A Prospective, Open-label, Multicenter Clinical Follow-up Investigation of the ARGOS-01 and ARGOS-02 Patients to Assess the Long-term Safety and Performance of the ARGOS-IO Intraocular Pressure Sensor System in Subjects With Primary Open Angle Glaucoma (POAG)
Phase: NA
Conditions: Primary Open-angle Glaucoma
Sponsor: Implandata Ophthalmic Products GmbH

 
Clinical Investigation Plan  
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CONFIDENTIALITY NOTE 
The content of this document is confidential and proprietary to  
Implandata Ophthalmic Products GmbH 
Unauthorized use, disclosure or reproduction is strictly prohibited. 
 
 
CLINICAL INVESTIGATION PLAN 
 
 
A prospective, open-label, multicenter clinical follow-up investigation of the 
ARGOS-01 and ARGOS-02 patients to assess the long-term safety and 
performance of the ARGOS-IO intraocular pressure sensor system in 
subjects with Primary Open Angle Glaucoma (POAG) 
 
 
 
Reference Number: ARGOS-03 
 
 
 
 
 
 
Revision: 
Rev. C 
Release Date: 
April 25th, 2018 
Sponsor: 
Implandata Ophthalmic Products GmbH 
Kokenstrasse 5 
30169 Hannover 
Germany 
 

lmplandata Ophthalmie Producls GmbH 
Clinicallnvestigation Plan 
ARGOS-03 
Coordinating lnvestigator Signature Page 
ARGOS-03 
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A prospective open-label, multicenter clinical follow-up investigation of the ARGOS-01 and ARGOS-02 
patients to assess the Iang-term safety and performance of the ARGOS-10 intraocular pressure 
sensor system in subjects with Primary Open Angle Glaucoma (POAG) 
Germany 
Prof. Dr. med. Hagen Thieme 
Institution 
ARGOS-03 
CIP Rev C
20180425
Signature 
University Eye Clinic Magdeburg 
Leipziger Str. 44 
39120 Magdeburg 
CONFIDENTIAL 
Date 

 
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Investigator Signature Page 
ARGOS-03 
A prospective open-label, multicenter clinical follow-up investigation of the ARGOS-01 and ARGOS-02 
patients to assess the long-term safety and performance of the ARGOS-IO intraocular pressure 
sensor system in subjects with Primary Open Angle Glaucoma (POAG) 
 
Investigator Statement 
I have read this protocol and agree to conduct this study in accordance with all stipulations of the 
Clinical Investigation Plan, any applicable standards for the conduct of clinical investigations with 
human patients, any requirements imposed by the responsible competent authority/ethics 
committee, any other applicable local, institutional or legal requirements and in accordance with the 
principles outlined in the Declaration of Helsinki. 
 
 
<Investigator Name> 
 
 
 
 
Signature  
 
Date 
 
 
Institution 
 
 
 
 
 
 
 
 
 
Institutional address / stamp 
 
 

 
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Responsibilities and Contact Information 
Sponsor 
Implandata Ophthalmic Products GmbH 
Kokenstrasse 5 
30159 Hannover, Germany 
Phone: +49 (0) 511 2204 2580 
Fax: +49 (0) 511 2204 2589 
Max Ostermeier, Managing Director 
mostermeier@implandata.com 
Stefan Meyer, Chief Technology Officer 
smeyer@implandata.com 
Dr. med. Kaweh Mansouri, Chief Medical 
Officer 
kmansouri@implandata.com 
Coordinating Investigator 
Prof. Dr. med. Hagen Thieme 
University Eye Clinic Magdeburg 
Leipziger Str. 44 
39120 Magdeburg, Germany 
Phone: +49 (0) 391 6713571 
Email: augenklinik@ovgu.de 
Country Lead Investigators 
Germany 
Prof. Dr. med. Hagen Thieme 
University Eye Clinic Magdeburg 
Leipziger Str. 44 
39120 Magdeburg, Germany 
Phone: +49 (0) 391 6713571 
Email: augenklinik@ovgu.de 
Investigational Sites 
A list of investigational sites is filed separately in 
the TMF. A final list will be shown in the clinical 
investigation report. 
Data Management and Statistics 
GCP-Service International Ltd. & Co.KG 
Anne-Conway-Str. 2 
28359 Bremen, Germany 
Phone: +49 (0) 421 89676617Email: 
germany@gcp-service.com 
Clinical Safety 
MDSS GmbH 
Schiffgraben 41 
30175 Hannover, Germany 
Phone: +49 (0) 511 6262 8630 
Fax: +49 (0) 511 6262 8633  
Email: info@mdss.com 

 
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SYNOPSIS 
Title 
A prospective open-label, multicenter clinical follow-up investigation of the 
ARGOS-01 and ARGOS-02 patients to assess the long-term safety and 
performance of the ARGOS-IO intraocular pressure sensor system in subjects 
with Primary Open Angle Glaucoma (POAG) 
Study Number 
ARGOS-03 
Sponsor 
Implandata Ophthalmic Products GmbH 
Name of MD 
ARGOS-IO System 
The ARGOS-IO system is composed of the implant and its accessories: 
Implant: ARGOS-IO pressure sensor implant for sulcus placement  
Accessories: MESOGRAPH reading device, the MESOGRAPH antenna patch and 
the telemetric Multiline Connector  
Study Design 
This study is a prospective open-label, multicenter study for clinical follow-up of 
the ARGOS-01 and ARGOS-02 patients 
Patient 
Population 
Subjects of the ARGOS-01 and ARGOS-02 study with an implanted ARGOS-IO 
pressure sensor.  
From the ARGOS-01 to the ARGOS-02 study, some modifications were made to 
the form of the ARGOS-IO implant in consequence of the outcomes of the 
ARGOS-01 study. 
Maximal 5 patients of the ARGOS-01 study and maximal 21 patients of the 
ARGOS-02 study will take part in this study. 
The sensor was always implanted in one eye only which will be the study eye. 
Study Purpose 
The purpose of this study is to evaluate the long-term safety and performance 
of the ARGOS-IO system in patients with Primary Open Angle Glaucoma (POAG) 
Study 
Objectives/ 
Evaluation 
Criteria 
Primary Objectives 
Safety 
- 
To evaluate the long-term safety and tolerability of the ARGOS-IO pressure 
sensor under consideration of incidence, nature, severity and seriousness 
of observed medical device related adverse and serious adverse events. 

 
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Performance 
- 
To evaluate the limits of agreement between measurements with 
Goldmann Applanation Tonometry (GAT), Pascal Dynamic Contour 
tonometry (DCT) and the ARGOS-IO system 
- 
Incidence and nature of observed device malfunctions of the ARGOS-IO 
system  
 
Secondary Objectives 
- 
Evaluating the patient’s compliance in IOP self-monitoring 
- 
Evaluating the impact of IOP self-monitoring on glaucoma progression 
- 
Evaluation of incidence in glaucoma medication change 
- 
Evaluation of number of unscheduled visits due to self-measured increased 
intraocular pressure 
Data Collection 
Procedures 
Baseline (V01) 
Consenting subjects will be enrolled. Baseline visit will include: 
• 
Demographics 
• 
Medical history and planned surgeries 
• 
Comparative measurements ARGOS-IO and GAT between the end of 
ARGOS-01/ARGOS-02 and study start of ARGOS-03 
• 
Check of the functionality of the Mesograph and Multiline Connector 
(exchange if necessary) 
• 
Confirmation of the correct function of the ARGOS-IO sensor 
(adjustment if necessary) 
• 
Handout of patient diary 
General 
• 
Best-corrected visual acuity (BCVA) using ETDRS 
• 
Perimetry 
• 
Concomitant medication 
• 
Glaucoma medication 
• 
National Eye Institute Vision-related Quality of Life Questionnaire – 
VFQ-25 
Anterior segment 
• 
External eye photography (Slit-lamp), including iris retroillumination 
• 
Slit-lamp biomicroscopy 

 
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• 
Optical coherence tomography (OCT) of cornea and anterior chamber 
• 
Corneal endothelial cell density measurement 
• 
Gonioscopy 
Posterior segment  
• 
Funduscopy 
• 
Optical coherence tomography (OCT) of macula and optic nerve 
• 
Fundus photography 
IOP measurement  
• 
Goldmann Applanation Tonometry (GAT) 
• 
Pascal DCT tonometry 
• 
ARGOS-IO measurements 
Semiannual Follow-up (V02-V07) 
The examinations performed at each visit are listed without mentioning the 
single visit in parentheses. Examinations that are carried out only at distinct 
visits are indicated in parentheses. The follow-up visits will include:  
General 
• 
ADE/SAE/SADE 
• 
Device deficiency 
• 
Concomitant medication 
• 
Glaucoma medication 
• 
BCVA (EDTRS) 
• 
Perimetry  
• 
National Eye Institute Questionnaire – VFQ-25 (V03, V05 and V07) 
• 
Check patient diary for completeness 
Anterior Segment 
• 
External eye photography (slit-lamp), including iris retroillumination 
• 
Slit-lamp biomicroscopy  
• 
Optical coherence tomography (OCT) of cornea and anterior chamber 
• 
Corneal endothelial cell density measurement 
• 
Gonioscopy 
Posterior segment measurement 
• 
Funduscopy 
• 
Optical coherence tomography (OCT) of macula and optic nerve 

 
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• 
Fundus photography (V03, V05 and V07) 
IOP measurement 
• 
Goldmann Applanation Tonometry (GAT) 
• 
Pascal DCT tonometry 
• 
ARGOS-IO measurements  
• 
ARGOS-IO self-measurements 
Data Collection 
Data will be collected using an electronic based Case Report Form (eCRF). 
Study Duration 
3 years 
 
 
 
 

 
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TABLE OF CONTENTS 
RESPONSIBILITIES AND CONTACT INFORMATION .............................................................. 5 
SYNOPSIS .......................................................................................................................... 6 
TABLE OF CONTENTS ....................................................................................................... 10 
LISTINGS OF FIGURES AND TABLES .................................................................................. 15 
2. ABBREVIATIONS AND DEFINITIONS ........................................................................... 16 
3. BACKGROUND INFORMATION .................................................................................. 18 
3.1 
Glaucoma...................................................................................................................... 18 
3.2 
Glaucoma Treatment .................................................................................................... 18 
3.3 
Measurement of IOP .................................................................................................... 18 
3.3.1 Principle and Gold Standard ................................................................................. 18 
3.3.2 Available Devices .................................................................................................. 19 
3.3.2.1 Direct Tonometer ......................................................................................... 19 
3.3.2.2 Non-Contact Tonometer .............................................................................. 19 
3.3.3 Limitations ............................................................................................................. 20 
4. IDENTIFICATION AND DESCRIPTION OF THE ARGOS-IO SYSTEM ................................. 21 
4.1 
Summary Description of the ARGOS-IO System and its intended Purpose ............... 21 
4.2 
State of Device Development ....................................................................................... 22 
4.3 
Anticipated clinical Benefits .......................................................................................... 25 
5. STUDY OBJECTIVES ................................................................................................... 27 
5.1 
Objectives ..................................................................................................................... 27 
5.1.1 Primary Objectives ................................................................................................ 27 
5.1.1.1 Safety ........................................................................................................... 27 
5.1.1.2 Performance ................................................................................................ 27 
5.1.2 Secondary Objectives ........................................................................................... 27 

 
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5.2 
Claims and intended Performance of the ARGOS-IO System to be verified .............. 28 
5.3 
Risks and anticipated Adverse Device Effects to be assessed ................................... 28 
6. DESIGN OF THE CLINICAL OBSERVATIONAL STUDY .................................................... 28 
6.1 
General Aspects ........................................................................................................... 28 
6.1.1 Description of the Type of Clinical Trial ................................................................ 28 
6.1.2 Equipment to be used to assess the clinical trial variables and arrangements     
for monitoring maintenance and calibration.......................................................... 29 
6.2 
ARGOS-IO and comparator(s) ..................................................................................... 29 
6.2.1 Justification of the choice of comparator .............................................................. 29 
6.2.2 Other medical devices or medication to be used ................................................. 29 
6.3 
Subjects ........................................................................................................................ 30 
6.3.1 Inclusion Criteria.................................................................................................... 30 
6.3.2 Discontinuation or Withdrawal Criteria.................................................................. 30 
6.3.2.1 Premature subject withdrawal ..................................................................... 30 
6.3.2.2 Completed Subjects ..................................................................................... 31 
6.3.2.3 Subjects lost to Follow-up ............................................................................ 31 
6.3.3 Point of Enrolment ................................................................................................. 31 
6.3.4 Expected Duration of each Subject’s Participation............................................... 31 
6.4 
Study Procedures ......................................................................................................... 31 
6.4.1 Informed Consent .................................................................................................. 31 
6.4.2 Allocation of Patient Number ................................................................................ 32 
6.4.3 Methods and Timing for assessing, recording, and analyzing Parameters ......... 32 
6.4.3.1 Safety ........................................................................................................... 32 
6.4.3.2 Performance ................................................................................................ 32 
6.4.4 Assessments ......................................................................................................... 33 
6.4.4.1 Patient Demographics/other Baseline Characteristics ................................ 33 
6.4.4.2 Comparative Measurements ....................................................................... 33 
6.4.4.3 Medical History ............................................................................................ 33 
6.4.4.4 Concomitant Medication, Treatments and Devices .................................... 33 
6.4.4.5 ADEs/SAEs/SADEs ..................................................................................... 33 
6.4.4.6 Check of functionality of the Mesograph and Multiline Connector ............. 33 
6.4.4.7 Confirmation of the correct function of the ARGOS-IO sensor ................... 33 
6.4.4.8 Device Malfunctions ..................................................................................... 34 
6.4.4.9 Patient diary ................................................................................................. 34 
6.4.4.10 Visual Acuity (VA) ..................................................................................... 34 

 
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6.4.4.11 Visual Field (Perimetry)............................................................................. 34 
6.4.4.12 National Eye Institute – Vision-related Quality of Life Questionnaire- 
25 (VFQ-25)………………………………………………………………………….... 34 
6.4.4.13 Anterior Segment Evaluation .................................................................... 34 
6.4.4.14 Posterior Segment .................................................................................... 35 
6.4.4.15 Intraocular Pressure (IOP) Measurement ................................................ 36 
6.4.5 Concomitant Medication........................................................................................ 37 
6.5 
Study Visits ................................................................................................................... 37 
6.5.1 Baseline Visit, V01 (Day 0) ................................................................................... 37 
6.5.2 Follow-up Visits V02-V07 (D180, D360, D540, D720, D900, Day 1080) ............. 39 
6.6 
Visit Schedule and Assessments ................................................................................. 40 
7. STATISTICS ................................................................................................................ 42 
7.1 
Variables for Analysis ................................................................................................... 42 
7.1.1 Disposition ............................................................................................................. 42 
7.1.2 Demographics ....................................................................................................... 42 
7.1.3 Medications and Medical History .......................................................................... 42 
7.1.4 Primary Outcome Variables .................................................................................. 42 
7.1.5 Secondary Outcome Variables ............................................................................. 43 
7.1.6 Additional Outcome Variables............................................................................... 43 
7.2 
Statistical Design, Method and analytical Procedures ................................................. 44 
7.2.1 Subject Disposition ................................................................................................ 44 
7.2.2 Demographic and Baseline Characteristics.......................................................... 44 
7.2.3 Analysis of Primary Safety Outcome Variables .................................................... 44 
7.2.4 Analysis of Primary Performance Outcome Variables ......................................... 45 
7.2.5 Analysis of Secondary Outcome Variables .......................................................... 46 
7.2.6 Analysis of Additional Outcome Variables ............................................................ 46 
7.2.7 Sample Size Calculation ....................................................................................... 46 
7.3 
Level of Significance and the Power of the clinical Investigation ................................ 47 
7.4 
Interim Analysis ............................................................................................................ 47 
7.5 
Procedures for reporting of Deviations from the original statistical Plan ..................... 47 
7.6 
Specification of Subgroups for Analysis ....................................................................... 47 
7.7 
Treatment of missing, unused and spurious Data, including Drop-outs and 
Withdrawals .................................................................................................................. 47 
7.8 
Datasets to be analyzed ............................................................................................... 48 

 
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8. DATA MANAGEMENT ............................................................................................... 48 
8.1 
Site Monitoring .............................................................................................................. 48 
8.2 
Data Collection ............................................................................................................. 48 
8.3 
Database Management and Quality Control ................................................................ 49 
8.4 
Verification, Validation and Security of electronic Data System .................................. 49 
8.5 
Data Retention and Retention Period .......................................................................... 50 
8.5.1 Investigator Records Retention............................................................................. 50 
8.5.2 Sponsor Records Retention .................................................................................. 50 
9. ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND DEVICE DEFICIENCIES ................... 52 
9.1 
Definitions ..................................................................................................................... 52 
9.1.1 Adverse Event (AE) ............................................................................................... 52 
9.1.1.1 Adverse Device Effect (ADE) ...................................................................... 52 
9.1.1.2 Serious Adverse Events .............................................................................. 52 
9.1.1.3 Serious Adverse Device Effect (SADE) ...................................................... 53 
9.1.1.4 Anticipated Serious Adverse Device Effect (ASADE) ................................ 53 
9.1.1.5 Unanticipated Serious Adverse Device Effect (USADE) ............................ 53 
9.1.1.6 Device Deficiency........................................................................................ 53 
9.1.2 Recording of Adverse Device Effects (ADEs) ...................................................... 53 
9.1.3 Reporting of Serious Adverse Events (SAEs) ...................................................... 56 
9.1.4 Device Deficiencies ............................................................................................... 58 
9.1.5 Medical Care ......................................................................................................... 58 
9.1.6 Sponsor Responsibilities ....................................................................................... 58 
10. ADMINSTRATIVE PROCEDURES AND RESPONSIBILITIES ............................................. 60 
10.1 
Informed Consent ......................................................................................................... 60 
10.2 
Regulatory and Ethical Compliance ............................................................................. 61 
10.3 
Approval from Ethics Committee or Regulatory Authority ........................................... 61 
10.4 
Investigator Responsibilities for Ethics Committees and Regulatory Authorities ........ 61 
10.5 
Reporting Responsibilities ............................................................................................ 62 
10.5.1 Investigator reporting Responsibilities .................................................................. 62 
10.5.2 Sponsor reporting Responsibilities ....................................................................... 62 
10.6 
Insurance ...................................................................................................................... 62 
10.7 
Subject follow-up Requirements................................................................................... 62 

 
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10.8 
Investigator and Site Selection ..................................................................................... 62 
11. PUBLICATION POLICY ................................................................................................ 64 
11.1 
Clinical Investigation Report (CIR) ............................................................................... 64 
11.2 
Publication of Study Results ......................................................................................... 64 
12. REFERENCES ............................................................................................................. 65 
 
 

 
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LISTINGS OF FIGURES AND TABLES 
Table 1  Assessment Schedule ................................................................................................................... 40 
 
Table 2. SAE reporting Requirements ......................................................................................................... 57 
 
Table 3. Sponsor reporting Responsibilities................................................................................................. 59 
 
 
 

 
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2. 
ABBREVIATIONS AND DEFINITIONS 
Abbreviation 
Definition 
ACA 
Anterior Chamber Angle 
ACD 
Anterior Chamber Depth 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASADE 
Anticipated serious adverse device effect 
ASIC 
Application specific integrated circuit  
BfArM 
Bundesinstitut für Arzneimittel und Medizinprodukte 
CA 
Competent Authority 
CIP 
Clinical Investigation Plan 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
D 
Day 
DCT 
Dynamic contour tonometry 
EC 
Ethics Committee 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
GAT 
Goldmann Applanation Tonometry 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
IFU 
Instruction for Use 
IO 
Intraocular 
IOL 
Intraocular lens 
IOP 
Intraocular Pressure 
ISF 
Investigator Site File 
ISO 
International Organization for Standardization 
MD 
Medical Device 
MHz 
Megahertz 
Mm 
Millimeter 
mmHg 
millimeter(s) of mercury (a unit of pressure equal to the pressure that can 
support a column of mercury 1 millimeter high) 
MPG 
Medizinproduktegesetz 
MRI 
Magnetic resonance imaging 
N 
Sample number 

 
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NCT 
Non-contact tonometry 
NPG 
Normal Pressure Glaucoma 
OCT 
Optical coherence tomography 
PCB 
Printed circuit board 
PIC 
Patient informed consent 
POAG 
Primary open angle glaucoma 
Rev. 
Revision 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMD 
Surface mounted 
SDV  
Source Data Verification 
TMF 
Trial Master File 
UBM 
Ultrasound Biomicroscopy  
V 
Visit 
VA 
Visual acuity 
USADE 
Unanticipated serious adverse device effect 
 
 

 
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3. 
BACKGROUND INFORMATION 
3.1 
Glaucoma 
An estimated 1 in 40 adults over the age of 40 has glaucoma, a group of conditions that result in 
damage to the optic nerve head, characterized by a progressive thinning of the retinal nerve fiber 
layer and the neuroretinal rim that appears as a central depression in the optic disc. It leads to loss of 
visual field and if not controlled eventually to blindness, of which it is the second most common 
cause worldwide (Quigley, 2011) (Mansouri & Shaarawy, 2011) (King, 2013). There are two types of 
primary glaucoma. In primary open angle glaucoma (POAG), which accounts for approximately 70% 
of the glaucoma cases seen, aqueous outflow from the eye is restricted, possibly due to increased 
resistance in the trabecular meshwork. In closed angle glaucoma, ocular tissue, usually the iris, 
obstructs the drainage pathway (King, 2013). 
3.2 
Glaucoma Treatment 
Glaucoma often remains asymptomatic until late in the disease, when irreversible vision problems 
become evident. Although it may be present with normal intraocular pressures (IOP), the higher the 
IOP, the more rapidly the damage progresses (Quigley, 2011). Reduction of IOP is the only known 
treatment, the main goal of which is the prevention of visual disability in the patient’s lifetime (King, 
2013). Lowering the IOP of patients with POAG by 20 to 40% can halve the rate of progressive 
damage (Quigley, 2011).  
IOP reducing treatments generally begin with eye drops containing prostaglandin analogues or ß-
adrenergic antagonists, although as in other chronic asymptomatic diseases, patient adherence to 
treatment is often poor. If eye drops do not satisfactorily reduce IOP, surgical methods such as laser 
trabeculoplasty or trabeculectomy to reduce production of intraocular fluid, or insertion of an 
artificial shunt into the anterior chamber to increase its drainage may be used (Quigley, 2011) 
3.3 
Measurement of IOP 
3.3.1 
Principle and Gold Standard 
Glaucoma generally develops slowly, with no obvious symptoms. For this reason the only way to 
determine if treatment is working is to monitor IOP regularly. The only method currently available to 
measure IOP directly requires the insertion of a large gauge needle into the eye and is rarely if ever 
used. Under normal clinical conditions, IOP is determined indirectly with one of numerous available 

 
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tonometer devices. Most of these are based on the Imbert-Fick principle that the force needed to 
flatten a defined area of a sphere is proportional to the pressure inside the sphere resisting the 
deformation (Frampton, 2012), (Kakaday, Hewitt, Voelcker, Li, & Craig, 2009). 
3.3.2 
Available Devices 
A number of different tonometric devices are available. These can be categorized based on whether 
or not they involve direct corneal contact. 
3.3.2.1 
Direct Tonometer 
The Goldmann Applanation Tonometer (GAT) was first described in the 1950’s and is considered to 
this day to be the gold standard to which all other methods for measuring IOP are compared. It 
measures the force required to applanate the cornea by pressing a probe of defined area directly 
against it. The Perkins Tonometer is a hand-held tonometer that works on the same principles as the 
Goldmann Tonometer (Burr, et al., 2012).  
Dynamic contour tonometry (DCT) determines IOP by measuring the force required to mold the 
cornea to the shape of the concave probe (Frampton, 2012), while rebound tonometers calculate it 
from the induction current produced when a small plastic-tipped magnetized metal probe is bounced 
against the cornea (Burr, et al., 2012). 
The TonoPen is a hand-held portable tonometer that uses a transducer in its probe tip to measures 
the force required to applanate/indent the cornea, while the Ocuton S, another hand-held 
tonometer, requires direct contact of its prism with the cornea (Cihara, 2008). 
The Sensimed Triggerfish, a new system consisting of a micro-electromechanical strain gauge 
embedded in a disposable silicon contact lens, an adhesive antenna and a portable recorder, allows 
24 hour out-patient monitoring of changes in the diameter of the corneoscleral junction that results 
from changes in IOP (Mansouri & Shaarawy, 2011). 
3.3.2.2 
Non-Contact Tonometer 
In non-contact (air-puff) tonometry (NCT) a rapid air pulse is used to applanate the cornea. 
Advantages to NCT include lack of direct contact with the eye and hence no need for anesthesia, and 
low/no risk of corneal abrasion or infection transmission. The probe of the Ocular Response Analyzer 
applies a slightly stronger force to actually indent the cornea and uses a pneumatic sensor to take 
two measurements, the force at which the cornea is applanated initially and at which it applanates as 

 
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it returns to normal. The difference between these two pressures is due to the viscous damping of 
the cornea (Frampton, 2012). 
In transpalpebral tonometry, IOP is calculated from the rebound of a free-falling rod as it hits the 
tarsal plate of the eyelid over the sclera (Burr, et al., 2012) 
3.3.3 
Limitations 
The accuracy of most of these devices is limited to the degree that the secondary biometric 
parameters they measure are affected by factors other than IOP, such as corneal thickness (Krug, 
Kompa, & Schrage, 2002). The majority of the direct tonometers require use of corneal anesthetics. 
The greatest limitation however is that almost all of the devices are cumbersome and require skill 
and training to use, which in effect limits their use to the clinic /office setting. 
The cost and inconvenience of the required office visits result in treatment decisions that are made 
based on only a few IOP measurements taken months apart. However fluctuations in IOP due to 
patient activity and circadian rhythm are normal. The level of imprecision in repeated IOP 
measurements has been estimated at +/- 5 mmHg, meaning that to be 95% certain there is any 
treatment effect, a difference greater than 7 mmHg must be seen between single pre- and post- 
treatment IOP levels (Rotchford & King, 2012). When 24 hour IOP profiles are taken, which require 
patients be admitted to the clinic, peak values – thought to be the most relevant for patient outcome 
in the long term – are seen outside of normal office hours in 80% of the cases, resulting in changes to 
treatment (Liang, Lee, & Shields, 2009) (Mansouri & Shaarawy, 2011). 
For these reasons, alternative methods are being sought that would allow more frequent IOP 
assessments in the home setting. 
According to company information, Sensimed Triggerfish measures a “profile of 24h ocular 
dimensional changes”, displayed in [arbitrary units], rather than changes in IOP in [mmHg]. To date, 
it is unknown how the measured changes in corneal curvature relate to IOP, especially in magnitude. 
 

 
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4. 
IDENTIFICATION AND DESCRIPTION OF THE ARGOS-IO SYSTEM 
4.1 
Summary Description of the ARGOS-IO System and its intended Purpose 
The ARGOS-IO system was developed for the wireless, contactless measurement of the hydrostatic 
pressure of the aqueous humor (IOP, intraocular pressure) in patients with diagnosed glaucoma, or 
elevated or instable IOP that places them at a risk of ocular damage and loss of visual acuity. It is 
made up of four components: the ARGOS-IO implant, the external hand-held Mesograph reading 
device, the implant injector and the Multiline Connector. 
The ARGOS-IO implant is comprised of a micro-electromechanical system application specific 
integrated circuit (ASIC) bound to a micro-coil of gold and encapsulated in a silicone-rubber material 
that has been widely used for intraocular lenses. It is intended to be implanted during cataract 
surgery, and to remain in place indefinitely. The implant is introduced into the area between the 
intraocular lens and the iris (ciliary sulcus) using standard procedures that employ an implant injector 
similar to those commonly used to insert IOLs. 
Activation of the Mesograph reading device in the near vicinity of the eye establishes an inductive 
current between it and the micro-coil, thereby supplying the ASIC with power and permitting data 
transmission. Pressure-sensor cells and an A/D converter incorporated in the ASIC measure IOP 
directly and transmit the digitized data to the reader. When connected to the reader at the site or 
the patient’s home, the Multiline Connector uploads the data recorded by the reader to a secure 
dedicated data base that can be accessed remotely by the Investigator. Data is redundantly stored in 
non-volatile memory inside the reader device, preventing data loss in case of an error. 
Because the sensors are implanted in the eye, the ARGOS-IO pressure sensor measures IOP directly, 
without interference from corneal properties or due to operator skill. It enables numerous IOP 
measurements daily, providing a complete IOP profile for the entire interval between office visits, 
and allowing timely detection of both peaks due to patient activities and circadian rhythms and 
trends due to disease progression. It also permits easy patient self-monitoring, thereby providing 
patients immediate feedback on their IOP, which in turn should encourage adherence to the 
treatment regimen. 
A Mesograph antenna patch allows continuous 24h-measurements which are triggered automatically 
at regular intervals (e.g. every hour). This makes night measurements possible without the need of 
waking up the patient which can also influence the IOP. designed as follows: A flexible printed circuit 
board (PCB) representing a coil/antenna structure and tuned miniature surface mounted (SMD) 

 
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capacitors soldered onto the PCB result in the coil/antenna structure to resonate and induce an 
electromagnetic field when excited with a 13.56 MHz RF voltage. A low loss connector cable (coaxial) 
is connected to the PCB in a ruggedized fashion. The cable is terminated by a cable connector 
matching the Mesograph reader device RF connector. The PCB is protected from moisture ingress, 
and insulating the voltages induced within the resonating coil. 
The PCB/cable assembly is laminated into a custom skin fixation system designed as an oval patch 
that is surrounding the eye, avoiding obstruction of the optical axis, minimizing patient discomfort, 
and securely fixating the coil/antenna in close proximity to the EYEMATE implantable device for 
>24h. All materials having skin contact are medical grade with an appropriate level of 
documentation. 
The skin fixation system is a complex, multi-layer construction of highly breathable materials, 
conforming facial features surrounding the orbit. The adhesive layer design is emphasizing on sparing 
out facial hair, avoiding cosmetic issues and patient discomfort upon patch removal.   
 
4.2 
State of Device Development 
In the early feasibility ARGOS-01 study, six glaucoma patients (4 POAG and 2 NPG) at a single 
university eye clinic in Germany had an earlier version of the ARGOS-IO pressure sensors implanted 
in the ciliary sulcus concomitantly to cataract surgery. Promising concurrence was seen between IOP 
profiles obtained with ARGOS-IO, GAT and DCT over the 12 months follow-up period and the ARGOS-
IO system was easily used by the patients in the home setting. However, after two fibrin reactions 
classified as procedure-related SAEs were observed, as were multiple adverse events possibly caused 
by the size and/or form of the implant, the sponsor stopped the study to investigate the cause.  
Analysis of an extensive databank of eye MRIs, obtained from MRI Research Inc., a company 
supported by the American National Institute of Health National Eye Institute, demonstrated that the 
ciliary sulcus undergoes a distortion in the first months following cataract extraction. This distortion, 
which is extenuated by the use of single piece IOLs such as those received by all patients in the 
ARGOS-01 study, caused a radial force to be exerted on the ARGOS-IO pressure sensor. In vitro 
testing was then conducted using a tool specially designed to mimic such pressure in a controlled 
manner. It was determined that when exposed to such force, the original ARGOS-IO pressure sensor 
prototype produces aberrant pressure readings and develops a curvature in its horizontal plane.  

 
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As a result of these tests and the ARGOS-01 study, modifications were made to the form of the 
device and the implantation procedure to improve the device’s safety profile. The implant thickness 
was reduced from 0.9 mm to 0.5 mm overall, tapering to a rounded outer edge of only 0.1 mm, and 
haptics were added to the device to better maintain its positional stability and to reduce mechanical 
stresses of the sensor on the eye. In addition, four haptic arms and two allantoid protrusions on the 
posterior surface of the ring were added to the ring to improve its positional stability, facilitate 
unfolding and better distribute pressure on the ring. When subjected to radial force, the redesigned 
sensor ring did not show the abnormalities in pressure readings or the plane distortions seen in the 
earlier version. The implant is also now available in three different diameters to allow selection of 
the implant size that best fits the individual participant. Related procedural changes, including the 
use of a cartridge injector similar to those used to insert foldable IOLs to insert the implant and first 
use of the sensor at 30 days post-surgery instead of at day 1 to 3 as in the previous study, are 
expected to reduce potential stress to the patients’ anterior chambers during surgery and the initial 
post-surgical period. Together, these changes are expected to reduce irritation of the iris and 
pressure drifting observed in the ARGOS-01 study.  
Due to the unique form of the human eye, and the exacting nature of the fit, it is not possible to 
assess the effects of the design modification in animals.  
The ARGOS-02 study investigated the safety and performance of the ARGOS-IO system (second 
generation) in patients with primary open angle glaucoma. Over a one year period, 22 patients 
undergoing phacoemulsification and IOL implantation for cataract received ARGOS-IO implants in an 
add-on procedure. Their eye condition and IOP were followed over the course of 12 months. 
The reported results indicate, that the modifications to the sensor design implemented after the 
ARGOS-01 trial as well as the introduction of an injector device for the implantation of the ARGOS-IO 
pressure sensor have led to a significant improvement of the safety and performance profile of the 
investigational device. The most notable clinical differences compared to the first generation of the 
device are as follows: 
• 
Less inflammation: while all patients in the ARGOS-02 trial experienced at least some degree of 
postsurgical inflammation, in most cases this inflammatory response was similar in intensity and 
duration to that observed after standard cataract surgery. Most notably, not a single case of 
hypopyon occurred during the ARGOS-02 trial compared to two cases (33.3%) in the ARGOS-01 
trial. There were still five patients (21,7%) who experienced fibrin exudation after surgery 

 
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(compared to 66.7% in the ARGOS-01 trial), two of which were briefly hospitalized and treated 
accordingly. All instances of anterior chamber inflammation resolved quickly however and the 
number of other inflammation related adverse events (corneal edema, cystoid macular edema) 
was low and comparable to rates reported in literature for cataract surgery alone. 
• 
Less pigment dispersion: pigment dispersion, which may lead to increased intraocular pressure, 
was reported as adverse event for five out of six patients in the ARGOS-01 and eight out of 22 
patients in the ARGOS-02 trial, thus constituting a significant reduction of pigment release to a 
rate similar to that seen in cataract surgery with sulcus fixed intraocular lenses. Further 
improvements can be expected, when the level of experience with the redesigned device 
increases.  
• 
Better performance: concordance between ARGOS-IO measurements and GAT IOP was 
significantly better than in the ARGOS-01 trial. The mean difference between IOP obtained 
through ARGOS-IO and GAT was 10.2 mmHg in the ARGOS-01 trial and 2.8 mmHg in the ARGOS-
02 trial. The 95% limits of agreement changed from -7.58 mmHg and 30.01 mmHg in the ARGOS-
01 trial to -1.7 mmHg and 7.4 mmHg in the ARGOS-02 trial.  
• 
Better fit in the ciliary sulcus: while in the ARGOS-01 trial the thickness and rigidity of the 
implant led to the flattening of the anterior chamber and some patients, no AC flattening was 
seen in the ARGOS-02 trial. At least one serious adverse event was related to the implant size in 
the ARGOS-02 trial (see SAE DE-07-001). This was due to the outer diameter of the implant, 
rather than its thickness, and led to the revision of the clinical investigation plan: in order to 
better estimate the diameter of the ciliary sulcus UBM is preferable to determination of the 
white to white distance (corneal diameter). 
• 
In the ARGOS-01 trial, a sudden and unexpected offsets in IOP measurements occurred in one 
patient without discernible external cause. Two similar offsets in ARGOS-02 trial where the 
direct result of external manipulation of the eye: one patient experienced an offset after 
ultrasound biomicroscopy (UBM), one of the patient had an offset after YAG capsulotomy during 
follow-up. In both cases, the sensor could be successfully recalibrated. 
Overall, the second generation ARGOS-IO pressure sensor and the use of an implant injector 
significantly improve the outcome of implantation and got a CE-Certificate on May 24th, 2017. 

 
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4.3 
Anticipated clinical Benefits 
Reduction of IOP is to date the only proven therapy for glaucoma (Quigley, 2011). Improved control 
of IOP is linked to better long-term outcomes for glaucoma patients (King, 2013). Most of the 
currently available methods to measure IOP require office or clinic visits and are not feasible for 
frequent, round-the-clock or continuous use or for use in the patient’s daily environment. At the 
same time, IOP fluctuates as a result of the patient’s daily activities and circadian rhythm. Peak 
values – which are thought to be the most significant for long-term outcomes – are often not 
detected. Under normal clinical conditions for example in Germany, IOP of patients with diagnosed 
glaucoma is measured only once every 3 months, which does not provide enough information to 
adequately adjust patient treatment. The ARGOS-IO system makes numerous IOP measurements 
every day on a permanent basis, requiring only that the patient hold the external reader near the eye 
to activate the implant and download the readings several times daily. The physician is able to access 
the readings so recorded, thereby obtaining a complete profile of IOP changes, including peak values 
and values as influenced by all patient activities, for the entire time interval since the last treatment 
visit.  
One objective of this study is to verify the device’s accuracy in the patient population. Until this is 
done, only the control readings made via GAT will be used as the basis for treatment decisions. Study 
patients will however benefit from a more intensive than normal monitoring of their IOP during the 
study and are enabled to measure IOP daily themselves. If and when the device’s usefulness has 
been verified, the patients and the general patient population will benefit from the increased insight 
gained from a continuous long-term monitoring of IOP independent from visits to the 
ophthalmologist. If the device proves successful, the Sponsor plans to develop an internet platform 
that will permit the physician to remotely access information from individual readings, allowing 
patients’ IOP to be monitored between visits. This should permit a more rapid response to changes in 
IOP and a better fine-tuning of treatment protocols. 
Because glaucoma progresses slowly and does not generally cause any immediate symptoms, 
patients have no way of registering the success or failure of their treatment between clinic visits. As a 
result, as with other chronic diseases, adherence to prescribed treatment regimens may be poor 
(Hermann, Bron, & Creuzot-Garcher, 2010). The consequences of poor IOP control are however 
serious and irreversible loss of vision and accompanying handicap. The frequent feedback the patient 

 
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will receive from the device is expected to motivate better compliance with the treatment regimen, 
thereby facilitating improved IOP control and optimizing long-term patient outcome. 
 
 

 
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5. 
STUDY OBJECTIVES  
5.1 
Objectives 
The aim of this trial is to verify the long-term safety and performance of the ARGOS-IO system in 
patients with Primary Open Angle Glaucoma (POAG). The measurements of intraocular pressure 
through the pressure sensor shall be compared with Goldmann Applanation Tonometry (GAT), which 
is generally accepted as the clinical gold standard and the Pascal Dynamic Contour Tonometer (DCT). 
5.1.1 
Primary Objectives 
5.1.1.1 
Safety 
• 
The primary objective of this clinical trial is to evaluate the long-term safety and tolerability 
of the ARGOS-IO pressure sensor under consideration of incidence, nature, severity and 
seriousness of observed medical device related adverse and serious adverse events. 
5.1.1.2 
Performance 
• 
To evaluate the performance of the ARGOS-IO system compared to Goldmann Applanation 
Tonometry (GAT) and Pascal Dynamic Contour tonometry (DCT)  
• 
Incidence and nature of observed device malfunctions of the ARGOS-IO system 
5.1.2 
Secondary Objectives 
• 
Evaluating the patient’s compliance in IOP self-monitoring 
➢ 
Daily self-measurements with the ARGOS-IO sensor should be done at least 4 
times daily (morning, noon, afternoon, evening) 
• 
Evaluating the impact of IOP self-monitoring on glaucoma progression 
➢ Parameters to evaluate the glaucoma progression are visual field, cup/disc ratio, OCT 
of the optic nerve and the IOP. 
• 
Evaluation of incidence in glaucoma medication change 
• 
Evaluation of number of unscheduled visits due to self-measured increased intraocular 
pressure 
➢ The patients decide to come for a visit by their own due to any reason. This will be 
documented. 

 
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5.2 
Claims and intended Performance of the ARGOS-IO System to be verified 
This study aims to estimate the agreement of measurements taken with the ARGOS-IO system to 
those obtained using GAT, Pascal DCT and to collect further information on the occurrence of ADEs 
and SADEs and about the reliability of the device in humans. 
5.3 
Risks and anticipated Adverse Device Effects to be assessed 
Information will be collected on all ADEs. Particular attention will be paid to the following AEs (AEs of 
special interest):  
• 
Signs of toxicity of the implant 
• 
Uncontrolled increase in IOP 
• 
Changes in anterior chamber structures including ACD and ACA 
• 
Anterior chamber inflammation (Tyndall/flare/anterior chamber cells) 
• 
Fibrin reaction (e.g. anterior chamber fibrin, fibrin deposition on lens)  
• 
Corneal endothelial cell loss 
• 
Pigment dispersion  
• 
Iris transillumination defect 
6. 
DESIGN OF THE CLINICAL OBSERVATIONAL STUDY 
6.1 
General Aspects 
6.1.1 
Description of the Type of Clinical Trial 
The trial will be conducted as a prospective, open-label, multicenter clinical follow-up trial.  
The trial will include the ARGOS-01 patients (max. 5 patients) and the ARGOS-02 patients (max. 21 
patients). From the ARGOS-01 study to the ARGOS-02 study, some modifications to the form of the 
ARGOS-IO implant were made in consequence of the outcomes of the ARGOS-01 study. 
The design modifications made included: 
• 
Addition of 4 haptics at the outer edge of the implant 
• 
Reduction in device thickness from a uniform 0.9 mm to 0.5 mm overall, tapering to a 0.1 
mm rounded outer edge 

 
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• 
Addition of two allantoid protrusions runnine on either side of the posterior surface from 
the middle of the ring to the ASIC. 
The ARGOS-IO implant used in the ARGOS-01 study had an outer diameter size of 11.3 mm, an inner 
diameter size of 7 mm and an overall thickness of 0.9 mm. In the ARGOS-02 study three different 
sizes were used: Ø 11.3 mm, Ø 11.7 mm and Ø 12.1 mm; all with an inner diameter of 7 mm and 
thickness of 0.5 mm. 
All consenting ARGOS-IO patients are eligible for enrolment into the study. 
6.1.2 
Equipment to be used to assess the clinical trial variables and arrangements for 
monitoring maintenance and calibration 
Sites will use their own ophthalmology diagnostic devices. The requested calibration intervals have to 
be followed. 
Following any ocular procedure and at least once a year the correct function of the ARGOS-IO 
implant must be confirmed by an experienced and qualified specialist using GAT (the average of 3 
ARGOS-IO measurements are compared to one GAT measurement), and adjusted if necessary (please 
refer to the Mesograph IFU for details). 
6.2 
ARGOS-IO and comparator(s) 
6.2.1 
Justification of the choice of comparator 
GAT is the standard tonometry method to which all other tonometers have traditionally been 
compared. Pascal DCT Is designed to eliminate some of the measurement errors in GAT that come 
from variations in corneal thickness and rigidity. It is believed to be closer to true IOP, especially at 
higher IOPs. It is also less prone to “user error”. 
6.2.2 
Other medical devices or medication to be used 
No other medical devices or medications will be used specifically for this clinical study, except for 
standard of care during surgeries, standard devices for ophthalmic diagnostics, surgery follow up or 
Glaucoma treatment. 

 
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6.3 
Subjects 
6.3.1 
Inclusion Criteria 
ARGOS-01 and ARGOS-02 patients who are willing to provide written informed consent.  
6.3.2 
Discontinuation or Withdrawal Criteria 
6.3.2.1 
Premature subject withdrawal 
Subjects will be informed that they have the right to withdraw from the study at any time. The 
investigator must determine whether voluntary withdrawal is due to safety concerns. 
All subjects who withdraw from the study before completing the last follow-up visit (V7) will be 
considered to be drop-outs. Unless the patient revokes his/her permission to use it, any data 
collected up to the point of the patient’s withdrawal will be included in the safety analysis. The data 
of all subjects will be included in the efficacy analysis under the Full Analysis Set. 
A patient will be withdrawn for any of the following reasons: 
• 
The patient withdraws informed consent. 
• 
The ARGOS-IO pressure sensor must be removed or replaced for any reason (e.g. in 
consequence of an AE related to a study device or procedure). 
Any subject who has been discontinued from the study because of an AE related to a study device or 
procedure will be followed as deemed appropriate by the investigator until resolution or stabilization 
of the event. This will be documented in the medical chart and in the CRF. Any patient who has been 
discontinued from the study because of an AE not related to a study device or procedure will be 
followed as deemed appropriate by the investigator. 
The investigator will classify the termination reason of each subject at the end of the study in the 
termination page of the CRF according to the following: 
• 
AE 
• 
Non-compliance with clinical investigation plan (CIP) 
• 
Lost to follow up 
• 
Voluntary withdrawal not for AE 
• 
Death 

 
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• 
Removal of the ARGOS-IO sensor 
• 
Other reason. 
6.3.2.2 
Completed Subjects 
A completed subject is considered to be a subject that completed the last follow-up visit (V7). In 
addition, a subject who completed the study according to the clinical investigation plan is defined as 
a subject who attended all study visits. 
6.3.2.3 
Subjects lost to Follow-up 
If a subject fails to appear for a follow-up examination, reasonable effort should be made to locate or 
contact them to at least to determine their health status while fully respecting the subject’s rights. 
Reasonable effort consists of documented attempts to contact the patient by phone or post. These 
efforts should be documented in both the source documents and the subject’s CRF. 
6.3.3 
Point of Enrolment 
A subject is considered as being enrolled into the clinical trial when he/she gives consent in writing to 
participate in this study. 
6.3.4 
Expected Duration of each Subject’s Participation 
The maximum duration of each patient’s participation in this clinical intervention is 3 years. The point 
of enrolment is considered to be the time point at which potentially eligible subjects sign the 
informed consent form. The patient will be followed-up for 3 years to obtain data on safety and 
performance. 
6.4 
Study Procedures 
6.4.1 
Informed Consent 
Eligible patients may only be included in the study after providing written informed consent as 
described in Section 12.1. Failure to obtain signed informed consent renders the patient ineligible for 
the study. 

 
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6.4.2 
Allocation of Patient Number 
Each subject is uniquely identified in the study by a combination of his/her country identifier, site 
number and patient number. The number will be the same number as in the ARGOS-01 or ARGOS-02 
study. 
6.4.3 
Methods and Timing for assessing, recording, and analyzing Parameters 
During the study, subjects will attend 7 clinic visits V01-V07 (days 0, 180, 360, 540, 720, 900 and 
1080). The assessment schedule in Table 2 summarizes all visits and the assessments to be 
performed at each visit. The study protocol does not define exact referral dates for follow-up visits. 
However, follow-up visits should be scheduled +/- 3 weeks around the respective date. 
6.4.3.1 
Safety 
At each follow-up visit, the Investigator will examine the patient and record information about any 
new or ongoing adverse device effects or clinically significant ophthalmic adverse events. In addition, 
the Investigator or designated site staff will ask the patient non-leading questions to ascertain if the 
patient experienced any adverse event between visits. 
6.4.3.2 
Performance 
IOP level will be assessed at every visit with GAT, Pascal DCT and the ARGOS-IO system. 
Measurements will be performed in series of 2 GAT measurement followed by 3 consecutive 
measurements with the ARGOS-IO system and 2 DCT measurements followed by 3 consecutive 
measurements with the ARGOS-IO system. 
To assess device deficiencies, at each visit site staff will record any deficiencies observed during the 
visit and will examine the patient’s hand-held reader device and ask patients non-leading questions 
to determine if any device deficiencies occurred during the home use. 
To ensure accuracy and comparability of the recorded parameters, all responsible site personnel will 
be thoroughly instructed on the agreed measurement methods. In particular, to ensure that IOP 
measurements will be comparable between each patient’s individual assessments as well as between 
the different subjects and sites.  

 
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6.4.4 
Assessments 
6.4.4.1 
Patient Demographics/other Baseline Characteristics 
Patient demographic and baseline characteristic data to be collected on all subjects include: year of 
birth, sex, race, weight, height and educational level 
6.4.4.2 
Comparative Measurements 
All ARGOS-IO measurements which were performed in the clinic between study end of the ARGOS-
01/ARGOS-02 trial and which have a comparative GAT measurement should be entered in the eCRF. 
6.4.4.3 
Medical History 
Relevant medical history/current medical condition data includes data five years back until start of 
the study and everything what is important of the investigator’s point of view. Relevant medical 
history should be supplemented by review of the subject’s medical chart and/or by documented 
dialog with the subject’s referring physician. If possible, diagnoses and not symptoms are to be 
recorded. 
6.4.4.4 
Concomitant Medication, Treatments and Devices 
There are no restrictions for the use of concomitant medications and treatments required for 
ophthalmological or systemic diseases during this clinical trial. The use of concomitant medication 
and treatments will be documented in the patient’s file and in the CRF. 
6.4.4.5 
ADEs/SAEs/SADEs 
All ADEs/SAE/SADEs will be recorded. 
6.4.4.6 
Check of functionality of the Mesograph and Multiline Connector 
At V01, the Mesograph will be tested for no error messages, enough storage and filled charged 
battery. The Multiline Connector will be tested for proper data transmission. If necessary, the devices 
will be changed. 
6.4.4.7 
Confirmation of the correct function of the ARGOS-IO sensor 
The correct function of the ARGOS-IO implant must be confirmed  using GAT (the average of 3 
EYEMATE-IO measurements are compared to one GAT measurement), and adjusted if necessary 
(please refer to the Mesograph IFU for details). 

 
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6.4.4.8 
Device Malfunctions 
All observed device malfunctions will be recorded. 
6.4.4.9 
Patient diary 
At V01, the investigator hand out a patient diary to the patient in order to document their 
medication administration and activities at the “IOP day” once a month. 
At the follow-up visits, the investigator should check it for completeness and if the diary is not kept 
regularly, the investigator should brief the patient again. 
6.4.4.10 Visual Acuity (VA) 
The best corrected visual acuity will be determined after objective and subjective determination of 
refraction with the ETDRS chart in accordance with the ETDRS protocol. The number of characters 
read and the reading distance will be recorded. The standard testing distance is 4 meters. 
6.4.4.11 Visual Field (Perimetry) 
The purpose of visual field testing is to determine both the outer limits of visual perception by the 
peripheral retina and the varying qualities of vision within that area. Perimetry is performed to 
obtain an accurate examination of the peripheral extent of the visual field. Automated perimeters 
will be used either with standard glaucoma field, field 30-2 or equivalent. This should always be done 
on both eyes in order to compare study and fellow eyes. 
A change of the perimeter during the study should be avoided. 
6.4.4.12 National Eye Institute – Vision-related Quality of Life Questionnaire-25 (VFQ-25) 
The VFQ-25 is a standardized questionnaire about quality of life relating the patient’s vision. It should 
be completed by the patient at V01, V03, V05 and V07. 
6.4.4.13 Anterior Segment Evaluation 
External Eye Photography (Slit-lamp) 
External eye photography will be performed in order to document potential changes to the anterior 
segment of the eye involving the conjunctiva, cornea, iris (e.g. iris transillumination) or pupil 
structure. 

 
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Slit-lamp Biomicroscopy 
Slit-lamp biomicroscopy involves the examination of the external eye and anterior segment 
structures. The following anatomic parameters will be assessed by using the slit-lamp biomicroscopy: 
a) Lids 
b) Conjunctiva (irritation) 
c) Cornea (edema, Descemet folds) 
d) Anterior chamber (cells/flares (SUN-Classification), fibrin, flattening) 
e) Iris (transillumination, pigment dispersion) 
f) Pupil  
g) Lens 
h) Anterior vitreous (cells/haze (NIH-Grading)) 
Optical Coherence Tomography (OCT) 
Standard anterior segment OCT will be used to evaluate effects on change in chamber angle and to 
assess the central corneal thickness. A change of the OCT device should be avoided during the study. 
Confocal Microscopy 
tandard confocal microscop will be  to determine corneal endothelial cell density. 
A change of the  should be avoided during the study. 
Gonioscopy 
Standard gonioscopy will be used to confirm glaucoma classification and to assess other problems 
within the anterior chamber, such as the presence of foreign bodies hidden in the recess of the 
angle. The gonioscopic grading system according to Shaffer is used in this study. 
6.4.4.14 Posterior Segment  
Funduscopy (dilated) 
The posterior segment will be examined using a slit lamp in combination with a 90D or “Superfield” 
or comparable lenses. The entire fundus should be assessed including optic disc, posterior pole 
including macula and peripheral retina. Any variations of the norm, defects or lesions should be 
documented. 

 
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Optical Coherence Tomography (OCT) 
Posterior segment OCT will be used to assess both macular structures and the peripapillary nerve 
fiber layer (RNFL). 
If available, it should be used the Heidelberg Engineering Spectralis Glaucoma-Module Premium 
Edition (Minimum rim width at Bruch membrane opening (BMO-MRW), RNFLT and macula). This 
should always be done on both eyes in order to compare study and fellow eyes. 
Fundus Photography 
Standard fundus photography will be performed at baseline D180 and then once a year to document 
potential changes to the interior surface of the eye, including the retina. Additionally, a photo of the 
optic nerve and nerve fiber layer will be performed in red-free illumination. 
6.4.4.15 Intraocular Pressure (IOP) Measurement 
Intraocular pressure (IOP) will be measured using three techniques. Goldmann Applanation 
Tonometry (GAT) and Pascal Dynamic Contour Tonometer (DCT) will be performed in the clinic at 
every visit. ARGOS-IO will be performed in the clinic at every visit and by the patient at home 
between visits. Only GAT will be used to guide any treatment decisions. The GAT and DCT must be 
performed by as few dedicated investigators as possible at each site to reduce potential bias. 
IOP Measurement in the Clinic 
Each IOP measurement will be conducted as a series of 2x GAT (with difference more than 2mmHg, a 
third GAT-measurement is required) followed by 3x ARGOS-IO system. When series of measurements 
are made, GAT must always be used first to avoid potential operator bias. For the ARGOS-IO 
measurements the patient has to stay in the same position as for the GAT-measurements (chin on 
chin rest, forehead installed). Then a series of 2x DCT (with difference more than 2mmHg, a third 
DCT-measurement is required) followed by 3x ARGOS-IO will be performed after the series of GAT 
and ARGOS-IO measurements. For the ARGOS-IO measurements, the patient has to stay in the same 
position as for the DCT-measurements (chin on chin rest, forehead installed). 

 
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ARGOS-IO System Measurement by the Patient at Home 
The patients will be requested to perform IOP measurements with the Mesograph 4 times daily at 
home. The measurements should be done in the morning (7-9 o’clock), about noon (11.30-13.30 
o’clock), in the afternoon (15-17 o’clock) and in the evening (19-24 o’clock).  
Once a month, a fixed “IOP-day” will be scheduled where the patients are asked to measure their IOP 
every hour and additionally 1 hour pre and post drug administration. For these days, patients are 
requested to document their activities in the delivered patient dairy. The day will be scheduled at the 
convenience of the patient and investigator and should remain the same for every month and the 
study duration (e.g. first day of the month, first Saturday of the month etc.).  
Quarterly and optional for the patients, one of the “IOP-days” will be scheduled for night 
measurements (22-6 o’clock) in addition to the day measurements every hour. The patient will be 
supplied therefore with the MESOGRAPH antenna patch which will do the measurements 
automatically.  
Patients will also be requested to connect the reader to the Multiline Connector on a regular basis to 
transfer the recorded IOP data directly into the secure database. No manual recording of data by the 
patient will be required. 
Patients shall be instructed to bring the Mesograph reading device to every visit to permit site staff 
to check its functionality and to delete the measured IOP data from the device. The device routinely 
stores up to 3.000 measurements. 
6.4.5 
Concomitant Medication  
The use of concomitant medication is at the discretion of the investigator.  
6.5 
Study Visits 
6.5.1 
Baseline Visit, V01 (Day 0) 
At the Baseline visit, the investigator will conduct the informed consent process (section 12.1), 
ensuring that the subject’s signature has been obtained on the patient informed consent (PIC) form 
and that the subject has received a copy before any study specific procedures are conducted. Once 
the PIC is signed, the subject will be assigned a patient number (section 6.4.2). 
In addition, the following procedures will be performed at this visit: 

 
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• 
Collection of background information about the subject including: demographics, medical 
history with prior treatments and current medications and comparative measurements (see 
6.4.4.2) 
• 
Check of the functionality of the Mesograph and Multiline Connector (exchange if necessary) 
• 
Confirmation of the correct function of the ARGOS-IO sensor (adjustment if necessary) 
• 
Handout of patient diary 
• 
Best corrected visual acuity (BCVA) using ETDRS  
• 
Visual field (standard automated static perimetry, see section 6.4.4.8) 
• 
National Eye Institute – Vision-related Quality of Life Questionnaire-25 (VFQ-25) 
• 
Anterior Segment  
o External eye photography (Slit-lamp), including iris retro illumination 
o Slit-lamp biomicroscopy 
o OCT of cornea and anterior chamber 
o Corneal endothelial cell density measurement 
o Gonioscopy 
• 
Posterior Segment Measurement  
o Funduscopy 
o OCT of macula and optic nerve 
o Fundus photography 
• 
IOP Measurement: 
• 
GAT and ARGOS-IO system 
o 2x GAT, 3x ARGOS-IO (Measurement by investigator with the patient’s head still in 
the headrest from GAT, see 6.4.4.12) 
• 
DCT and ARGOS-IO system  
o 2x DCT, 3x ARGOS-IO (Measurement by investigator with the patient’s head still in 
the headrest from DCT, see 6.4.4.12) 
• 
ARGOS-IO self-measurements at home (4 measurements daily, “IOP-day” once a 
month see 6.4.4.12) 
• 
Instruct subjects on the need to report as soon as possible any SAEs occurring at any time 
during the study  

 
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• 
Complete the CRF and arrange the next visit 
 
6.5.2 
Follow-up Visits V02-V07 (D180, D360, D540, D720, D900, Day 1080) 
Procedures to be conducted at the visits include: 
• Recording of eye related AEs,  ADEs, AEs and SADEs  
• Device deficiencies 
• Concomitant medications 
• Check patient diary for completeness 
• BCVA (EDTRS) 
• Perimetry  
• 
National Eye Institute – Vision-related Quality of Life Questionnaire-25 (VFQ-25) (V03, V05, 
V07) 
• Anterior Segment Measurements:  
o External eye photography, including iris retroillumination 
o Slit-lamp microscopy   
o OCT of cornea and anterior chamber 
o Corneal endothelial cell density measurement 
o Gonioscopy  
• Posterior Segment Measurements: 
o Funduscopy  
o OCT of macula and optic nerve 
o Fundus photography (V03, V05, V07) 
• IOP Measurement: 
• 
 GAT and ARGOS-IO system 
o 2x GAT, 3x ARGOS-IO (Measurement by investigator with the patient’s head still in 
the headrest from GAT, see 6.4.4.11) 
• 
DCT and ARGOS-IO system  

 
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o 2x DCT, 3x ARGOS-IO (Measurement by investigator with the patient’s head still in 
the headrest from DCT, see 6.4.4.11) 
• 
ARGOS-IO self-measurements at home (4 measurements daily, “IOP-day” once a month 
see 6.4.4.12) 
• Complete the CRF and arrange the next visit 
 
 
6.6 
Visit Schedule and Assessments 
Table 1  lists all assessments and indicates with an “X” the visits at which they and related 
assessments are to be performed. The visit window given in the table should be adhered to as closely 
as possible. 
 
Table 1  Assessment Schedule 
Visits 
V01 
V02 
V03 
V04 
V05 
V06 
V07 
Indicative Days (D) 
D0 
D180 
+/- 
3 wks 
D360 
+/-
3wks 
D540 
+/- 
3wks 
D720 
+/- 
3wks 
D900 
+/- 
3wks 
D1080 
+/- 
3wks 
General 
 
Informed Consent 
X 
 
 
 
 
 
 
Handout of the patient diary 
X 
 
 
 
 
 
 
Demographics 
X 
 
Past and current significant 
medical history 
X 
 
 
 
 
 
 
Comparative measurements 
X 
 
 
 
 
 
 
Check of the functionality of the 
Mesograph and Multiline 
Connector 
X 
 
 
 
 
 
 
Confirmation of the correct 
function of the ARGOS-IO 
sensor 
X 
 
 
 
 
 
 
Visual acuity (EDTRS)1 
(both eyes) 
X 
X 
X 
X 
X 
X 
X 
Perimetry (both eyes) 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Eye related AEs/ADE/SAE/SADE 
X 
X 
X 
X 
X 
X 
X 
NEI VFQ-25 
X 
 
X 
 
X 
 
X 
Device deficiency 
 
X 
X 
X 
X 
X 
X 
Check patient diary for 
completeness 
 
X 
X 
X 
X 
X 
X 

 
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Visits 
V01 
V02 
V03 
V04 
V05 
V06 
V07 
Indicative Days (D) 
D0 
D180 
+/- 
3 wks 
D360 
+/-
3wks 
D540 
+/- 
3wks 
D720 
+/- 
3wks 
D900 
+/- 
3wks 
D1080 
+/- 
3wks 
Anterior Segment (both eyes) 
 
External eye photography 
 (Slit lamp) 
X 
X 
X 
X 
X 
X 
X 
Slit-lamp biomicroscopy 
X 
X 
X 
X 
X 
X 
X 
Optical coherence tomography2 
X 
X 
X 
X 
X 
X 
X 
Corneal endothelial cell density  
X 
X 
X 
X 
X 
X 
X 
Gonioscopy 
X 
X 
X 
X 
X 
X 
X 
Posterior Segment (both eyes) 
 
 Funduscopy 
X 
X 
X 
X 
X 
X 
X 
Optical coherence tomography3 
X 
X 
X 
X 
X 
X 
X 
Fundus photography4 
X 
X 
X 
X 
IOP measurement5 
 
Goldmann Applanation  
(both eyes) 
X 
X 
X 
X 
X 
X 
X 
Pascal DCT (both eyes) 
X 
X 
X 
X 
X 
X 
X 
ARGOS-IO clinic 
X 
X 
X 
X 
X 
X 
X 
ARGOS-IO home6 
X 
X 
X 
X 
X 
X 
X 
1The best corrected visual acuity will be determined after objective and subjective determination of refraction with the 
EDTRS chart. 
2 Anterior segment OCT is performed to assess the central cornea thickness and to evaluate effects on change in 
chamber angle after implantation. 
3 Posterior segment OCT is used to assess macular structures and the peripapillary nerve fiber layer thickness (RNFLT) 
and (if possible) BMO-MRW 
4 The fundus should be photographed in order to document potential changes to the optic nerve (cup/disc ration) and 
nerve fiber layer (red-free illumination). 
5 IOP-measurements will be performed in series of 2 GAT measurement (with difference more than 2mmHg, a third 
GAT-measurement is required) and 3 directly consecutive measurements with the ARGOS-IO system followed by 2 
Pascal tonometry (with difference more than 2mmHg, a third DCT-measurement is required) and 3 directly 
consecutive measurements with the ARGOS-IO system.  
For the non-study eye, only GAT and DCT measurements will be performed as described above. 
All measurements should be performed directly one after another. 
6 Measurements at home shall be taken at least 4 times per day (morning, noon, afternoon, evening). Once a month, an 
“IOP day” will be scheduled with measurements every hour and additionally one hour pre and post drug 
administration. The activities on that day will be documented in a patient dairy. 
Optional: Quarterly additional night measurements on one of the “IOP days”. Patients will be supplied therefore with 
the MESOGRAPH antenna patch which will do the measurements automatically.  
 
 

 
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7. 
STATISTICS 
This section describes the most important aspects of the statistical analyses intended at the time of 
investigation planning. Further details on the statistical and analytical aspects will be presented in 
the Statistical Analysis Plan (SAP). The Statistical Analysis Plan will be finalized before study database 
lock.  
7.1 
Variables for Analysis 
7.1.1 
Disposition 
- 
Number of subjects enrolled 
- 
Number of subjects who completed the study (according to protocol),  
- 
Number of subjects who discontinued the study including the reason for discontinuation 
- 
Number of subjects per visit 
- 
Time to discontinuation / study completion 
7.1.2 
Demographics 
- 
Age calculated by:  Year fraction of date of V01 - Year of birth 
- 
Sex 
- 
Race 
- 
Weight 
- 
Height 
- 
BMI calculated from weight and height by: Weight [kg] / Height [m]^2 
- 
Educational level 
7.1.3 
Medications and Medical History 
- 
Past and current medical history 
- 
Concomitant medication 
- 
Glaucoma medication 
7.1.4 
Primary Outcome Variables 
Safety: 
- 
Incidence of medical-device related adverse events 

 
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- 
Incidence of medical-device related serious adverse event.  
o An AE is considered to be device-related if there is at least a possible relationship to the 
medical device according to the rating of the investigator  
o An AE is considered to be serious if it meets any of the criteria defined in Section 9.1.1.2 
The analysis will be split by nature, severity and seriousness of medical device related adverse and 
serious adverse events.  
Performance:  
- 
Limits of agreement between IOP measurements made using GAT and the ARGOS-IO system at 
each study visit.  
- 
Limits of agreement between IOP measurements made using DCT and the ARGOS-IO system at 
each study visit.  
- 
Incidence of observed device malfunctions and nature of device malfunction (e.g. difference of 
more than 5 mmHg between ARGOS-IO and GAT, readout error of the Mesograph because of 
measurements outside -2 and +70mmHG).  
7.1.5 
Secondary Outcome Variables 
- 
Progression of visual field, cup/disc ratio, OCT results for the optic nerve and IOP over the course 
of the study.  
- 
Number of changes in glaucoma medication.  
- 
Number of unscheduled visits due to self-measured increased IOP. 
7.1.6 
Additional Outcome Variables 
- 
Best corrected visual acuity at each visit (both eyes). 
- 
Scores for the National Eye Institute Vision-related Quality of Life Questionnaire – VFQ-25 at the 
respective visit. 
- 
Device deficiencies. 
- 
External eye photography results at each visit (both eyes) 
- 
Slit-lamp biomicroscopy results at each visit (both eyes) 
- 
Corneal endothelial cell density results at each visit (both eyes) 
- 
Gonioscopy results at each visit (both eyes) 
- 
Funduscopy results at each visit (both eyes) 

 
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- 
IOP self-measurements 
7.2 
Statistical Design, Method and analytical Procedures 
The statistical analysis of this study will include an explorative and descriptive analysis of the 
outcome variables described above. Generally, summary tables will be presented. These are either 
frequency tables (ordinal or nominal data) or summary statistics with mean, standard deviation, 
median, minimum, maximum, lower and upper quartile (metric data).  
Outcome variables that are recorded separately for the study eye, i.e. the eye with implanted 
ARGOS-IO sensor, and the fellow eye, i.e. the eye without ARGOS-IO sensor, will be also analyzed 
separately to allow comparisons between the study and fellow eyes.  
All details regarding calculated variables and proposed format and content of tables will be described 
in the SAP.  
7.2.1 
Subject Disposition 
The variables describing the subject disposition will be tabulated using the descriptive statistics 
defined at the beginning of Section 7.2. 
7.2.2 
Demographic and Baseline Characteristics 
Demographic characteristics (year of birth, sex, race, weight, height, BMI, educational level) and all 
other outcome variables including medications and medical history assessed at V01 will be tabulated 
using the descriptive statistics defined at the beginning of Section 7.2. 
Frequencies of previous and concomitant medications will be given based on different ATC code 
levels. Medical history and concomitant diseases will be described based on MedDRA system organ 
class and preferred term levels. 
7.2.3 
Analysis of Primary Safety Outcome Variables 
All recorded AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) in 
effect at the time the database is closed. Only eye-related AEs will be included in the analysis. 
Incidences will be calculated for eye-related AEs, medical-device related AEs and, in case there are 
more than 5 events, also for medical-device related SAEs on the system organ class level and on the 
preferred term level. 
In addition to incidences in total, incidences of will be given by severity and seriousness. 

 
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In order to evaluate the long-term safety, the incidence rate of medical-device related adverse 
events per 10 patient years and accompanying exact 95% confidence intervals will be calculated for 
the safety population, assuming that the number of such adverse events is Poisson distributed. The 
incidence rate per 10 patient years will be calculated as the number of medical-device related AEs 
divided by patient years covered in the study multiplied by 10 patient years. Patient years covered in 
the study will be defined as the sum of the individual on-study times from Baseline Visit (V01) until 
date of study completion.  
This calculation will be also done for AEs of special interest and medical-device related SAEs.  
Since reliability of the incidence rates strongly depends on the number of patient years covered by 
the single patients in the study, the on study time of each patient will be analyzed additionally. 
Listings for eye-related AEs leading to discontinuation, serious AEs, and deaths will also be provided. 
7.2.4 
Analysis of Primary Performance Outcome Variables 
Limits of Agreement 
The Bland-Altman method, which compares the mean of paired measurements to their difference 
will be used to determine the upper and lower limits of agreement expected to contain 95% of the 
IOP value pairs obtained with the ARGOS-IO system and GAT. For this purpose, the mean of each 
series with the respective device will be calculated and used for comparison. The agreement 
evaluation will be based on the assumption that the measurements are constant within the 
measurement series but not between measurement series with the same device. The two-sided 95% 
confidence intervals for each of the agreement limits will be calculated using the Mover method 
(Zou, 2011) to account for repeated observations. IOP values will be displayed as Bland-Altman plots 
of individual measurement pairs by measurement technique for each visit and overall as well as 
mean plots over time.  
Because the ARGOS-IO implant is in direct contact with the aqueous humor and gives a digital 
readout of IOP, it is anticipated to objectively measure the true IOP. In comparison, although GAT is 
considered the gold standard, it measures IOP indirectly through applanation of the cornea and is 
known to be influenced by corneal thickness and biomechanical properties (Burr, et al., 2012). In 
addition, measurements with GAT are known to be subject to operator bias. 
Consequently, the absolute IOP values obtained with the ARGOS-IO system are expected to show a 
systematic shift in measurements compared to those obtained from indirect methods. The Pascal 

 
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Dynamic Contour Tonometer (DCT) is constructed to alleviate some of the operator bias of GAT 
measurements as well as eliminate most of the corneal biomechanical influence on IOP readings.  
Therefore the limits of agreement between the ARGOS-IO system and DTC measurements will be 
also calculated by the described procedure. 
Device Malfunctions 
Incidence of observed device malfunctions and nature of device malfunction will be summarized for 
subjects using the descriptive statistics defined at the beginning of Section 7.2. In addition, the rate 
of device malfunctions per 10 patient years and accompanying exact 95% confidence intervals will be 
calculated, assuming that the number of such device malfunctions is Poisson distributed. The 
procedure will be analogous to the procedure for incidence rates of AEs. 
7.2.5 
Analysis of Secondary Outcome Variables 
Progression of visual field, cup/disc ratio, OCT results for the optic nerve and IOP over the course of 
the study will be summarized for the subjects by eye and visit using the descriptive statistics defined 
at the beginning of Section 7.2. The Change from baseline will be calculated for continuous outcome 
variables and, where meaningful, shift-tables for categorical variables. 
Analysis of changes in glaucoma medication and number of unscheduled visits due to self-measured 
increased IOP will be analyzed analogue to the analysis for incidence rates of AEs. The rate of 
changes in medication / unscheduled visits per 10 patient years and accompanying exact 95% 
confidence intervals will be calculated, assuming that the number of such events is Poisson 
distributed. 
7.2.6 
Analysis of Additional Outcome Variables 
For all additional outcome variables, except for the IOP self-measurements and device deficiencies, 
summaries will be provided per visit and eye or, in case of the VFQ-25, only per visit. Further details 
about the analysis of additional outcome variables will be provided in the SAP. 
7.2.7 
Sample Size Calculation 
Given the exploratory nature of this study, the sample size is not driven by the need for a formal 
statistical hypothesis test with a certain degree of power. Instead, this study is driven by the desire to 
obtain a clinically meaningful amount of data to evaluate the long-term safety and performance of 

 
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the ARGOS-IO system in patients who have been already implanted with the study device. Therefore 
the maximum sample size is 26. This maximum sample size is composed of maximal 5 available 
subjects from the ARGOS-01 study and maximal 21 available subjects from the ARGOS-02 study. It is 
envisaged to enroll all of these subjects. 
The minimal sample size for this study is at the Sponsor’s discretion. This is considered to be 
appropriate since no experimental treatments are planned and all assessments with exception of IOP 
measurement using the ARGOS-IO device are established standard methods.  
7.3 
Level of Significance and the Power of the clinical Investigation 
If not specified otherwise, the level of significance for confidence intervals is 5%. A power calculation 
is not required for this exploratory study since no statistical test is envisaged.  
7.4 
Interim Analysis 
An annual interim analysis for primary and secondary outcome variables is planned. The study status 
and ongoing safety information will be reported to DEKRA on a regular basis. 
7.5 
Procedures for reporting of Deviations from the original statistical Plan 
Significant deviations from the original statistical analysis plan will be listed and clarified in the final 
clinical investigation report. 
7.6 
Specification of Subgroups for Analysis 
In order to investigate the impact of certain characteristics on performance, the primary endpoints 
will also be examined, provided that there are enough subjects in the respective subgroup, by the 
following variables: 
• 
ARGOS-01 patients 
• 
ARGOS-02 patients 
• 
Gender 
• 
Age groups  
• 
Size of ARGOS-IO implant 
• 
Educational level. 
The extent of the subgroup analysis will be described in more detail in the SAP. 
7.7 
Treatment of missing, unused and spurious Data, including Drop-outs and 
Withdrawals 
The handling of missing data will be detailed in the statistical analysis plan. 

 
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7.8 
Datasets to be analyzed 
All subjects enrolled in this study will be included in the analysis since all subjects already have the 
ARGOS-IO sensor implanted and evaluable data for the primary performance are already recorded at 
the baseline visit (V01). As described in the previous section, the handling of missing data will be 
detailed in the statistical analysis plan. Depending on the number of drop-outs during the course of 
the study, sensitivity analyses with subsets of subjects might be planned in the SAP if deemed 
necessary for the correct interpretation of the results. 
8. 
DATA MANAGEMENT 
All Data Management procedures will be detailed in a separate document known as the Data 
Management Plan (DMP). The DMP will also describe the Clinical Data Management System (CDMS) 
that will be used to collect data with an electronic Case Report Form (eCRF) in detail. Relevant study 
data for statistical analysis and study reports according to this protocol have to be recorded in this 
web-based electronic data capture system. 
8.1 
Site Monitoring 
The study will be monitored in compliance with the Declaration of Helsinki, ISO 14155:2011, the 
Clinical Investigation Plan (CIP) and all applicable national and local regulations. All monitoring 
activities will be conducted by trained and qualified monitors, who will document each individual 
monitoring visit. In general, during monitoring visits the monitor will ensure that the study is being 
conducted according to the CIP, ISO 14155:2011, ICH GCP (International Conference on 
Harmonisation Good Clinical Practice) and other applicable regulations, and will compare the CRF 
entries to original source data. He/she will also make sure the informed consent procedure has been 
appropriately carried out and will ensure that all SAEs have been reported within applicable 
timeframes. Detailed monitoring procedures will be described in a separate monitoring plan. 
8.2 
Data Collection 
Data will be collected through an electronic-based Case Report Form (eCRF) provided by the sponsor 
or its designee to the centers prior to study start. The site will enter study data directly into the CRF 
during or as soon after the visit as possible. 

 
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8.3 
Database Management and Quality Control 
The investigator is responsible for maintaining accurate, complete, and up-to-date records for each 
subject. This includes maintaining any source documentation related to the study. The anonymity of 
participating subjects must be maintained. The sites will maintain a list of the subjects´ names and 
the Patient ID assigned to each individual patient. Documents that identify the subject beyond the 
Patient ID will not be submitted to the sponsor (e.g. the signed informed consent document) and 
must be maintained in strict confidence by the investigator, except to the extent necessary to allow 
inspections by the regulatory authorities and audits by the study monitor or sponsor representatives. 
The investigator must promptly review the completed CRFs for each subject. As the person ultimately 
responsible for the accuracy of all CRF data, the investigator must confirm the entries with his/her 
signature at the end of each documented subject’s visit in the CRF. 
Inconsistencies in the data will be queried to the investigators via the electronic data capture system. 
Answers to queries or changes to the data will also be documented in this system directly by the 
physician respectively an authorized member of the investigator’s staff. The audit trail in the eCRF 
documents all changes. Edit checks trigger automatically queries during data entry when a field is not 
populated to specifications defined in the Data Validation Plan (DVP). Manual queries can be issued 
during medical or safety review and data management review. These processes will be performed on 
an ongoing basis as outlined in the DMP until all queries are resolved. 
All queries must be answered and the database locked before any (interim) analysis of the data may 
begin.  
8.4 
Verification, Validation and Security of electronic Data System 
It has been verified by the sponsor that only validated and secure electronic data systems will be 
used in this clinical trial. Electronic data systems include the clinical data management database and 
the ARGOS-IO system measurement database. Database validation and security follow the respective 
national and international requirements. 

 
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8.5 
Data Retention and Retention Period 
8.5.1 
Investigator Records Retention 
All study documents must be retained by the investigator for a period of at least 15 years after 
completion of the study. The investigator at each investigational site must maintain adequate 
records of the clinical study, including: 
• Completed case report forms 
• Medical records 
• Signed informed consent forms 
• Product accountability 
• Shipment and receipt records  
• Adverse Events reports  
• All correspondence between the Investigator and the Ethics Committee, Regulatory 
Authorities, the sponsor and the CRO  
• Any other pertinent data relevant to the study 
The investigator must not destroy any study specific documentation before receiving written 
permission for this from the sponsor. Hospital records will be archived according to local regulations. 
8.5.2 
Sponsor Records Retention 
The sponsor will maintain the following records for at least 15 years after the last device has been 
manufactured or until the company ceases to exist: 
• All correspondence pertaining to the investigation 
• Signed and dated Investigator Agreements and signed and dated investigator curriculum 
vitae that were current at the time of the study 
• Copies of all EC approval letters, the EC review and approval procedures, and relevant EC 
correspondence  
• Names and addresses of the institutions where the clinical investigation was conducted, as 
well as records of approval from site administration 
• Correspondence with authorities as required by national legislation 
• Insurance certificates 
• Adverse Events report forms 

 
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• Names/contact addresses of monitors 
• Statistical analyses and underlying supporting data 
• Final and all interim reports of the clinical investigation 
• Study training records for site personnel and sponsor/CRO personnel. 
• Quality assurance 
To assure accurate, complete and reliable data, the sponsor or its representatives will do the 
following: 
• Provide instructional material to the investigational sites as appropriate 
• Perform a detailed initiation visit to instruct and train the investigational site personnel 
concerning the investigational device and all relevant study procedures 
• Perform regular monitoring visits at the investigational sites 
• Be available for consultation and stay in contact with study site personnel by mail telephone 
and fax 
• Review and evaluate CRF data on a regular basis 
• Conduct assessment of the site’s electronic patient database. 
In addition, the sponsor or its representatives may periodically check a sample of subject data 
recorded against source documents at the study site. 
To ensure the safety of study patients, and to ensure accurate, complete, and reliable data, the 
investigator will keep records of clinical notes and subject medical records in the patient files as 
original source documents for the study. If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ethical committees with direct access to original 
source documents. 
The study may be audited by the sponsor or its representatives at any time. Such an audit will be 
conducted according to a specific audit plan. Investigators will be given notice before an audit occurs. 
The regulatory authorities, both national and foreign, may inspect the study site at any time. The  
Investigator is responsible for notifying the sponsor of such an inspection immediately upon gaining 
knowledge of it. During the audit or inspection, the investigator/institution will permit the auditor, 
and regulatory inspector(s) direct access to all relevant medical records and other source data, study 
related files and CRFs. 

 
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9. 
ADVERSE 
EVENTS, 
ADVERSE 
DEVICE 
EFFECTS 
AND 
DEVICE 
DEFICIENCIES  
9.1 
Definitions 
The following definitions are based on ISO 14155:2011 and MEDDEV 2.7/3 (2010). 
9.1.1 
Adverse Event (AE) 
An Adverse Event (AE) is defined as any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in a subject, whether or not 
related to the investigational medical device 
NOTE 1: This definition includes events related to the investigational medical device or the control. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events related to investigational 
medical devices. 
9.1.1.1 
Adverse Device Effect (ADE) 
Any Adverse Event (AE) that is related to the use of the investigational medical device is defined as 
Adverse Device Effect (ADE). 
NOTE 1: This definition includes adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device. 
9.1.1.2 
Serious Adverse Events 
A Serious Adverse Event is defined as any Adverse Event that: 
• Led to death 
• Led to a serious deterioration in the health of a subject that: 
1. Resulted in a life-threatening illness or injury 
2. Resulted in a permanent impairment of a body structure or body function 
3. Required in-patient hospitalization or prolongation of existing hospitalization 

 
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4. Resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function 
• Led to fetal distress, fetal death or a congenital abnormality or birth defect  
NOTE: An Adverse Event is considered ‘Serious’ if any one of the conditions 1, 2, 3, or 4 applies in 
combination with serious deterioration in health (e.g. a pre-planned hospitalization for a pre-existing 
condition, without a serious deterioration in health, is not considered to be a SAE). 
NOTE for Germany: In Germany the term SAE is defined according to §2 Section 5 MPSV [Medical 
Devices Safety Plan Ordinance]. 
9.1.1.3 
Serious Adverse Device Effect (SADE) 
An Adverse Device Effect that has resulted in any of the consequences characteristic of a SAE. 
9.1.1.4 
Anticipated Serious Adverse Device Effect (ASADE) 
A Serious Adverse Device Effect (SADE) which by its nature, incidence, severity or outcome has been 
identified in the risk analysis report is defined as an Anticipated Serious Adverse Device Effect 
(ASADE).  
9.1.1.5 
Unanticipated Serious Adverse Device Effect (USADE) 
A Serious Adverse Device Effect (SADE) which by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report is defined as an Unanticipated 
Serious Adverse Device Effect (USADE). 
9.1.1.6 
Device Deficiency 
An inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or 
performance is defined as a Device Deficiency. 
NOTE: Device Deficiencies include malfunctions, use errors, and inadequate labeling. 
9.1.2 
Recording of Adverse Device Effects (ADEs) 
All Adverse Device Effects (ADEs) will be documented from the V01 until the subject is discharged 
from the study. 
ADEs will be collected with a non-leading question at each visit: “Have you had any new or worsening 
health problems since the last visit?” as well as by reporting those events directly observed and 

 
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spontaneously reported by the subject. Clearly related signs, symptoms and abnormal diagnostic 
procedures should preferably be grouped together and recorded as a single diagnosis or syndrome 
whenever possible. Seriousness, severity (mild, moderate or severe), outcome and relationship to 
investigational device as well as expectedness and action taken will be recorded in the AE page of 
the CRF. Start and end date and time of the event will also be recorded. 
Seriousness 
Seriousness will be recorded as described in section 11.1.2.2. 
Intensity/Severity 
Severity of AEs will be assessed according to the following definitions: 
• Mild: sign or symptom of the AE is apparent but is easily tolerated by the subject 
• Moderate: the AE interferes somewhat with the subject’s usual activities (disturbing)  
• Severe: the AE prevents the subject from working or performing his/her usual activities 
(unacceptable).  
Relationship to Study Device 
Assessment of causality is based on the following considerations: associative connections (time 
and/or place), pharmacological explanations, previous knowledge of the device, presence of 
characteristic clinical or pathological phenomena, exclusion of other causes, and/or absence of 
alternative explanations. 
The investigator will assess causal relationship to the investigational device according to following 
classifications: 
• None: The time course between use of the device and occurrence or worsening of the AE 
rules out causal relationship; and/or another cause is confirmed and no indication for 
involvement of the study device in the occurrence/worsening of the AE exists 
• Unlikely: The time course between use of the device and occurrence/worsening of the AE 
makes causal relationship unlikely; and/or the known effects of the device provides no 
indication for involvement of the study device in the occurrence/worsening of the AE; and/or 
although it is conceivable based on previous knowledge that study device may have causal 
relationship to occurrence/worsening of the AE, another cause is much more probable; 

 
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and/or another cause is confirmed and involvement of the study device in the 
occurrence/worsening of the AE is unlikely 
• Possible: It is conceivable based on previous knowledge that study device may have causal 
relationship to the occurrence/worsening of the AE but other factors exist that are equally 
likely to be causative factors; or although the previous knowledge on study device does not 
provide any support for causal relationship, no other possible causative factors exist. 
• Probable: Time relationship exists; and previous knowledge on study device supports causal 
relationship although another cause cannot be ruled out. 
• Definite: The criteria for probable relationship are fulfilled and no other possible causative 
factors exist. 
Action taken 
The investigator will document the action taken in relation to the investigational device and to other 
treatments. The categories in relation to the investigational device are: 
• No action taken 
• Device removed 
• Subject withdrawn from the study 
• Other, specify 
The categories in relation to other treatments are: 
• No action 
• Medication given (must be specified in the concomitant medication page) 
• Non-medication treatment given (must be specified) 
• Hospitalization 
• Other, specify 
Outcome The investigator will document the outcome by choosing one of the following alternatives: 
• Recovered 
• Recovered with sequelae 
• Recovering 
• Not recovered 
• Death 

 
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• Unknown. 
All AEs will be recorded on an Adverse Event Form, one for each Adverse Event, which is part of the 
Case Report Form.  
9.1.3 
Reporting of Serious Adverse Events (SAEs) 
The site must report the following events to the sponsor immediately after becoming aware of them:   
1. Any SAE affecting a subject, regardless of its relationship to the device or the study-procedures 
(beginning with the implantation of the ARGOS-IO sensor) 
2. An SADE affecting a user or third party (all) 
3. A device deficiency that might have led to an SAE involving a subject, user or third party if 
suitable action or intervention had not been taken or if circumstances had been less fortunate 
(all) 
If the site is uncertain as to whether an event is an SAE, they should report it to the sponsor as if it 
were. 
The sponsor will report SAEs to the Competent Authority in accordance with ISO 14155, Annex X of 
Directive 93/42/EEC, its amendment Directive 2007/47/EC, Annex 7 of Directive 90/385/EEC, 
MEDDEV 2.7/3 (Dec 2010), the German Ordinance on Medical Device Vigilance (MPSV) (effective 
25 July 2014) and applicable local laws and regulations. Reporting modalities defined in the MPSV 
and MEDDEV 2.7.3 (Dec 2010) will be followed. All SAEs will be documented completely. SAEs for 
which a relationship to the study device or diagnostic or therapeutic procedures performed as part of 
the clinical trial or other conditions of the trial cannot be excluded will be reported to BfArM 
immediately using the SAE report form found on the BfArM website.  A summary report for all other 
SAEs will be submitted to BfArM every three months or as requested by BfArM using the SAE 
summary table from MEDDEV 2.7.4. 
Information reported on the SAE shall include: 
• 
The date the event was reported to the sponsor 
• 
The country  
• 
Site and Patient ID  

 
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• 
The date the subject underwent implantation with the study device 
• 
The date of event onset  
• 
The affected organ system 
• 
A description of the event 
• 
Actions, treatments and patient outcome as a result of the event  
• 
The date the event was first noticed by or reported to the investigator 
• 
An assessment of the relatedness of the event to the procedure  
• 
An assessment of the relatedness of the event to the device  
• 
The expectedness of a SADE  
• 
The event status  
• 
The date of event resolution 
Initial SAE reporting may be done by telephone or email, followed by the completed SAE form. 
Contact information is given on each SAE form and is available in the Investigator Site File. 
All Adverse Events will be documented in the source documents and reported on the Adverse Event 
form in the CRF in a timely manner after the investigator first learns of the event. 
Regulatory authorities and ECs will be informed about SAEs according to local regulations as 
described in Table 3. 
Table 2. SAE reporting Requirements 
Reporting 
Party 
Reports to 
Causal Relationship to 
Study Devices or 
Procedures 
Reporting Timeline 
Reporting Method 
Investigator 
Sponsor 
All SAEs, regardless of 
relationship 
Immediately upon 
learning of the event 
Phone, fax or email to 
MDSS GmbH and 
monitor or other 
sponsor representative 
Sponsor 
BfArM 
Relatedness cannot be 
excluded 
Immediately upon 
learning of the event 
Submission of  
SAE report form for 
single events  
(BfArM website) 
Relatedness can be 
excluded 
Summary report 
every 3 months or as 
otherwise requested 
by BfArM 
Submission of 
MEDDEV 2.7.3 Summary 
Table 
 
 

 
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In case of an immediately reportable Adverse Event the investigators can contact MDSS GmbH via 
Phone, Fax or Email. 
Please send the completed form to: 
MDSS GmbH 
Schiffgraben 41 
30175 Hannover, Germany 
Phone: +49 (0) 511 6262 8630 
Fax: +49 (0) 511 6262 8633 
Email: info@mdss.com 
The sponsor should be informed in a parallel process. 
9.1.4 
Device Deficiencies 
The investigator will record all observed device deficiencies by completing a Device Deficiency Form. 
The reporting modalities are defined in ISO 14155:2011 and MEDDEV 2.7/4 in line with the 
requirements of Annex X of Directive 93/42/EEC and its amendment Directive 2007/47/EC, Annex 7 
of 90/385/EEC and local laws and regulations. 
All device deficiencies must be reported to the sponsor immediately. Any Investigational Medical 
Device Deficiency that might have led to a SAE if a) suitable action had not been taken or b) 
intervention had not been made or c) if circumstances had been less fortunate must be reported as 
described in Table 8.6.3 following the SAE reporting modalities. 
9.1.5 
Medical Care 
At all times during the study, the medical care of the subject is at the discretion of the investigator. 
Following the study, the subjects will return for standard control visits as needed. 
9.1.6 
Sponsor Responsibilities 
The Sponsor is responsible for reporting Serious Adverse Events, interim or annual safety reports, 
premature termination or suspension of the clinical trial, and the final Study Report to Regulatory 
Authorities, the ECs and investigators. Refer to table 4 for details.  
 
 
 

 
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Table 3. Sponsor reporting Responsibilities 
Reporting Responsibility 
Reports to 
Description 
Serious Adverse Events 
(SAEs) 
Regulatory Authorities, 
ECs 
See Sections 11.1.2.2 for details 
Interim or annual safety 
reporting 
ECs and/or CA per local 
regulations 
An interim or annual safety report may be required 
by country regulations, or may be specifically 
requested by the EC/CA 
Premature termination or 
suspension of the clinical 
investigation 
Investigators, ECs, 
relevant Regulatory 
Authorities 
Provide prompt notification of termination or 
suspension and reasons.  
GERMANY: According to MPG §23a, Abs. 1, the 
Sponsor is required to notify BfArM of the completion 
of the clinical investigation within 90 days after close-
out. 
GERMANY: According to MPG §23a, Abs. 2, the 
Sponsor is required to notify BfArM of the premature 
termination of the clinical investigation within 15 
days after termination. 
Final Study Report 
Investigators, ECs, 
relevant Regulatory 
Authorities 
The sponsor will notify the investigators of the 
completion or termination of the study. A Final 
Study Report will be submitted to the 
investigators and the ECs following local 
regulations. Germany: According to MPG §23a, a 
CIR has to be submitted to BfArM within 12 
month completion or premature termination of 
the clinical investigation. 
 

 
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10. 
ADMINSTRATIVE PROCEDURES AND RESPONSIBILITIES 
10.1 
Informed Consent 
Eligible patients may only be included in the study after providing written informed consent as 
approved by the responsible ethic committee. The Patient Informed Consent (PIC) form must be fully 
signed and dated prior to any study related activities required by the protocol (including any 
diagnostic testing, questionnaires, or other study-related procedures). Failure to obtain signed 
informed consent renders the patient ineligible for the study. 
A proposed PIC that complies with the ISO 14155:2011 standard and is considered appropriate for 
this study will be submitted to the Ethics Committees. The PIC will be translated into the local 
language of each country in which the study will be conducted and will contain language that is non-
technical and understandable to the patient. Any changes to the PIC suggested by the investigator 
must be agreed to by Implandata Ophthalmic Products GmbH before submission to the EC and a 
copy of the EC approved version must be provided to the monitor after EC approval. 
The Investigator or designated sub-investigator must explain the study to the patient in detail, talking 
through all points described in the PIC. The patient must be given the opportunity to ask questions 
and ample time to consider his/her participation. The patient will also be informed of his/her right to 
withdraw from the study at any time without giving a reason. If the patient is willing to participate in 
the study, he/she must sign and date two copies of the PIC, which must also be signed and dated at 
the same time by the investigator or designated sub-investigator who explained the study.  
One copy of the PIC will be given to the patient and the other will be retained in the Investigator Site 
File (ISF). 
Subject information and the PIC will be revised if new information becomes available or a CIP 
amendment is issued regarding patient’s safety, study procedures or any aspects of the study that 
could potentially influence the patient’s willingness to continue in the study. After the new patient 
information documents have been approval by EC and regulatory authorities, the patient will be 
informed of the changes and will be asked to sign the new consent form to confirm his/her 
continuation in the study. The investigator is to ensure that the patient is informed in a timely 
manner about any new safety-relevant information that could affect the patient’s willingness to 
continue in the study and agrees to request the patient’s consent again, if necessary. 

 
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10.2 
Regulatory and Ethical Compliance 
This clinical study was designed and shall be implemented and reported in accordance with ISO 
14155:2011, with applicable local laws and regulations, and with the ethical principles laid down in 
the Declaration of Helsinki and described in the ICH-GCP guidelines. 
10.3 
Approval from Ethics Committee or Regulatory Authority 
The Clinical Investigation Plan (CIP) and the proposed PIC must be reviewed and approved by a 
properly constituted Ethics Committee (EC) before study start. A signed and dated statement from 
the EC that the CIP and PIC have been approved by the EC must be given to Implandata Ophthalmic 
Products GmbH before study initiation. 
The study must be reviewed and approved by the responsible Regulatory Authorities before study 
initiation, according to local and national regulations, if required. When an approval process is not 
required by the Regulatory Authority at least a notification shall be performed. Any additional 
requirements imposed by the EC or Regulatory Authority will be followed. 
If any alterations, other than changes of an administrative nature only, are made to the study CIP, a 
formal CIP amendment will be issued and submitted to the relevant EC for approval. The amendment 
will not be implemented until EC approval, except in cases where immediate implementation is 
necessary to eliminate or prevent imminent hazard to the subjects. 
10.4 
Investigator Responsibilities for Ethics Committees and Regulatory Authorities 
Prior to study start, the investigator is required to sign a protocol signature page confirming his or 
her agreement to conduct the study in accordance with all of the instructions and procedures found 
in this protocol and associated documents and to give access to all relevant data and records to 
Implandata Ophthalmic Products GmbH, monitors, auditors, Quality Assurance representatives, 
designees, Ethics Committees, and regulatory authorities as required. If an inspection of the 
investigational site is requested by a regulatory authority, the investigator must immediately inform 
Implandata Ophthalmic Products GmbH that this request has been made. 

 
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10.5 
Reporting Responsibilities 
10.5.1 
Investigator reporting Responsibilities 
The investigator or designee is responsible for completing (including review and signature) and 
submitting to the sponsor all case report forms, as well as reports of any Adverse Events (according 
to country-specific collection requirements), deaths or deviations from the clinical investigation plan. 
If any action is taken by the EC with respect to the investigation, the investigator will forward the 
information to the sponsor as soon as possible. Reports are subject to inspection and to the 
retention requirements as described in section 10.5. Refer to Table 3 for SAE reporting 
responsibilities. 
10.5.2 
Sponsor reporting Responsibilities 
The sponsor is responsible for reporting Serious Adverse Events, interim or annual safety reports, 
premature termination or suspension of the clinical trial, and the Final Study Report. Refer to Table 4 
for details. 
10.6 
Insurance  
The Sponsor maintains appropriate clinical trial liability insurance coverage as required under 
applicable laws and regulations and will comply with applicable local law and custom concerning 
specific insurance coverage. If required, proof of the clinical trial insurance policy will be provided to 
the Ethics Committee. If required by national regulations, indemnification will be provided. 
10.7 
Subject follow-up Requirements 
All pregnancies will be followed to birth. All ongoing ADEs will be followed-up until resolution or until 
7 days after the last subject has been discharged from the study. All SAEs will be followed-up until 
resolution or stabilization. 
10.8 
Investigator and Site Selection 
Site selection will be based on the sites of the ARGOS-01 and ARGOS-02 study. Sites need to meet 
the following criteria: 
• Compliance: 

 
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▪ Willing to comply with the Clinical Investigation Plan (CIP), all required procedures, the 
Declaration of Helsinki, ISO 14155 and national and local regulations 
▪ Patient enrolment and site commitment not expected to be impacted by any 
competing studies 
• Clinical support staff  
▪ Study nurse/assistant/coordinator or equivalent who are adequately trained and 
willing to invest time in study administration and electronic data input 
• Time investment 
▪ Investigator has sufficient time to fulfill the study requirements, including reporting, 
and to attend the study meetings. 
• Equipment / Procedures 
▪ Separate rooms to perform study procedures 
▪ Sufficient, lockable storage capacities for study materials. 
 
 

 
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11. 
PUBLICATION POLICY 
11.1 
Clinical Investigation Report (CIR) 
The sponsor is responsible for generating a Clinical Study Report of the study after the study is 
completed. This report, or parts of it, must be submitted to the relevant authorities if applicable. 
In Germany, according to MPG §23a, a CIR has to be submitted to BfArM within 12 month 
completion or premature termination of the clinical trial. Also see Table 7 in chapter 11.1.8 for 
further details. 
11.2 
Publication of Study Results 
The publication of study results will be agreed between the sponsor and the investigator(s). The 
sponsor is interested in publishing the results of the study, but to prevent publication of any 
confidential information, the sponsor retains the right to review all publications and presentations 
before they are made public. 
 
 

 
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