505 subjects were 
randomized to one of two treatment groups, as follows: the CyPass group underwent cataract 
surgery and received the CyPass Micro-Stent, while the Control group underwent cataract 
surgery alone. All subjects randomized were followed for 24 months postoperatively, Vold 
2016.
The study was performed in 2 phases. During the initial phase, 75 subjects were randomized. 
After FDA review of 3-month or longer postoperative data on these subjects, approval was 
granted for enrollment and randomization of the remaining 430 subjects in the study 
expanded phase. Enrollment in the initial study phase began in September 2009 and ended in 
August 2010. Enrollment in the expanded phase of the study began in July 2011 and the last 
study subject was randomized in March 2013.
The COMPASS XT trial was designed to collect safety data beyond 24 months 
postoperatively for subjects who completed the COMPASS trial until 60 months. Study 
enrollment was initiated April 2016 and the last subject visit occurred in April 2018, 
Ianchulev 2019, and Reiss 2019.
5.2
Purpose of the Study
The purpose of this study is to assess long-term (10 years post-CyPass implantation) status of 
the corneal endothelium in subjects who were implanted with the CyPass Micro-Stent in the 
COMPASS trial.
At the end of the study, a clinical study report will be prepared in accordance with applicable 
regulatory requirements and standards.
Results of the study are intended for publication on the databases in which they are 
registered. Results may be offered for additional publication if they are of scientific interest.
5.3
Risks and Benefits
There may also be unknown risks to use of CyPass Micro-Stent. Any risk to subjects in this 
clinical study will be minimized by compliance with the eligibility criteria and study 
procedures, clinical oversight and monitoring.
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Refer to the product label for additional information.
6
STUDY OBJECTIVES
6.1
Safety Objective(s)
Table 6–1
Safety Objective(s)
Objective(s)
Endpoint(s)
Assess long-term (10 years post CyPass 
implantation) status of the corneal 
endothelium in subjects who were 
implanted with the CyPass Micro-Stent in 
the COMPASS trial

Rate of occurrence of sight-
threatening adverse events (AEs)

Rate of occurrence of ocular AEs

Central and peripheral (nasal) ECD 
measurements

Analyses of rate of loss and rate of 
low ECD (ie, ≤1000 cells/mm2)

Assessment of stabilization of ECL

Corneal sequelae associated with 
ECL

Association between peripheral and 
central ECD count and number of 
observed rings

Secondary surgical interventional 
(SSIs) to modify the device position 
(eg, repositioning, trimming, 
explantation)

Effects of SSIs on central and 
peripheral ECD

CyPass Micro-Stent movement 
and/or malposition

Corneal AEs (eg, corneal 
decompensation, tube corneal touch, 
corneal edema, etc.) caused by 
CyPass Micro-Stent

Losses in Best Corrected Visual 
Acuity (BCVA) ≥10 letters

Change in visual field mean 
deviation (MD)

Change in central corneal thickness
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7
INVESTIGATIONAL PLAN
7.1
Study Design
This is a prospective, non-interventional, observational, non-randomized, multicenter, single 
arm clinical study. Up to 374 subjects who were implanted with a CyPass Micro-Stent in the 
COMPASS trial will be enrolled. Subjects will be considered enrolled in the study after 
informed consent is obtained during the first study visit.
Subject participation in this study is variable depending on the number of follow-up visits 
expected. Annual follow-up visits will be scheduled for each subject based on the date of 
CyPass implantation and an exit visit will occur when the subject has reached 10 years post-
CyPass implantation. For some subjects, the first visit will be at or after 10 years post-CyPass 
implantation, and therefore the first visit may coincide with the 120-Month/Exit visit. 
 
 
 The study is expected to be completed in approximately 4 years.
7.2
Rationale for Study Design 
This study is designed in accordance with Alcon’s agreement with the United States Food 
and Drug Association (FDA) in order to evaluate the long-term safety of subjects who had 
been implanted with CyPass Micro-Stent.
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7.2.1
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations
Interim reports pertaining to the progress of the post-approval study will be submitted to the 
FDA for review every 6 months for the first 2 years and annually thereafter, starting from the 
date of FDA approval of the protocol, until study completion.
7.3
Rationale for Duration of Treatment/Follow-Up
The follow-up period is aligned with Alcon’s agreement with the United States FDA. 
7.4
Rationale for Choice of Control Product
Not applicable.
7.5
Data Monitoring Committee
Not applicable.
7.6
Milestones 
The study milestone timeline presented below is based upon the expectation that, following 
initiation of the first site, the remaining study sites will be activated at a rate of approximately 
4 per month. The enrollment rate at activated sites will be approximately 4 subjects per 
month per site. Timelines for the activation of sites and subject enrollment will vary greatly 
due to the time that has elapsed since these subjects were observed in previous studies. 
Enrollment will continue throughout the study and new subjects will be enrolled up until the 
completion of the study. The IRB approval rate is expected to be 4 sites per month, until all 
sites are IRB-approved.
Table 7-1
Study Milestones
Key Milestone
Target Date
First Site Activated
May 2020
First Subject First Visit
May 2020
Last Subject First Visit
June 2021
Last Subject Last Visit
August 2023
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Database Lock
September 2023
Submit PAS Final Report
December 2023
8
STUDY POPULATION
The study population consists of any subject who was implanted with a CyPass Micro-Stent 
as a participant in the COMPASS trial. It is aimed to enroll (consent) up to 374 subjects in up 
to 24 sites in the United States. Subjects who participated in the COMPASS trial will be 
enrolled for the duration of the study.
8.1
Inclusion Criteria
Written informed consent must be obtained before any study specific assessment is 
performed. Upon signing informed consent, the subject is considered enrolled in the study.
Subjects eligible for inclusion in this study must fulfill all of the following criteria:
1.
Subject must be able to understand and sign an IRB/IEC approved Informed 
Consent form (ICF).
2.
Any subject who was implanted with a CyPass Micro-Stent as a participant in the 
COMPASS trial.
3.
Able to understand the requirements of the study, willing to follow study 
instructions, and agree to comply with all study requirements, including the required 
study follow-up visits.
8.2
Exclusion Criteria
Subjects fulfilling any of the following criteria are not eligible for participation in this study.
1.
Inability to comply with the protocol or required follow-up visit/procedures.
8.3
Rescreening of Subjects
Due to the nature of the study, any subject implanted under the original COMPASS trial that 
presents for enrollment will be considered whether the subject has been previously screened 
for this protocol or not.
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9
TREATMENTS ADMINISTERED
9.1
Investigational Product(s)
Test Product(s):
CyPass Micro-Stent
Control Product(s) (If applicable):
Not applicable
Table 9–1
Test Product
Test Product
CyPass Micro-Stent
Manufacturer
Alcon Vision, LLC
6201 South Freeway
Fort Worth, Texas 76134-2099
USA
Indication for use 
and intended 
purpose in the 
current study 
The CyPass system is indicated for use in conjunction with cataract 
surgery, or in a standalone procedure in pseudophakic subjects, for 
the reduction of IOP in adult subjects with mild to moderate POAG.
Product description 
and parameters 
available for this 
study
Test Product: CyPass Micro-Stent
The CyPass system consists of the CyPass Micro-Stent, which is 
contained in a loading device (loader tip), and the CyPass applier.
The CyPass Micro-Stent is a polyimide tube with a fenestrated 
lumen. The stent has a single piece design and is 0.25" (6.35 mm) 
long. The inner diameter of the stent is 0.012" (0.30 mm) and the 
outer diameter is 0.017" (0.43 mm). The CyPass Micro-Stent is 
designed for placement in the angle of the eye, with the proximal 
end extending from the angle into the AC and the distal end residing 
in the supraciliary space.
When properly implanted, the CyPass Micro-Stent is intended to 
allow outflow of aqueous fluid from the AC, where the device 
proximal end resides, through and around the fenestrated lumen and 
distal end of the tube into the supraciliary and suprachoroidal space 
via the uveoscleral pathway.
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The CyPass applier is the hand-held surgical instrument used to 
implant the CyPass Micro-Stent. The applier consists of a medical-
grade polymer handpiece with a guidewire assembly. The guidewire 
assembly includes a nitinol implant delivery guidewire extending 
from inside the handpiece through and beyond the distal end of a 
stainless steel tube (guidewire tube) that supports the guidewire. 
The guidewire is 0.011" (0.28 mm) in diameter and formed with a 
0.48" (12 mm) radius of distal curvature and a blunt distal tip to 
facilitate location and blunt dissection of the plane between the 
ciliary body and sclera. The CyPass applier delivers the CyPass 
Micro-Stent to the desired location within the eye.
Once the guidewire has positioned the CyPass Micro-Stent at the 
desired location within the eye, the implant is released from the 
guidewire using the front button on the CyPass applier. This action 
withdraws the guidewire back into the guidewire tube, leaving the 
CyPass Micro-Stent in position in the eye.
Formulation
N/A
Usage
N/A
Packaging 
description
N/A
Labeling description
N/A
Storage conditions
N/A
Supply
N/A
More information on the test product can be found in the CyPass Micro-Stent Package Insert.
9.2
Other Medical Device or Medication Specified for Use During the 
Study
No other medical devices or medications are required to be used in conjunction with the 
treatments during the clinical study.
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9.3
Treatment Assignment / Randomization
In this non-interventional, observational follow-up study, there is no treatment assignment.
A subject will be assigned a subject number that will be captured in the electronic data 
capture system. The subject number will be linked to the subject number previously assigned 
under the COMPASS protocol. Subjects will not be randomized in this study.
9.4
Treatment masking
Not applicable.
9.5
Accountability Procedures
Not applicable.
9.6
Changes to Ocular Hypotensive Medications, Treatments/ Procedures
After the subject is enrolled into the study, the Investigator must instruct the subject to notify 
the study site about:

Any new medications 

Alterations in dose or dose schedules for current medications, 

Any medical procedure or hospitalization that occurred or is planned

Any non-drug therapies (including physical therapy and blood transfusions). 
The Investigator must document this information in the subject’s case history source 
documents.
10 STUDY PROCEDURES AND ASSESSMENTS
10.1 Informed Consent and Screening
The Investigator or delegate must explain the purpose and nature of the study, and have the 
subject read, sign, and date the IRB/IEC-approved informed consent document. The subject 
must sign the ICF BEFORE any study-specific procedures or assessments can be performed, 
including study-specific screening procedures. Additionally, have the individual obtaining 
consent from the subject and a witness, if applicable, sign and date the informed consent 
document. 
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The Investigator or delegate must provide a copy of the signed document to the subject and 
place the original signed document in the subject’s chart, or provide documentation as 
required by local regulations.
Every effort should be made to locate the subjects who were implanted with a CyPass Micro-
Stent in the COMPASS trial so that as much study information as possible may be obtained. 
The Investigator, or designee, must document at least 3 attempts to contact the subject within 
a reasonable timeframe to locate the subject.
10.2 Description of Study Procedures and Assessments
Detailed descriptions of assessments and procedures are provided in the MOP. The 
Investigator is responsible for ensuring responsibilities for all procedures and assessments are 
delegated to appropriately qualified site personnel.
10.2.1
Demographics
Obtain demographic information including age, race, and sex at the first study visit.
10.2.2
Inclusion/Exclusion Criteria
Evaluate inclusion/exclusion criteria at the first study visit.
10.2.3
Ocular Medical History
Collect ocular medical history information. These may include but are not limited to corneal 
haze/edema and device malposition.
10.2.4
Ocular Surgical History
Collect ocular surgical history information. These may include but are not limited to device 
explantation, device trimming, and/or device repositioning.
10.2.6
Best Corrected Visual Acuity: Safety Assessment
Perform monocular BCVA testing using ETDRS for the study eye at all study visits 
(84-Month Visit [±120 days] to 120-Month Visit [±120 days]) prior to any assessment 
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requiring administration of eye drops to dilate the eyes, or any assessment requiring contact 
with the eye. This assessment must be performed study personnel who have successfully 
completed the training required to conduct the assessment.
10.2.8
Pachymetry CCT: Safety Assessment
Measure central corneal thickness for the study eye at all study visits (84-Month Visit 
[±120 days] to 120-Month Visit [±120 days]) using a standalone pachymeter or the Konan 
specular microscope.
10.2.9
Gonioscopy: Safety Assessment
Perform gonioscopy for the study eye at all study visits (84-Month Visit [±120 days] to 
120-Month Visit [±120 days]) using a gonioprism and a slit-lamp microscope. Assess both 
Shaffer Grade in all four quadrants and the number of CyPass rings visible and document per 
PI judgement. Take gonio photographs to document CyPass position at all study visits 
(84-Month Visit [±120 days] to 120-Month Visit [±120 days]).
10.2.10 UBM/OCT: Safety Assessment
If available, perform imaging with UBM or OCT for the study eye at all study visits 
(84-Month Visit [±120 days] to 120-Month Visit [±120 days]). The same instrument should 
be used throughout the study.
10.2.11 Slit-Lamp Exam: Safety Assessment
SLE of the cornea, iris/anterior chamber and lens must be performed in the study eye before 
instillation of any diagnostic eye drops at every study visit (84 Month Visit [±120 days] to 
120 Month Visit [±120 days]).
10.2.12 Visual Field
All visual fields will be obtained with a Humphrey automated perimeter using the 24-2 SITA 
standard testing method. The visual fields must be performed with a non-dilated pupil unless, 
in the opinion of the investigator, the pupil is so miotic that dilation is required (eg, < 3 mm). 
If dilation was performed at the first study visit’s visual field examination(s), it should be 
performed at all subsequent visual field examinations for that subject.
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10.2.13 Dilated Fundus Exam: Safety Assessment
Dilated fundus examination includes ophthalmoscopic assessments of the vitreous, retina, 
macula, choroid, and optic nerve of the study eye at all study visits (84-Month Visit 
[±120 days] to 120-Month Visit [±120 days]). The C:D ratio will be assessed on both the 
horizontal and vertical axis.
10.2.14 Specular Microscopy
Perform specular microscopy (central and peripheral ECD) for the study eye at all study 
visits (84-Month Visit [±120 days] to 120-Month Visit [±120 days]) using the Konan specular 
microscope. Details regarding imaging methods are contained in the MOP. Analysis will be 
conducted by a reading center per International Standard Organization (ISO) 11979-7(2018)
recommendations.
10.2.15 Adverse Event Collection: Safety Assessment
Assess and record ocular adverse events that are observed or reported, including those 
associated with changes in concomitant medication dosing since the previous visit.
Requirements for reporting adverse events in the study can be found in Section 11.
10.2.16 Device Deficiencies: Safety Assessment
Assess and record any Device Deficiencies that are reported or observed, including those 
associated with changes in concomitant medication dosing since the previous visit.
Requirements for reporting device deficiencies in the study can be found in Section 11.
10.3 Unscheduled Visits
If a subject visit occurs between any regularly scheduled study visits, this visit must be 
documented as an Unscheduled Visit. During all unscheduled visits, the Investigator must 
conduct the following procedures: 

Collect ocular Adverse Event information

Record changes in ocular hypotensive medication

Follow standard of care procedures and document the results
The Investigator may perform additional procedures for proper diagnosis and treatment of the 
subject. The Investigator must document this information in the subject’s case history source 
documents.
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If during an Unscheduled Visit the subject is discontinuing from the study, the Investigator 
must conduct Exit procedures according to Table 3–1 Schedule of Study Procedures and 
Assessments as possible.
10.4 Discontinued Subjects
10.4.1
Screen Failures
Not Applicable.
10.4.2
Discontinuations
Discontinued subjects are individuals who voluntarily withdraw or are withdrawn from the 
study by the Investigator after any study-related ophthalmic assessments have been 
completed.
Subject numbers of discontinued subjects must not be re-used.
Subjects may discontinue from study at any time for any reason. Subjects may also be 
discontinued from the study at any time if, in the opinion of the Investigator, continuing the 
study assessments pose a risk to their health.
For subjects discontinuing from the study, the Investigator must complete all Exit procedures 
according to Table 3–1 Schedule of Study Procedures and Assessments and Section 10.4.3, if 
the subject is willing and able, and if in the opinion of the Investigator it is safe for the 
subject to do so.
The Investigator must document the reason for study or treatment discontinuation in the 
subject’s case history source documents.
To ensure the safety of all subjects who discontinue early, Investigators must assess each 
subject and, if necessary, advise them of any therapies and/or medical procedures that may be 
needed to maintain their health.
10.4.3
Schedule of Procedures and Assessments for Subjects Discontinued 
from Investigational Product 
Not applicable.
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10.5 Clinical Study Termination
The Study Sponsor reserves the right to close the investigational site or terminate the study in 
its entirety at any time.
If the clinical study is prematurely terminated or suspended by the Study Sponsor: 

The Study Sponsor must:
o
Immediately notify the Investigator(s) and subsequently provide 
instructions for study termination.
o
Inform the Investigator and the regulatory authorities of the 
termination/suspension and the reason(s) for the termination/suspension. 

The Investigator must:
o
Promptly notify the IRB/IEC of the termination or suspension and of the 
reasons. 
o
Provide subjects with recommendations for post-study treatment options 
as needed.
The Investigator may terminate the site’s participation in the study for reasonable cause.
10.5.1
Follow-Up of Subjects after Study Participation Has Ended
Following this study, the subject will return to their eye care professional for their routine eye 
care.
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES
11.1 General Information
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, 
whether or not related to the investigational medical device (test article). Refer to the 
Glossary of Terms for categories of AEs, ADEs, and SAEs.
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Figure 11–1
Categorization of All Adverse Events
Figure 11-2
Categorization of All Serious Adverse Events
11.1.1
Postoperative Adverse Events
Anticipated postoperative AEs include, but are not limited to, the following complications.
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a)
BCDVA loss of 2 lines (10 letters) or more on the ETDRS chart in comparison with 
the best BCDVA reported in COMPASS/COMPASS XT 
b)
Persistent (at time of study exit) BCDVA loss of 3 or more lines compared to best 
BCDVA achieved during the course of study, including both the COMPASS trial, 
and the COMPASS XT trial
c)
2-point worsening to severe on the slit-lamp examination findings (other than cells 
and flare) not associated with a pre-existing condition
d)
Endophthalmitis
e)
Flat AC with lens cornea touch
f)
Shallow AC with iridocorneal apposition
g)
Shallow AC with peripheral iridocorneal apposition
h)
Aqueous misdirection
i)
Chronic iritis
j)
Conjunctivitis
k)
Keratitis
l)
Corneal edema 
m)
Corneal opacification 
n)
Corneal decompensation
o)
Hyphema (defined as persistent hyphema of > 2 mm)
p)
Vitreous hemorrhage
q)
Retinal detachment
r)
Other retinal complications (eg, dialysis, flap tears, or proliferative 
vitreoretinopathy)
s)
Increase in C:D ratio of ≥0.3 units on slit-lamp biomicroscopic examination
t)
Confirmed worsening in the visual field mean deviation (MD) of ≥2.5 dB 
compared to the MD determined at the exit of the COMPASS trial or the 
COMPASS XT trial
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u)
Choroidal hemorrhage or choroidal effusion, defined as a choroidal effusion or 
detachment with at least a partially hemorrhagic component that obstructs vision or 
causes pain (including both peripheral and “kissing” choroidal detachments) lasting 
longer than 1 month 
v)
Peripheral anterior choroidal effusion
w)
Maculopathy associated with hypotony
x)
Maculopathy associated with cystoid edema
y)
Hypotony (defined as IOP < 6 mmHg) 
z)
Clinically significant hypotony, defined as IOP < 6 mmHg with any of the following 
findings:
i.
Maculopathy
ii.
Flat AC chamber requiring reformation
iii.
Corneal folds
iv.
Worsening of with-the-rule astigmatism by ≥1 diopter, or rotation of 
against-the-rule astigmatism to ≥1 diopter of with-the-rule astigmatism
v.
Choroidal effusion requiring surgical drainage
vi.
Suprachoroidal hemorrhage
vii.
BCDVA loss of ≥2 lines from the best postoperative BCDVA
aa)
Elevated mean IOP ≥10 mmHg than the qualifying baseline mean IOP at or after 
1 month postoperative
bb)
CyPass device obstructed by iris, vitreous, lens, fibrous overgrowth, fibrin, or blood
cc)
CyPass device malposition – positioning after deployment such that there is a 
clinical sequelae resulting from device position including, but not limited to:
i.
Secondary surgical intervention to modify device position (eg, 
repositioning, proximal end trimming or explantation)
ii.
Corneal endothelial touch by device
iii.
Corneal edema leading to loss of BCDVA > 2 lines in comparison with 
preoperative BCDVA
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iv.
Progressive ECL, defined as ongoing reduction in endothelial cell count of 
30% or more relative to the screening ECD value, where ‘ongoing 
reduction in endothelial cell count’ is defined as losses continuing after 
6 Months
v.
Erosion of device through sclera
vi.
Device obstruction requiring secondary surgical intervention
dd)
CyPass device dislodgement or movement, without sequelae, where device 
movement is defined as a change by at least 1 in the number of CyPass rings visible 
that is not attributable to variations in gonioscopic viewing angle or illumination, 
changes in angle anatomy due to concomitant findings such as resolution of 
hyphema, change in AC depth, or development of focal peripheral anterior 
synechiae
ee)
CyPass device explantation associated with CyPass placement and stability
ff)
CyPass device explantation NOT associated with CyPass placement and stability
gg)
Unplanned ocular surgical reintervention associated with CyPass placement and 
stability
hh)
Unplanned ocular surgical reintervention NOT associated with CyPass placement 
and stability (other than posterior capsulotomy)
ii)
Significant ptosis
jj)
Atrophy/phthisis
kk)
Wound dehiscence/leak (persistent aqueous leak or fistula formation)
ll)
Subconjunctival hemorrhage
mm) Chronic pain in the study eye 
nn)
Significant foreign body sensation 
oo)
IOL subluxation
11.1.2
Sight Threatening Adverse Events
Of the postoperative AEs listed in Section 11.1.1, the following are pre-defined as sight 
threatening and must therefore be reported as SAEs per the guidelines for reporting in 
Section 11.3:
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
Persistent (at time of study exit) BCDVA loss of 3 or more lines compared to best 
BCDVA achieved during the course of study

Endophthalmitis

Corneal decompensation

Retinal detachment

Severe choroidal hemorrhage or detachment

Aqueous misdirection
Other AEs may also be considered potentially sight threatening, or may meet other 
seriousness criteria. Any AE meeting any SAE seriousness criterion, as defined in the 
Glossary of Terms, must be reported as an SAE per Section 11.3.
11.1.3
Device Deficiencies
A device deficiency includes malfunctions, use errors, and inadequate labeling and may or 
may not be associated with subject harm (ie, ADE or SADE); however, not all ADEs or 
SADEs are due to a device deficiency. The Investigator should determine the applicable 
category for the identified or suspect device deficiency and report any subject harm 
separately. Any AE resulting from device deficiencies including device malfunction will be 
captured and reported in the case report form. Only AEs related to the device will also be 
captured as an ADE on a separate case report form. Examples of device deficiencies include, 
but are not limited to the following:

CyPass Micro-Stent issues
o
CyPass Micro-Stent damage
o
Defective CyPass Micro-Stent surface or interior lumen

Other device issues
11.2 Monitoring of Ocular Adverse Events
At each visit, the Investigator should inquire about any ocular AEs occurring since the last 
study visit.

“Have you had any health problems since your last study visit?”

“Have there been any changes in the medicines you take since your last study visit?”
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11.3 Procedures for Recording and Reporting
Any ocular AEs occurring since the Exit visit from the COMPASS trial or the COMPASS XT 
trial (whichever was the last study visit) will be collected from the time of informed consent. 
Any pre-existing medical conditions or signs/symptoms present in the subject in the 
COMPASS trial or COMPASS XT trial are not considered AEs in the study and should be 
recorded in the Medical History section of the eCRF. However, a worsening of the pre-
existing ocular AEs are considered AEs.
For each recorded event, the ADEs and SAEs documentation must include: date of 
occurrence, severity, treatment (if applicable), outcome, and assessments of the seriousness 
and causality. In addition, the Investigator must document all device deficiencies reported or 
observed with test and control articles on the Device Deficiency eCRF. The site must submit 
all available information on ADEs, SAEs, and device deficiencies to the Study Sponsor 
immediately as follows:

All SAEs must be reported immediately (within 24 hours) of the Investigator’s or 
site’s awareness.

ADEs that do not meet seriousness criteria and device deficiencies must be reported 
within 10 calendar days of the Investigator’s or site’s awareness.
A printed copy of the completed Serious Adverse Event and Adverse Device Effect and/or 
Device Deficiency eCRF must be included with product returns.

Additional relevant information after initial reporting must be entered into the eCRF 
as soon as the data become available.

Document any changes to concomitant medications on the appropriate eCRFs.

Document all relevant information from Discharge Summary, Autopsy Report,
Certificate of Death etc., if applicable, in narrative section of the Serious Adverse 
Event and Adverse Device Effect eCRF.
Note: Should the EDC system become non-operational, the site must complete the 
appropriate paper Serious Adverse Event and Adverse Device Effect and/or Device 
Deficiency Form. The completed form is emailed to the Study Sponsor at 
msus.safety@alcon365.com according to the timelines outlined above; however, the 
reported information must be entered into the EDC system once it becomes 
operational.
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Any AEs and device deficiencies for non-study marketed devices/products will be considered 
and processed as spontaneous (following the postmarket vigilance procedures) and should be 
communicated to the device’s/product’s manufacturer as per local requirements.
Study Sponsor representatives may be contacted for any protocol related question and their 
contact information is provided in the Manual of Procedures that accompanies this protocol.
Further, depending upon the nature of the AE or device deficiency being reported, the Study 
Sponsor may request copies of applicable portions of the subject’s medical records. The
Investigator must also report all AEs and device deficiencies that could have led to a SADE 
according to the requirements of regulatory authorities or IRB/IEC.
11.3.1
Intensity and Causality Assessments
Where appropriate, the Investigator must assess the intensity (severity) of the AE based on 
medical judgment with consideration of any subjective symptom(s), as defined below:
Intensity (Severity)
Mild 
An AE is mild if the subject is aware of but can easily tolerate the sign or 
symptom.
Moderate 
An AE is moderate if the sign or symptom results in discomfort significant 
enough to cause interference with the subject’s usual activities.
Severe 
An AE is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities.
For every AE in the study, the Investigator must assess the causality (Related or Not Related 
to the medical device or study procedure). An assessment of causality will also be performed 
by Study Sponsor utilizing the same definitions, as shown below:
Causality
Related
An AE classified as related may be either definitely related or possibly related 
where a direct cause and effect relationship with the medical device or study 
procedure has not been demonstrated, but there is a reasonable possibility that 
the AE was caused by the medical device or study procedure.
Not Related 
An AE classified as not related may either be definitely unrelated or simply 
unlikely to be related (ie, there are other more likely causes for the AE).
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The Study Sponsor will assess the AEs and may upgrade the Investigator’s assessment of 
seriousness and/or causality. The Study Sponsor will notify the Investigator of any AEs that is 
upgraded from non-serious to serious or from unrelated to related.
11.4 Return Product Analysis
Study Sponsor representatives and their contact information are provided in the MOP that 
accompanies this protocol.
Alcon products associated with device deficiencies and/or product related AEs should be 
returned and must include the Complaint #, which will be provided by Study Sponsor after 
the case is entered in the Study Sponsor’s Global Product Complain Management System 
(GPCMS).
11.5 Unmasking of the Study Information
Not applicable; this study is an unmasked, observational, single-arm study.
11.6 Follow-up of Subjects with Adverse Events
The Investigator is responsible for adequate and safe medical care of subjects during the 
study and for ensuring that appropriate medical care and relevant follow-up procedures are 
maintained after the study. 
The Investigator should provide the Study Sponsor with any new safety information (which 
includes new AEs and changes to previously reported AEs) that may affect the safety 
evaluation of the device. For AEs that are unresolved/ ongoing at time of subject exit from 
study, any additional information received at follow-up should be documented in the eCRFs 
up to study completion (ie, database lock). 
All complaints received after this time period will be considered and processed as 
spontaneous (following the postmarket vigilance procedures) and should be communicated to 
the medical device’s manufacturer as per local requirements.
11.7 Pregnancy in the Clinical Study
Pregnancy is not reportable as an AE; however, complications may be reportable and will be 
decided on a case-by-case basis. An Alcon form will be utilized to capture all pregnancy-
related information until birth of the child.
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12 ANALYSIS PLAN
12.1 Subject Evaluability
Final subject evaluability must be determined prior to locking the database, based upon the 
Deviations and Evaluability Plan.
12.2 Analysis Sets
12.2.1
Enrolled
The analysis set for both the safety and effectiveness analyses will be the set of all enrolled 
subjects. Only subjects enrolled in this study will be summarized.
12.3 Demographic and Baseline Characteristics
Demographic characteristics will be summarized overall. Counts and percentages will be 
presented for categorical variables such as sex, age and race. Baseline ECD will be 
summarized overall. Study eye will be tabulated.
12.4 Safety Analyses
The primary objective of the study is to assess long-term (10 years post-CyPass implantation) 
status of the corneal endothelium in subjects who were implanted with the CyPass Micro-
Stent in the COMPASS trial.
The safety endpoints are: 

Rate of occurrence of sight-threatening adverse events (AEs) 

Rate of occurrence of ocular AEs 

Central and peripheral (nasal) ECD measurements 

Analyses of rate of loss and rate of low ECD (ie, ≤1000 cells/mm2) 

Assessment of stabilization of ECL

Corneal sequelae associated with ECL 

Association between peripheral and central ECD count and number of observed rings 

Secondary surgical interventions (SSIs) to modify the device position (eg, 
repositioning, trimming, explanation) 

Effects of SSIs on central and peripheral ECD 

CyPass Micro-Stent movement and/or malposition 
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
Corneal AEs (eg, corneal decompensation, tube corneal touch, corneal edema, etc.) 
caused by CyPass Micro-Stent 

Losses in Best Corrected Visual Acuity (BCVA) ≥10 letters 

Change in visual field mean deviation (MD) 

Change in central corneal thickness
There are no safety hypotheses planned in this study. The focus of the safety analysis will be 
to assess the long-term status of the corneal endothelium and a comprehensive descriptive 
assessment of occurrence of adverse events as well as the other listed parameters.
All adverse events reported to Alcon will be accounted for in the reporting. Since some of the 
data collection for this study will be retrospective, some of the adverse events will have 
occurred prior to the date of informed consent. Descriptive summaries (counts and 
percentages) and listings will be presented.
12.4.1
Rate of Occurrence of Sight-Threatening Adverse Events (AEs)
12.4.1.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.1.2
Analysis Methods
Descriptive statistics for sight-threatening adverse events will be presented for study eyes. 
The rates of all sight-threatening adverse events will be provided with counts and 
percentages, and these rates will be accompanied by two-sided exact 95% confidence 
intervals. An eye with multiple ocular adverse events of the same preferred term is only 
counted once toward the total of this preferred term. The list of adverse events which are 
considered to be sight-threatening can be found in Section 11.1.2.
12.4.2
Rate of Occurrence of Ocular AEs
12.4.2.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.2.2
Analysis Methods
Descriptive statistics for ocular adverse events (including SSIs) will be presented for study 
eyes. The rates of all adverse events will be provided with counts and percentages, and these 
rates will be accompanied by two-sided exact 95% confidence intervals. An eye with multiple 
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ocular adverse events of the same preferred term is only counted once toward the total of this 
preferred term. 
12.4.3
Central and Peripheral (Nasal) ECD Measurements
12.4.3.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.3.2
Analysis Methods
Central and peripheral (nasal) endothelial cell density will be summarized at each visit. The 
number of eyes, mean, standard deviation, and the following percentiles will be reported: 0th, 
5th, 25th, 75th, 95th, and 100th. A 95% confidence interval based on the t-distribution will be 
reported for the mean at each visit.
The central endothelial cell coefficient of variation and hexagonality will be summarized by 
visit, in separate tables. The number of eyes, mean, standard deviation, and the following
percentiles will be reported: 0th, 5th, 25th, 75th, 95th, and 100th.
12.4.4
Analyses of Rate of Loss and Rate of Low ECD (ie, 
≤1000 cells/mm2)
12.4.4.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.4.2
Analysis Methods
Change in central endothelial cell density (within-eye) from baseline and percent change in 
central endothelial cell density will be summarized by visit. Baseline central endothelial cell 
density is the data collected at the COMPASS Study baseline visit. All references to baseline 
endothelial cell density data throughout this protocol refer to data from this visit. The 
proportion of subjects with central endothelial cell density less than 1000 cells/mm2, the 
proportion of subjects with peripheral endothelial cell density less than 1000 cells/mm², the 
proportion of subjects with central endothelial cell density less than 500 cells/mm2, the 
proportion of subjects with peripheral endothelial cell density less than 500 cells/mm², and 
the proportion of subjects with central endothelial cell loss over 30% from baseline will also 
be reported at these time points. A 95% exact binomial confidence interval will be presented 
for the proportions. The following statistics will be presented for change in central 
endothelial cell density and percent change in central endothelial cell density at each visit: 
number of eyes, means, standard deviations, and the following percentiles: 0th, 5th, 25th, 75th, 
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95th, and 100th. A 95% confidence interval based on the t-distribution will be reported for the 
means at each visit. This analysis will be performed using central endothelial cell density data 
from visits in the COMPASS, COMPASS XT, and COMPASS XXT studies, where available, 
and using peripheral cell density data collected in this study. Summary statistics for 
peripheral (nasal) endothelial cell density will be presented for each study visit.
12.4.5
Assessment of Stabilization of ECL
12.4.5.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.5.2
Analysis Methods
The annualized rate of change and percent rate of change in central endothelial cell density 
will be summarized at each year of observation. A 95% confidence interval based on the 
t-distribution will be produced along with the mean, standard deviation, minimum, median 
and maximum. This analysis will be performed using central endothelial cell density data 
from visits in the COMPASS, COMPASS XT, and COMPASS XXT studies, where available.
12.4.6
Corneal Sequelae Associated with ECL
12.4.6.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.6.2
Analysis Methods
A listing of corneal sequelae associated with ECL will be provided.
12.4.7
Association between Peripheral and Central ECD Count and 
Number of Observed Rings
12.4.7.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.7.2
Analysis Methods
Summary statistics for peripheral ECD count will be provided, stratified by visit and by 
number of rings observed at the visit, for all COMPASS XXT study visits. Summary statistics 
for central ECD count will be provided, stratified by the number of rings observed at the 
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visit, for all visits with available data from the COMPASS, COMPASS XT, and COMPASS 
XXT studies. 
12.4.8
Secondary Surgical Interventions (SSIs) to Modify the Device 
Position (eg, Repositioning, Trimming, Explanation)
12.4.8.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.8.2
Analysis Methods
A listing of SSIs to modify the device position will be provided.
12.4.9
Effects of SSIs on Central and Peripheral ECD
12.4.9.1
Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.9.2
Analysis Methods
A listing of central and peripheral ECD measurements will be produced for subjects with 
SSIs. The date of the SSI will be noted in this listing for each subject.
12.4.10 CyPass Micro-Stent Movement and/or Malposition
12.4.10.1 Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.10.2 Analysis Methods
The rate of all CyPass Micro-Stent movement and/or malposition will be presented with a 
count and percentage, and will be accompanied by a two-sided exact binomial 95% 
confidence interval.
12.4.11 Corneal AEs (eg, Corneal Decompensation, Tube Corneal Touch, 
Corneal Edema, etc.) Caused by CyPass Micro-Stent
12.4.11.1 Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
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12.4.11.2 Analysis Methods
A listing of corneal AEs caused by the CyPass Micro-Stent will be provided, which will 
include central and peripheral ECD measurements, where available.
12.4.12 Losses in Best Corrected Visual Acuity (BCVA) ≥10 letters
12.4.12.1 Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.12.2 Analysis Methods
A listing of BCVA loss of 10 letters or more will be provided, and will include all available 
BCVA data from the COMPASS, COMPASS XT, and COMPASS XXT studies for the 
subject. BCVA loss of 2 lines (10 letters) or more will be reported as an adverse event, so 
adverse event data will be the data source for this analysis.
12.4.13 Change in Visual Field Mean Deviation (MD)
12.4.13.1 Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
12.4.13.2 Analysis Methods
Change in visual field mean deviation at each visit postoperative as compared to the recorded 
value at the COMPASS screening visit will be reported. Observed values and change from 
screening values will be presented descriptively (N, mean, median, standard deviation, 
standard error, minimum, and maximum) at each study visit for each device. 
Counts and percentages of subjects will be presented according to the following categories: 
increase > 2.0 dB; no change (-2.0 to 2.0 dB); decrease > 2.0 dB. Denominators will consist 
of the number of subjects with non-missing visual field data at both time points.
12.4.14 Change in Central Corneal Thickness
12.4.14.1 Statistical Hypotheses
No hypothesis testing of the endpoint is planned.
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12.4.14.2 Analysis Methods
Change in central corneal thickness from baseline at each follow-up visits will be 
summarized. A mean, standard deviation, minimum, median, maximum, and a 
95% confidence interval based on the t-distribution will be provided for the change and 
percentage change from baseline at each visit.
12.4.16 Comparison of COMPASS XXT Subjects to Original COMPASS 
Subjects Implanted with CyPass
Analysis will be conducted to compare subjects followed in this COMPASS XXT study to
the full CyPass cohort implanted in the COMPASS trial.
ECD at baseline will be summarized for the two cohorts (COMPASS XXT vs. COMPASS).
These summaries will include number of eyes, mean, standard deviation, and the following 
percentiles: 0th, 5th, 25th, 75th, 95th, and 100th.
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The number and percent of eyes having ECD < 1000 will be reported for each cohort at 
6 months and 24 months.
The within-eye ECD loss from baseline and % ECD loss from baseline at 6 months and 
24 months will be summarized for the two cohorts. These summaries will include the number 
of eyes, mean, standard deviation, and the following percentiles: 0th, 5th, 25th, 75th, 95th, and 
100th.
The within-eye ECD loss from 6 months to 24 months, and the % ECD loss from 6 months to 
24 months will be summarized for the two cohorts. These summaries will include the number 
of eyes, mean, standard deviation, and the following percentiles: 0th, 5th, 25th, 75th, 95th, and 
100th.
The number and percentage (specifying the denominator) of eyes with each level of observed 
rings at the 24-month visit will be reported for each cohort.
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12.6 Interim Analyses and Reporting
Interim reports pertaining to the progress of the post-approval study will be submitted to the 
FDA for review every 6 months for the first 2 years and annually thereafter, starting from the 
date of FDA approval of the protocol, until study completion.
12.7 Handling of Missing Data
Missing data imputation will not be performed.
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12.8 Sample Size Justification
Sample size (374) is based on the number of subjects who were implanted with a CyPass 
Micro-Stent in the COMPASS trial. It is not based on statistical power. 374 subjects were 
implanted with CyPass in the COMPASS trial. Of these, 215 volunteered to enroll in 
COMPASS XT. The total enrolled in this trial will be a subset of the 374 COMPASS CyPass 
subjects, is not restricted to those enrolled in COMPASS XT, and may be above or below the 
total enrolled in the COMPASS XT trial.
13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS
13.1 Subject Confidentiality
The Investigator must ensure that the subject’s anonymity is maintained throughout the 
course of the study. In particular, the Investigator must keep an enrollment log with 
confidential identifying information that corresponds to the subject numbers and initials of 
each study participant. At the end of the clinical study, the Study Sponsor will collect a copy 
of the enrollment log without any identifying subject information. All documents submitted 
to the Study Sponsor will identify the subjects exclusively by number and demographic 
information. No other personally identifying information will be transmitted to the Study 
Sponsor.
The Study Sponsor may release anonymized study data to external researchers for purposes 
of future research directly related to the study objectives, or future research that is beyond the 
scope of the current study objectives. The Informed Consent Form explains this to study 
subjects. Anonymization means that all identifiable information will be removed from the 
dataset and all links to the subjects in the study will be removed. Anonymization of the data 
will maintain confidentiality of the subjects who participate in the study so that they cannot 
be identified by external researchers. The anonymized data set will contain records from all 
of the subjects in the current study, but the anonymization process might change the data set 
in some ways, so external researchers will be informed that they might not be able to 
duplicate some of the results from this study.
13.2 Completion of Source Documents and Case Report Forms
The nature and location of all source documents will be identified to ensure that original data 
required to complete the CRFs exist and are accessible for verification by the site monitor, 
and all discrepancies shall be appropriately documented via the query resolution process. Site
monitors are appointed by the Study Sponsor and are independent of study site staff.
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If electronic records are maintained, the method of verification must be determined in
advance of starting the study. 
At a minimum, source documents include the following information for each subject:

Subject identification (name, sex, race/ethnicity)

Documentation of subject eligibility

Date of informed consent

Dates of visits

Documentation that protocol specific procedures were performed

Results of study parameters, as required by the protocol

IP accountability records (if applicable)

Documentation of AEs and other safety parameters (if applicable)

Records regarding medical histories and the use of concomitant therapies prior to and 
during the study

Date of study completion and reason for early discontinuation, if applicable
It is required that the author of an entry in the source documents be identifiable. Direct access 
to source documentation (medical records) must be allowed for the purpose of verifying that 
the data recorded on the CRF are consistent with the original source data.
Only designated individuals at the site will complete the CRFs. The CRFs must be completed 
at regular intervals following the clinical study visit schedule. It is expected that all data 
reported have corresponding entries in the source documents. The Principal Investigator is 
responsible for reviewing and certifying that the CRFs are accurate and complete. The only 
subject identifiers recorded on the CRFs will be subject number, and subject demographic 
information. 
13.3 Data Review and Clarifications
A review of CRF data to the subject’s source data will be completed by the site monitor to 
ensure completeness and accuracy. After the CRFs have been completed, additional data 
clarifications and/or additions may be needed as a result of the data cleaning process. Data 
clarifications are documented and are part of each subject’s CRF.
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13.4 Sponsor and Monitoring Responsibilities
The Study Sponsor will designate a monitor to conduct the appropriate site visits at the 
appropriate intervals according to the study monitoring plan. The clinical investigation will 
be monitored to ensure that the rights and well-being of the subjects are protected, the 
reported data are accurate, complete, and verifiable from the source documents, and the study 
is conducted in compliance with the current approved protocol (and amendments[s], if 
applicable), with current GCP, and with applicable regulatory requirements.
The site may not screen subjects or perform the informed consent process on any subject until 
it receives a notification from an appropriate Study Sponsor representative that the site may 
commence conducting study activities. Monitoring will be conducted periodically while the 
clinical study is ongoing. Monitoring methods may include site visits, telephone, written and 
fax correspondence. Close-out visits will take place after the last visit of the last subject at the 
site.
A Coordinating Investigator may be identified by the Study Sponsor to review and endorse 
the final study report. In cases where a Coordinating Investigator is engaged, the Study 
Sponsor will select the Coordinating Investigator based upon their experience, qualifications, 
active study participation, and their willingness and availability to take on this role.
13.5 Regulatory Documentation and Records Retention
The Investigator is required to maintain up-to-date, complete regulatory documentation as 
indicated by the Study Sponsor and the Investigator’s files will be reviewed as part of the 
ongoing study monitoring. Financial information is to be kept separately. 
Additionally, the Investigator must keep study records and source documents consistent with 
the terms of the clinical study agreement with the Study Sponsor. If the Investigator retires, 
relocates, or for any other reason withdraws from responsibility of keeping the study records, 
then the Study Sponsor must be notified and suitable arrangements made for retention of 
study records and source documents needed to comply with national and international 
regulations.
13.6 Quality Assurance and Quality Control
The Study Sponsor will secure agreement from all involved parties to ensure direct access to 
all study related sites, source data and documents, and reports for the purpose of monitoring 
and auditing by the Study Sponsor, and inspection by domestic and foreign regulatory 
authorities. Quality control will be applied to each stage of data handling to ensure that all 
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data are reliable and have been processed correctly. Agreements made by the Study Sponsor 
with the Investigator/Institution and any other parties involved in the clinical study will be 
provided in writing as part of the protocol or as a separate agreement.
14 ETHICS
This clinical study must be conducted in accordance with the ethical principles contained 
within: 

The Declaration of Helsinki, and in compliance with the ICH E6 GCP Consolidated 
Guideline, ISO 14155:2011, and the applicable US FDA 21 CFR Regulations. 

SOPs of the Study Sponsor and contract research organizations participating in the 
conduct of the clinical study and all other applicable regulations. 

Notifications and timelines for reporting protocol deviations should be based upon
applicable Ethics Committee requirements
The Investigator must ensure that all personnel involved in the conduct of the study are 
qualified to perform their assigned responsibilities through relevant education, training, and 
experience. The Investigator and all clinical study staff must conduct the clinical study in 
compliance with the protocol. Deviations from this protocol, regulatory requirements and/or 
GCP must be recorded and reported to the Sponsor prior to database lock. If needed, 
corrective and preventive action should be identified, implemented, and documented within 
the study records. Use of waivers to deviate from the clinical protocol is prohibited.
Before clinical study initiation, this protocol, the informed consent form, any other written 
information given to subjects, and any advertisements planned for subject recruitment must 
be approved by an IRB/IEC. The Investigator must provide documentation of the IRB/IEC 
approval to the Study Sponsor. The approval must be dated and must identify the applicable 
protocol, amendments (if any), informed consent form, assent form (if any), all applicable 
recruiting materials, written information for subject, and subject compensation programs. The 
IRB/IEC must be provided with a copy of the Package Insert, any periodic safety updates, 
and all other information as required by local regulation and/or the IRB/IEC. At the end of 
the study, the Investigator must notify the IRB/IEC about the study’s completion. The 
IRB/IEC also must be notified if the study is terminated prematurely. Finally, the Investigator 
must report to the IRB/IEC on the progress of the study at intervals stipulated by the 
IRB/IEC.
Voluntary informed consent must be obtained in writing from every subject and the process 
shall be documented before any procedure specific to the clinical investigation is applied to 
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the subject. The Investigator must have a defined process for obtaining consent. Specifically, 
the Investigator, or their delegate, must explain the clinical study to each potential subject and 
the subject must indicate voluntary consent by signing and dating the approved informed 
consent form. The subject must be provided an opportunity to ask questions of the 
Investigator, and if required by local regulation, other qualified personnel. The Investigator 
must provide the subject with a copy of the consent form written in a language the subject 
understands. The consent document must meet all applicable local laws and provide subjects 
with information regarding the purpose, procedures, requirements, and restrictions of the 
study, along with any known risks and potential benefits associated with the IP and the study, 
the available compensation, and the established provisions for maintaining confidentiality of 
personal, protected health information. Subjects will be told about the voluntary nature of 
participation in the study and must be provided with contact information for the appropriate 
individuals should questions or concerns arise during the study. The subject also must be told 
that their records may be accessed by appropriate authorities and Sponsor-designated 
personnel. The Investigator must keep the original, signed copy of the consent (file in 
subject’s medical records) and must provide a duplicate copy to each subject according to 
local regulations. 
The Study Sponsor assures that the key design elements of this protocol will be registered on 
www.clinicaltrials.gov as required by current regulations and, if applicable, other public 
databases as required by local country regulations. In addition, results of this study will be 
made publicly available on www.clinicaltrials.gov regardless of outcome as required by 
current regulations and, if applicable, in other public databases as required by local country 
regulations.
15 REFERENCES
15.1 References Applicable for All Clinical Studies

ISO 14155:2011 Clinical investigation of medical devices for human subjects - Good 
clinical practice
15.1.1
US References Applicable for Clinical Studies

21 CFR Part 11 - Electronic Records; Electronic Signatures

21 CFR Part 50 - Protection of Human Subjects

21 CFR Part 56 - Institutional Review Boards

21 CFR Part 812 - Investigational Device Exemptions

21 CFR Part 54 - Financial Disclosure by Clinical Investigators
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
The California Bill of Rights
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Signature Page for V-CLN-0006690 v3.0
Signature Page for V-CLN-0006690 v3.0