Clinical trial NCT04615403
Conditions: Open Angle Glaucoma
Sponsor: Glaukos Corporation
Start date: 2020-11-19; Completion date: 2022-02-28
Enrollment: 33 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The study objective is to evaluate the safety of the operative and surgical exchange procedure of Travoprost Intraocular Implant in subjects with open-angle glaucoma or ocular hypertension.

Detailed description:
This prospective, non-randomized, open-label, multi-center, single arm, clinical trial intends to implant approximately 45 male and female subjects over 18 years old who have been diagnosed with open-angle glaucoma (OAG) or ocular hypertension (OHT). All subjects are required to meet eligibility criteria at Visit 1 (Screening). The purpose of this study is to evaluate the safety of the implantation and exchange of a Travoprost Intraocular Implant in subjects with open-angle glaucoma or ocular hypertension. Postoperatively, there are 6 follow-up visits over a 12 month period.

Arms: arm 1: Subjects will undergo implantation and exchange of a Travoprost Intraocular Implant through a small temporal clear corneal incision.
Interventions: intervention 1: Travoprost
Intervention descriptions: intervention 1: Implantation and exchange of a Travoprost Intraocular Implant through a clear corneal incision

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL 
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PROSPECTIVE, NON-RANDOMIZED, OPEN-
LABEL, MULTI-CENTER, SINGLE ARM STUDY
OF EXCHANGE OF TRAVOPROST INTRAOCULAR
IMPLANT 
PROTOCOL # IDOS-106-EXCH 
DATE:  AUGUST 24, 2020 
Sponsor: 
GLAUKOS CORPORATION 
229 Avenida Fabricante │ San Clemente, CA 92672 │ 001-949- 367-9600 
NCT04615403






CONFIDENTIAL 
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Table of Contents 
1 
INTRODUCTION ............................................................................................9 
2 
OBJECTIVE ...................................................................................................10 
3 
STUDY DESIGN ...........................................................................................10 
3.1 
Discussion of Study Design ....................................................................11 
4 
STUDY MEASURES.....................................................................................11 
4.1 
Efficacy Measures ...................................................................................11 
4.2 
Safety Measures ......................................................................................12 
4.3 
Other ........................................................................................................12 
5 
MATERIALS .................................................................................................12 
5.1 
Study Medications ...................................................................................12 
6 
METHODS .....................................................................................................13 
6.1 
Subjects ...................................................................................................13 
6.2 
Eligibility Requirements .........................................................................14 
6.3 
Procedures ...............................................................................................18 
6.4 
Concomitant Therapies ...........................................................................22 
6.5 
Post-Treatment Management of IOP and Rescue Medications ..............22 
7 
EXTENT OF EXPOSURE AND TREATMENT COMPLIANCE ...............23 
8 
STATISTICAL ANALYSES .........................................................................23 
8.1 
Sample Size .............................................................................................23 
8.2 
Analysis Populations ...............................................................................23 
8.3 
General Statistical Methods ....................................................................23 
8.4 
Efficacy Analyses ....................................................................................23 
8.5 
Safety Analyses .......................................................................................24 
8.6 
Interim Analyses .....................................................................................24 
9 
ADVERSE EVENTS .....................................................................................24 
9.1 
Serious Adverse Event ............................................................................26 
9.2 
Unexpected Adverse Event .....................................................................27 
9.3 
Suspected, Unexpected, Serious, Adverse Reaction (SUSAR) ..............28 
9.4 
Adverse Events Follow-up ......................................................................28 
10 MAINTAINING THE MASK........................................................................28 
11 INFORMED CONSENT ................................................................................28 


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12 INSTITUTIONAL REVIEW .........................................................................28 
13 CONFIDENTIALITY/PUBLICATION OF THE STUDY ...........................28 
14 STATEMENT OF COMPLIANCE ...............................................................29 
15 RECORD KEEPING ......................................................................................29 
15.1 Source Documents...................................................................................29 
15.2 Data Collection ........................................................................................30 
15.3 Study Supply Accountability ..................................................................30 
15.4 Record Retention .....................................................................................31 
16 REFERENCES ...............................................................................................32 
List of Figures 
Figure 1. Glaukos Travoprost Intraocular Implant ............................................... 12 
Figure 2. Glaukos Travoprost Intraocular Implant and Inserter ........................... 13 
List of Appendices 
APPENDIX A:  SCHEDULE OF VISITS AND MEASUREMENTS ................ 33 
APPENDIX B:  OBLIGATIONS OF THE INVESTIGATOR ............................ 34 


 
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SYNOPSIS 
 
This prospective, non-randomized, open-label, multi-center, single arm, clinical 
trial intends to exchange the implant in approximately 
 male and female 
subjects who were previously implanted with the Travoprost Intraocular Implant 
in the GC-009 study (1st Cycle).  All subjects are required to meet eligibility 
criteria at Visit 1 (Screening).  The purpose of this study is to evaluate the safety 
of the exchange of a Travoprost Intraocular Implant in subjects with a previously 
implanted Travoprost Intraocular Implant.  Postoperatively, there are 6 follow-up 
visits over a 12 month period. 
 
Test Article(s): 
Travoprost Intraocular Implant, 
 
 
STUDY OBJECTIVE 
The study objective is to evaluate the safety of the surgical exchange procedure of 
Travoprost Intraocular Implant in subjects with a previously implanted Travoprost 
Intraocular Implant.  
 
STUDY TREATMENTS 
Subjects will undergo an exchange of a Travoprost Intraocular Implant through a 
small temporal clear corneal incision. 
 
Structure: 
Single arm 
 
Number of Centers: 
Approximately 15 centers 
 
Masking:  
Open-label  
 
Method of Subject Assignment: 
After Visit 1 (Screening), qualified subjects will be scheduled to undergo 
treatment with the G2TR-
 implant. 
 
Randomization: 
No 
 
Total Sample Size: 
Approximately 
subjects 
 
Statistical Rationale Provided: 
Please refer to Statistical Section, Section 8 
 
STUDY OVERVIEW 
Subjects will be assessed for inclusion/exclusion criteria at Visit 1 (Screening). At 
this visit, all subjects must meet all entry criteria.  Subjects who meet criteria at 
Visit 1 (Screening) may be scheduled for Visit 2 (Operative Exchange Day 0) (on 
a separate day).   


 
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Visit Schedule: 
This study will consist of 8 visits over approximately a 12 month period:  Visit 1 
(Screening), Visit 2 (Operative Exchange Day 0), Visit 3 (Day 1 Post-Exchange), 
Visit 4 (Day 10 Post-Exchange), Visit 5 (Week 4 Post-Exchange), Visit 6 (Month 
3 Post-Exchange), Visit 7 (Month 6 Post-Exchange), and Visit 8 (Month 12 Post-
Exchange).  
 
Study Measures will be collected for the study eye only: 
Safety  
- 
Intra-operative adverse events  
- 
Post-operative adverse events 
- 
Corrected visual acuity (logMAR score using ETDRS chart) 
- 
Slit-lamp biomicroscopy findings 
- 
Gonioscopy findings 
- 
Specular microscopy findings  
- 
Intraocular Pressure  
- 
Ophthalmoscopy findings 
- 
Visual field evaluation 
 
Other  
- 
Operative and surgical assessments 
 
Specified Plan for Data Analysis:  Yes (refer to Section 8) 
 
Power and Sample Size: The sample size of 
 who undergo an exchange 
of a Travoprost Intraocular Implant was determined empirically. This sample size 
is considered adequate to support the objective of this study. 
 
STUDY VARIABLES AND STATISTICAL ANALYSIS 
 
Efficacy Variable 
There is no efficacy variable in this study.  Intraocular pressure is assessed for 
safety. 
 
Safety Variables 
Adverse events (intra-operative and post-operative [TEAEs]) in the study eye will 
be monitored and summarized. 
Ocular safety variables, i.e., best spectacle corrected visual acuity, biomicroscopy 
findings, gonioscopy findings, specular microscopy findings, intraocular pressure, 
ophthalmoscopy findings (including cup-to-disc ratio), and visual field evaluation, 
will be summarized. 
 
Analysis Populations 
All subjects who undergo the exchange procedure will be included in the safety 
population. The safety population will be used for all data tabulations and listings. 


 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Abbreviation/Term 
Definition 
α-agonists 
α-adrenergic receptor agonists 
AC Tap 
Anterior Chamber Aqueous Humor Sample 
AE 
Adverse Event 
BAK 
Benzalkonium chloride 
β-blockers 
β-adrenergic receptor antagonists 
BSCVA 
Best Spectacle Corrected Visual Acuity 
CAI 
Carbonic Anhydrase Inhibitor 
CRF 
Case Report Form 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
IOP 
Intraocular Pressure 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent-To-Treat 
LogMAR 
Logarithm of the Minimum Angle of Resolution 
MA 
Medical Affairs 
MedDRA 
Medical Dictionary for Regulatory Activities 
mmHg 
Millimeters of mercury 
OAG 
Open-angle glaucoma 
OHT 
Ocular hypertension 
PAS 
Peripheral Anterior Synechia 
PE 
Post-Exchange 
PGA 
Prostaglandin Analogue 
PP 
Per protocol 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
TEAE 
Treatment Emergent Adverse Event 
VA 
Visual acuity 
 
 
 


 
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1 
INTRODUCTION 
Glaucoma is a group of eye diseases characterized by progressive, irreversible 
and largely asymptomatic vision loss caused by optic nerve damage, which is 
most commonly associated with elevated levels of intraocular pressure. 
Glaucoma is a chronic condition that progresses slowly over long periods of 
time and can have a devastating impact on a patient's vision and quality of 
life.  Reducing intraocular pressure currently is the only proven treatment for 
glaucoma.  
Treatment for open-angle glaucoma (OAG) traditionally has started with 
topical ocular hypotensive medical therapy.  Development of more effective 
medications has increased the popularity of this approach as initial treatment 
compared to more invasive incisional or drainage device surgery. 
Furthermore, the more benign medication treatments preserve the ocular 
tissues in the event that more invasive surgical approaches are eventually 
required. 
The various topical ocular medications available to reduce IOP include 
miotics, β-adrenergic receptor antagonists (β-blockers), carbonic anhydrase 
inhibitors (CAIs), α-adrenergic receptor agonists (α-agonists), and 
prostaglandin analogues (PGAs).  The PGAs are a class of ocular hypotensive 
agents that have been proven effective in lowering IOP in subjects with OAG 
or OHT.  Other advantages of this class of medications is that the systemic 
side effects associated with α-agonists (e.g., dry mouth, drowsiness) 
and  β- blockers (e.g., depression, fatigue, bradycardia) do not appear to be 
associated with PGAs.  Furthermore, the ocular side effects typically 
associated with a-agonists (e.g., allergic reactions), and cholinergic agents 
(e.g., reduced vision), do not seem to manifest with the use of PGAs. 
However, PGAs have been shown to be associated with side effects such as 
ocular hyperemia, iris hyperchromia, periorbital atrophy, increased eyelash 
growth, general ocular surface discomfort and headache.1-5 These side effects 
and other factors including cost, compliance, and the difficulty of proper 
instillation, can sometimes hinder the proper use of topical medications.6,7 
Some patients may possess or develop an intolerance to topical medications or 
the preservatives in their formulations. 
The Travoprost Intraocular Implant was developed to remove or minimize the 
issue of patient compliance with topical hypotensive medication.  This clinical 
protocol will evaluate the second cycle of the Travoprost Intraocular Implant:  
Model G2TR-
.  
This implant has the potential for providing important benefits to patients. The 
long duration of drug therapy provided by the implant avoids the problem of 
compliance with topical ocular hypotensive medications.  In addition, the 
small clear corneal incision required for implantation and the minimally 


 
CONFIDENTIAL 
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invasive implant size avoids some of the complications of more invasive 
surgical procedures for treating glaucoma.  
 Model G2TR-
 has been investigated in clinical trials conducted in 
(Phase 1/2) as well as the United States (Phase 2 and Phase 3).  The 
results from the U.S. Phase 2 trial have demonstrated that the Model G2TR-
 implant has long-term IOP-lowering effects and is also generally well-
tolerated by study subjects.  These results support the continued evaluation of 
the implant model in this clinical trial.   
2 
OBJECTIVE 
The study objective is to evaluate the safety of the surgical exchange 
procedure of Travoprost Intraocular Implant in subjects with a previously 
implanted Travoprost Intraocular Implant.   
3 
STUDY DESIGN 
This is a prospective, non-randomized, open-label, multi-center, single arm, 
clinical trial of the safety of the exchange of the Travoprost Intraocular 
Implant in subjects who were previously implanted with the Travoprost 
Intraocular Implant in the GC-009 study (1st Cycle).  Approximately 
 
 will be enrolled into this study and will be followed through 12 
months postoperative.   
 
 
Screening Procedure: 
After providing informed consent, prospective subjects will be evaluated 
against the Screening criteria.  At Visit 1 (Screening), all subjects must meet 
all entry criteria. 
Subjects who qualify at Visit 1 (Screening) may be scheduled for Visit 2 
(Operative Exchange Day 0) on a separate day.   
The eye previously implanted with a Travoprost Intraocular Implant in the 
GC-009 study (study eye) will be assessed at Visit 1 (Screening).  The subject 
may then be scheduled for study treatment.  Subjects will be treated 
unilaterally, only the implanted eye (study eye) will go through the study 
treatment. The fellow eye will be treated outside the parameters of the study 
per investigator discretion using their standard of care options. 
 


 
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Treatment Procedure: 
The Operative and Postoperative scheduled visits are listed in the following table:  
Visit 
Number 
Visit Timepoint 
2 
Operative Exchange Day 0 
3 
Day 1 Post-Exchange 
4 
Day 10 Post-Exchange (10 days ± 3) 
5 
Week 4 Post-Exchange (28 days ± 3) 
6 
Month 3 Post-Exchange (91 days ± 14) 
7 
Month 6 Post-Exchange (182 days ± 30) 
8 
Month 12 Post-Exchange (365 days ± 30) 
 
At Visit 2 (Operative Exchange Day 0), subjects will have the first implant 
which was inserted in Study GC-009 exchanged with a second G2TR-
 
implant.  
 
At Visit 1 (Screening), IOP can be measured at any time.  At all other 
scheduled visits, Day 10 Post-Exchange, Week 4 Post-Exchange, Month 3 
Post-Exchange, Month 6 Post-Exchange, and Month 12 Post-Exchange), IOP 
measurements will be taken once daily at the same time as screening ± 60 
minutes.  Study follow-up will continue until Visit 8 (Month 12 Post-
Exchange), after which subjects will be exited from the study. 
 
3.1 
 Discussion of Study Design 
This prospective, non-randomized, open-label, multi-center, single arm, 
clinical trial intends to perform an exchange procedure on approximately 
 
male and female subjects who were previously implanted with the Travoprost 
Intraocular Implant in the GC-009 study (1st Cycle).  All subjects are required 
to meet eligibility criteria at Visit 1 (Screening).  The study objective is to 
evaluate the safety of the surgical exchange procedure of Travoprost 
Intraocular Implants in subjects with a previously implanted Travoprost 
Intraocular Implant. Postoperatively, there are 6 follow-up visits over a 12 
month period.  
 
4 
STUDY MEASURES 
4.1 
Efficacy Measures 
There are no efficacy measures in this study.  IOP is assessed for safety. 


 
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4.2 
Safety Measures 
Ocular safety measures include intra-operative adverse events, post-operative 
adverse events (TEAEs), IOP, corrected visual acuity, slit lamp 
biomicroscopy findings, gonioscopy findings, specular microscopy findings, 
intraocular pressure, ophthalmoscopy findings (including cup-to-disc ratio), 
and visual field evaluation.  
 
4.3 
Other 
Operative and Surgical Assessments. 
 
5 
MATERIALS 
5.1 
Study Medications 
Subjects will undergo surgery to receive the implants using the test article 
described below in Section 5.1.1 
 
5.1.1 TEST ARTICLE:  TRAVOPROST INTRAOCULAR 
IMPLANT MODEL G2TR-
 
 
 
 
 
 
 
.   
 
Figure 1. Glaukos Travoprost Intraocular Implant 
 




 
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6.2 
Eligibility Requirements 
6.2.1 INCLUSION CRITERIA  
6.2.1.1 
Visit 1 (Screening) Inclusion Criteria 
At the Visit 1 (Screening), all subjects must meet the following 
criteria: 
1) Subject status as follows: 
a. able and willing to attend scheduled follow-up exams for the 
duration of the study 
b. able and willing to provide written informed consent on the 
IRB/IEC-approved Informed Consent Form 
 
2) Best spectacle corrected visual acuity of 20/80 or better in each eye. 
  
3)  Previously implanted with the Travoprost Intraocular Implant in 
the GC-009 study that is present in the study eye (1st Cycle).  Only 
the eye with the Travoprost Intraocular Implant may be assessed 
for exchange at Visit 1 (Screening). 
 
 
All subjects (OAG and OHT) must meet the rest of the following 
criteria: 
4) Angle anatomy defined as follows:  
a. 
 
 
 
 
 
 
 
 


 
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6.2.2  EXCLUSION CRITERIA 
6.2.2.1 
Visit 1 (Screening) Exclusion Criteria  
Subjects who meet any of the following criteria in the study eye at 
Visit 1 (Screening) are not eligible to participate in the study: 
 
1) Glaucoma status as follows: 
a. traumatic, uveitic, neovascular, or angle-closure glaucoma; or 
glaucoma associated with vascular disorders 
b. 
 
 
 
 
 
 
 
2) Corneal status as follows: 
a. any active inflammation or edema
 
b. clinically significant dystrophy 
 
 
 
 
  
e. 
 
 during the course of the study, that may interfere 
with IOP measurement reliability 
f. opacities or disorders that would inhibit visualization of the 
nasal angle. 
 
3) Congenital or traumatic cataract 
 
 
4) 
 
 
 
 
 
 
 
 


 
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6) Other ocular status as follows: 
a. clinically significant sequelae from trauma 
 
 
b. history or chronic ocular inflammatory disease or presence of 
active ocular inflammation 
 
 
 
 
 
 
 
 
 
7) Fellow eye status as follows: 
a. fellow eye actively enrolled in this trial or any other clinical trial. 
 
8) Subject status as follows: 
a. pregnant or planning to become pregnant during the course of 
the study 
b. uncontrolled systemic disease (e.g., diabetes, hypertension) that 
could compromise their participation in the study 
c. current participation in any study, or participation within 30 
calendar days of Visit 1 (Screening) 
d. immunodeficiency conditions 
e. 
 
 
 
 
 
 
 
 
 
 
 


 
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6.2.3 CRITERIA FOR EARLY STUDY EXIT  
Subjects may voluntarily withdraw from the study at any time.  The 
investigator may elect to discontinue any subject for reasons unrelated to 
the study product.  Details of a subject’s exit from the study should be 
recorded in the subject’s clinical records.  Subjects who prematurely 
discontinue the study may be replaced.  Subjects exited after signing the 
informed consent form and prior to study completion will be handled as 
follows: 
 
6.2.3.1 
Prior to Implantation 
Subjects will be ineligible for the study if they fail to meet eligibility 
criteria (Section 6.2), if they withdraw consent, or if study enrollment 
goals have been met. 
 
6.2.3.2 
After 2nd Cycle Implantation 
Subjects may be exited (discontinued) from the study in the event of a 
condition that may cause them harm if participation were to be 
continued.  Subjects may also withdraw voluntarily.   
 
6.2.3.3 
Lost to Follow-up 
Subjects who miss postoperative study visits and cannot be contacted 
within a reasonable timeframe via letter or telephone, will be 
considered lost to follow-up.  The site will make at least three attempts 
to contact the subject via telephone.  If unsuccessful, the site will send 
a letter to the subject.  The letter will request the subject to contact and 
return to the study site.  If the subject does not contact the site within a 
week after the letter was received, he/she will be considered lost to 
follow-up, and the site will send a second letter to notify the subject of 
study exit due to lack of response to the telephone calls and first 
registered letter.  A Study Exit CRF may then be completed for the 
subject. 
 
All attempts to contact the subject (including telephone call logs, 
copies of letters) must be documented and maintained with the 
subject’s study source documentation. 
 
6.2.4 STUDY TERMINATION 
The study may be terminated by Glaukos at any time following 
appropriate notification to the study site and subjects. 
 


 
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6.3 
Procedures 
Study visits and assessments are listed below; a table overview of study 
procedures by visit is provided in APPENDIX A:  SCHEDULE OF VISITS 
AND MEASUREMENTS 
 
6.3.1 DURATION OF STUDY 
Following the initial implantation, the treatment period will be 3 months in 
duration. 
 
6.3.2 ENROLLMENT  
All subjects must give written informed consent before undergoing any 
study-related change in their treatment or any study related procedures. 
 
 
 
 
 
 
6.3.3 PREOPERATIVE PROCEDURES 
6.3.3.1 
Visit 1 (Screening) 


 
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If the subject is ineligible for the study, complete the appropriate CRF. 
 
6.3.4 TREATMENT PROCEDURES 
6.3.4.1 
Visit 2 (Operative Exchange Day 0) 


 
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6.3.4.2 
Visit 3 (Day 1 Post-Exchange, 1 days) 
6.3.4.3 
Visit 4 (Day 10 Post-Exchange, 10 ± 3 days) 
 
 
 
 
 
 
 
  
 
 
  
 
  
 
6.3.4.4 
Visit 5 (Week 4 Post-Exchange, 28 days ± 3) 
1) 
 
 
 
 
 
 
 
 
 
.  


 
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6.3.4.5 
Visit 6 (Month 3 Post-Exchange, 91 days ± 14) 
 
6.3.4.6 
Visit 7 (Month 6 Post-Exchange, 182 days ± 30) 






 
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8.5 
Safety Analyses 
8.5.1 ADVERSE EVENTS 
Adverse events (AEs) in the study eye will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA) nomenclature. Treatment 
Emergent Adverse Events (TEAE) are defined as those AEs that occur after 
the initial treatment at Visit 2 (Operative Exchange Day 0).   
AEs that occur on the date of the procedure are classified as either intra-
operative or post-operative. Post-operative AEs are considered to be TEAEs. 
Intra-operative AEs and TEAEs will be summarized separately and presented  
in separate listings.  
A line listing of serious adverse events will be provided. 
 
8.5.2 OTHER SAFETY MEASURES 
Details of analyses for other safety measures (see Section 5.2) will be provided 
in the SAP.  
 
8.6 
Interim Analyses 
No interim analyses are planned. 
 
9 
ADVERSE EVENTS   
An Adverse Event (AE) is defined as any untoward and unintended medical 
occurrence (e.g., sign, symptom, disease, syndrome, intercurrent illness) that 
occurs in a study subject, regardless of the suspected cause during the study. 
Adverse events will be clearly documented on the study source document and 
monitored throughout the course of the study.   
Events occurring after signing the informed consent but prior to the implant o 
procedure should be documented in the medical history.  Events observed 
during or after the initial implant or exchange procedure until the final study 
visit, are to be recorded as AEs if they are in the study eye and deemed related 
to the implant or procedure.  
Any clinically significant change in a subject's condition after receiving the 
study treatments, regardless of causality, is to be considered an adverse event, 
unless the change is determined to be a continuation of a pre-existing 
condition that is documented in the subject's medical history.  If an adverse 
event occurs, an AE form must be completed.   


 
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An AE includes any of the following: 
• An exacerbation or an unexpected increase in frequency or intensity of a 
pre-existing condition, including intermittent or episodic conditions 
• New conditions or illnesses detected or diagnosed after the implant 
procedure 
• A suspected interaction with any of the study treatments 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
any of the study treatments or a concomitant medication 
• Any clinically significant laboratory finding that was not present prior to 
receiving any of the study treatments 
An AE does NOT include any of the following: 
• Anticipated day-to-day fluctuations of any pre-existing conditions, 
including the disease under study (OAG and OHT). 
• Medical or surgical procedure, (e.g., colonoscopy or hernia repair).  The 
condition that led to the procedure may be an AE, if not present in medical 
history. 
• Hospitalizations where an untoward medical occurrence did not occur 
(social or convenience admission to the hospital). 
• Pre-existing conditions or diseases that were present before receiving any 
of the study treatments that do not worsen or that are chronic but stable 
• Changes in a chronic condition or disease that are consistent with natural 
disease progression.  (These medical conditions should be adequately 
documented).   
• Lack of efficacy of the study treatment for the condition being 
investigated.   
 
AEs will be graded on a 3-point scale and reported in detail as indicated on 
the CRF: 
Mild: 
easily tolerated, causing minimal discomfort and not 
interfering with normal everyday activities 
Moderate: 
sufficiently discomforting to interfere with normal 
everyday activities 
Severe:  
incapacitating and/or preventing normal everyday activities 
 


 
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The relationship of each AE to study treatment should be determined by the 
investigator using the following explanations: 
 
Definitely Unrelated: 
the event is clearly related to other factors such as the 
subject’s clinical state, therapeutic interventions, or 
concomitant medications administered to the subject 
 
Unlikely Related: 
the event is most likely produced by other factors such as 
the subject’s clinical state, therapeutic interventions, or 
concomitant medications administered to the subject; and 
does not follow a known response pattern to the study 
medication 
 
Possibly Related: 
the event follows a reasonable temporal sequence from 
the time of drug administration; and/or follows a known 
response pattern to the study medication; but could have 
been produced by other factors such as the subject’s 
clinical state, therapeutic interventions, or concomitant 
medications administered to the subject 
 
Probably Related: 
the event follows a reasonable temporal sequence from 
the time of drug administration; and/or follows a known 
response pattern to the study medication; and is not likely 
to have been produced by other factors such as the 
subject’s clinical state, therapeutic interventions, or 
concomitant medications administered to the subject 
 
Definitely Related: the event follows a reasonable temporal sequence from 
the time of drug administration; and follows a known 
response pattern to the study medication; and cannot be 
reasonably explained by other factors such as the 
subject’s clinical state, therapeutic interventions, or 
concomitant medications administered to the subject 
 
9.1 
Serious Adverse Event 
Serious adverse events are defined as any findings that suggest a significant 
hazard, contraindication, side effect, or precaution.  Any adverse event is 
considered a serious adverse event if it results in any of the following outcomes: 
- 
Death 
- 
Life- or sight-threatening 
- 
Required admission to the hospital or prolongation of an existing 
hospitalization (emergency room visits that do not result in admission 
to the hospital should be evaluated for one of the other serious 
outcomes) 
- 
A persistent or significant disability/incapacity 
- 
A congenital anomaly/birth defect 


 
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The terms “mild,” “moderate,” and “severe” are measures of intensity; thus a 
severe AE is not necessarily serious.  For example, nausea of several hours 
duration may be rated as severe, but may not be clinically serious. 
 
Important medical events that may not result in death, be life-threatening, or 
require admission to the hospital may be considered a serious adverse drug 
experience when, based upon appropriate medical judgment, they may 
jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed above.  A life-threatening event is any 
event that places the subject at substantial risk of death from the event as it 
occurred; it does not refer to an event that hypothetically might have caused 
death if it were more severe.  A sight-threatening event is any event that 
places the subject at risk of permanently losing vision in either eye as a direct 
result of the event. 
 
Serious adverse events must be reported to Glaukos immediately (preferably 
within 24 hours of knowledge of the event). 
Email:  
 
When new significant information (including the outcome of the event) is 
obtained, the investigator should inform Glaukos as soon as possible.  
Depending on the nature of the AE, Glaukos may request copies of the 
ophthalmic and medical records of the subject.  If the subject was hospitalized 
for a study-treatment related serious adverse event, a copy of the discharge 
summary must be forwarded to Glaukos as soon as possible. 
 
9.2 
Unexpected Adverse Event 
An adverse event is considered “unexpected” if it is not listed in the 
investigator brochure or is not listed at the specificity or severity that has been 
observed, or is not consistent with the risk information described in the 
general investigational plan or protocol.   
Unexpected adverse events must be reported to Glaukos immediately 
(preferably within 24 hours of knowledge of the event).   
 
Email:  
 
When new significant information (including the outcome of the event) is 
obtained, the investigator should inform Glaukos as soon as possible.  
Depending on the nature of the AE, Glaukos may request copies of the 
ophthalmic and medical records of the subject.  If the subject was hospitalized 
for a study-treatment related unexpected adverse event, a copy of the 
discharge summary must be forwarded to Glaukos as soon as possible. 
 


 
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9.3 
Suspected, Unexpected, Serious, Adverse Reaction (SUSAR) 
A Suspected, Unexpected, Serious, Adverse Reaction (SUSAR) is any AE for 
which there is evidence to suggest a causal relationship between the 
Travoprost Intraocular Implant and the AE, and which is assessed as both 
unexpected and serious.  An unexpected adverse reaction, i.e. any untoward 
and unintended response to any of the study treatments, is one for which the 
nature and severity is inconsistent with the applicable reference safety 
information (e.g., Investigator’s Brochure).  
 
9.4 
Adverse Events Follow-up 
Adverse events will be followed and documented until the time of complete 
resolution, or resolution with sequelae, or exit from the study with an 
assessment of the outcome.  
 
10 MAINTAINING THE MASK 
Not applicable. 
 
11 INFORMED CONSENT 
The investigator or designee will discuss the purpose and pertinent details of 
the study with each subject.  The Informed Consent Form must be approved 
by the governing Institutional Review Board (IRB) or Independent Ethics 
Committee (IEC).  Prior to undergoing any study related change in their 
treatment or any study related procedures, a subject must understand, sign, 
and date the appropriate IRB-approved Informed Consent Form.  The signed 
and dated Informed Consent Form will be retained with the study records, and 
a copy of the signed Informed Consent will be given to the subject. 
 
12 INSTITUTIONAL REVIEW 
This study must be reviewed and approved by an appropriate Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC).  A copy of the 
letter indicating IRB approval must be provided to Glaukos (or designee) prior 
to study initiation.  Updates must be provided to the IRB by the investigator at 
least annually or as required by the IRB. 
 
13 CONFIDENTIALITY/PUBLICATION OF THE STUDY 
The existence of this clinical study is confidential, and it should not be 
discussed with persons outside of the study.  Additionally, the information in 
this document and regarding this study contains trade secrets and 
commercially sensitive information that is confidential and may not be 
disclosed unless such disclosure is required by federal or state law or 


 
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regulations.  Subject to the foregoing, this information may be disclosed only 
to those persons involved in the study who have a need to know, but all such 
persons must be instructed not to further disseminate this information to 
others.  These restrictions of disclosure will apply equally to all future 
information supplied to you that is indicated as confidential. 
 
The data generated by this clinical study are the property of Glaukos (the 
Sponsor) and should not be disclosed without the prior written permission of 
Glaukos.  These data may be used by Glaukos now and in the future for 
presentation or publication at Glaukos' discretion or for submission to 
governmental regulatory agencies.  Glaukos reserves the right of prior review 
of any publication or presentation of data from this study. 
 
In signing this protocol, the investigator agrees to the release of the data from 
this study, and acknowledges the above publication policy. 
 
14 STATEMENT OF COMPLIANCE 
This study will be conducted in compliance with the protocol, good clinical 
practices (GCP), and all applicable laws and regulations. 
 
The clinical investigator must maintain all information supplied by Glaukos in 
confidence, and when this information is submitted to an institutional review 
board (IRB), independent ethics committee (IEC) or another group, it will be 
submitted with a designation that the material is confidential. 
 
The clinical investigator must ensure that all persons assisting with the trial 
are adequately informed about the protocol, the investigational product(s), and 
their trial-related duties and functions. 
 
15 RECORD KEEPING 
15.1 Source Documents 
The clinical investigator must maintain detailed source documents on all study 
subjects.  Source documents include investigator subject study files, subject 
medical records, hospital charts, clinic charts, as well as the results of 
diagnostic tests (e.g., laboratory tests, visual field test printouts). 
The following minimum information should be entered into the subject's 
medical record: 
- 
The date the subject entered the study and the subject number 
- 
The study protocol number and the name of Glaukos 
- 
The date that informed consent was obtained 
- 
Evidence that the subject meets study eligibility requirements (e.g., 
medical history, study procedures and/or evaluations) 


 
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- 
The dates of all study related subject visits 
- 
Evidence that required procedures and/or evaluations were completed 
- 
Use of any concurrent medications 
- 
Documentation of study medication accountability, including a copy of 
study medication labels 
- 
Occurrence and status of any adverse events 
- 
The date the subject exited the study, and a notation as to whether the 
subject completed the study or was discontinued, including the reason 
for discontinuation 
 
15.2 Data Collection 
The clinical investigator must maintain detailed records on all enrolled 
subjects.  Data for enrolled subjects will be collected with an electronic data 
capture system.  The electronic database, which is Title 21 CFR Part 11 
compliant, will be managed by a data management vendor.  Access to the 
database will be granted to authorize study personnel based on their role after 
training; and the access will be password-protected.  The data clarification 
process will be managed within the electronic data capture system by either 
system-generated or manually generated electronic queries.  Accuracy of data 
will be verified by source data verification at regular intervals, and all 
corrections to data will be made in the database.  CRF forms are completed 
for all enrolled subjects, regardless of their final study status (e.g., subject 
discontinuation, study termination). 
 
15.3 Study Supply Accountability 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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15.4 Record Retention 
All records relating to the conduct of this study are to be retained by the 
investigator until notified by Glaukos that the records may be destroyed. 
The investigator will allow representatives of Glaukos' monitoring team (or 
designee), the governing institutional review board, the Food and Drug 
Administration (FDA), and other applicable regulatory agencies to inspect all 
study records, CRFs, and corresponding portions of the subject's office and/or 
hospital medical records at regular intervals throughout the study.  These 
inspections are for the purpose of verifying adherence to the protocol, 
completeness, and exactness of the data being entered onto the CRF, and 
compliance with FDA or other regulatory agency regulations. 
 




 
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APPENDIX A:  SCHEDULE OF VISITS AND MEASUREMENTS 
 


 
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APPENDIX B:  OBLIGATIONS OF THE INVESTIGATOR 
 
In summary, the clinical investigator has agreed to the following obligations: 
- 
Obtaining informed consent from every subject prior to enrollment in the 
study and maintaining records of consent as part of the study records. 
- 
Obtaining approval from the Institutional Review Board (IRB) before 
enrolling any subject; submitting verification of the approval to the 
Sponsor; submitting periodic progress reports (at least annually) and final 
report to IRB. 
- 
Approving the protocol and conducting the study according to the protocol 
and applicable regulations; informing the Sponsor of all deviations from 
the protocol. 
- 
Informing the IRB of all protocol amendments/modifications; sending the 
Sponsor a copy of the letter from the IRB approving the 
amendment/modification. 
- 
Reporting to the Sponsor and the IRB any adverse experiences that occur 
in the course of the investigation. 
- 
Keeping careful and accurate records of all clinical study data (study 
records must be considerably more exact and complete than those kept in 
ordinary medical practice); maintaining records of all materials submitted 
to the IRB and of all action by the IRB regarding the study. 
- 
Making study records available for inspection by the Sponsor and 
representatives of the Food and Drug Administration and other applicable 
regulatory agencies; keeping records until notified by the Sponsor that 
they may be destroyed. 
- 
Maintaining proper control and documentation of all test and control 
articles. 
- 
Submitting the following records and reporting to the Sponsor (See I, II, 
and III). 
 
I. Prior to Beginning the Study 
- 
A signed Form FDA-1572 or Statement of Investigator. 
- 
A current curriculum vitae (CV) if not submitted to Glaukos 
previously or if updated. 
- 
CVs for all sub-investigators listed on the 1572. 
- 
A letter from the Institutional Review Board (IRB) indicating that the 
protocol was approved, including the name and address of the IRB. 
- 
A copy of the consent form approved by IRB. 
- 
A list of current members of the IRB. 
 


 
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II. While the Study is in Progress 
- 
Acknowledgment of receipt of the test and control articles; 
documentation of disposition of all test and control articles. 
- 
Original Case Report Forms for each subject enrolled in the study. 
- 
Information regarding all deviations from the protocol. 
- 
Information regarding all adverse medical events occurring to a 
subject while enrolled in the study. 
- 
Annual progress report (if study is ongoing for more than one year). 
Letter from the IRB indicating approval of the annual progress report. 
 
III. Once the Study is Completed 
- 
Disposition of all used and/or unused test and control articles, as well 
as documentation of all drug accountability. 
- 
A final study report (if requested). 
 
 
 
 

SAP_001.pdf: 
CONFIDENTIAL 
Statistical Analysis Plan [IDOS-106-EXCH] 
Glaukos Corporation 
1 
Statistical Analysis Plan 
Prospective, Non-Randomized, Open-Label, Multi-Center, Single Arm Study 
of Exchange of Travoprost Intraocular Implant 
Protocol Number: 
IDOS-106-EXCH 
Product Name:   
Travoprost Intraocular Implant, model G2TR-125 
Sponsor Name: 
GLAUKOS CORPORATION 
26600 Aliso Viejo Parkway  
Aliso Viejo, CA  92656 
Version: 
1.0 
Date: 
2MAR2022 
NCT04615403




CONFIDENTIAL 
Statistical Analysis Plan [IDOS-106-EXCH] 
 
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3 
Table of Contents 
Statistical Analysis Plan Approval Signatures ............................................................................2 
Table of Contents ...........................................................................................................................3 
List of Abbreviations .....................................................................................................................5 
Version History ..............................................................................................................................6 
1. 
Introduction .....................................................................................................................7 
2. 
Objectives and Study Design .........................................................................................8 
2.1. 
Objectives .........................................................................................................................8 
2.2. 
Endpoints ..........................................................................................................................8 
2.3. 
Study Design .....................................................................................................................8 
2.4. 
Schedule of Visits and Measurements ..............................................................................9 
2.5. 
Sample Size Determination ............................................................................................10 
3. 
Analysis Sets ..................................................................................................................11 
4. 
General Statistical Considerations ..............................................................................12 
4.1. 
Definition of Variables ...................................................................................................12 
4.1.1. 
Baseline Measure ............................................................................................................12 
4.1.2. 
Change and Percent Change from Baseline ....................................................................12 
4.1.3. 
Study Days ......................................................................................................................12 
5. 
Demographic and Baseline Characteristic Analyses .................................................13 
5.1. 
Subject Disposition .........................................................................................................13 
5.2. 
Protocol Deviations.........................................................................................................13 
5.3. 
Demographic and Baseline Characteristics ....................................................................13 
5.4. 
Medical and Surgical History .........................................................................................14 
5.5. 
Prior and Concomitant Medications ...............................................................................14 
5.6. 
Concurrent Ocular Procedures ........................................................................................14 
6. 
Efficacy Analyses ..........................................................................................................15 
6.1. 
Primary Endpoint Efficacy Analysis ..............................................................................15 
6.2. 
Secondary Endpoint Efficacy Analysis ..........................................................................15 
6.3. 
Exploratory Endpoint Efficacy Analysis ........................................................................15 
7. 
Safety Analyses ..............................................................................................................16 
7.1.1. 
Extent of Exposure ..........................................................................................................16 
7.1.2. 
Adverse Events ...............................................................................................................16 
7.1.3. 
Additional Safety Assessments .......................................................................................17 
8. 
Other Analyses ..............................................................................................................22 
8.1.1. 
Other Variables and/or Parameters .................................................................................22 
8.1.2. 
Operative and Surgical Analyses ....................................................................................22 
8.1.3. 
Subgroup Analyses .........................................................................................................22 
9. 
Interim Analysis ............................................................................................................23 
10. 
Changes to Protocol-planned Analyses .......................................................................24 
11. 
Supporting Documentation ..........................................................................................25 


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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4 
11.1. 
Appendix: Data Derivation Rules ...................................................................................25 
11.1.1. Corrected Visual Acuity Derivation ...............................................................................25 
11.1.2. IOP Derivation ................................................................................................................25 
12. 
References ......................................................................................................................26 
 


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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List of Abbreviations 
Abbreviation 
Definition 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
BSCVA 
Best Spectacle Corrected Visual Acuity 
CRF 
Case Report Form 
ECD 
Endothelial Cell Density 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
IOP 
Intraocular Pressure 
LogMAR 
Logarithm of the Minimum Angle of Resolution 
MedDRA 
Medical Dictionary for Regulatory Activities 
MD 
Mean Deviation 
mmHg 
Millimeters of Mercury 
OAG 
Open-Angle Glaucoma 
OHT 
Ocular Hypertension 
PE 
Post-Exchange 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
VA 
Visual Acuity 
VF 
Visual Field 
WHO 
World Health Organization 


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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Version History 
This Statistical Analysis Plan (SAP) for IDOS-106-EXCH is based on the protocol dated 
24AUG2020. 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-106-EXCH] 
 
Glaukos Corporation 
7 
1. 
Introduction 
This statistical analysis plan (SAP) describes the statistical methods to analyze all safety data 
from protocol IDOS-106-EXCH.  Any changes to this plan will be reflected as amendments 
before the database lock and/or documented in the clinical study report.  One database lock will 
occur after all subjects have completed the Month 12 Post-Exchange (PE) visit or have exited the 
study prior to that time. 
Specifications of tables, figures, and data listings are provided in another document. 
 


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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8 
2. 
Objectives and Study Design 
2.1. 
Objectives 
The study objective is to evaluate the safety of the surgical exchange procedure of the Travoprost 
Intraocular Implant in subjects with a previously implanted Travoprost Intraocular Implant. 
2.2. 
Endpoints 
Safety Endpoints: 
• Intraoperative adverse events 
• Postoperative adverse events 
• Corrected visual acuity (logMAR score using ETDRS chart) 
• Slit-lamp biomicroscopy findings 
• Gonioscopy findings 
• Specular microscopy findings 
• Intraocular Pressure 
• Ophthalmoscopy findings 
• Visual field evaluation 
2.3. 
Study Design 
This is a prospective, non-randomized, open-label, multi-center, single arm clinical trial of the 
safety of the exchange of the Travoprost Intraocular Implant.  Approximately 45 male and 
female subjects who were previously implanted with the Travoprost Intraocular Implant in the 
GC-009 study (1st Cycle) were to be enrolled into the study.  Subjects will be screened for 
qualification as per the inclusion/exclusion criteria (refer to Sections 6.2.1 and 6.2.2 of study 
protocol).  Qualified subjects will have the first implant (
 Implant), 
which was inserted in Study GC-009, exchanged with a second implant (G2TR-125 Implant).  
Subjects using ocular hypotensive medications at Screening are not required to undergo a 
medication washout period.  Post-treatment management of ocular hypotensive medications is up 
to the investigator’s discretion.  Study follow-up will continue until the Month 12 Post-Exchange 
visit.   
The study consists of eight visits: Visit 1 (Screening), Visit 2 (Operative Exchange Day 0), Visit 
3 (Day 1 Post-Exchange), Visit 4 (Day 10 Post-Exchange), Visit 5 (Week 4 Post-Exchange), 
Visit 6 (Month 3 Post-Exchange), Visit 7 (Month 6 Post-Exchange), and Visit 8 (Month 12 Post-
Exchange).  Subjects will exit the study at the conclusion of the Month 12 Post-Exchange visit. 


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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2.4. 
Schedule of Visits and Measurements1 




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3. 
Analysis Sets 
For the purposes of analysis, the following analysis set is defined: 
The safety analysis set will be used for all data tabulations and listings. 
Analysis Set 
Description 
Safety 
All subjects who undergo the exchange procedure. 


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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4. 
General Statistical Considerations 
Demographic and safety data collected on the case report forms (CRFs) will be displayed in 
tabulations and data listings.  Only data from scheduled visits will be used in tabulations unless 
otherwise specified.  No formal statistical testing will be performed.  All data summaries and 
statistical analyses will be performed using SAS software, Version 9.4 or higher.   
Continuous data will be summarized using the number of observations, mean, standard 
deviation, median, minimum, and maximum.  Continuous data may also be dichotomized, or 
otherwise split, into clinically meaningful categories and may be further analyzed as categorical 
data as specified in the individual endpoints.  
Categorical data will be summarized using frequency counts and percentages.  Unless otherwise 
stated, subjects with missing visit data will be omitted from both the numerator and denominator 
of such calculations. 
4.1. 
Definition of Variables 
4.1.1. 
Baseline Measure 
The baseline measure is defined as the last non-missing measure prior to the initiation of the 
investigational product within this study (i.e., second implant at the operative exchange visit).   
4.1.2. 
Change and Percent Change from Baseline 
The change from baseline and the percent change from baseline values are calculated as 
• Change from baseline value = follow-up visit value – baseline value. 
• Percent Change from baseline value = (change from baseline value / baseline value) * 
100. 
4.1.3. 
Study Days 
The number of study days is defined relative to the Operative Exchange visit, starting with the 
Operative visit as study day 1.  For each date following the Operative visit, the study day value 
increases by 1.  For each date prior to the Operative visit, the study day value decreases by 1, 
with the date preceding the Operative visit as study day -1.  Note that the operative visit is 
sometimes referred to as the Operative Exchange Day 0 visit in the protocol.  In the statistical 
analysis plan and summaries, this visit will be considered day 1. 




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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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Demographic and baseline characteristic data will be listed. 
5.4. 
Medical and Surgical History 
All medical and surgical history will be coded to the Medical Dictionary for Regulatory 
Activities (MedDRA) nomenclature, 
.  Ocular and non-ocular medical and surgical 
history will be tabulated by System Organ Class (SOC) and preferred term (PT).  The ocular 
history tabulation will present summaries for the study eye, non-study eye, and overall groups.  
Subjects with more than one medical history within a given SOC or PT will only be counted 
once within that SOC or PT.  Ocular and non-ocular medical and surgical history will be listed 
by subject.  
5.5. 
Prior and Concomitant Medications 
Prior medications are defined as those medications taken within 30 days prior to the start of 
Screening with a stop date prior to study drug administration.  Concomitant medications are 
defined as those medications taken (1) prior to study drug administration and continuing for any 
period of time following the first administration of study drug or (2) at any time following the 
first administration of study drug.   
Medications will be coded using the World Health Organization (WHO) Drug Dictionary 
 and will be summarized to the anatomical therapeutic chemical (ATC) class 
and preferred name.  Prior and concomitant ocular medications will be tabulated separately. The 
tabulations will present summaries for the study eye, non-study eye, and overall groups.  
Subjects will be counted only once under each ATC class or preferred name for which they have 
at least one medication.  All prior and concomitant medications will be listed. 
5.6. 
Concurrent Ocular Procedures 
Concurrent ocular procedures are defined as any ocular procedures that occurred in the study eye 
on or after the date of the exchange surgery.  Ocular procedures will be coded using the 
MedDRA nomenclature, 
.  Ocular procedures will be tabulated by SOC and PT.  
Subjects with more than one ocular procedure within a given SOC or PT will only be counted 
once within that SOC or PT.  All concurrent ocular procedures will be listed.  
  


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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6. 
Efficacy Analyses 
6.1. 
Primary Endpoint Efficacy Analysis 
There are no primary efficacy endpoints in this study. 
6.2. 
Secondary Endpoint Efficacy Analysis 
There are no secondary efficacy endpoints in this study. 
6.3. 
Exploratory Endpoint Efficacy Analysis 
There are no exploratory efficacy endpoints in this study. 


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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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7. 
Safety Analyses 
All safety analyses will be based on the safety analysis set and will be described in more detail in 
the following sections. 
7.1.1. 
Extent of Exposure 
Summaries of the extent of exposure to study treatment, which include the number of 
participants exposed and descriptive statistics of the duration of exposure in study days, will be 
provided for the study.  Extent of exposure to study treatment in days will be calculated as date 
of study exit – date of exchange surgery + 1.  If the date of study exit is missing for a subject 
with early study exit, the date of the last recorded visit will be used for calculations.  A listing of 
extent of exposure will be provided. 
7.1.2. 
Adverse Events 
Adverse events (AEs) will be coded to the MedDRA nomenclature, 
. Treatment 
Emergent Adverse Events (TEAEs) are defined as AEs that occur after the initiation of the 
exchange surgery at Visit 2 (Operative Exchange Day 0). 
A summary of the number and percentage of subjects with TEAEs will be provided for the safety 
analysis set.  The summary will include study eye TEAEs, non-ocular or non-study eye TEAEs, 
treatment-related TEAEs, TEAEs by maximum severity, TEAEs resulting in study 
discontinuation, serious TEAEs, and deaths. 
The number and percentage of subjects with TEAEs will be tabulated by SOC and PT for: 
• Ocular TEAEs 
• Non-ocular TEAEs 
• Ocular TEAEs related to study treatment 
• Non-ocular TEAEs related to study treatment  
• Ocular TEAEs by maximum severity 
• Non-ocular TEAEs by maximum severity   
• Ocular serious TEAEs 
• Non-ocular serious TEAEs 
All tabulations of ocular TEAEs will contain summaries for the study eye, non-study eye, and 
overall groups.   
All AEs will be presented in a listing by subject.  Separate listings for intraoperative AEs, serious 
adverse events (SAEs) including deaths, AEs leading to early study exit, and AEs leading to 
removal of implant will also be presented.   
Relationship to study treatment is defined as the possibility that the study treatment caused the 
event and is described in the study protocol.  The relationship to study treatment categories 
utilized on the CRF are definitely unrelated, unlikely related, possibly related, probably related, 
and definitely related.  For all tabulations, the categories of possibly related, probably related, 
and definitely related will be classified as related and only related AEs will be presented.  AEs 














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9. 
Interim Analysis  
No interim analyses will be performed. 
 


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10. 
Changes to Protocol-planned Analyses 
No changes to the protocol-planned analyses have occurred. 
 




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Statistical Analysis Plan [IDOS-106-EXCH] 
 
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12. 
References