Conditions: Glaucoma, Open-Angle Ocular Hypertension
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 210
Healthy volunteers: no

Brief summary:
To evaluate the performance of the Travoprost Intracameral Implant by determining residual drug in explanted implants of the Travoprost Intracameral Implant and by determining aqueous humor concentrations of travoprost free acid at specified timepoints post administration through 24 months

Detailed description:

Arms:
arm 1: Travoprost Intracameral Implant Exchanged at Month 12 arm 2: Travoprost Intracameral Implant Exchanged at Month 3 arm 3: Travoprost Intracameral Implant Exchanged at Month 6 arm 4: Travoprost Intracameral Implant Exchanged at Month 24 arm 5: Travoprost Intracameral Implant Exchanged at Month 21 arm 6: Travoprost Intracameral Implant Exchanged at Month 18 arm 7: Travoprost Intracameral Implant Exchanged at Month 15

Interventions: intervention 1: Travoprost Intracameral Implant exchanged at Month 12 intervention 2: Travoprost Intracameral Implant exchanged at Month 3 intervention 3: Travoprost Intracameral Implant exchanged at Month 6 intervention 4: Travoprost Intracameral Implant exchanged at Month 24 intervention 5: Travoprost intracameral implant exchanged at Month 21 intervention 6: Travoprost intracameral implant exchanged at Month 18 intervention 7: Travoprost intracameral implant exchanged at Month 15
Intervention descriptions: intervention 1: intracameral implant containing travoprost 75 mcg implanted on Day 1 and exchanged at Month 12 intervention 2: intracameral implant containing travoprost 75 mcg implanted on Day 1 and exchanged at Month 3 intervention 3: intracameral implant containing travoprost 75 mcg implanted on Day 1 and exchanged at Month 6 intervention 4: intracameral implant containing travoprost 75 mcg implanted on Day 1 and exchanged at Month 24 intervention 5: intracameral implant containing travoprost 75 mcg implanted on Day 1 and exchanged at Month 21 intervention 6: intracameral implant containing travoprost 75 mcg implanted on Day 1 and exchanged at Month 18 intervention 7: intracameral implant containing travoprost 75 mcg implanted on Day 1 and exchanged at Month 15

Protocol document:
Prot_000.pdf: 
CLINICAL PROTOCOL 
Date: 
Protocol No.: 
September 18, 2019 
IDOS-402-IVIV 
CONFIDENTIAL 
 page 1 of 53 
PROSPECTIVE, NON-RANDOMIZED, OPEN-
LABEL, SINGLE CENTER STUDY TO EVALUATE
THE
PERFORMANCE OF THE TRAVOPROST
INTRAOCULAR IMPLANT 
PROTOCOL # IDOS-402-IVIV 
DATE:  SEPTEMBER 18, 2019 
Sponsor: 
GLAUKOS CORPORATION 
229 Avenida Fabricante │ San Clemente, CA 92672 │ 001-949- 367-9600 
Clinical Trials.gov Identifier: NCT06582732






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Table of Contents 
SYNOPSIS ...............................................................................................................6 
1 
INTRODUCTION ..........................................................................................10 
2 
OBJECTIVE ...................................................................................................11 
3 
STUDY DESIGN ...........................................................................................11 
4 
STUDY MEASURES.....................................................................................13 
4.1 
Efficacy ...................................................................................................13 
4.2 
Safety .......................................................................................................13 
4.3 
Other ........................................................................................................14 
5 
MATERIALS .................................................................................................14 
5.1 
Study Medications ...................................................................................14 
6 
METHODS .....................................................................................................15 
6.1 
Subjects ...................................................................................................15 
6.2 
Eligibility Requirements .........................................................................16 
6.3 
Procedures ............................................... Error! Bookmark not defined. 
6.4 
Concomitant Therapies ...........................................................................26 
7 
EXTENT OF EXPOSURE AND TREATMENT COMPLIANCE ...............27 
8 
STATISTICAL ANALYSES .........................................................................27 
8.1 
Sample Size .............................................................................................27 
8.2 
Analysis Populations ...............................................................................27 
8.3 
General Statistical Methods ....................................................................27 
8.4 
Efficacy Analyses ....................................................................................27 
8.5 
Safety Analyses .......................................................................................28 
8.6 
Other ........................................................................................................28 
8.7 
Interim Analyses .....................................................................................28 
9 
ADVERSE EVENTS .....................................................................................28 
9.1 
Serious Adverse Event ............................................................................30 
9.2 
Unexpected Adverse Event .....................................................................31 
9.3 
Suspected, Unexpected, Serious, Adverse Reaction (SUSAR) ..............32 
9.4 
Adverse Events Follow-up ......................................................................32 
10 MAINTAINING THE MASK........................................................................32 


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11 INFORMED CONSENT ................................................................................32 
12 INSTITUTIONAL REVIEW .........................................................................32 
13 CONFIDENTIALITY/PUBLICATION OF THE STUDY ...........................33 
14 STATEMENT OF COMPLIANCE ...............................................................33 
15 RECORD KEEPING ......................................................................................33 
15.1 Source Documents...................................................................................33 
15.2 Data Collection ........................................................................................34 
15.3 Study Supply Accountability ..................................................................34 
15.4 Record Retention .....................................................................................35 
16 REFERENCES ...............................................................................................36 
 
List of Tables 
Table 1.  Cohorts in the Study .............................................................................. 12 
 
List of Figures 
Figure 1.  Glaukos Travoprost Intraocular Implant .............................................. 14 
Figure 2.  Glaukos Travoprost Intraocular Implant and Inserter .......................... 15 
 
List of Appendices 
APPENDIX A:  SCHEDULE OF VISITS & MEASUREMENTS: Group 12 .... 37 
APPENDIX B:  SCHEDULE OF VISITS & MEASUREMENTS: Group 3 ...... 38 
APPENDIX C:  SCHEDULE OF VISITS & MEASUREMENTS: Group 6 ...... 39 
APPENDIX D:  SCHEDULE OF VISITS & MEASUREMENTS: Group 24 .... 40 
APPENDIX E:  SCHEDULE OF VISITS & MEASUREMENTS: Group 21 ..... 41 
APPENDIX F:  SCHEDULE OF VISITS & MEASUREMENTS: Group 18 ..... 42 
APPENDIX G:  SCHEDULE OF VISITS & MEASUREMENTS: Group 15 .... 43 
APPENDIX H:  OBLIGATIONS OF THE INVESTIGATOR ............................ 44 
APPENDIX I:  DECLARATION OF HELSINKI ............................................... 46 
 
 
 
 






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STUDY VARIABLES AND STATISTICAL ANALYSIS 
Efficacy Variable 
There is no efficacy variable in this study.  IOP is assessed for safety. 
 
Safety Variables 
Adverse events (intra-operative and post-operative adverse events [TEAEs]) in 
the study eye will be monitored. 
  
IOP, best spectacle corrected visual acuity, slit lamp biomicroscopy findings, 
gonioscopy findings, and ophthalmoscopy findings (including cup-to-disc ratio) 
will be assessed. 
Operative and Surgical Assessments will be collected. 
 
Analysis Populations 
All subjects contributing aqueous humor samples and/or exchanged implants will 
be included in the correlation model development and analysis population. All 
subjects who receive an implant will be included in the safety population. The 
safety population will be used for all safety 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 
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 
IRB 
Institutional Review Board 
IEC 
Independent Ethics Committee 
LogMAR 
Logarithm of the Minimum Angle of Resolution 
MedDRA 
Medical Dictionary for Regulatory Activities 
mmHg 
Millimeters of Mercury 
OAG 
Open-angle Glaucoma 
OHT 
Ocular Hypertension 
PE 
Post Exchange 
PG 
Prostaglandin 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
 
 
TEAE 
Treatment Emergent Adverse Event 
VA 
Visual Acuity 
VF 
Visual Field 


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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 (PGs).  The PGs 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 PGs.  Furthermore, the ocular side effects typically associated 
with α-agonists (e.g., allergic reactions), and cholinergic agents 
(e.g., reduced vision), do not seem to manifest with the use of PGs. 
However, PGs 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
  
 
 








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4.3 
Other 
Aqueous humor samples and exchanged implants will be collected for 
analysis of travoprost free acid concentration and residual travoprost, 
respectively, using validated analytical methods. 
 
5 
MATERIALS 
5.1 
Study Medications 
Subjects will undergo surgery to receive the implants using the test articles 
described below in Section 5.1.1. 
 
5.1.1 TEST ARTICLE:  TRAVOPROST INTRAOCULAR 
IMPLANT MODEL G2TR-125 
The Travoprost Intraocular Implant is a microscopic titanium container, 1.84 
mm in length and 0.494 mm in outer diameter (see Figure 1).  The implant is 
filled with Travoprost formulation, then 
 
  The 
 
  Each implant is designed 
to be surgically anchored into the anterior chamber angle and elute the drug 
component slowly.   
 
Figure 1.  Glaukos Travoprost Intraocular Implant 
 
 
The Travoprost Intraocular Implant is provided sterile and pre-loaded 
onto an inserter in a blister tray, pouch and unit carton.  Each tray lid is 




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6.2 
Eligibility Requirements 
6.2.1 INCLUSION CRITERIA  
6.2.1.1 
Visit 1 (Screening) Inclusion Criteria 
At Visit 1 (Screening), all subjects must meet the following criteria: 
1) Subject status as follows: 
a. male or female, 18 years of age or older 
b. able and willing to attend scheduled follow-up exams for the 
duration of the study 
c. able and willing to provide written informed consent on the 
IRB/IEC-approved Informed Consent Form 
 
Both eyes may be assessed at Visit 1 (Screening). 
 
2) Diagnosis of either OAG (i.e. primary, pseudoexfoliation, or 
pigmentary glaucoma) or OHT.  
 
All subjects must meet the rest of the following criteria: 
3) Zero to three topical IOP lowering medications at the time of Visit 
1 (Screening) exam. Combination medications (e.g., Cosopt®, 
Combigan®) are to be counted as two medications. 
 
4) Best spectacle corrected visual acuity of 16 letters or more correctly 
read at 4 meters or better in each eye. 
 
5) Angle anatomy defined as follows:  
a. open angle as defined by Shaffer grade ≥ 3 at slit-lamp at the 
planned implantation site 
b. normal anatomy as determined by gonioscopy 
c. absence of peripheral anterior synechia (PAS), rubeosis or 
other angle abnormalities that could impair proper placement 
of the product at the planned implantation site. 
 
6) Lens status as follows: 
a. Phakic, with crystalline lens that does not have visually 
significant cataract expected to require cataract surgery for the 
duration of the study, OR 
b. Pseudophakic, with uncomplicated cataract surgery performed 
> 90 days prior and with implanted posterior chamber IOL 
fixated in the capsular bag 
 
7) Central corneal thickness ≥ 440 microns and ≤ 620 microns. 


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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. Functionally significant visual field loss, including severe 
nerve fiber bundle defects 
c. Prior incisional glaucoma surgery  
 
2) Corneal status as follows: 
a. any active inflammation or edema (e.g., keratitis, 
keratoconjunctivitis, kerato-uveitis) 
b. clinically significant dystrophy (e.g., bullous keratopathy, 
Fuch’s dystrophy) 
c. clinically significant guttata 
d. significant scarring or irregularities (including scars from prior 
corneal surgery such as PKP, RK, etc.), during the course of 
the study, that may interfere with IOP measurement reliability  
e. anticipated surgery of any type (including LASIK, LASEK, 
PRK, etc.), 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 (except Mittendorf dots). 
 
4) Choroidal detachment, effusion, choroiditis, neovascularization, or 
any active choroidopathy. 
 
5) Retinal or optic nerve disorders, either degenerative or evolutive, 
that are not associated with the existing glaucoma condition, 
including proliferative diabetic retinopathy, central retinal artery 
occlusion, central retinal vein occlusion, wet age-related macular 
degeneration, advanced dry age-related macular degeneration, 
(e.g., presence of numerous large drusen associated with 
disturbance to or elevation of the retinal pigment epithelium), 
significant retinal pigment epithelial changes or optic atrophy. 


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6) Other ocular status as follows: 
a. clinically significant sequelae from trauma (e.g., chemical 
burns, blunt trauma, etc.) 
b. history or chronic ocular inflammatory disease or presence of 
active ocular inflammation (e.g., uveitis, iritis, iridocyclitis, 
retinitis, ocular herpes) 
c. any pathology for which, in the investigator’s judgment, the 
following would be either at risk or contraindicated: 
i. 
implantation of Travoprost Intraocular Implant  
ii. 
compliance to elements of the study protocol (e.g., 
ophthalmic examinations, follow-up visits). 
 
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 participation in the study 
c. current participation in any study, or participation within 30 
calendar days of Visit 1 (Screening) 
d. immunodeficiency conditions 
e. change in an existing chronic systemic therapy that could 
substantially affect IOP or the study outcomes within 30 days 
prior to Visit 1 (Screening), or anticipated change in such 
therapy during the study duration 
f. anticipated to need a topical prostaglandin analogue medication 
for the duration of the study  
g. known allergy, hypersensitivity or contraindication to the study 
medications or their components, namely prostaglandin 
analogues 
h. any ocular disease or condition that in the opinion of the 
investigator or Medical Monitor may put the subject at 
significant risk, may confound the study results, or may 
interfere significantly with the subject's participation in the 
study.  In addition, the investigator or the Medical Monitor 
may declare any subject ineligible for any sound medical 
reason. 
 


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9) The inability to visualize the implantation site via surgical 
gonioscopy. 
 
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 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 time frame 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 should 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. 
 


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6.2.4 STUDY TERMINATION 
The study may be terminated by Glaukos at any time following 
appropriate notification to the study site and subjects. 
 
6.3 
Procedures 
Study visits and assessments are listed below; a table overview of study 
procedures by visit is provided for each cohort in APPENDICES A-G:  
SCHEDULE OF VISITS & MEASUREMENTS 
 
6.3.1 DURATION OF STUDY 
Following the initial implantation, the treatment period will be 4 to 25 
months in duration depending on their cohort assignment. 
 
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. A 
subject is considered enrolled at the time the subject undergoes surgery at 
the First Operative visit (Visit 2). At this visit the subject will be assigned 
to a cohort in sequential order of study entry. Each individual cohort must 
have the complete number of subjects (Table 1) enrolled before a subject 
can be assigned to the next cohort. 
 
Each subject will be assigned a unique subject numbe
 
If a 
subject is discontinued from the study for any reason, the subject number 
will not be reused.   
 
6.3.3 PREOPERATIVE PROCEDURES 
6.3.3.1 
Visit 1 (Screening) 
1) 
Written informed consent. 
2) 
Assign subject number.  
3) 
Demographics, medical and surgical history, current ocular and 
systemic conditions, prescription medications, and medications 
known or suspected to lower IOP. 
4) 
A pregnancy test (if applicable) may be administered at any time 
during this visit. 


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5) 
Measure best spectacle corrected visual acuity through manifest 
refraction (ETDRS) in each eye. 
6) 
Perform slit-lamp biomicroscopy (including crystalline lens). 
7) 
Measure IOP (can be measured at any time) and record the time.  
8) 
Pachymetry. 
9) 
Perform a gonioscopic examination. 
10) Perform a dilated ophthalmoscopy/fundus examination. 
11) Assess optic nerve abnormality (ophthalmoscopy). 
12) Assess vertical C/D ratio.  
13) Review screening inclusion and exclusion criteria.  Do not 
continue screening any subject who does not meet the screening 
eligibility requirements.  
 
If the subject is qualified: 
1) 
Schedule the subject for Visit 2 (First Operative Day 0). 
2) 
 
 
 
 
3) 
Advise the subject to discontinue taking their topical hypotensive 
medication beginning the morning of visit 2 (First Operative 
Day) 
 
 
 
 
If the subject is ineligible for the study, complete the appropriate CRF. 
 
6.3.4 TREATMENT PROCEDURES 
6.3.4.1 
Visit 2 (First Operative Day 0) 
1) Assess demographics, medical and surgical history, current ocular 
and systemic conditions, prescription medications, and 
medications known or suspected to lower IOP.  
2) Assess any adverse events. 
3) Prepare subject for surgery. 


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4) Administer an additional drop of antibiotic 30 minutes 
preoperatively. 
5) Visually confirm Shaffer grade angle and target implant location.  
6) Obtain a treatment kit.     
7) Administer anesthetic (topical, general, retrobulbar, peribulbar). 
8) Perform surgery.  
9) Record clinical data from the surgical procedure on the First 
Operative Day 0 CRF, noting study eye intra-operative AEs and 
post-operative AEs. 
 
Postoperatively: 
10) Schedule the subject to return for Visit 3 (Day 1).  
11) Dispense other postoperative medications and instruct the subject 
as follows: 
 
 
 
 
 
 
 
 
 
 
 
6.3.4.2 
Visit 3 (Day 1 Exam, 1 days postoperative) 
1) Update subject’s medical status and concomitant medications. 
2) Assess study eye adverse events. 
3) Measure pinhole visual acuity (Snellen). 
4) Perform slit-lamp biomicroscopy.  
5) Measure IOP (can be measured at any time) and record the time 
(observer). 
6) Schedule the subject to return for Visit 4 (Day 10).   
 
6.3.4.3 
Visit 4 (Day 10 Exam, 10 ± 3 days postoperative) 
1) Update subject’s medical status and concomitant medications. 
2) Assess study eye adverse events. 
3) Measure pinhole visual acuity (Snellen). 
4) Perform slit-lamp biomicroscopy.  
5) Measure IOP (can be measured at any time) and record the time 
(observer).  


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6) Schedule the subject to return for Visit 5 (Week 4).   
 
6.3.4.4 
Visit 5 (Week 4 Exam, 28 days ± 3 postoperative) 
1) Update subject’s medical status and concomitant medications. 
2) Assess study eye adverse events. 
3) Measure corrected visual acuity (ETDRS).  A manifest refraction 
and best spectacle corrected visual acuity (ETDRS) should be 
performed if corrected VA (ETDRS) has decreased by 2 or more 
lines (≥10 letters) from Visit 1 (Screening). 
4) Perform slit-lamp biomicroscopy.  
5) Measure IOP (can be measured at any time) and record the time 
(observer). 
6) Perform a gonioscopic examination. 
7) Schedule the subject to return for the next visit(s) if applicable 
(see next section) 
 
6.3.4.5 
Depending on the cohort, the subject may have one or 
more of the following visits (please see APPENDIX A-G:  
SCHEDULE OF VISITS & MEASUREMENTS): 
Visit 5.1, (Month 6, 182 days ± 14) 
Visit 5.2, (Month 12, 365 days ± 14) 
Visit 5.3, (Month 18, 547 days ± 14) 
1) Update subject’s medical status and concomitant medications. 
2) Assess study eye adverse events. 
3) Measure corrected visual acuity (ETDRS).  A manifest refraction 
and best spectacle corrected visual acuity (ETDRS) should be 
performed if corrected VA (ETDRS) has decreased by 2 or more 
lines (≥10 letters) from Visit 1 (Screening). 
4) Perform slit-lamp biomicroscopy.  
5) Measure IOP (can be measured at any time) and record the time 
(observer). 
6) Perform a gonioscopic examination. 
7) Schedule the subject to return for Visit 6 (Pre-Exchange Exam).  
Remind the subject of the following: 
i. Visit 6 (Pre-Exchange Exam) is the visit prior to the Second 
Operative Visit  
ii. 
 
 
 


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6.3.4.6 
Visit 6 (Pre-exchange Exam), to occur within 10 days 
prior to Visit 7 (Second Operative / Exchange Exam) 
1) Update subject’s medical status and concomitant medications. 
2) Assess study eye adverse events. 
3) Measure corrected visual acuity (ETDRS).  A manifest refraction 
and best spectacle corrected visual acuity (ETDRS) should be 
performed if corrected VA (ETDRS) has decreased by 2 or more 
lines (≥10 letters) from Visit 1 (Screening). 
4) Perform slit-lamp biomicroscopy.  
5) Measure IOP (can be measured at any time) and record the time 
(observer). 
6) Perform a gonioscopic examination. 
7) Schedule the subject to return for Visit 7.  Remind the subject of 
the following: 
i. Visit 7 is the Second Operative / Exchange Visit  
ii. 
 
 
 
 
 
 
 
 
 
 
 
6.3.4.7 
Visit 7 (Second Operative / Exchange Exam)   
Depending on the cohort, the subject may have their 
Visit 7 (Second Operative / Exchange Exam) occur on 
one of the following visits (please see APPENDIX A-G:  
SCHEDULE OF VISITS & MEASUREMENTS): 


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(Month 12, 365 days ± 14) 
(Month 3, 91 days ± 14) 
(Month 6, 182 days ± 14) 
(Month 24, 730 days ± 14) 
(Month 21, 637 days ± 14) 
(Month 18, 547 days ± 14) 
(Month 15, 456 days ± 14) 
1) Update subject’s medical status and concomitant medications. 
2) Assess study eye adverse events. 
3) Prepare subject for surgery. 
4) 
 
 
 
The following steps will be performed in the Operating Room: 
5) Visually confirm Shaffer grade angle and target implant location. 
6) Collect an anterior chamber aqueous humor sample (AC tap).  
Please follow instructions in the procedure manual.  
 
After collecting the AC Tap and performing all assessments: 
7) Obtain a treatment kit.     
8) Administer anesthetic 
 
9) Perform second surgery (Exchange). 
10) Collect the first implant for shipment back to sponsor.  
11) Record clinical data from the surgical procedure on the Second 
Operative CRF, noting study eye intra-operative AEs and post-
operative AEs. 
12) Schedule the subject to return for Visit 8 (Day 1 Post Exchange). 
 
6.3.4.8 
Visit 8 (Day 1 Post-Exchange Exam) 
1) Update subject’s medical status and concomitant medications. 
2) Assess study eye adverse events. 
3) Measure pinhole visual acuity (Snellen). 
4) Perform slit-lamp biomicroscopy  
5) Measure IOP (can be measured at any time) and record the time 
(observer).  
6) Schedule the subject to return for Visit 9 (Day 10 Post -
Exchange).   
 








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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.   
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 
 


CLINICAL PROTOCOL 
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Protocol No.: 
September 18, 2019 
 
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CONFIDENTIAL 
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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 
- 
Overnight hospitalization or prolongation of an existing hospitalization 
- 
A persistent or significant disability/incapacity 
- 
A congenital anomaly/birth defect 


CLINICAL PROTOCOL 
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September 18, 2019 
 
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CONFIDENTIAL 
 page 31 of 53 
 
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 overnight hospitalization 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). 
 
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).   
 
 
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. 
 


CLINICAL PROTOCOL 
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September 18, 2019 
 
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CONFIDENTIAL 
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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 subject's 
signature will be witnessed by the individual administering informed consent 
if other than the investigator.  If the investigator administers informed 
consent, then the subject's signature should be witnessed by another individual 
(e.g., member of the site staff).  The investigator will sign and date the 
Informed Consent Form where designated.  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/IEC approval must be provided to Glaukos (or designee) 
prior to study initiation.  Updates must be provided to the IRB/IEC by the 
investigator at least annually or as required by the IRB/IEC. 
 


CLINICAL PROTOCOL 
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September 18, 2019 
 
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CONFIDENTIAL 
 page 33 of 53 
 
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 
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). 


CLINICAL PROTOCOL 
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Protocol No.: 
September 18, 2019 
 
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CONFIDENTIAL 
 page 34 of 53 
 
The following minimum information should be entered into the subject's 
medical record: 
- 
The date the subject completed the screening visit and the subject 
number assigned 
- 
The study protocol number and the name of Glaukos 
- 
The date that informed consent was obtained including the version 
number and date of the consent form used 
- 
Evidence that the subject meets study eligibility requirements (e.g., 
medical history, study procedures and/or evaluations) 
- 
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 
The principal investigator is responsible for ensuring that study material, 
including investigational product, is logged and placed in inventory upon 
receipt of the clinical supplies and that the clinical study supplies are stored as 
instructed.  The receipt of clinical supplies should be completed, signed, and 
returned as directed by Glaukos (or designee).  A copy must be maintained at 
the site for the investigator's records.  The principal investigator will keep a 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
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CONFIDENTIAL 
 page 35 of 53 
 
current record of the inventory and dispensing of all study medications.  This 
record will be made available to the Glaukos monitor (or designee) for the 
purpose of accounting for all clinical supplies.  Any significant discrepancy 
and/or deficiency must be recorded with an explanation.  All supplies sent to 
the investigator must be accounted for and in no case will study medications 
be used in any unauthorized situation.  It is the responsibility of the principal 
investigator to return or destroy any used and unused supplies to the Glaukos 
monitor (or designee) at the conclusion of the study. 
 
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. 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
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16 REFERENCES 
 
1. Camras C, Siebold E, Lustgarten J, Serle J, Frisch S, Podos S, Bito L. 
Maintained reduction of intraocular pressure by prostaglandin F2alpha-1-
Isopropyl ester applied in multiple doses in ocular hypertensive and 
glaucoma patients.  Ophthalmology. 1989; 96: 1329-1337. 
2. Ziai N, Dolan J, Kacere R, Brubaker R.  The effects on aqueous dynamics 
of phXA41, a new prostaglandin f2 alpha Analogue, after topical 
application in normal and ocular hypertensive human eyes. Arch 
Ophthalmol. 1993; 111: 1351-1358. 
3. Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 
0.005% latanoprost applied once daily, evening or morning. 
Ophthalmology. 1995; 102: 1743-1752. 
4. Mishima H, Masuda K, Kitazawa Y, Azuma I, Araie M. A comparison of 
latanoprost and timolol in primary open-angle glaucoma and ocular 
hypertension. Arch Ophthalmol. 1996; 114: 929-932. 
5. Eisenberg D, Camras C.  A preliminary risk-benefit assessment of 
latanoprost and unoprostone in open-angle glaucoma and ocular 
hypertension. Drug Safety. 1999; 20: 505-514. 
6. Tsai JC, McClure CA, Ramos SE, et al.  Compliance Barriers in 
Glaucoma:  A Systematic Classification.  Journal of Glaucoma 2003; 
12:393-398. 
7. Newman-Casey PA, Robin AL, Blachley T, et al.  The most common 
barriers to glaucoma medication adherence:  A cross-sectional survey.  
Ophthalmology 2015; 122:1308-1316. 
 
 
 
 


CLINICAL PROTOCOL 
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Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 37 of 53 
 
 
  
 
 
  
 
APPENDIX A:  SCHEDULE OF VISITS & MEASUREMENTS: Group 12 
(12 months from 1st Implant Insertion to 2nd Implant Insertion, 
) 
Parameter 
Screening 
Operative Day 0 
Day 1 
Day 10, 10 days ± 3 
Week 4, 28 days ± 3 
Month 6, 182 days ± 14 
Pre-exchange3 
Month 12, 365 days ± 14 
Day 1 Post Exchange (PE) 
Day 10 PE, 10 days ± 3 
Week 4 PE, 28 days ± 3 
Visit Number 
1 2 3 4 5 5.1 6 7 8 9 10 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
x 
 
 
 
 
 
 
 
 
 
 
Demographics, Medical/Ocular History 
x x 
 
 
 
 
 
 
 
 
 
Concomitant Medication Assessment 
x x x x x x x x x x x 
Adverse Event Assessment 
 
x x x x x x x x x x 
Corrected VA (ETDRS) 
 
 
 
 
x x x 
 
 
 
x 
Manifest Refraction & BSCVA (ETDRS) 
x 
 
 
 
x1 x1 x1 
 
 
 
x1 
Pinhole VA (Snellen) 
 
 
x x 
 
 
 
 
x x 
 
Slit Lamp Exam  
x 
 
x x x x x 
 
x x x 
IOP 
x 
 
x x x x x 
 
x x x 
Gonioscopy  
x 
 
 
 
x x x 
 
 
 
x 
Pachymetry 
x 
 
 
 
 
 
 
 
 
 
 
Dilated Fundus Exam and Nerve 
Assessment, Vertical C/D ratio 
x 
 
 
 
 
 
 
 
 
 
 
Aqueous Humor Sample (AC Tap) 
 
 
 
 
 
 
 
x 
 
 
 
Operative Procedure and Surgical 
Assessments 
 
x 
 
 
 
 
 
x2 
 
 
 
 
1 Only required if Corrected VA (ETDRS) has decreased by 2 or more lines (≥10 letters) from Visit 1 (Screening).  
2 Second Operative / Exchange is done AFTER collecting the anterior chamber aqueous humor sample and all assessments 
3 Pre-exchange exam to occur within 10 days prior to Visit 7 (Second Operative / Exchange Exam) 
 
Operative Visits are in Red 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 38 of 53 
 
APPENDIX B:  SCHEDULE OF VISITS & MEASUREMENTS: Group 3 
(3 months from 1st Implant Insertion to 2nd Implant Insertion, 
) 
Parameter 
Screening 
Operative Day 0 
Day 1 
Day 10, 10 days ± 3 
Week 4, 28 days ± 3 
Pre-Exchange3 
Month 3, 91 days ± 14 
Day 1 Post Exchange (PE) 
Day 10 PE, 10 days ± 3 
Week 4 PE, 28 days ± 3 
Visit Number 
1 2 3 4 5 6 7 8 9 10 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
x 
 
 
 
 
 
 
 
 
 
Demographics, Medical/Ocular History 
x x 
 
 
 
 
 
 
 
 
Concomitant Medication Assessment 
x x x x x x x x x x 
Adverse Event Assessment 
 
x x x x x x x x x 
Corrected VA (ETDRS) 
 
 
 
 
x x 
 
 
 
x 
Manifest Refraction & BSCVA (ETDRS) 
x 
 
 
 
x1 x1 
 
 
 
x1 
Pinhole VA (Snellen) 
 
 
x x 
 
 
 
x x 
 
Slit Lamp Exam  
x 
 
x x x x 
 
x x x 
IOP  
x 
 
x x x x 
 
x x x 
Gonioscopy  
x 
 
 
 
x x 
 
 
 
x 
Pachymetry 
x 
 
 
 
 
 
 
 
 
 
Dilated Fundus Exam and Nerve 
Assessment, Vertical C/D ratio 
x 
 
 
 
 
 
 
 
 
 
Aqueous Humor Sample (AC Tap) 
 
 
 
 
 
 
x 
 
 
 
Operative Procedure and Surgical 
Assessments 
 
x 
 
 
 
 
x2 
 
 
 
 
1 Only required if Corrected VA (ETDRS) has decreased by 2 or more lines (≥10 letters) from Visit 1 (Screening).  
2 Second Operative / Exchange is done AFTER collecting the anterior chamber aqueous humor sample and all assessments 
3 Pre-exchange exam to occur within 10 days prior to Visit 7 (Second Operative / Exchange Exam) 
 
 
Operative Visits are in Red 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 39 of 53 
 
APPENDIX C:  SCHEDULE OF VISITS & MEASUREMENTS: Group 6 
(6 months from 1st Implant Insertion to 2nd Implant Insertion, 
) 
Parameter 
Screening 
Operative Day 0 
Day 1 
Day 10, 10 days ± 3 
Week 4, 28 days ± 3 
Pre-Exchange3 
Month 6, 182 days ± 14 
Day 1 Post Exchange (PE) 
Day 10 PE, 10 days ± 3 
Week 4 PE, 28 days ± 3 
Visit Number 
1 2 3 4 5 6 7 8 9 10 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
x 
 
 
 
 
 
 
 
 
 
Demographics, Medical/Ocular History 
x x 
 
 
 
 
 
 
 
 
Concomitant Medication Assessment 
x x x x x x x x x x 
Adverse Event Assessment 
 
x x x x x x x x x 
Corrected VA (ETDRS) 
 
 
 
 
x x 
 
 
 
x 
Manifest Refraction & BSCVA (ETDRS) 
x 
 
 
 
x1 x1 
 
 
 
x1 
Pinhole VA (Snellen) 
 
 
x x 
 
 
 
x x 
 
Slit Lamp Exam  
x 
 
x x x x 
 
x x x 
IOP  
x 
 
x x x x 
 
x x x 
Gonioscopy  
x 
 
 
 
x x 
 
 
 
x 
Pachymetry 
x 
 
 
 
 
 
 
 
 
 
Dilated Fundus Exam and Nerve 
Assessment, Vertical C/D ratio 
x 
 
 
 
 
 
 
 
 
 
Aqueous Humor Sample (AC Tap) 
 
 
 
 
 
 
x 
 
 
 
Operative Procedure and Surgical 
Assessments 
 
x 
 
 
 
 
x2 
 
 
 
 
1 Only required if Corrected VA (ETDRS) has decreased by 2 or more lines (≥10 letters) from Visit 1 (Screening).  
2 Second Operative / Exchange is done AFTER collecting the anterior chamber aqueous humor sample and all assessments 
3 Pre-exchange exam to occur within 10 days prior to Visit 7 (Second Operative / Exchange Exam) 
 
Operative Visits are in Red 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 40 of 53 
 
APPENDIX D:  SCHEDULE OF VISITS & MEASUREMENTS: Group 24 
(24 months from 1st Implant Insertion to 2nd Implant Insertion, 
) 
Parameter 
Screening 
Operative Day 0 
Day 1 
Day 10, 10 days ± 3 
Week 4, 28 days ± 3 
Month 6, 182 days ± 14 
Month 12, 365 days ± 14 
Month 18, 547 days ± 14 
Pre-Exchange3 
Month 24, 730 days ± 14 
Day 1 Post Exchange (PE) 
Day 10 PE, 10 days ± 3 
Week 4 PE, 28 days ± 3 
Visit Number 
1 2 3 4 5 5.1 5.2 5.3 6 7 8 9 10 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics, Medical/Ocular History 
x x 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication Assessment 
x x x x x x x x x x x x x 
Adverse Event Assessment 
 
x x x x x x x x x x x x 
Corrected VA (ETDRS) 
 
 
 
 
x x x x x 
 
 
 
x 
Manifest Refraction & BSCVA (ETDRS) 
x 
 
 
 
x1 x1 x1 x1 x1 
 
 
 
x1 
Pinhole VA (Snellen) 
 
 
x x 
 
 
 
 
 
 
x x 
 
Slit Lamp Exam  
x 
 
x x x x x x x 
 
x x x 
IOP 
x 
 
x x x x x x x 
 
x x x 
Gonioscopy  
x 
 
 
 
x x x x x 
 
 
 
x 
Pachymetry 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Dilated Fundus Exam and Nerve 
Assessment, Vertical C/D ratio 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Aqueous Humor Sample (AC Tap) 
 
 
 
 
 
 
 
 
 
x 
 
 
 
Operative Procedure and Surgical 
Assessments 
 
x 
 
 
 
 
 
 
 
x2 
 
 
 
 
1 Only required if Corrected VA (ETDRS) has decreased by 2 or more lines (≥10 letters) from Visit 1 (Screening).  
2 Second Operative / Exchange is done AFTER collecting the anterior chamber aqueous humor sample and all assessments 
3 Pre-exchange exam to occur within 10 days prior to Visit 7 (Second Operative / Exchange Exam) 
 
Operative Visits are in Red 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 41 of 53 
 
APPENDIX E:  SCHEDULE OF VISITS & MEASUREMENTS: Group 21 
(21 months from 1st Implant Insertion to 2nd Implant Insertion, 
) 
Parameter 
Screening 
Operative Day 0 
Day 1 
Day 10, 10 days ± 3 
Week 4, 28 days ± 3 
Month 6, 182 days ± 14 
Month 12, 365 days ± 14 
Month 18, 547 days ± 14 
Pre-Exchange3 
Month 21, 637 days ± 14 
Day 1 Post Exchange (PE) 
Day 10 PE, 10 days ± 3 
Week 4 PE, 28 days ± 3 
Visit Number 
1 2 3 4 5 5.1 5.2 5.3 6 7 8 9 10 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics, Medical/Ocular History 
x x 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication Assessment 
x x x x x x x x x x x x x 
Adverse Event Assessment 
 
x x x x x x x x x x x x 
Corrected VA (ETDRS) 
 
 
 
 
x x x x x 
 
 
 
x 
Manifest Refraction & BSCVA (ETDRS) 
x 
 
 
 
x1 x1 x1 x1 x1 
 
 
 
x1 
Pinhole VA (Snellen) 
 
 
x x 
 
 
 
 
 
 
x x 
 
Slit Lamp Exam  
x 
 
x x x x x x x 
 
x x x 
IOP  
x 
 
x x x x x x x 
 
x x x 
Gonioscopy  
x 
 
 
 
x x x x x 
 
 
 
x 
Pachymetry 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Dilated Fundus Exam and Nerve 
Assessment, Vertical C/D ratio 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Aqueous Humor Sample (AC Tap) 
 
 
 
 
 
 
 
 
 
x 
 
 
 
Operative Procedure and Surgical 
Assessments 
 
x 
 
 
 
 
 
 
 
x2 
 
 
 
 
1 Only required if Corrected VA (ETDRS) has decreased by 2 or more lines (≥10 letters) from Visit 1 (Screening).  
2 Second Operative / Exchange is done AFTER collecting the anterior chamber aqueous humor sample and all assessments 
3 Pre-exchange exam to occur within 10 days prior to Visit 7 (Second Operative / Exchange Exam) 
 
Operative Visits are in Red 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 42 of 53 
 
APPENDIX F:  SCHEDULE OF VISITS & MEASUREMENTS: Group 18 
(18 months from 1st Implant Insertion to 2nd Implant Insertion, 
) 
Parameter 
Screening 
Operative Day 0 
Day 1 
Day 10, 10 days ± 3 
Week 4, 28 days ± 3 
Month 6, 182 days ± 14 
Month 12, 365 days ± 14 
Pre-Exchange3 
Month 18, 547 days ± 14 
Day 1 Post Exchange (PE) 
Day 10 PE, 10 days ± 3 
Week 4 PE, 28 days ± 3 
Visit Number 
1 2 3 4 5 5.1 5.2 6 7 8 9 10 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
x 
 
 
 
 
 
 
 
 
 
 
 
Demographics, Medical/Ocular History 
x x 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication Assessment 
x x x x x x x x x x x x 
Adverse Event Assessment 
 
x x x x x x x x x x x 
Corrected VA (ETDRS) 
 
 
 
 
x x x x 
 
 
 
x 
Manifest Refraction & BSCVA (ETDRS) 
x 
 
 
 
x1 x1 x1 x1  
 
 x1 
Pinhole VA (Snellen) 
 
 
x x 
 
 
 
 
 
x x 
 
Slit Lamp Exam  
x 
 
x x x x x x 
 
x x x 
IOP  
x 
 
x x x x x x 
 
x x x 
Gonioscopy  
x 
 
 
 
x x x x 
 
 
 
x 
Pachymetry 
x 
 
 
 
 
 
 
 
 
 
 
 
Dilated Fundus Exam and Nerve 
Assessment, Vertical C/D ratio 
x 
 
 
 
 
 
 
 
 
 
 
 
Aqueous Humor Sample (AC Tap) 
 
 
 
 
 
 
 
 
x 
 
 
 
Operative Procedure and Surgical 
Assessments 
 
x 
 
 
 
 
 
 
x2 
 
 
 
 
1 Only required if Corrected VA (ETDRS) has decreased by 2 or more lines (≥10 letters) from Visit 1 (Screening).  
2 Second Operative / Exchange is done AFTER collecting the anterior chamber aqueous humor sample and all assessments 
3 Pre-exchange exam to occur within 10 days prior to Visit 7 (Second Operative / Exchange Exam) 
 
Operative Visits are in Red 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 43 of 53 
 
APPENDIX G:  SCHEDULE OF VISITS & MEASUREMENTS: Group 15 
(15 months from 1st Implant Insertion to 2nd Implant Insertion, 
) 
Parameter 
Screening 
Operative Day 0 
Day 1 
Day 10, 10 days ± 3 
Week 4, 28 days ± 3 
Month 6, 182 days ± 14 
Month 12, 365 days ± 14 
Pre-Exchange3 
Month 15, 456 days ± 14 
Day 1 Post Exchange (PE) 
Day 10 PE, 10 days ± 3 
Week 4 PE, 28 days ± 3 
Visit Number 
1 2 3 4 5 5.1 5.2 6 7 8 9 10 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
x 
 
 
 
 
 
 
 
 
 
 
 
Demographics, Medical/Ocular History 
x x 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication Assessment 
x x x x x x x x x x x x 
Adverse Event Assessment 
 
x x x x x x x x x x x 
Corrected VA (ETDRS) 
 
 
 
 
x x x x 
 
 
 
x 
Manifest Refraction & BSCVA (ETDRS) 
x 
 
 
 
x1 x1 x1 x1  
 
 x1 
Pinhole VA (Snellen) 
 
 
x x 
 
 
 
 
 
x x 
 
Slit Lamp Exam  
x 
 
x x x x x x 
 
x x x 
IOP  
x 
 
x x x x x x 
 
x x x 
Gonioscopy  
x 
 
 
 
x x x x 
 
 
 
x 
Pachymetry 
x 
 
 
 
 
 
 
 
 
 
 
 
Dilated Fundus Exam and Nerve 
Assessment, Vertical C/D ratio 
x 
 
 
 
 
 
 
 
 
 
 
 
Aqueous Humor Sample (AC Tap) 
 
 
 
 
 
 
 
 
x 
 
 
 
Operative Procedure and Surgical 
Assessments 
 
x 
 
 
 
 
 
 
x2 
 
 
 
 
1 Only required if Corrected VA (ETDRS) has decreased by 2 or more lines (≥10 letters) from Visit 1 (Screening).  
2 Second Operative / Exchange is done AFTER collecting the anterior chamber aqueous humor sample and all assessments 
3 Pre-exchange exam to occur within 10 days prior to Visit 7 (Second Operative / Exchange Exam) 
 
Operative Visits are in Red 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 44 of 53 
 
APPENDIX H:  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. 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 45 of 53 
 
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). 
 
 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 46 of 53 
 
APPENDIX I:  DECLARATION OF HELSINKI 
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
 
Ethical principles for medical research involving human subjects. 
 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and 
amended by the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, 
October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington DC, USA, October 2002 
(Note of Clarification added) 
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of 
Clarification added) 
59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
 
Preamble 
1.         The World Medical Association (WMA) has developed the Declaration of 
Helsinki as a statement of ethical principles for medical research involving 
human subjects, including research on identifiable human material and 
data. 
The Declaration is intended to be read as a whole and each of its 
constituent paragraphs should be applied with consideration of all other 
relevant paragraphs. 
 
2.         Consistent with the mandate of the WMA, the Declaration is addressed 
primarily to physicians.  The WMA encourages others who are involved in 
medical research involving human subjects to adopt these principles. 
 
General Principles 
3.         The Declaration of Geneva of the WMA binds the physician with the 
words, “The health of my patient will be my first consideration,” and the 
International Code of Medical Ethics declares that, “A physician shall act 
in the patient’s best interest when providing medical care.” 
 
4.         It is the duty of the physician to promote and safeguard the health, well-
being and rights of patients, including those who are involved in medical 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 47 of 53 
 
research. The physician’s knowledge and conscience are dedicated to the 
fulfilment of this duty. 
 
5.         Medical progress is based on research that ultimately must include studies 
involving human subjects. 
 
6.         The primary purpose of medical research involving human subjects is to 
understand the causes, development and effects of diseases and improve 
preventive, diagnostic and therapeutic interventions (methods, procedures 
and treatments).  Even the best proven interventions must be evaluated 
continually through research for their safety, effectiveness, efficiency, 
accessibility and quality. 
 
7.         Medical research is subject to ethical standards that promote and ensure 
respect for all human subjects and protect their health and rights. 
 
8.         While the primary purpose of medical research is to generate new 
knowledge, this goal can never take precedence over the rights and 
interests of individual research subjects. 
 
9.         It is the duty of physicians who are involved in medical research to protect 
the life, health, dignity, integrity, right to self-determination, privacy, and 
confidentiality of personal information of research subjects.  The 
responsibility for the protection of research subjects must always rest with 
the physician or other health care professionals and never with the 
research subjects, even though they have given consent. 
 
10.       Physicians must consider the ethical, legal and regulatory norms and 
standards for research involving human subjects in their own countries as 
well as applicable international norms and standards.  No national or 
international ethical, legal or regulatory requirement should reduce or 
eliminate any of the protections for research subjects set forth in this 
Declaration. 
 
11.       Medical research should be conducted in a manner that minimises possible 
harm to the environment. 
 
12.       Medical research involving human subjects must be conducted only by 
individuals with the appropriate ethics and scientific education, training 
and qualifications.  Research on patients or healthy volunteers requires the 
supervision of a competent and appropriately qualified physician or other 
health care professional. 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 48 of 53 
 
 
13.       Groups that are underrepresented in medical research should be provided 
appropriate access to participation in research. 
 
14.       Physicians who combine medical research with medical care should 
involve their patients in research only to the extent that this is justified by 
its potential preventive, diagnostic or therapeutic value and if the 
physician has good reason to believe that participation in the research 
study will not adversely affect the health of the patients who serve as 
research subjects. 
 
15.       Appropriate compensation and treatment for subjects who are harmed as a 
result of participating in research must be ensured. 
 
Risks, Burdens and Benefits 
16.       In medical practice and in medical research, most interventions involve 
risks and burdens. 
Medical research involving human subjects may only be conducted if the 
importance of the objective outweighs the risks and burdens to the 
research subjects. 
 
17.       All medical research involving human subjects must be preceded by 
careful assessment of predictable risks and burdens to the individuals and 
groups involved in the research in comparison with foreseeable benefits to 
them and to other individuals or groups affected by the condition under 
investigation. 
Measures to minimise the risks must be implemented.  The risks must be 
continuously monitored, assessed and documented by the researcher. 
 
18.       Physicians may not be involved in a research study involving human 
subjects unless they are confident that the risks have been adequately 
assessed and can be satisfactorily managed. 
When the risks are found to outweigh the potential benefits or when there 
is conclusive proof of definitive outcomes, physicians must assess whether 
to continue, modify or immediately stop the study. 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 49 of 53 
 
Vulnerable Groups and Individuals 
19.       Some groups and individuals are particularly vulnerable and may have an 
increased likelihood of being wronged or of incurring additional harm. 
All vulnerable groups and individuals should receive specifically 
considered protection. 
 
20.       Medical research with a vulnerable group is only justified if the research is 
responsive to the health needs or priorities of this group and the research 
cannot be carried out in a non-vulnerable group.  In addition, this group 
should stand to benefit from the knowledge, practices or interventions that 
result from the research. 
 
Scientific Requirements and Research Protocols 
21.       Medical research involving human subjects must conform to generally 
accepted scientific principles, be based on a thorough knowledge of the 
scientific literature, other relevant sources of information, and adequate 
laboratory and, as appropriate, animal experimentation.  The welfare of 
animals used for research must be respected. 
 
22.       The design and performance of each research study involving human 
subjects must be clearly described and justified in a research protocol. 
The protocol should contain a statement of the ethical considerations 
involved and should indicate how the principles in this Declaration have 
been addressed.  The protocol should include information regarding 
funding, sponsors, institutional affiliations, potential conflicts of interest, 
incentives for subjects and information regarding provisions for treating 
and/or compensating subjects who are harmed as a consequence of 
participation in the research study. 
In clinical trials, the protocol must also describe appropriate arrangements 
for post-trial provisions. 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 50 of 53 
 
Research Ethics Committees 
23.       The research protocol must be submitted for consideration, comment, 
guidance and approval to the concerned research ethics committee before 
the study begins.  This committee must be transparent in its functioning, 
must be independent of the researcher, the sponsor and any other undue 
influence and must be duly qualified.  It must take into consideration the 
laws and regulations of the country or countries in which the research is to 
be performed as well as applicable international norms and standards but 
these must not be allowed to reduce or eliminate any of the protections for 
research subjects set forth in this Declaration. 
The committee must have the right to monitor ongoing studies.  The 
researcher must provide monitoring information to the committee, 
especially information about any serious adverse events.  No amendment 
to the protocol may be made without consideration and approval by the 
committee.  After the end of the study, the researchers must submit a final 
report to the committee containing a summary of the study’s findings and 
conclusions. 
 
Privacy and Confidentiality 
24.       Every precaution must be taken to protect the privacy of research subjects 
and the confidentiality of their personal information. 
 
Informed Consent 
25.       Participation by individuals capable of giving informed consent as 
subjects in medical research must be voluntary.  Although it may be 
appropriate to consult family members or community leaders, no 
individual capable of giving informed consent may be enrolled in a 
research study unless he or she freely agrees. 
 
26.       In medical research involving human subjects capable of giving informed 
consent, each potential subject must be adequately informed of the aims, 
methods, sources of funding, any possible conflicts of interest, 
institutional affiliations of the researcher, the anticipated benefits and 
potential risks of the study and the discomfort it may entail, post-study 
provisions and any other relevant aspects of the study.  The potential 
subject must be informed of the right to refuse to participate in the study 
or to withdraw consent to participate at any time without reprisal.  Special 
attention should be given to the specific information needs of individual 
potential subjects as well as to the methods used to deliver the 
information. 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 51 of 53 
 
After ensuring that the potential subject has understood the information, 
the physician or another appropriately qualified individual must then seek 
the potential subject’s freely-given informed consent, preferably in 
writing.  If the consent cannot be expressed in writing, the non-written 
consent must be formally documented and witnessed. 
All medical research subjects should be given the option of being 
informed about the general outcome and results of the study. 
 
27.       When seeking informed consent for participation in a research study the 
physician must be particularly cautious if the potential subject is in a 
dependent relationship with the physician or may consent under duress.  In 
such situations the informed consent must be sought by an appropriately 
qualified individual who is completely independent of this relationship. 
 
28.       For a potential research subject who is incapable of giving informed 
consent, the physician must seek informed consent from the legally 
authorised representative.  These individuals must not be included in a 
research study that has no likelihood of benefit for them unless it is 
intended to promote the health of the group represented by the potential 
subject, the research cannot instead be performed with persons capable of 
providing informed consent, and the research entails only minimal risk 
and minimal burden. 
 
29.       When a potential research subject who is deemed incapable of giving 
informed consent is able to give assent to decisions about participation in 
research, the physician must seek that assent in addition to the consent of 
the legally authorised representative.  The potential subject’s dissent 
should be respected. 
 
30.       Research involving subjects who are physically or mentally incapable of 
giving consent, for example, unconscious patients, may be done only if the 
physical or mental condition that prevents giving informed consent is a 
necessary characteristic of the research  group.  In such circumstances the 
physician must seek informed consent from the legally authorised 
representative.  If no such representative is available and if the research 
cannot be delayed, the study may proceed without informed consent 
provided that the specific reasons for involving subjects with a condition 
that renders them unable to give informed consent have been stated in the 
research protocol and the study has been approved by a research ethics 
committee.  Consent to remain in the research must be obtained as soon as 
possible from the subject or a legally authorised representative. 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 52 of 53 
 
 
31.       The physician must fully inform the patient which aspects of their care are 
related to the research.  The refusal of a patient to participate in a study or 
the patient’s decision to withdraw from the study must never adversely 
affect the patient-physician relationship. 
 
32.       For medical research using identifiable human material or data, such as 
research on material or data contained in biobanks or similar repositories, 
physicians must seek informed consent for its collection, storage and/or 
reuse.  There may be exceptional situations where consent would be 
impossible or impracticable to obtain for such research.  In such situations 
the research may be done only after consideration and approval of a 
research ethics committee. 
 
Use of Placebo 
33.       The benefits, risks, burdens and effectiveness of a new intervention must 
be tested against those of the best proven intervention(s), except in the 
following circumstances: 
• 
Where no proven intervention exists, the use of placebo, or no 
intervention, is acceptable; or 
• 
Where for compelling and scientifically sound methodological 
reasons the use of any intervention less effective than the best 
proven one, the use of placebo, or no intervention is necessary to 
determine the efficacy or safety of an intervention 
• 
and the patients who receive any intervention less effective than 
the best proven one, placebo, or no intervention will not be subject 
to additional risks of serious or irreversible harm as a result of not 
receiving the best proven intervention. 
Extreme care must be taken to avoid abuse of this option. 
 
Post-Trial Provisions 
34.       In advance of a clinical trial, sponsors, researchers and host country 
governments should make provisions for post-trial access for all 
participants who still need an intervention identified as beneficial in the 
trial.  This information must also be disclosed to participants during the 
informed consent process. 
 
 


CLINICAL PROTOCOL 
Date: 
 
 
 
Protocol No.: 
September 18, 2019 
 
IDOS-402-IVIV 
 
 
CONFIDENTIAL 
 page 53 of 53 
 
Research Registration and Publication and Dissemination of Results 
35.       Every research study involving human subjects must be registered in a 
publicly accessible database before recruitment of the first subject. 
 
36.       Researchers, authors, sponsors, editors and publishers all have ethical 
obligations with regard to the publication and dissemination of the results 
of research.  Researchers have a duty to make publicly available the 
results of their research on human subjects and are accountable for the 
completeness and accuracy of their reports.  All parties should adhere to 
accepted guidelines for ethical reporting.  Negative and inconclusive as 
well as positive results must be published or otherwise made publicly 
available.  Sources of funding, institutional affiliations and conflicts of 
interest must be declared in the publication.  Reports of research not in 
accordance with the principles of this Declaration should not be accepted 
for publication. 
 
Unproven Interventions in Clinical Practice 
37.       In the treatment of an individual patient, where proven interventions do 
not exist or other known interventions have been ineffective, the 
physician, after seeking expert advice, with informed consent from the 
patient or a legally authorised representative, may use an unproven 
intervention if in the physician’s judgement it offers hope of saving life, 
re-establishing health or alleviating suffering.  This intervention should 
subsequently be made the object of research, designed to evaluate its 
safety and efficacy.  In all cases, new information must be recorded and, 
where appropriate, made publicly available.  
 

SAP_001.pdf: 
CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
Glaukos Corporation 
1 
Statistical Analysis Plan 
Prospective, Non-Randomized, Open-Label, Single Center Study to Evaluate 
 the Performance of the Travoprost Intraocular 
Implant 
Protocol Number: 
IDOS-402-IVIV 
Product Name:   
Travoprost Intraocular Implant, 
 (G2-TR-125) 
Sponsor Name: 
GLAUKOS CORPORATION 
26600 Aliso Viejo Parkway  
Aliso Viejo, CA  92656  
Version: 
1.0 
Date: 
March 23th, 2022 
ClinicalTrials.gov Identifier:  NCT06582732 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
2 
Statistical Analysis Plan Approval Signatures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
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 
2.3.1. 
Study Period ......................................................................................................................9 
2.4. 
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. 
Pre-Exchange Measure ...................................................................................................12 
4.1.3. 
Change from Baseline/Pre-Exchange .............................................................................12 
4.1.4. 
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 ..............................................................................................................21 
8.1.1. 
Operative and Surgical Analyses ....................................................................................21 
8.1.2. 
Subgroup Analyses .........................................................................................................21 
9. 
Interim Analysis ............................................................................................................22 
10. 
Changes to Protocol-planned Analyses .......................................................................23 
11. 
Supporting Documentation ..........................................................................................24 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
4 
11.1. 
Appendix A: Schedule of Visits & Measurements: Group 12........................................24 
11.2. 
Appendix B: Schedule of Visits & Measurements: Group 3 ..........................................25 
11.3. 
Appendix C: Schedule of Visits & Measurements: Group 6 ..........................................26 
11.4. 
Appendix D: Schedule of Visits & Measurements: Group 24........................................27 
11.5. 
Appendix E: Schedule of Visits & Measurements: Group 21 ........................................28 
11.6. 
Appendix F: Schedule of Visits & Measurements: Group 18 ........................................29 
11.7. 
Appendix G: Schedule of Visits & Measurements: Group 15........................................30 
 
 
 
 
 
 
12. 
References ......................................................................................................................32 
 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
5 
List of Abbreviations 
Abbreviation 
Definition 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
BSCVA 
Best Spectacle Corrected Visual Acuity 
CFB 
Change from Baseline 
CFPE 
Change from Pre-Exchange 
CRF 
Case Report Form 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
IOP 
Intraocular Pressure 
LogMAR 
Logarithm of the Minimum Angle of Resolution 
MedDRA 
Medical Dictionary for Regulatory Activities 
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 
WHO 
World Health Organization 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
6 
Version History 
This Statistical Analysis Plan (SAP) for IDOS-402-IVIV is based on the protocol dated 
18SEP2019. 
SAP Version 
Approval Date 
Change 
Rationale 
1 
 
Not Applicable 
Original version 
 
 
 
 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
7 
1. 
Introduction 
This statistical analysis plan (SAP) describes the statistical methods to analyze all safety data 
from protocol IDOS-402-IVIV.  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 Week 
4 Post-Exchange (PE) visit or have exited the study prior to that time. 
 
 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
8 
2. 
Objectives and Study Design 
2.1. 
Objectives 
The study objective is to evaluate 
 the performance of the Travoprost 
Intraocular Implant and to study the drug elution rate in vivo, as derived from the residual drug in 
the explant of the Travoprost Intraocular Implant, 
 
 
2.2. 
Endpoints 
Safety Endpoints:  
 Intraoperative adverse events 
 Postoperative adverse events 
 Intraocular pressure (IOP) 
 Corrected visual acuity (logMAR score using ETDRS chart) 
 Slit-lamp biomicroscopy findings 
 Gonioscopy findings 
 Ophthalmoscopy findings 
Other: 
 Operative and surgical assessments 
2.3. 
Study Design 
This is a prospective, non-randomized, open-label, single center trial evaluating 
 
 the performance of the Travoprost Intraocular Implant in subjects 
with open-angle glaucoma (OAG) or ocular hypertension (OHT).  Approximately 210 total 
subjects 
will 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 be assigned to a cohort and will be implanted with the 
Travoprost Intraocular Implant (G2-TR-125 Implant) in one eye.  
 
 
 
  All enrolled subjects will undergo a second operative visit, the exchange of the 
Travoprost Intraocular Implant, at Visit 7.  The duration of time for each cohort is the time 
between the implantation of the 1st implant at Visit 2 (Day 0) and the implantation of the 2nd 
implant at Visit 7 (Exchange procedure).  Depending on the cohort assignment, subjects will be 
follow for 4 – 25 months postoperatively (3 – 24 months after 1st implantation and 4 weeks after 
the 2nd implantation).  Study follow-up will continue until the Week 4 PE visit.   
Depending on the cohort assignment, the study consists of 10 to 13 visits: Visit 1 (Screening), 
Visit 2 (First Operative Day 0), Visit 3 (Day 1), Visit 4 (Day 10), Visit 5 (Week 4), Visit 5.1 
(Month 6), Visit 5.2 (Month 12), Visit 5.3 (Month 18), Visit 6 (Pre-Exchange Exam, within 10 
days prior to Visit 7), Visit 7 (Second Operative/ Exchange), Visit 8 (Day 1 PE), Visit 9 (Day 10 
PE), and Visit 10 (Week 4 PE).  Subjects will exit the study at the conclusion of the Week 4 PE 
visit. 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
9 
All subjects will have visits at post-operative Day 1, Day 10, Week 4, pre-exchange, and post-
exchange Day 1, Day 10, and Week 4.  Table 1 summarizes the remaining visits for each cohort 
along with other cohort information.  Appendices A-G show the schedule of visits and 
measurements for each cohort.   
Subjects will be assigned to their cohort sequentially as defined by the cohort order as they 
receive surgery.  Each cohort must be filled prior to starting the next cohort.   
Table 1.  Cohorts in the Study1 
2.3.1. 
Study Period 
All data will be categorized into one of two study periods which are referred to as the initial and 
post-exchange (PE) study periods.  The initial study period includes all data collected prior to the 
exchange of the intraocular implant at Visit 7 (Second Operative/ Exchange).  The PE study 
period includes all data collected after the exchange of the intraocular implant at Visit 7 (Second 
Operative/ Exchange), including any data collected during the exchange procedure.  Data may be 
summarized for the initial study period, PE study period, or across both periods (total study 
period) as indicated. 
                                                 
1 Table 1 can be found in Section 3 of protocol. 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
10 
2.4. 
Sample Size Determination 
The sample size of 210 subjects who undergo implantation and exchange of a Travoprost 
Intraocular Implant was determined to support the study objectives and is not based on statistical 
power calculations.  
 
 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
11 
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. 
Subject Analysis Set 
Description 
Safety analysis set 
 
All subjects who receive an implant. 


CONFIDENTIAL 
Statistical Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
12 
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.  In general, summary tables will be presented
 
.  Data may also be summarized by study period if indicated.  Data listings 
will present data either recorded on or derived using the CRF.  
 
  
No formal statistical testing will be performed.  All data summaries 
 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 implantation of the 
1st Travoprost intraocular implant at Visit 2 (First Operative Day 0).    
4.1.2. 
Pre-Exchange Measure 
The pre-exchange measure is defined as the last non-missing measure prior to the implantation of 
the 2nd Travoprost intraocular implant at Visit 7 (Second Operative/Exchange).  
4.1.3. 
Change from Baseline/Pre-Exchange 
The change from baseline (CFB) and the change from pre-exchange (CFPE) values are 
calculated as 
 CFB value = follow-up visit value – baseline value. 
 CFPE value = follow-up visit value – pre-exchange value. 
4.1.4. 
Study Days 
Two sets of study days are defined and will be referred to as the initial and PE study days.  The 
number of initial study days is defined relative to the First Operative visit (Visit 2), with the First 
Operative visit as study day 1.  The number of PE study days is defined relative to the Second 
Operative visit (Visit 7), with the Second Operative visit as study day 1.  For both sets of study 
days, the study day value increases by 1 for each date following the corresponding Operative 
visit.  For each date prior to the corresponding Operative visit, the study day value decreases by 
1, with the date preceding the Operative visits as study day -1. 
 


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5. 
Demographic and Baseline Characteristic Analyses 
5.1. 
Subject Disposition 
The number and percentage of subjects who were screened, screened but not enrolled (i.e., 
screen failures), and enrolled will be provided.  A subject is considered enrolled at the time the 
subject undergoes surgery at the First Operative visit (Visit 2).  Reason(s) for screen failure will 
also be presented in a table and subject listing. 
Subject disposition will be summarized 
 for all enrolled subjects.  The summary 
will include the number and percentage of subjects who completed the study and the number and 
percentage of subjects who exited early (with reasons for study exit) prior to the Week 4 PE 
examination.  The reasons for early study exit include: 
 Adverse Event 
 Death 
 Investigator Decision 
 Lost to Follow-up 
 Termination of Study by Sponsor or Regulatory Authority 
 Withdrew Consent 
 Other 
Subject disposition will also be summarized 
 for the initial and PE study periods.  
The summary will include the number and percentage of subjects who completed the respective 
study period and the number and percentage of subjects who exited early (with reasons for study 
exit) during the respective study period.   
Subject disposition and exit status will be listed by subject. 
5.2. 
Protocol Deviations 
Protocol deviations will be captured by the site and reviewed by a medical monitor during the 
study.  Classification of major deviations will be decided by the study team prior to the database 
lock.  For the safety analysis set, a summary of protocol deviations will be tabulated 
 
for the initial, PE, and total study periods.  A listing of all protocol deviations will be 
provided.   
5.3. 
Demographic and Baseline Characteristics 
Subject demographics and baseline characteristics will be tabulated 
 for the safety 
analysis set.  Demographic variables include age, sex, race, ethnicity, and eye color.  Age will be 
calculated for each subject by (Informed Consent Date – Date of Birth) ÷ 365.25 and rounded 
down to the nearest integer.  In addition to being summarized continuously, age will be 
summarized categorically for the following age groups: < 65 and ≥ 65 years of age. 
The following baseline characteristics will be summarized 
 for the study eye: 
 Type of Disease (OAG or OHT) 
 Number of Ocular Hypotensive Medication Classes 
 Medication Class 


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 IOP (mmHg) 
 Best Spectacle Corrected Visual Acuity (BSCVA) - LogMAR  
 Vertical Cup-to-Disc Ratio 
 Corneal Thickness (μm) 
 Shaffer Angle Grade 
 Study Eye (OD or OS) 
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, Version 21.0.  Medical and surgical history will be 
tabulated by System Organ Class (SOC) and preferred term (PT) 
.  Separate 
tabulations will be provided for study eye, non-study eye, and non-ocular histories.  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.  
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 
(Version MAR2018) and will be summarized to the anatomical therapeutic chemical (ATC) class 
and preferred name.  The number and percentage of subjects on medications will be tabulated by 
ATC, preferred name, 
 
 Prior medications in the study eye 
 Prior medications in the non-study eye 
 Non-ocular prior medications  
 Concomitant medications in the study eye for the initial, PE, and totally study periods 
 Concomitant medications in the non-study eye 
 Non-ocular concomitant medications 
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 First Operative visit at Visit 2.  Ocular procedures will be coded using 
the MedDRA nomenclature, Version 21.0.  Ocular procedures will be tabulated by SOC, PT, 
 
 for each study period.  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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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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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 each study period.  Extent of exposure to study treatment in days 
will be calculated differently by study period.  For the total study period, extent of exposure will 
be calculated as date of study exit – date of 1st Operative visit + 1.  For the initial study period, 
extent of exposure will be calculated as date of 2nd Operative visit – date of 1st Operative visit + 
1.  For the PE study period, extent of exposure will be calculated as date of study exit – date of 
2nd Operative visit + 1.  If the date of study exit, or the date of 2nd Operative visit for the initial 
study period, 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, Version 21.0. Treatment 
Emergent Adverse Events (TEAEs) are defined as AEs that occur after the initiation of the first 
surgery at Visit 2 (First Operative Day 0). 
AEs will be categorized into either the initial or PE study periods, as described in Section 2.3.1.  
AEs that extend between study periods (i.e., beginning during the initial study period and 
extending into the PE study period), will be categorized into the initial study period.  However, if 
an increase in severity or change in relationship to study treatment occurs during the PE study 
period, the AE will be categorized into both the initial and PE study periods.     
A summary of the number and percentage of subjects with TEAEs 
 will be 
provided for each study period.  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 study eye TEAEs, non-study eye TEAEs, and non-
ocular TEAEs will be provided by SOC, PT, 
 for: 
 TEAEs 
 TEAEs related to study treatment 
 TEAEs by maximum severity 
 Serious TEAEs 
Tabulations of study eye TEAEs for each of the above categories will be provided for each study 
period.   
All AEs will be presented in a listing by subject.  Separate listings for intraoperative AEs, serious 
adverse events (SAEs), AEs leading to deaths, AEs leading to study discontinuation, and AEs 
leading to removal of implant will also be presented.   


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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 presenting relationship to study treatment, the 
categories of possibly related, probably related, and definitely related will be classified as related 
and only related AEs will be presented.  AEs with missing relationships are counted as related.  
Subjects experiencing more than one treatment related AE within a given SOC or PT will be 
counted once within that SOC or PT.   
Severity is a measure of intensity and is graded on a 3-point scale as outlined in the study 
protocol.  AEs will be rated as either mild, moderate, or severe.  AEs with missing severities are 
counted as severe.  For all tabulations, subjects experiencing more than one AE within a given 
SOC or PT will be counted once within that SOC or PT at the maximum severity. 
7.1.3. 
Additional Safety Assessments 
Additional safety measures will be summarized for the Safety analysis set.  Only data in the 
study eye will be presented in tabulations.  Data may be tabulated by visit and/or for the overall 
study period (i.e. subjects with at least one finding during the study period) as indicated.  
Summaries for the overall study period will include data from unscheduled visits. 
The change in safety data may be summarized by study period as indicated.  In general, only the 
CFB will be presented for visits belonging to the initial study period and both the CFB and the 
CFPE will be presented for visits belonging to the PE study period.   
The criteria for clinical significance varies by measure.  Unless otherwise specified, 
 
 
 
 
 
 
7.1.3.1. 
Visual Acuity 
Best spectacle corrected visual acuity (BSCVA) is measured at Screening using the Early 
Treatment Diabetic Retinopathy Study (ETDRS) letter chart.  Corrected VA (ETDRS) is 
collected at Week 4, Month 6, Month 12, Month 18, Pre-Exchange, and Week 4 PE unless a 
decrease of 2 or more lines (≥ 10 letters) from Screening occurs, at which time BSCVA is also 
measured.  Pinhole VA (Snellen) is collected at the Day 1, Day 10, Day 1 PE and Day 10 PE 
visits.   
Corrected VA and BSCVA will be presented in tabulations.  If both corrected VA and BSCVA 
are collected, only BSCVA will be presented in the tabulations.   
The worst change in VA will be summarized 
 for the 
total, initial, and PE study periods.  The worst change in VA is defined as the largest decrease, or 
smallest increase if there is no decrease, in number of letters read correctly across all 


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postoperative visits (scheduled or unscheduled) in the study period.  For the initial and total 
study periods, only the worst CFB will be presented.  For the PE study period, the worst CFPE 
will also be presented.  The number and percentage of subjects with a worst decrease of greater 
than or equal to 15 letter (3 lines) will also be summarized for each study period.   
The actual and CFB in number of letters read correctly will be summarized by visit 
 
.  The number and percentage of subjects with a decrease of greater than or equal to 
15 letters (3 lines) will also be summarized by visit 
.  For visits belonging to 
the PE study period, the CFPE will also be summarized both continuously and categorically as 
outlined.   
A visual acuity subject listing will be provided for all visual acuity data including pinhole VA. 
 
7.1.3.2. 
Slit Lamp Examinations 
Slit lamp measures collected on the CRF include corneal edema, corneal opacity, epithelium, 
endothelium, guttata, anterior chamber depth, anterior chamber cells, anterior chamber flare, and 
pupil.  All slit lamp measures are collected at Screening and each postoperative visit within both 
study periods (Day 1, Day 10, Week 4, Month 6, Month 12, Month 18, Pre-Exchange, Day 1 PE, 
Day 10 PE, and Week 4 PE).     
For each measure, the number and percentage of subjects in each severity grade/category will be 
summarized by visit 
.   
Slit lamp findings will also be summarized by time interval within each study period.  For the 
initial study period, the time intervals will consist of after Baseline through Week 4, after Week 
4 to Month 12, and after Month 12 to Month 24.  For the PE study period, only the time interval 
of after pre-exchange to Week 4 PE will be summarized.  The summaries will include the 
number and percentage of subjects with at least one clinically significant worsening during the 
specified time interval (including data from unscheduled visits)
.  For the 
initial study period, only a clinically significant worsening from baseline will be presented.   For 
the PE study period, both a clinically significant worsening from baseline and a clinically 
significant worsening from pre-exchange will be presented.  
 
  For findings not associated with a severity grade, a status change 
from normal/absent to abnormal/present at any postoperative visit during the time interval will 
be summarized.  
All slit lamp data will be listed.  Two additional slit lamp listings will be provided – one for 
subjects with a worsening from baseline and one for subjects with a worsening from pre-
exchange.  For each subject, the listings will present findings at each visit only for measures with 
either 
(1) at least one clinically significant worsening at any follow-up visit during the study for 
findings associated with severity grade or  
(2) a status change (i.e., a change from normal/absent to abnormal/present at a follow up 
visit) at any follow-up visit during the study for findings not associated with severity 
grade.   
Other slit lamp findings will also be listed. 


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7.1.3.3. 
Lens Findings 
Lens measures are collected at Screening and each postoperative visit within both study periods 
(Day 1, Day 10, Week 4, Month 6, Month 12, Month 18, Pre-Exchange, Day 1 PE, Day 10 PE, 
and Week 4 PE).  Lens measures include lens status, posterior capsule opacification, nuclear lens 
opacity, cortical lens opacity, and posterior subcapsular lens opacity.     
For each measure, the number and percentage of subjects in each severity grade/category will be 
summarized by visit 
   
Lens findings will also be summarized by time interval within each study period.  For the initial 
study period, the time intervals will consist of after Baseline to Week 4, after Week 4 to Month 
12, and after Month 12 to Month 24.  For the PE study period, only the time interval of after pre-
exchange to Week 4 PE will be summarized.  The summaries will include the number and 
percentage of subjects with at least one clinically significant worsening for the specified time 
interval (including data from unscheduled visits) 
.  For the initial study 
period, only a clinically significant worsening from baseline will be presented.   For the PE study 
period, both a clinically significant worsening from baseline and a clinically significant 
worsening from pre-exchange will be presented. 
All lens data will be listed.  Two additional listings of lens findings will be provided – one for 
subjects with a worsening from baseline and one for subjects with a worsening from pre-
exchange.  For each subject, the listings will present findings at each visit only for measures with 
at least one clinically significant worsening at any follow-up visit during the study.  Other lens 
findings will also be listed.  Lens status (phakic or pseudophakic) will be listed and not tabulated. 
7.1.3.4. 
Ophthalmoscopy Examinations 
Dilated fundus, nerve abnormality, and vertical cup-to-disc ratio assessments are evaluated at 
Screening.  All ophthalmoscopy data will be presented in a listing. 
7.1.3.5. 
Gonioscopy 
Gonioscopy assessments are performed at Screening, Week 4, Month 6, Month 12, Month 18, 
Pre-Exchange, and Week 4 PE.  Gonioscopy findings include goniosynechiae, angle rubeosis, 
and other angle abnormalities.   
The number and percentage of subjects with gonioscopy findings will be provided by visit 
 
.   
A summary of status change findings will be provided 
 for each study period.  
For the initial and total study periods, only the number and percentage of subjects with a status 
change from baseline will be provided by visit and for the overall study period.  For the PE study 
period, the number and percentage of subjects with a status change from pre-exchange will also 
be provided by visit and for the overall study period.       
All gonioscopy data will be listed by subject.  Two additional listings will be provided – one for 
subjects with status change findings from baseline and one for subjects with status change 
findings from pre-exchange.  For each subject, the listings will present findings at each visit only 
for measures with at least one status change at any follow-up visit during the study. 


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7.1.3.6. 
Implant Visibility 
Implant visibility is collected at Week 4, Month 6, Month 12, Month 18, Pre-Exchange, and 
Week 4 PE.  
 implant visibility will be summarized discretely by visit for 
the following implant visibility categories:  
 Original Target Position  
 Anchored but Migrated  
 Not Anchored (if implant visibility in original target position is reported as “No” and the 
implant is not “anchored but migrated”) 
A data listing will be provided for all implant visibility data. 
7.1.3.7. 
Corneal Pachymetry 
Corneal pachymetry assessments are performed at Screening.  All pachymetry data, including 
central corneal thickness (µm), will be presented in a listing. 
7.1.3.8. 
Intraocular Pressure 
IOP is assessed for safety and is measured at Screening and all postoperative visits within each 
study period (Day 1, Day 10, Week 4, Month 6, Month 12, Month 18, Pre-Exchange, Day 1 PE, 
Day 10 PE, and Week 4 PE).  IOP measurements will be taken once daily, unless surgery is 
performed.  At each visit, IOP may be collected at any time of the day.   
The actual and CFB in IOP (mmHg) will be summarized by visit 
.  The 
number and percentage of subjects will also be tabulated by visit 
 for the 
following categories:  
 IOP ≥ 30 mmHg  
 IOP Increase ≥ 10 mmHg    
For visits belonging to the PE study period, the CFPE will also be summarized both continuously 
and categorically as outlined. 
A subject listing presenting all IOP data will be provided. 
 


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8. 
Other Analyses 
Other analyses will be summarized as outlined in the subsequent sections. 
8.1.1. 
Operative and Surgical Analyses 
  
 
 
   
8.1.2. 
Subgroup Analyses 
No subgroup analyses are planned. 


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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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11. 
Supporting Documentation 
11.1. 
Appendix A: Schedule of Visits & Measurements: Group 12 
 
 


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11.2. 
Appendix B: Schedule of Visits & Measurements: Group 3 
 
 


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11.3. 
Appendix C: Schedule of Visits & Measurements: Group 6 
 
 


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11.4. 
Appendix D: Schedule of Visits & Measurements: Group 24 
 
 
 
 


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11.5. 
Appendix E: Schedule of Visits & Measurements: Group 21 
 
 
 
 
 


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11.6. 
Appendix F: Schedule of Visits & Measurements: Group 18 
 
 
 


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11.7. 
Appendix G: Schedule of Visits & Measurements: Group 15 
 
 


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11.8. 
Appendix H: Data Derivation Rules 
 
 
 
 
 
   
 
 
 
   
 
 
 
 
 
 
 
 


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12. 
References 
There are no references. 


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Pharmacokinetic Data Analysis Plan [IDOS-402-IVIV] 
 
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Pharmacokinetic Data Analysis Plan 
 
Prospective, Non-Randomized, Open-Label, Single Center Study to Evaluate 
 the Performance of the Travoprost Intraocular 
Implant 
 
Protocol Number:  
IDOS-402-IVIV 
Product Name:   
Travoprost Intraocular Implant, 
 (G2-TR-125) 
 
Sponsor Name:   
GLAUKOS CORPORATION 
26600 Aliso Viejo Parkway  
Aliso Viejo, CA  92656  
 
Version: 
 
1.0 
Date: 
 
January 10, 2024 
 
 




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Table of Contents 
Pharmacokinetic Data Analysis Plan Approval Signatures.......................................................2 
Table of Contents ...........................................................................................................................3 
List of Abbreviations .....................................................................................................................4 
Version History ..............................................................................................................................5 
1. 
Introduction .....................................................................................................................6 
2. 
Objectives and Study Design .........................................................................................6 
2.1. 
Objectives .........................................................................................................................6 
2.2. 
Endpoints ..........................................................................................................................6 
2.3. 
Study Design .....................................................................................................................6 
2.4. 
Sample Size Determination ..............................................................................................8 
3. 
Analysis Sets ....................................................................................................................8 
4. 
Methods............................................................................................................................8 
4.1. 
Software ............................................................................................................................8 
4.2. 
Methodology of Measurements ........................................................................................8 
4.2.1. 
Aqueous Humor Collection and Analysis Methodology ..................................................8 
4.2.2. 
Implant Exchange and Travoprost Analysis Methodology ..............................................8 
4.3. 
Data Handling and Storage ...............................................................................................9 
5. 
Data Analysis ...................................................................................................................9 
5.1. 
Pharmacokinetics ..............................................................................................................9 
5.2. 
In Vivo Drug Elution Rate Calculations ...........................................................................9 
5.3. 
Data Summarization .......................................................................................................10 
5.4. 
Statistical Analysis ..........................................................................................................10 
5.5. 
Presentation of Final Results ..........................................................................................10 
6. 
References ......................................................................................................................11 
7. 
Supporting Documentation ..........................................................................................12 
7.1. 
Appendix A: Schedule of Visits & Measurements: Group 12........................................12 
7.2. 
Appendix B: Schedule of Visits & Measurements: Group 3 ..........................................13 
7.3. 
Appendix C: Schedule of Visits & Measurements: Group 6 ..........................................14 
7.4. 
Appendix D: Schedule of Visits & Measurements: Group 24........................................15 
7.5. 
Appendix E: Schedule of Visits & Measurements: Group 21 ........................................16 
7.6. 
Appendix F: Schedule of Visits & Measurements: Group 18 ........................................17 
7.7. 
Appendix G: Schedule of Visits & Measurements: Group 15........................................18 
 
 
 


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List of Abbreviations 
Abbreviation 
Definition 
AH 
Aqueous Humor 
CSR 
Clinical Study Report 
DAP 
Data Analysis Plan 
EDC 
Electronic Data Capture 
OAG 
Open-Angle Glaucoma 
OHT 
Ocular Hypertension 
PE 
Post-Exchange 
PK 
Pharmacokinetics 
SAP 
Statistical Analysis Plan 
TFA 
Travoprost Free Acid 
 
 
 


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Version History 
This Pharmacokinetic Data Analysis Plan (PK DAP) for IDOS-402-IVIV is based on the 
protocol dated 18SEP2019. 
SAP Version 
Approval Date 
Change 
Rationale 
1 
 
Not Applicable 
Original version 
 
 
 
 
 
 
 


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1. 
Introduction 
The data analyses outlined in this document are to support clinical study IDOS-402-IVIV. In this 
study, measurements will be made for travoprost (prodrug) in exchanged Travoprost Intraocular 
Implants and travoprost free acid (TFA, active moiety) in aqueous humor (AH). This data 
analysis plan (DAP) outlines how data analyses of these measurements will be conducted. 
Additional analyses not specified in the protocol include measurements for fluprostenol (also 
known as TFA) and other travoprost related substances in exchanged Travoprost Intraocular 
Implants, as defined in the analytical test method. Safety analyses are described separately in the 
Statistical Analysis Plan (SAP). Any changes to this plan will be reflected as amendments before 
the database lock and/or documented in the pharmacokinetic contributing report to the clinical 
study report.   
2. 
Objectives and Study Design 
2.1. 
Objectives 
The study objective is to evaluate 
 the performance of the Travoprost 
Intraocular Implant and to study the drug elution rate
 as derived from the residual drug in 
the explant of the Travoprost Intraocular Implant, 
 
 
2.2. 
Endpoints 
This data analysis plan describes analyses for the following study endpoints: 
• Aqueous humor samples and exchanged implants will be collected for analysis of 
travoprost free acid concentration 
• Exchanged implants will be analyzed for residual travoprost  
2.3. 
Study Design 
This is a prospective, non-randomized, open-label, single center trial evaluating 
 
 the performance of the Travoprost Intraocular Implant in subjects 
with open-angle glaucoma (OAG) or ocular hypertension (OHT).  Approximately 210 total 
subjects (14 cohorts of 15 subjects) will 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 be assigned to a cohort and will be implanted with the 
Travoprost Intraocular Implant (G2-TR-125 Implant) in one eye.  Each cohort will consist of a 
specified duration 
 
 
  All enrolled subjects will undergo a second operative visit, the exchange of the 
Travoprost Intraocular Implant, at Visit 7.  The duration of time for each cohort is the time 
between the implantation of the 1st implant at Visit 2 (Day 0) and the implantation of the 2nd 
implant at Visit 7 (Exchange procedure and collection of the aqueous humor and explant).   


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Depending on the cohort assignment, subjects will be followed for 4 – 25 months postoperatively 
(3 – 24 months after 1st implantation and 4 weeks after the 2nd implantation).  Study follow-up 
will continue until the Week 4 post-exchange (PE) visit.   
Depending on the cohort assignment, the study consists of 10 to 13 visits: Visit 1 (Screening), 
Visit 2 (First Operative Day 0), Visit 3 (Day 1), Visit 4 (Day 10), Visit 5 (Week 4), Visit 5.1 
(Month 6), Visit 5.2 (Month 12), Visit 5.3 (Month 18), Visit 6 (Pre-Exchange Exam, within 10 
days prior to Visit 7), Visit 7 (Second Operative/ Exchange), Visit 8 (Day 1 post-exchange [PE]), 
Visit 9 (Day 10 PE), and Visit 10 (Week 4 PE).  Subjects will exit the study at the conclusion of 
the Week 4 PE visit. 
All subjects will have visits at post-operative Day 1, Day 10, Week 4, pre-exchange, and post-
exchange Day 1, Day 10, and Week 4.  Table 1 summarizes the remaining visits for each cohort 
along with other cohort information.  Appendices A-G show the schedule of visits and 
measurements for each cohort.   
Subjects will be assigned to their cohort sequentially as defined by the cohort order as they 
receive surgery.  Each cohort must be filled prior to starting the next cohort.   


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2.4. 
Sample Size Determination 
The sample size of 210 subjects who undergo implantation and exchange of a Travoprost 
Intraocular Implant was determined to support the study objectives and is not based on statistical 
power calculations.  
 
 
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. 
4. 
Methods 
4.1. 
Software 
Pharmacokinetic analysis, summarization of concentration-time data, statistical analysis, and 
graphical visualization of aqueous humor or implant exchange data will be performed using 
 
 
4.2. 
Methodology of Measurements 
4.2.1. 
Aqueous Humor Collection and Analysis Methodology 
A single aqueous humor sample will be collected from each subject at Visit 7 (Exchange visit). 
The timing of Visit 7 will be dependent on the cohort to which each subject is assigned and will 
occur at Month 3, Month 6, Month 12, Month 15, Month 18, Month 21, or Month 24 post-
implantation. A total of 150 µL of aqueous humor will be collected through an anterior chamber 
tap. The aqueous humor sample will be separated into two 75 µL aliquots (a primary and 
backup) and stored at
 
 
 
 
Aqueous humor concentrations of TFA will be determined using a validated liquid 
chromatography-tandem mass spectrometry method 
 
 
 
4.2.2. 
Implant Exchange and Travoprost Analysis Methodology 
Travoprost Intraocular Implants will be exchanged at the timepoints noted in Section 4.2.1. Upon 
insertion of the second implant, the first implant will be explanted and collected for measurement 
Subject Analysis Set 
Description 
Pharmacokinetic analysis set 
• 
All subjects contributing aqueous humor and/or exchanged 
implants. 






CONFIDENTIAL 
Pharmacokinetic Data Analysis Plan [IDOS-402-IVIV] 
 
Glaukos Corporation 
11 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. 
References