Comparison of the Performance and Safety of T2769 Versus Vismed® Multi in the Treatment of Moderate to Severe Dry Eye Syndrome
Phase: NA
Conditions: Dry Eye
Sponsor: Laboratoires Thea

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1. GENERAL 
1.1.IDENTIFICATION OF THE CLINICAL INVESTIGATION PLAN 
1.1.1 
Clinical Investigation References 
 
 
CLINICAL INVESTIGATION PLAN 
 
Investigation No. LT2769-002  
the clinical investigation will be registered in Clinicaltrials.gov 
 
 
 
 
Initial Clinical Investigation Plan: 
Version 1.0 dated 04.04.2023 
 
Current Clinical Investigation Plan: 
Version 2.0 dated 15.06.2023 
 
 
 
 
 
 
 
 
 
 
 
 

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1.1.2 
CIP Amendments 

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TITLE: Comparison of the performance and safety of T2769 versus Vismed® Multi in 
the treatment of moderate to severe Dry Eye Syndrome. 
 
 
LABORATOIRES THÉA 
 
Clinical Investigation Plan (CIP) No.: 
LT2769-002 
 
 
Investigational Medical Device (IMD): 
T2769 
 
 
Indication: 
Moderate to severe dry eye syndrome 
 
 
International Coordinating Investigator: 
 
 
 
Sponsor’s Medical Expert: 
  
 
 
This confidential clinical investigation plan is the property of Laboratoires THÉA. No unpublished information contained 
herein may be disclosed without prior written approval of Laboratoires THÉA. 
 
 
 

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1.1.3 
Abbreviations and Acronyms 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ALCOCCEA 
Attributable, Legible, Contemporaneous, Original,  Accurate, 
Complete, Consistent, Enduring and Available 
ANOVA 
Analysis of variance 
ASADE 
Anticipated Serious Adverse Device Effect 
ATC 
Anatomic Therapeutic Chemical 
BCVA 
Best Corrected Visual Acuity 
BSA 
Biological Safety Assessment 
CA 
Competent Authority 
CI 
Confidence Interval 
CIP 
Clinical Investigational Plan 
CIR 
Clinical Investigation Report 
 
 
CNIL 
Commission Nationale de l’Informatique et des Libertés 
CRF 
Case Report Form 
CRO 
Contract Research Organisation 
DD 
Device Deficiency 
DED 
Dry Eye Disease 
DES 
Dry Eye Syndrome 
DEWS 
Dry Eye Workshop 
DMP 
Data Management Plan 
e-CRF 
Electronic Case Report Form 
EDTRS 
Early Treatment Diabetic Retinopathy Study 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
IA 
Interim Analysis 
ICF 
Informed Consent Form 
IEC 
Independent Ethics Committee 
IFU 
Instructions For Use 
IMD 
Investigational Medical Device 
IRT 
Interactive Response Technology 
ITT 
Intent-To-Treat 
IWRS 
Interactive Web Response System 
KSC 
Keratoconjunctivitis Sicca 
LFU 
Lacrimal Functional Unit 
 
 
LS 
Least Squares Means 
MAR 
Missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
 
 

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MMRM 
Mixed Model for Repeated Measures 
NA 
Not applicable 
NRS 
Numeric Rating Scale 
OSDI 
Ocular Surface Disease Index 
PP 
Per Protocol 
QoL 
Quality Of Life 
Q1 
First Quartile 
Q3 
Third Quartile 
 
 
RMP 
Risk Management Plan 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDV 
Source Data Verification 
SH 
Sodium Hyaluronate 
SOC 
System Organ Class 
SOTA 
State Of The Art 
TBUT 
Tear Break Up Time 
TEAE 
Treatment Emergent Adverse Event 
USADE 
Unanticipated Serious Adverse Device Effect 
VAS 
Visual Analogue Scale 
WHODrug 
World Health Organisation Drug dictionary 
 
 

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1.3.PRINCIPAL INVESTIGATOR, COORDINATING INVESTIGATOR AND 
INVESTIGATION SITE(S) 
1.3.1 Investigators details 
The Sponsor will maintain an updated list of Principal Investigators and investigation sites, 
separately from this CIP, throughout the duration of the clinical investigation. The definitive 
list will be provided with the Clinical Investigation Report (CIR). 
Roles, responsibilities and qualifications of investigators are detailed in the CIP. 
1.3.2 External Organizations Details 
 
Name and Functions 
Details 
Regulatory Submissions, Monitoring, 
Project Management, Data-Management, 
Statistics 
 
 
 
 
 
 
         
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
1. 
GENERAL ........................................................................................................................................... 1 
1.1. 
Identification of the Clinical Investigation Plan .......................................................................... 1 
1.1.1 
Clinical Investigation References ............................................................................................ 1 
 
 
1.1.3 
Abbreviations and Acronyms .................................................................................................. 4 
1.2. 
Sponsor ........................................................................................................................................... 6 
1.3. 
Principal Investigator, Coordinating Investigator and Investigation Site(s) ........................... 7 
1.3.1 
Investigators details .................................................................................................................. 7 
1.3.2 
External Organizations Details ................................................................................................ 7 
 
 
2. 
IDENTIFICATION AND DESCRIPTION OF THE IMD ........................................................... 26 
2.1. 
Summary Description of the IMD and its Intended Purpose .................................................. 26 
2.2. 
Details Concerning the Manufacturer of the IMD. .................................................................. 26 
2.3. 
Packaging and Labelling ............................................................................................................. 26 
2.3.1 
Packaging ................................................................................................................................. 26 
2.3.2 
Labelling .................................................................................................................................. 27 
2.4. 
Intended Purpose of the IMD in the Proposed Clinical Investigation .................................... 27 
2.5. 
The Populations and Indications for which the IMD is Intended ........................................... 27 
2.6. 
Description of the IMD ................................................................................................................ 28 
2.7. 
Storage Conditions and INSTRUCTIONS OF Use .................................................................. 29 
2.8. 
Investigator Brochure and InSTRUCTIONs For Use .............................................................. 29 
2.9. 
Description of Comparative DEVICE........................................................................................ 29 
3. 
JUSTIFICATION FOR THE DESIGN OF THE CLINICAL INVESTIGATION .................... 30 
3.4 
Description of the Clinical Development Stage ......................................................................... 33 
4. 
BENEFITS AND RISKS OF THE IMD, CLINICAL PROCEDURE AND CLINICAL 
INVESTIGATION ............................................................................................................................ 33 
4.1 
Anticipated Clinical Benefits ...................................................................................................... 33 

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4.3 
Risks Associated with Participation in the Clinical Investigation ........................................... 34 
4.4 
Possible Interactions with Concomitant Medical Treatments ................................................. 34 
 
 
 
 
5. 
OBJECTIVES AND HYPOTHESES OF THE CLINICAL INVESTIGATION ....................... 36 
5.1 
Claims for Clinical Performance, Effectiveness or Safety of thE imd .................................... 36 
5.2 
Objectives, Primary 
 ........................................................................................... 36 
5.3 
Scientific Justification and Clinical Relevance for Effect Sizes, Non-Inferiority 
Margins or Equivalence Limits .................................................................................................. 36 
 
 
6. 
DESIGN OF THE CLINICAL INVESTIGATION ....................................................................... 38 
6.1 
General .......................................................................................................................................... 38 
6.1.1 
Justification of the Investigation Design ............................................................................... 38 
6.1.2 
Description of the Measures to be Taken to Minimize or Avoid Bias ................................ 39 
6.1.3 
Primary 
 with rationale for their selection and 
measurement ........................................................................................................................... 41 
6.1.4 
Methods and Timing for Assessing, Recording, and Analysing Variables ........................ 43 
6.1.5 
Equipment to be used for Assessing the Clinical Investigation Variables and 
Arrangements for Monitoring Maintenance and Calibration ............................................ 48 
6.1.6 
Procedures for the Replacement of Patients ........................................................................ 48 
6.1.7 
Investigation Sites ................................................................................................................... 48 
6.1.8 
Definition of Completion of the Clinical Investigation ........................................................ 48 
6.2 
IMD(s) and Comparator(s) ......................................................................................................... 49 
6.2.1 
Description of the Exposure to the IMD ............................................................................... 49 
6.2.2 
List of any Other Medical Device or Medication to be Used during the Clinical 
Investigation ............................................................................................................................ 49 
6.2.3 
Number of IMD to be Used, Together with a Justification ................................................. 50 
6.2.4 
Justification ............................................................................................................................. 50 
6.3 
Patients .......................................................................................................................................... 50 
6.3.1 
Inclusion Criteria .................................................................................................................... 50 
6.3.2 
Exclusion Criteria ................................................................................................................... 51 
6.3.3 
Criteria and Procedures for Treatment/Investigation Withdrawal or 
Discontinuation ....................................................................................................................... 53 
6.3.4 
Point of Enrolment.................................................................................................................. 54 
6.3.5 
Point of Randomisation .......................................................................................................... 54 

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7.9 
Management of Bias and, when Randomisation, Matching or Blinding are Applied, 
Plan for Assessment of Success thereof. ..................................................................................... 72 
7.10 
Management of Potential Confounding Factors ....................................................................... 72 
7.11 
Description of Procedures for Multiplicity Control and Adjustment of Error 
Probabilities .................................................................................................................................. 72 
7.12 
Specification of Subgroups .......................................................................................................... 72 
7.15 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan ..................... 73 
7.17 
Define a Strategy for Pooling Data, if Applicable. .................................................................... 73 
8. 
DATA MANAGEMENT .................................................................................................................. 73 
8.1 
Methods for Data Entry and Collection ..................................................................................... 73 
8.2 
Procedures Used for Data Review, Database Cleaning, and Issuing and Resolving 
Data Queries ................................................................................................................................. 73 
8.3 
Procedures for Verification, Validation and Securing of Electronic Clinical Data 
Systems .......................................................................................................................................... 73 
8.4 
Procedures to Maintain and Protect Patient Privacy ............................................................... 74 
8.5 
Methods for Database Locking at the Start of the Analysis and Storage upon 
Completion of the Clinical Investigation ................................................................................... 74 
8.6 
Confidentiality .............................................................................................................................. 75 
8.7 
Data Retention Procedures and specified retention priod ....................................................... 75 
8.8 
Other Aspects of Clinical Quality Assurance ............................................................................ 75 
8.8.1 
Monitoring/Data Audits ......................................................................................................... 75 
8.8.2 
On-site Audits/Regulatory Inspection ................................................................................... 75 
9. 
APPROVAL OF THE CLINICAL INVESTIGATION AND AMENDMENTS ........................ 76 
10. 
DEVIATIONS FROM CIP .............................................................................................................. 76 
11. 
IMD ACCOUNTABILITY .............................................................................................................. 78 
11.1 
Description of the Procedures FOR THE Accountability OF IMD ........................................ 78 
11.2 
Procedures and Particular Materials and Instructions for the Safe Return of imd, 
including those that are Potentially Hazardous ........................................................................ 78 
12. 
STATEMENTS OF COMPLIANCE .............................................................................................. 79 
13. 
INFORMED CONSENT PROCESS ............................................................................................... 79 
14. 
ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND DEVICE 
DEFICIENCIES ................................................................................................................................ 81 

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14.1 
Definition of Adverse Event (AE) and Adverse Device Effect (ADE) ..................................... 81 
14.2 
Definition of Device Deficiencies ................................................................................................. 81 
14.3 
Definition of a Serious Adverse Event (SAE) or Serious Adverse Device Effect 
(SADE) and Unanticipated Serious Adverse Device Effects .................................................... 81 
14.3.1 
Definition of the Severity of an Adverse Event .................................................................... 82 
14.3.2 
Causality Relatedness to the IMD ......................................................................................... 82 
14.4 
Recording AEs .............................................................................................................................. 84 
14.5 
Reporting of SAE ......................................................................................................................... 84 
14.6 
Reporting of Device Deficiencies ................................................................................................ 86 
14.7 
Follow-Up of Patient after AE .................................................................................................... 86 
14.8 
Management of Pregnancy .......................................................................................................... 86 
14.9 
List of Foreseeable AEs and Anticipated Adverse Device Effects, Together with 
their Likely Incidence, Mitigation or Treatment ...................................................................... 87 
15. 
VULNERABLE POPULATION ..................................................................................................... 87 
16. 
SUSPENSION OR PREMATURE TERMINATION OF THE CLINICAL 
INVESTIGATION ............................................................................................................................ 88 
16.1 
Temporary Halt of the Investigation .......................................................................................... 88 
16.2 
Early Termination of the Investigation ...................................................................................... 88 
16.3 
Requirements for Patient Follow-Up and Continued Care...................................................... 89 
17. 
PUBLICATION POLICY ................................................................................................................ 91 
18. 
REFERENCES .................................................................................................................................. 92 
19. 
APPENDICES ................................................................................................................................... 94 
 
 
 
 
 
 
 
 
 
 
 
 

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2. IDENTIFICATION AND DESCRIPTION OF THE IMD 
2.1.SUMMARY DESCRIPTION OF THE IMD AND ITS INTENDED PURPOSE 
The patient will be trained for the correct instillation technique of IMD. The patient will be provided 
with an information on the informed consent form and on the labels on the IMD boxes. 
 
 
 
Test device: T2769 (Thealoz Total) 
 
T2769 is a sterile, phosphate-free and pH neutral solution. It contains Trehalose, Sodium 
Hyaluronate (SH) and Naaga.  
T2769 device is presented in the ABAK® multi-dose bottle (12.5 mL).  
As per Instructions For Use (IFU), T2769 is indicated in case of moderate to severe dry eye 
syndrome. 
 
Comparative device: Vismed® Multi  
Vismed® Multi: eye drops presented in multi-dose container. It contains SH. 
Vismed® Multi is recommended for moderate and severe dry eye conditions.  
2.2.DETAILS CONCERNING THE MANUFACTURER OF THE IMD. 
The legal manufacturer of T2769 according to the European (EU) Medical Device Regulation 
(MDR)) 2017/745 is Laboratoires THÉA.  
 
2.3.PACKAGING AND LABELLING 
2.3.1 
Packaging  
The IMD and Hydrabak® will be packaged by approved contractor. in accordance with  ISO 14155 
and Regulation (UE) 2017/745. The IMDs will be prepared according to the packaging list provided 
by the statistician. 
Hydrabak® is supplied in the ABAK® multi-dose bottle. This innovative and patented device 
provides eye drops through a 0.2 µm filter, preventing any bacterial contamination of the solution 
without the use of any preservatives. 
T2769 is packaged in a multidose white polyethylene ABAK® system bottle. The dispenser is 
already used in several currently marketed eye drops. This innovative and patented device provides 
eye drops through a 0.2 µm filter, preventing any bacterial contamination of the solution without 
the use of any preservatives: 

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Figure 1. Diagram of the ABAK® III bottle 
 
The complete treatment for one patient and for the complete investigation duration will be as 
following: 
Each patient will receive 1 preservative-free multidose bottle of Hydrabak® (ABAK system) during 
the run-in period and 4 preservative-free multidose bottles of the IMD during the investigation. 
2.3.2 
Labelling 
All labels will be written in the local language. The content of the labelling is in accordance with 
ISO 14155 and Regulation (UE) 2017/745 specifications and requirements. 
Each bottle of run-in treatment and IMD will carry one label. 
The carboard box of Hydrabak will also carry a detachable label (flag label) bearing at least the CIP 
number and the batch number. 
The cardboard carton of IMD will also carry a detachable label (flag label) bearing at least the CIP 
number and IMD number. This label will be torn off by the person dispensing the IMD to the patient 
and will be stuck in the space provided in the IMD allocation form in order to record the dispensing 
procedure. 
2.4.INTENDED PURPOSE OF THE IMD IN THE PROPOSED CLINICAL 
INVESTIGATION 
T2769 is intended to hydrate and soothe itchy, red or irritated eyes in case of moderate to severe dry 
eye syndrome (patients over or equal than 18 years excluding pregnant or breastfeeding women).  
  
2.5.THE POPULATIONS AND INDICATIONS FOR WHICH THE IMD IS INTENDED 

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2.7.STORAGE CONDITIONS AND INSTRUCTIONS OF USE 
All IMD should be stored in its original packaging, protected from light and moisture, at a 
temperature between 8 and 25°C and the expiry date refers to the last day of that month as long as 
the packaging is intact, and it has been stored correctly. 
Do not refrigerate or freeze. 
Until dispensed to the patient, products should be in a secure area with restricted access. The 
investigator, the hospital pharmacist or other personnel allowed to store and dispense IMD(s) will 
be responsible for ensuring that the IMD(s) are securely maintained as specified by the Sponsor and 
in accordance with the applicable regulatory requirements. 
T2769 should not be used after the expiry date indicated on the outer cardboard box. 
The product can be used until 24 months before opening and 3 months after first opening. The expiry 
date refers to the intact correctly stored packaging. 
The IMD should not be used if the bottle is damaged. 
If significant changes and/or update on labelling, handling and storage are required during the 
investigation, the corresponding sections will be updated by notifying or submitting to Competent 
Authorities (CAs) concerned accordingly. All investigators’ sites will be immediately informed 
about any change by the Sponsor, investigator or a delegate will inform the patient, if any. 
Accordingly, the Sponsor may decide to halt temporary the recruitment (see Section 16.1). In any 
way, the reasons and the procedures for any changes will be justified and described by the Sponsor. 
2.8.INVESTIGATOR BROCHURE AND INSTRUCTIONS FOR USE 
All details concerning the IMD are specified in separate documents as the IB and the IFU. These 
documents will be updated whenever necessary and all applicable versions will be provided to each 
investigation site throughout the clinical investigation. 
At time of writing the CIP, validated and applicable versions are 
- 
For the IB: V3, MAR-2023 
- 
For the IFU: V8, MAR-2023 
2.9.DESCRIPTION OF COMPARATIVE DEVICE 
Vismed® Multi is purchased from Horus Pharma. 
Vismed® Multi is a sterile solution for ocular use.  
Packaging and labelling are provided in Section 2.32.3. 
Batch number and expiration dates will be specified on the packaging. 
Storage conditions are specified in Section 2.7. 
Table 4 
Vismed® Multi details the composition and function of the comparative device 
Vismed® Multi.  

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Table 4 
Vismed® Multi 
Name of ingredients 
Formula Per 100 mL 
HA, sodium salt 
0.18% 
Sodium chloride 
Potassium chloride 
Magnesium chloride 
Calcium chloride 
Disodique hydrogenophosphate, 
Sodium citrate  
Hydrochloric acid 
Purified water, to 
0.279% 
0.103 g  
0.0092% 
0.0089% 
0.032% 
0.0026%  
Ad pH 7.2 – 7.4 
100 mL 
 
 
3. JUSTIFICATION FOR THE DESIGN OF THE CLINICAL 
INVESTIGATION 

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3.4 DESCRIPTION OF THE CLINICAL DEVELOPMENT STAGE 
The investigation is defined as a pre-market, pivotal stage (cf ISO 14155:2020). The clinical 
investigation design is confirmatory. 
 
4. BENEFITS AND RISKS OF THE IMD, CLINICAL PROCEDURE 
AND CLINICAL INVESTIGATION 
4.1 ANTICIPATED CLINICAL BENEFITS 
The following clinical benefits are expected with the use of T2769: 
- 
Improvement of (global) ocular comfort and relief from the symptoms of dry eyes 
- 
Soothing of ocular sensations (from itchiness and irritations)  
- 
Reduction of the redness of the eyes 
- 
Good level of tolerance on the eye  
 

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4.3 RISKS ASSOCIATED WITH PARTICIPATION IN THE CLINICAL 
INVESTIGATION 
Laboratoires Théa performed a risk analysis according to the current ISO 14971 standard. 
All risks identified in Laboratoires Théa’s risk analysis were mitigated. The remaining residual risks 
were considered to be of negligible or acceptable levels. The risks mitigated to this latter risk level 
(acceptable) are the following:  
- The device is not biocompatible (use of the device beyond the expiry date) 
- The product is not sterile (loss of the sterile barrier due to inappropriate storage conditions by the 
user) 
- The device is contaminated (the user lets the tip of the container touch something (eye, eyelid, 
objects, user's hand OR the user shares the device with another person (cross contamination)) 
- The device leaks (primary packaging deterioration due to inappropriate storage conditions) 
- The patient gets hurt while using the device (the user uses a sharp object to remove the cap/open 
the device and damages the device and/or gets hurt OR the patient drives or uses machines while 
experiencing blurred vision) 
- Continuous use of the device is not ensured (the user uses another product by mistake) 
- A child swallows a component of the device (bottle cap) 
 
All the possible warnings have been put in place in the instructions for use as well as on the 
secondary and primary packaging if possible.  
These hazards cannot arise in the normal conditions of use. 
4.4 POSSIBLE 
INTERACTIONS 
WITH 
CONCOMITANT 
MEDICAL 
TREATMENTS 
To avoid possible interactions with a concomitant treatment, patients should be asked to wait at least 
15 minutes between using two different eye products.  

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5. OBJECTIVES 
AND 
HYPOTHESES 
OF 
THE 
CLINICAL 
INVESTIGATION 
5.1 CLAIMS FOR CLINICAL PERFORMANCE, EFFECTIVENESS OR SAFETY 
OF THE IMD 
There is no claim concerning the clinical performance of THEALOZ TOTAL in the IFU. However, 
the following clinical performances support the claimed clinical benefits: 
- 
THEALOZ TOTAL reduces ocular surface damages 
- 
THEALOZ TOTAL increases tear film stability/quantity 
 
As per the IFU, the claim on clinical safety of THEALOZ TOTAL is: 
- 
THEALOZ TOTAL is well tolerated on the ocular surface 
 
As per the IFU, the clinical benefits of THEALOZ TOTAL are:  
- 
THEALOZ TOTAL relieves from the symptoms of dry eyes 
- 
THEALOZ TOTAL soothes the eyes (from itchiness and irritation sensations)  
- 
THEALOZ TOTAL reduces the redness of the eyes  
 
As per Laboratoires THEA, other clinical benefit of THEALOZ TOTAL is: 
- 
THEALOZ TOTAL improvement of (global) ocular comfort  
 
5.2 OBJECTIVES, PRIMARY 
 
The primary objective of the investigation is to demonstrate the non-inferiority of T2769 versus 
Vismed® Multi in terms of total ocular surface staining (Oxford score) in patients with DES, after 
35 days of treatment. 
 
5.3 SCIENTIFIC JUSTIFICATION AND CLINICAL RELEVANCE FOR EFFECT 
SIZES, NON-INFERIORITY MARGINS OR EQUIVALENCE LIMITS 
Estimation of the standard deviation and determination of the non-inferiority limit are based upon 
data of previous studies and literature. 
Concerning the non-inferiority limit, according to clinicians, a variation of 2 points in the total 
Oxford grade, which corresponds to a variation of less than 1 grade in the three areas (corneal, 
temporal and nasal), is considered as not clinically significant. 

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The packaging list is to be kept by the company responsible for manufacturing and labelling of the 
treatment unit. 
The randomisation and the IMD kit number will be allocated to the patients according to 
randomisation list using an Interactive Response Technology (IRT).  
 
Randomisation will occur at Randomisation visit (Day 1; Visit#2) after all procedures have been 
performed and eligibility for the investigation confirmed. The patient who meets the eligibility 
criteria will be randomly assigned to treatment and associated to a randomisation number. 
 
6.1.2.2 
Masking and Code Breaking  
Serious biases may occur in a clinical investigation including investigator bias (which may arise due 
to knowledge by the investigator of treatment allocated to a particular patient), evaluator bias and 
placebo effects. To protect an investigation against these potential biases, masking will be used.  
This will be an investigator-masked clinical investigation. 
The masked investigator will remain masked to the IMD (T2769 – Vismed® Multi). He/She will 
not receive the returned IMD from the patients. 
The following-up and the number of returned IMDs will be recorded by unmasked collaborator 
throughout the clinical investigation. 
The unmasked collaborator will also be in charge of returned/unreturned IMD (T2769 – Vismed® 
Multi) counting. 
Masking will be achieved by coding the interventions, providing each product unit with identical 
cardboard box and by identifying it by an IMD kit number. 
The code should not be broken except: 
• in case of medical emergency (where knowledge of the IMD received would affect the 
treatment of the emergency), 
• or when it is a regulatory requirement (e.g., for Unanticipated Serious Adverse Device 
Effect [USADE]). 
The investigator is responsible for accessing the IRT System to obtain the name of the IMD received 
by the patient.   
If an emergency code breaking becomes necessary, the investigator should notify the Sponsor.  
When a code is broken, the date, time and reason must be recorded in the patient’s Source, and in 
any associated AE report. The identity of the IMD should not be disclosed in these documents. 
Further to a USADE assessment by the Global Drug Safety & Medical Information Department, the 
code might be broken for reporting purposes. The relevant Laboratoires THÉA, Contract Research 
Organization (CRO) and masked investigator and masked staff remain unaware of the identification 
of the IMD as per the above-mentioned process. 
The overall randomisation list will be broken for data analysis after database lock. 
 
6.1.2.3 
Dispensing  
IMD will be dispensed by the masked collaborator and/or pharmacist delegate for selected tasks. 
Each IMD dispensation will be recorded in the related documentation. 

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During the whole investigation treatment period, the masked investigator and/or delegate will 
remain masked to the IMD (T2769 – Vismed® Multi). He/she will not receive the returned IMD 
from the patients. 
All information regarding the usage of the IMDs will be contained in the package given to patients. 
The IMDs must be dispensed only to patients in accordance with the Clinical Investigational Plan 
(CIP) and the randomisation.  
Once all screening criteria have been checked, the patient will receive a box including Run-in 
Hydrabak® treatment for the run-in period. 
At the randomisation visit#2 (Day 1), once inclusion and exclusion criteria have been checked and 
once the patient is eligible, the randomisation will be performed and the IRT will provide the IMD 
kit number allocated to the patient. 
At the other visit (visit#3, Day 15 days±1 day after the randomisation) with dispensation, the IRT 
will provide the IMD kit number allocated to the patient. 
Two dispensations will be performed as follows: 
- 
At randomisation visit#2(Day 1): one box containing enough bottles for the treatment period 
Day 1 to Day 15 ± 1 day will be provided by the investigator (or delegate) or pharmacist 
with the number assigned by the IRT. 
 
- 
At Visit#3 (Day 15): one box containing enough bottles for the treatment period Day 15± 1 
day to Day 36 + 3 days will be provided by the investigator (or delegate) or pharmacist with 
the number assigned by the IRT. 
The site team member will instruct patient on the method of instilling the doses and will train his / 
her patient to not disclose the IMD characteristics neither during the visit not when reporting / 
discussing AE / Device Deficiency (DD). 
 
6.1.3 
Primary 
, with rationale for their selection and 
measurement 
6.1.3.1 
Primary performance endpoint 
The primary performance endpoint is the change from baseline in total ocular surface staining. It is 
the most commonly used endpoints in clinical trials with DED patients. It is performed to detect 
ocular damage surface, which is considered as a hallmark sign of DED. 
 
 
Thus, the change from baseline (Day 1) in total ocular surface staining grade according to Oxford 
0-15 grading scheme (corneal and conjunctival staining by fluorescein with a yellow filter) at D36 
in the study eye  was set as the primary performance endpoint to evaluate the performance of the 
treatment. 
 
Different ocular surface staining scales have been developed and despite common usage, a 
universally accepted “gold standard” grading scale does not exist for corneal and conjunctival 
staining.  This investigation will use the Oxford scale, a widely used and standardised grading scale. 
International regulatory agencies such as the Food and Drug Administration (FDA) rely on corneal 
and conjunctival staining measurement as a primary endpoint in clinical trials of commercially 
registered dry eye treatments (Begley et al. 2019). 

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6.1.4 
Methods and Timing for Assessing, Recording, and Analysing Variables 
Four visits are scheduled during the course of the investigation as presented below: 
Visit #1: Day 1-10/Day 1-7 Screening visit (run-in period) 
Visit #2: Day 1 Randomisation visit (D1) 
Visit#3: Day15 (±1 day) (D15) 
Visit #4: Final visit Day 36 (+3 days) or premature discontinuation visit. 
Visits should be performed at the same hour (±4 hours) 
The schedule of visits, including the timing of examinations and assessments is presented in Table 
2 
Schedule of Visits and Procedures 
 
Screening Period  
Visit#1: Screening visit (Day1-10/Day1-7) 
 
Visit#1 will consist of the following procedures and examinations to be done according to the 
following order and in each eye. 
Visit#1 will consist of the following procedures by the masked investigator or authorised delegate who 
will perform the ophthalmologic examination during all the visits. 
 
By the masked investigator or delegate for selected tasks (according to local requirements, the 
investigator may delegate tasks to collaborator) 
 
• Information for the patient and signature of the consent (can be done up 7 days before this visit). 
See Section 13. 
 
 On paper CRF 
• Ocular discomfort (VAS)  
 
 On eCRF 
• Demography 
• History of dry eye 
• Urine pregnancy testing 
• Questioning about ocular and systemic medical and surgical history (other than dry eye) 
• Questioning about previous and concomitant ocular and non-ocular treatments 
• Measurement of Far BCVA 
• Questioning about ocular symptoms within the last 48 hours 
• Slit lamp examination for measuring*: 
- Measurement of conjunctival hyperaemia with 
 photographic scale 
- TBUT 

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- Oxford 0-15 grading scheme (corneal and conjunctival staining by fluorescein 
with a yellow filter) 
• Schirmer test without anaesthesia, 
• Verification of inclusion and exclusion criteria, 
• Status of the patient, (start of run-in period or not), 
• Run-in treatment dispensation, 
• Patient diary dispensation (instructions)**. 
 
* Examination must be performed by the masked investigator or delegate for selected tasks  for all visits and using the same 
slit lamp. 
** The patient diary will be an aid to compliance assessment, it will not be recorded in the database. 
The next visit must be scheduled between 7 and 10 days after Visit#1 at the same hour (± 4 hours). 
Treatment Period 
Visit#2: Randomisation visit (Day 1) 
 
Visit#2 will consist of the following procedures and examinations to be done according to the 
following order and in each eye. 
Visit#2 will consist of the following procedures and examinations by the masked investigator or 
authorised delegate who will perform the ophthalmologic examination during all the visits. 
By the masked investigator (the same as the screening visit) or delegate for selected tasks (according 
to local requirements, the investigator may delegate tasks to collaborator) 
 
 On paper CRF 
• Questionnaire (OSDI) 
• Ocular discomfort (VAS)  
 
 On eCRF 
• Questioning about ocular symptoms within the last 48 hours 
• Questioning about Hydrabak® compliance during run-in period and last instillation (at least 6 
hours) before the visit and check of the patient diary completion with the patient, 
• Questioning about previous and concomitant ocular and non-ocular treatments 
• Slit lamp examination for measuring*: 
- Measurement of conjunctival hyperaemia with 
 photographic scale 
- TBUT 
- Oxford 0-15 grading scheme (corneal and conjunctival staining by fluorescein,  
with a yellow filter), 
• Schirmer test* (without anaesthesia), 
• AE reporting  
• Verification of inclusion and exclusion criteria 
• Status of the patient 
• Randomisation 
• IMD dispensation 

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• Patient diary dispensation. The patient who will be instructed to instil the IMD in both eyes and 
report in the patient diary the number of instillations/day and to bring back it at each visit. 
 
* Examination must be performed by the same masked investigator or delegate for selected tasks 
for all visits and using the same slit lamp. 
 
The next visit must be scheduled in 15 days (±1 day) at the same hour (± 4 hours). 
 
Visit#3: Day 15 (±1 day) 
Visit#3 will consist of the following procedures and examinations to be done according to the 
following order and in each eye. 
By the masked investigator (the same as the screening visit) or delegate for selected tasks according 
to local requirements, the investigator may delegate tasks to collaborator) 
 
 On paper CRF 
• Questionnaire (OSDI) 
• Ocular discomfort (VAS)  
 
 On eCRF 
• Questioning about ocular symptoms upon instillation  
• Questioning about ocular symptoms within the last 48 hours 
• Questioning about soothing sensation 15 min after IMD instillation 
• Assessment of global patient satisfaction with the use of bottle 
• Assessment of global satisfaction by the patient 
• Assessment of the ocular tolerance by the patient 
• Questioning about ocular and non-ocular concomitant treatments 
• Review of the completion patient diary  
• Questioning about IMD dose regimen compliance 
• Slit lamp examination for measuring*: 
- Measurement of conjunctival hyperaemia with 
 photographic scale 
- TBUT 
-  Oxford 0-15 grading scheme (corneal and conjunctival staining by fluorescein 
with a yellow filter), 
• Schirmer test* (without anaesthesia), 
• AE reporting  
• Device deficiency 
• Assessment of the ocular tolerance by the investigator 
• Assessment of the performance by the investigator 
* Examination must be performed by the same masked investigator or delegate for selected tasks 
for all visits and using the same slit lamp. 
  
 

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By the unmasked collaborator: 
 
• Recording the number of returned used and unused IMD in document source (the accountability 
is expected for the amount of bottles) and transfer this information to masked investigator. 
 
The next visit must be scheduled at Day 36 later (+3days)  
 
Visit#4: Day 36 (+3days) 
Visit#4 will consist of the following procedures and examinations to be done according to the 
following order and in each eye. 
By the masked investigator (the same as the screening visit) or delegate for selected tasks 
(according to local requirements, the investigator may delegate tasks to collaborator). 
 
 On paper CRF 
• Questionnaire (OSDI) 
• Ocular discomfort (VAS)  
 
 On eCRF 
• Questioning about ocular symptoms upon instillation questionnaire 
• Questioning about ocular symptoms within the last 48 hours  
• Questioning about soothing sensation 15 min after IMD instillation 
• Assessment of global patient satisfaction with the use of bottle 
• Assessment of global satisfaction by the patient 
• Assessment of the ocular tolerance by the patient 
• Questioning about ocular and non-ocular concomitant treatments 
• Measurement of Far Best Corrected Visual Acuity,  
• Review of the completion patient diary  
• Questioning about IMD dose regimen compliance 
• Slit lamp examination for measuring*: 
- Measurement of conjunctival hyperaemia with 
 photographic scale 
- TBUT 
-  Oxford 0-15 grading scheme (corneal and conjunctival staining by fluorescein, 
with a yellow filter), 
• Schirmer test* (without anaesthesia), 
• AE reporting  
• Device deficiency 
• Assessment of the ocular tolerance by the investigator 
• Assessment of the performance by the investigator 
• Status of the patient 

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* Examination must be performed by the same masked person for all visits and using the same slit 
lamp. 
 
 
 
By the unmasked collaborator: 
• Recording the number of returned used and unused IMD in source document (the accountability 
is expected for the amount of bottles),and transfer this information to masked investigator. 
 
Premature discontinuation Visit during the investigation 
A patient who prematurely discontinues from the investigation should have, if possible, a 
premature discontinuation visit. This last site visit should take place as soon as possible after the 
patient stops taking IMD. All follow-up procedures and examinations scheduled to be performed 
at the final visit should be performed at the patient’s premature discontinuation visit.  
If the patient is tested COVID-19 positive during the course of the study, the patient has to inform 
the investigator. Either the patient may continue the investigation when he/she can follow the 
protocol requirements safely and in accordance with the national/regional recommendations or 
the patient may be withdrawn from the investigation.   The last site visit should take place as 
soon as possible after the patient stops taking IMD.  
Note: Randomised patients who withdraw will not be replaced by another subject. The subject 
number and associated randomisation number of the withdrawn subject must not be reassigned 
to a different subject. 
 
Adaptive Follow-Up of Patients Prematurely Withdrawn due to an Exceptional Circumstance (e.g. 
COVID-19 pandemic) 
If the patient withdrew from the investigation due to an exceptional circumstance, and if an onsite 
visit was not authorised, a premature discontinuation visit by phone is required.  
 
- Premature discontinuation phone call  
- 
Check the IMD compliance with the patient  
- 
Instruct the patient to stop the IMD and keep used and unused IMD for later return  
- 
Ensure the continuity of artificial medication as per routine clinical practice  
- 
Collect AE/Serious Adverse Event (SAE) and any changes in concomitant treatments  
- 
Collect DD 
- 
Plan a safety onsite visit 4 weeks later (±7 days) and ensure that the patient understands all 
recommendations  
- 
Record the phone call and all information collected in the patient medical record  

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 Safety Follow-up visit on site1  
During the onsite follow-up visit done 4 weeks later (±7 days) after the premature discontinuation 
phone call, the following procedures are required: 
- 
Check the IMD compliance with the patient  
- 
Record the number of the returned used and unused IMD (by the authorised unmasked 
delegate) 
- 
Check that the patient had stopped the IMD and takes the new treatment, collect start 
and end dates of these medications  
- 
Ensure that dry eye is well controlled  
- 
Collect AE/SAE and any changes in treatments  
- 
Record the visit and all information collected in the patient medical record 
6.1.5 
Equipment to be used for Assessing the Clinical Investigation Variables and 
Arrangements for Monitoring Maintenance and Calibration 
A slit lamp will be used to measure the primary endpoint “Total ocular surface staining grade”. 
During the Site Qualification Visit and the Site Initiation Visit, the site must prove that he has a 
maintenance certificate for the slit lamp. During the study, the monitor should verify that the 
maintenance is performed (cf. manufacturer guidelines). 
During the study, the same slit lamp must be used for the same patient at each protocol visit. 
6.1.6 
Procedures for the Replacement of Patients  
The number of randomised patients will be followed in order to obtain at least 226 evaluable patients 
in the FAS population. 
6.1.7 
Investigation Sites 
Patients are to be enrolled in approximately 40 investigational sites in 9 countries. 
The Sponsor will maintain an updated list of Principal investigators and investigation sites, 
separately from this CIP, throughout the duration of the clinical investigation. The definitive list 
will be provided with the CIR. 
6.1.8 
Definition of Completion of the Clinical Investigation 
The clinical investigation completion is defined with the last visit of the last patient. 
In the case of early termination of the clinical investigation (see Section 16.2), the date of the early 
termination shall be deemed to be the date of the clinical investigation completion. 
 
 
1 If a safety onsite visit is still not possible, the follow-up will be done by phone and the patient is asked to return the 
used and unused investigation products later, when the situation improves or the pickup of the IMD directly from 
the patient will be organised. The compliance will be checked with the number of the returned used and unused 
IMD. 

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6.2 IMD(S) AND COMPARATOR(S) 
6.2.1 
Description of the Exposure to the IMD 
IMD will be administered by the patient every day for 36 + 3 days, one drop in each eye 3 to 6 times 
daily into the lower conjunctival sac of each eye.  
No IMD instillation at least 2 hours before Visit#3 and 4. However, the first instillation can be done 
any time after the patient has completed the randomisation visit.  
There will be two treatment groups: 
• T2769 (test device) 
• Vismed® Multi (reference device)  
A detailed description of T2769 and of Vismed® Multi is available in Section 2. 
6.2.2 
List of any Other Medical Device or Medication to be Used during the 
Clinical Investigation 
Run-in Treatment/Wash-out Treatment  
 
Once all screening criteria have been checked, the patient will receive a box containing 1 bottle of 
Hydrabak® treatment for the run-in period between Day-10/-7 to Day 1. 1 drop in each eye 3 to 6 
times daily 
Hydrabak® is an unpreserved NaCl 0.9% ophthalmic solution supplied in a 10 ml multidose ABAK® 
system bottle. Hydrabak® will be provided by Laboratoires Théa. 
Table 6 
Run-in Medical Device Sodium Chloride (Hydrabak®) 
Ingredient 
Function 
Percentage formula (g/100 mL) 
Sodium Chloride 
Isotonising agent 
0.900 
Disodium phosphate rate 
pH Buffer 
0.317% 
Sodium dihydrogen phosphate 
pH Buffer 
0.067% 
Water for injections 
Vehicle 
Ad 100 mL 
 
 
Batch number and expiration dates will be specified on the packaging. 
Auxiliary Products  
 
An auxiliary product is defined as a product used on site for the needs of a clinical 
investigation as described in the CIP, but not as an IMD. 

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Specific Exclusion Criteria Regarding Childbearing Potential Women [2.3]  
2.3.1 Pregnancy or breast-feeding.  
2.3.2 Childbearing potential woman neither surgically sterilized nor using an adequate 
contraception as oral contraceptive, intra-uterine device, subcutaneous contraceptive implant, 
vaginal ring, patch. 
 
Exclusion Criteria Related to General Conditions [2.4] 
2.4.1 Alcohol addiction and heavy smoker according to investigator’s judgement. 
2.4.2 
Inability of patient to understand the investigation procedures or to give informed consent. 
2.4.3 
Non-compliant patient (e.g., not willing to attend a visit or completing the self-
questionnaire; way of life interfering with compliance). 
2.4.4 
Participation in this investigation at the same time as another clinical investigation/study. 
2.4.5 
Participation in this investigation within the exclusion period of a previous 
study/investigation with a minimum of one month. 
2.4.6 
Patient previously included in this investigation. 
2.4.7 
Patient being institutionalised because of legal or regulatory order, inmate of psychiatric 
wards, prison or state institutions, or employee of the investigation sites or of the Sponsor’s 
company. 
2.4.8 
Patient not covered by the government health care scheme of the country in which he/she 
is living (if applicable). 
2.4.9 
Patient under guardianship/ward of court. 
 
Exclusion criteria related to previous and concomitant treatments (medications/non-
medicinal therapies/procedures) [2.5] 
 
 
2.5.1 
Patient with previous, current or anticipated prohibited listed treatment (or prohibited 
modification of treatment regimen). 
The prohibited treatments (or prohibited modifications of treatment regimen) and their periods of 
use prohibition are listed in the following table. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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If a patient is tested COVID-19 positive during the investigation, the patient has to inform the 
investigator.  
Either the patient may continue the investigation when he/she can follow the protocol requirements 
safely and in accordance with the national/regional recommendations or the patient may be 
withdrawn from the investigation. 
 
If a patient prematurely stops the IMD or should/wants to prematurely withdraw from the 
investigation for any reason, the masked investigator must make every effort to perform all 
the evaluations described for the premature investigation discontinuation visit/for the final 
visit (Visit#4) as soon as possible.  
The ophthalmologist investigator will prescribe the best appropriate treatment to the patient.  
In all cases, the reason(s) for withdrawal, and the primary reason, must be recorded on the Source 
and patient files (source documentation).  
The patient discontinued for AE(s) will be followed-up after discontinuation until the event is 
resolved or considered medically stable by the investigator.  
If a patient is lost-to-follow-up, the investigator must do his/her best to contact the patient initially 
by phone, then by letter, and finally by certified mail. If no response is obtained from the patient, 
the investigator is encouraged to contact one of the patient’s relatives or his/her general practitioner. 
The evidence of these contacts must be recorded in the patient files. 
Screen failures are defined as patient who consent to participate in the clinical investigation but are 
not subsequently randomised in the investigation. 
If a patient is screen-failed, all reasons of screen-failure must be documented in the Source 
document. The screen-failed patient may be rescreened one time. 
In the case of an exceptional circumstance (e.g. COVID-19 pandemic): See 6.1.4.4 
 
6.3.4 
Point of Enrolment 
The point of enrolment corresponds to the time at which a patient signs and dates his/her consent 
form. Patients are to be enrolled in different sites in EU or outside EU.  
6.3.5 
Point of Randomisation 
The point of randomisation corresponds to the time at which a patient is assigned with a 
randomisation number. This randomisation number will be allocated when all Inclusion / Exclusion 
criteria are verified. 
6.3.6 
Total Expected Duration of the Clinical Investigation 
This investigation is planned to start in August 2023 and to be completed in September 2024.  
6.3.7 
Expected Duration of each Patient's Participation 
The treatment period for each patient is 36 + 3 days and a total investigation duration of 49 days 
(maximum days comprising the run-in, treatment period).  

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6.3.8 
Number of Patients Required to be Randomised in the Clinical 
Investigation 
It is planned to randomise 250 patients in order to have 226 evaluable patients (113 per group) for 
the FAS analysis. 
Evaluable patients will be defined as randomised patients having received at least one dose of IMD 
and with at least one performance endpoint post-randomisation visit. 
6.3.9 
Estimated Time Needed to Select this Number (i.e. enrolment period) 
The enrolment period is estimated at about12 months. 
6.3.11 
Information on Vulnerable, Pregnant, and Breastfeeding Population 
This clinical investigation will not be conducted in vulnerable populations as children, pregnant or 
breastfeeding women (urine pregnancy testing will be performed at V1 and for other visits, this 
will be discussed verbally with patients).  
 
See Section 15 
 

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6.4 PROCEDURES 
Timing of procedures is presented in Table 2 
All procedures will be precisely described in the investigator manual. 
All procedures should be performed by the same masked investigator or delegate for selected tasks 
(according to local requirements, the investigator may delegate tasks to collaborator) 
 
6.4.1 
Description of all the Clinical-Investigation-Related Procedures that 
Patients Undergo during the Clinical Investigation. 
6.4.1.1. 
Demographics and Screening Characteristics 
The following characteristics will be collected: 
- 
Age (in years) and gender,  
- 
Previous and concomitant ocular and non-ocular medications, 
- 
History of the investigated disease 
- 
Ocular medical and surgical history with relevant diagnosis other than the investigated 
disease 
- 
Systemic medical and surgical history with relevant diagnosis 
 
6.4.1.2. 
Performance Measures  
- 
Ocular Surface Disease Index (OSDI) Questionnaire 
The OSDI questionnaire (Schiffman et al., 2000; Miller et al., 2010) must be completed by the 
patient at the beginning of a visit before medical history information is collected or any investigation 
assessments are performed. 
The total OSDI score range on a scale from 0 to 100.  
 
- 
Ocular discomfort (VAS) 
Ocular discomfort (global evaluation for both eyes) will be assessed by the patient at each visit 
according to the following:  
“Please mark a vertical line on the horizontal line, indicating your level of ocular discomfort due to 
ocular dryness within the last 48 hours”. VAS will be a 100 mm line: 0 mm = No discomfort, 100 
mm = Maximal discomfort. 
 
 
 
0 
 
100 
 
No discomfort 
Maximal discomfort. 

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- 
Soothing sensation 
Patient will be asked : “How would you rate your soothing sensation within 15 minutes after study treatment 
instillation(s)? 
The soothing sensation felt by the patient within 15 min after MD instillation after 15 and 36 days of treatment 
will be assessed according to the following scale. 
(0) =  
None, 
(1) =  
Mild,  
(2) =  
Moderate, 
(3) =  
Important 
The soothing sensation will be assessed in global for both eyes at each visit post-baseline.  
- 
Ocular symptoms within the last 48 hours  
 
Patient will be asked: “How do you judge the severity of your following ocular symptoms within 
the last 48 hours?” 
The severity of the following ocular symptoms will be assessed at each visit: burning/irritation, 
stinging/eye pain, light sensitivity, itching/pruritus, eye dryness feeling, tearing, foreign body 
sensation as follows: 
0 = Absent  
1 = Mild, present but not disturbing  
2 = Moderate, disturbing, but not limiting with daily activities  
3 = Severe, very distressing and interfering with daily activities  
The ocular symptoms will be assessed in global for both eyes at each visit. The value at D1 will be 
the baseline value. 
 
- 
Slit Lamp Examination 
• Conjunctival hyperaemia 
The level of severity of conjunctival hyperaemia will be scored using the 
 photographic 
scale (0 to 5) in each eye. 
 
 
• Tear Break-Up Time (TBUT) 
The tear film stability will be measured 3 times after the instillation of fluorescein. TBUT will be 
rapidly assessed and expressed in seconds. The sum of the 3 measures will also be expressed in 
seconds. 
TBUT will be measured in each eye. 
 
• Total ocular surface staining (Oxford scale) 

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The total ocular staining grade using Oxford 0-15 grading scheme will be assessed by the staining 
in corneal area and conjunctival areas (temporal and nasal) by fluorescein with a yellow filter.  
The Global Score (sum of score reported for each area: corneal + conjunctival) for each eye will be 
recorded. 
- 
Schirmer Test 
The Schirmer test will be performed without anaesthesia. 
The test should be done without touching directly the strip with the finger to avoid contamination 
of skin lipids.  
The strip should be placed in the temporal part to avoid any contact with the cornea. The patient 
should keep the eyes closed. Values should be measured just at the end of the 5 minutes. 
The Schirmer test will be measured in mm/5 min in each eye. 
- 
Performance Assessment by the investigator 
The investigator has to answer to the following question at the end of the patient examination:  
“Do you consider the IMD performance as: 
- 
Very satisfactory  
- 
Satisfactory  
- 
Not very satisfactory  
- 
Unsatisfactory” 
- 
Patient satisfaction 
 Global satisfaction assessment by the patient 
The patient has to answer to the questionnaire in local language.  
“In a scale from 0 to 10, where 0 is COMPLETELY UNSATISFIED and 10 is COMPLETELY 
SATISFIED, indicate the number which corresponds the best to your overall satisfaction” 
 
.  
 Global patient Satisfaction assessment with the use of the bottle  
 
 
The patient has to answer to this question in local language. 
“Are you satisfied with the use of the bottle?” 
- 
Very satisfactory  
- 
Satisfactory  
- 
Not very satisfactory  
- 
Unsatisfactory” 
 

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6.4.1.3. 
Safety measures 
Adverse Events and device deficiencies Ocular and systemic AEs will be collected by the 
investigator (or authorised assessor/delegate) at each visit. 
In case of appearance of a new clinically significant sign or symptom, it should be reported as an 
AE or SAE. 
In case of clinically significant worsening of a pre-existing sign or symptom, it should be reported 
as an AE or SAE. 
The handling of AEs is detailed in Section 14. 
DD will be also collected. 
• Ocular Symptoms Upon Instillation, 
The severity of ocular symptoms upon instillation will be assessed by the patient. 
“Since the last visit, have you felt any unusual ocular sensation immediately after study treatment 
instillation (s)? 
The following symptoms will be evaluated: 
- 
Burning/Irritation  
- 
Stinging/Eye Pain 
- 
Itching/pruritus 
- 
Eye dryness feeling 
- 
Foreign body sensation  
- 
 
Severity will be assessed based on a 4-point scale: 
0 =  
Absent, 
1 =  
Present but not disturbing, 
2 =  
Disturbing 
3 =  
Very disturbing. 
 
The translation of these terms will be provided to the site.  
• Visual Acuity  
Far (BCVA) will be assessed in each eye using the same chart throughout the study. It can be 
expressed using units as /10, decimal notation, MAR, logMAR, EDTRS or Snellen notation. It will 
be analysed after conversion in LogMar. 
). 
• Ocular Tolerance Assessment by the investigator 
The investigator has to answer to the following question in local language: 
“How do you consider the IMD ocular tolerance?  
- 
Very satisfactory 
- 
Satisfactory 
- 
Not very satisfactory 
- 
Unsatisfactory” 

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• Ocular Tolerance Assessment by the Patient 
The investigator has to ask the patient the following question in local language:  
“How do you consider the study treatment ocular tolerance?  
- 
Very satisfactory 
- 
Satisfactory 
- 
Not very satisfactory 
- 
Unsatisfactory” 
 
• Treatment Compliance Evaluation 
Patient will return all investigational products (IMDs and Hydrabak®), whether used or unused. 
For Hydrabak and IMD (T2769 or Vismed® Multi), the patient will also have to report information 
about his/her compliance on a paper patient diary during the treatment period. Each day the patient 
will enter the date and number of instillations* per day. Moreover, it will be asked to add the date 
and hour of last instillation before the beginning of each study visit.  
In addition, compliance will be assessed by questioning the patient during the visit (e.g. if there was 
any treatment interruption or missed instillation) and by checking on paper patient diary. 
* one instillation = 1 drop in each eye 
 
6.4.1.4. 
Prior and Concomitant Treatment  
At screening visit, the patient will be asked what treatment he/she has taken within the last 3 months; 
this will be recorded on the Source documenting product details, dose and treatment duration.  
Concomitant treatment means any medications or non-medicinal therapies given concurrently with 
the IMD. Any other local or systemic treatment necessary for the patient's welfare has also to be 
recorded on the Source documenting product details, dose and treatment duration. 
 
6.4.1.5. 
Prohibited Prior and Concomitant Medications or Treatments 
Prohibited treatments as well as modifications of prohibited treatments during the investigation are 
presented in the summary in the exclusion criteria and in Table 1 
6.4.2 
Description of those Activities Performed by Sponsor Representatives 
(excluding monitoring) 
Laboratoires THEA through CROs is responsible for selecting the investigator(s). Each investigator 
should be qualified by training and experience and should have adequate resources to properly 
conduct the investigation. 
Laboratoires THEA/representatives of Laboratoires THEA will remind the investigator upon his/her 
responsibilities and procedures for ensuring adequate and correct documentation. 
Laboratoires THEA will inform the investigator, directly or through CROs in charge of monitoring, 
prior to the commencement of the study of all relevant chemical, toxicological and clinical 
information required for the proper planning and conduct of the investigation and will update this 
as often as may be necessary during the course of the study. However, this obligation shall not 
require Laboratoires THEA to provide information which is already available in published material 

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or of which the investigator could reasonably be expected to have knowledge in view of his/her 
professional training. 
Laboratoires THEA or CROs will nominate a suitably trained person or persons to monitor the study 
and to liaise with the investigator. 
Laboratoires THEA/representatives of Laboratoires THEA, will also be responsible for complying 
with the local regulations applicable to clinical investigation. 
 
 
6.4.3 
Any Known or Foreseeable Factors that may Compromise the Outcome 
of the Clinical Investigation or the Interpretation of Results 
The population will be selected according to the inclusion and exclusion criteria to have a 
homogenous population. 
A run-in period with Hydrabak® is scheduled to have patient with the same treatment at the baseline 
visit. 
6.4.4 
Methods for Addressing these Factors in the Clinical Investigation 
However, to not compromise the outcome of the clinical investigation, the patient will be randomly 
assigned to 1 of the 2 treatment groups during the randomisation visit. 
6.4.5 
Description of the Follow-Up Period 
Not Applicable 
6.4.6 
Appropriate Specific Medical Care Address after the Clinical 
Investigation 
Not Applicable 
6.4.7 
Recommended Follow-Up Address after the Clinical Investigation 
Not Applicable 

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6.5.1 
Source Documents 
Each participating investigational site will maintain appropriate medical and research records in 
compliance with ISO14155 and any other regulatory and institutional requirements for the 
protection of patient’s confidentiality. 
Source data are all information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical investigation necessary for the reconstruction 
and evaluation of the investigation. Source data are contained in source documents. 
Source documents are any original documents, data and records. These may include, but are not 
limited to, patient medical records, hospital charts if any, clinic charts, laboratory notes, patient’s 
questionnaires, patient’s diaries if any, the investigator’s files, pharmacy dispensing records and 
recorded data from automated instruments. 
Some specific medical data gathered during routine medical practice visits prior to the participation 
can be used in screening visit and before informed consent form on the patient best care interest. 
All following patient’s assessments will be collected via a paper diary and paper questionnaire and 
will be considered as source data: 
- 
Run-in treatment compliance: number of instillations/day 
- 
IMD compliance: number of instillations/day 
- 
OSDI questionnaire 
- 
VAS 
The following information should be entered into the patient’s medical record: 
- 
Patient’s name, date of birth, gender 
- 
Patient’s contact information 
- 
The date the patient entered the study and patient’s number 
- 
The study title and/or the clinical investigation number 
- 
A statement that informed consent was obtained (including the date) and patient’s card was 
provided to the patient; data protection consent or other country and local patient privacy 
required documentation for this investigation have been obtained (including the date) 
- 
Date of all patient’s visits 
- 
Investigated disease history:  
o Diagnosis of DES for each eye 

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o Date of onset of the diagnosis in each eye (months/year) 
o Previous use of artificial tears 
- 
Ocular and systemic medical and surgery history (other than dry eye) 
For systemic medical history, the information could be collected via patient interview. For 
ophthalmic medical history of referred patient’s, a letter from the referring ophthalmologist is 
strongly recommended. 
- 
Prior and concomitant medications (list all prescription and non-prescription medications 
being taken at the time of enrolment and within 3 months before screening visit. At each 
subsequent visit, changes to the list of medications should be recorded.  
- 
Name/initials and signature of the persons who perform assessments 
- 
Visual acuity values (standard BCVA value with used chart name) 
- 
Slit-lamp examination results with score of ocular signs, conjunctival hyperemia, corneal and 
conjunctival staining by fluorescein with a yellow filter  and TBUT 
- 
Shirmer test results for both eyes 
- 
Occurrence and status of any AEs 
- 
Occurrence and status of any DD 
- 
Review of inclusion/exclusion criteria and patient’s status (confirmation of patient eligibility 
or not, reason for screen failure if applicable) 
- 
Ocular tolerance and performance assessment by Investigator  
- 
Information on diary dispensation to the patient and instructions correctly provided 
- 
Information on Run-in treatment dispensation, instruction for use and kit number provided to 
patient 
- 
Information on IMD dispensation, including kit number assignment with IRT notification  
- 
Run-in treatment compliance collected by reviewing patient’s diary and interview and 
checked against returned kit 
- 
IMD compliance collected by reviewing patient’s diary and interview and checked against 
returned IMD  
- 
Information on used/unused IMD by patient, assessed by unmasked collaborator 
- 
The date of the patient exited the study and a notation as to whether the patient completed 
the study or reason for discontinuation 
 
6.5.2 
Source Data Verification 
One of the primary responsibilities of monitoring is the review of source documentation (SDR= 
Source Data Review) to check quality of source, review CIP compliance, ensure the critical 
processes and source documentation are adequate, to ascertain Investigator involvement and 
appropriate delegation and assess compliance to other areas (e;g; SOPs, GCP, ISO 14155 current 
version). This will require direct access to all source documents, any original documents, data and 
records of each patient.  

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It will be verified that informed consent documentation is filed for all screened patients whether or 
not they were randomised into the investigation and that the information is listed in the source 
documents. 
 
Source Data Verification (SDV) will be recorded in e-CRF  and SAE/pregnancy related documents, 
consisting in a comparison of the source documentation and other records relevant to the 
investigation. 
The SDV will ensure the data are Attributable, Legible, Contemporaneous, Original,  Accurate, 
complete, consistent, enduring and available (ALCOACCEA guiding principles). 
Source Data Monitoring combines:   
 Site Monitor review of the source data for a subject in order to confirm that the site is 
compliant with ICH GCP and the Protocol 
 Evaluation of the conformity of the data presented in CRF, or other Sponsor-provided 
documents, with the available Source Data 
SDR  can be done alone, but SDV  cannot be done without prior SDR, since validating data 
transcription is not useful if protocol and GCP compliance have not been confirmed first. 
 
6.5.3 
Case Report Forms 
The patients will be monitored throughout the investigation and all results of evaluations will be 
recorded in an e-CRF. 
The e-CRF completion guidelines will be provided and reviewed with the investigation staff before 
the start of the investigation. 
The investigator and authorised delegate(s) will have secured access to enter the data in the 
appropriate sections of the e-CRF and to IRT (if applicable).  
e-CRF must be completed for each patient screened in the investigation. It should be completed as 
soon as possible after the patient visit.  
The investigator is required to prepare and maintain adequate and accurate ocular and systemic 
history designed to record all observations and other data pertinent to the investigation for each 
patient.  
The investigator is responsible for ensuring that data are properly recorded on each patient’s e-CRF 
and related documents.  
The investigator will be responsible for the punctuality, completeness, consistency and accuracy of 
e-CRF. e-CRF and source data will be retained by the investigator for data verification at each 
scheduled monitoring visit. 
The investigator should personally electronically validate and sign e-CRFs to ensure that the 
observations and findings are recorded on the e-CRF correctly and completely.  
All information recorded on the e-CRF for this investigation must be consistent with the patients’ 
source documentation (i.e., medical records). 
A copy of completed e-CRF pages, SAE / Pregnancy will be stored in the investigator's archives for 
at least 10 years after the last device has been placed on the market. 

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7. STATISTICAL DESIGN AND ANALYSIS 
The Statistical Analysis Plan (SAP) will provide, before locking the database and breaking the blind 
detailed methods for the analyses outlined below. 
Any changes from the planned analyses will be described and justified in the final CIR. 
7.1 ANALYSIS POPULATION AND PROCEDURES 
The following analysis sets will be considered: 
• Safety set: 
All enrolled patients, having received at least one dose of IMD and analysed as treated. 
The safety set will be the primary population for safety analysis. 
• Intent-to-treat (ITT) set: 
All randomised patients and analysed as randomised. 
• Full analysis set (FAS): 
All randomised patients, having received at least one dose of IMD, with at least one baseline and 
one post-randomisation performance assessment on treatment and analysed as randomised. 
The FAS will be the primary population for performance analysis. 
• Per protocol (PP) set: 
Subset of the FAS including patients without any major CIP violations likely to seriously affect the 
primary outcome of the study. Deviations from the CIP will be defined and assessed as “minor” or 
“major” in cooperation with the Sponsor during a blind review meeting before the database lock. 
The PP set will be considered as secondary population and will be used for sensitivity analyses of 
the primary
 endpoints. Patients will be analysed as treated. 
7.2 STATISTICAL ANALYSIS 
Statistical descriptions will be performed by groups. For disposition and demography description 
will also be presented overall. 
Demographics and baseline characteristics, including history of dry eye, medical/surgical history 
(by System Organ Class (SOC) and PT separately for ocular and systemic history), previous and 
concomitant ocular/non-ocular treatments will be summarised by treatment group and overall. 
Parameters recorded for both eyes will be described separately for the study eye and for the 
contralateral eye. 

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7.2.2 
Safety Analyses 
Safety endpoint will be analysed in the Safety set. 
Ocular and systemic adverse events (AEs) 
Ocular and systemic AE reported during the investigation will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA dictionary). 
Summary tables will be performed on TEAEs.  
Ocular and systemic TEAEs will be analysed separately on the basis of the localisation as recorded 
by the investigator in the CRF. 
TEAEs are AEs that occurred after the first IMD instillation. AEs that occurred the day of the first 
IMD instillation will be reviewed during a blind review meeting to decide if they have to be 
considered as TEAE or not.  
Separate descriptions of ocular and systemic TEAEs will be performed by treatment group: 
• 
Number and percentage of patients experiencing at least one AE, SAE, IMD-related AE, 
and AE leading to premature investigation IMD discontinuation. 
• 
Number and percentage of patients experiencing at least one AE, as well as the number 
of AEs, by SOC and PT. The same summary table will be performed for SAEs, IMD-
related AEs, IMD-related SAEs and AEs leading to premature investigation IMD 
discontinuation.  
• 
Number and percentage of patients with AEs, by SOC, PT and severity. 
• 
Number and percentage of patients with AEs, by SOC, PT and relationship with IMD. 
Documented list of individual data concerning TEAEs will be performed. 
Separated descriptions of ocular and systemic during the run-in period will be performed overall: 
• 
Number and percentage of patients experiencing at least one TEAE, as well as the number 
of TEAEs, by SOC and PT. The same summary table will be performed for SAEs (if any), 
and TEAEs related to run-in treatment. 
Individual patient data listings of TEAEs will be performed for overall AEs, SAEs and IMD-related 
SAEs, separately for ocular and systemic AEs. 
List will also be performed on non-TEAEs (before the first IMD instillation).  

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7.3 ANALYTICAL PROCEDURES 
Quantitative variables (Continuous data) will be summarized in summary tables indicating the 
number of non-missing observations (n), mean, SD, median, lower quartile (Q1), upper quartile 
(Q3), minimum and maximum, and 95% Confidence Interval (CI) of the mean/median.  
Qualitative variables (Categorical data) will be summarized in summary tables indicating the 
number of non-missing observations (n), count and percentage of each modality, and 95% CI. 
7.5 SAMPLE SIZE CALCULATION AND JUSTIFICATION 
The sample size is driven by the statistical hypotheses on the primary 
 
  

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7.6 RATIONALE FOR THE NUMBER OF PROCEDURES TO BE PERFORMED BY A 
SINGLE USER AS PART OF THE LEARNING CURVE AND HOW THESE DATA 
ARE TO BE ANALYSED 
Not applicable. 

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7.15 PROCEDURES FOR REPORTING ANY DEVIATION(S) FROM THE ORIGINAL 
STATISTICAL PLAN 
Any changes from the planned analyses will be described and justified in the SAP and the final 
clinical investigation report. 
7.17 DEFINE A STRATEGY FOR POOLING DATA, IF APPLICABLE. 
Not applicable. 
8. DATA MANAGEMENT 
8.1 METHODS FOR DATA ENTRY AND COLLECTION 
Each participating site will maintain appropriate medical and research records for this investigation 
in compliance with GCP - ISO 14155:2020 sections 3.47, 4.48 and 7.8.1 and any other regulatory 
and institutional requirements for the protection of patient’s confidentiality. 
8.2 PROCEDURES USED FOR DATA REVIEW, DATABASE CLEANING, AND 
ISSUING AND RESOLVING DATA QUERIES 
The investigator will ensure that his/her center has the necessary facilities, time and staff for the 
conduct of the investigation, and that these will be maintained for the duration of the investigation. 
The investigator and authorised delegate(s) will ensure that proper data for the clinical investigation 
are collected and accurately documented in the appropriate sections of e-CRFs. 
The investigator will cooperate with Laboratoires THÉA and any person nominated by Laboratoires 
THÉA to monitor or supervise the conduct of the investigation. 
8.3 PROCEDURES FOR VERIFICATION, VALIDATION AND SECURING OF 
ELECTRONIC CLINICAL DATA SYSTEMS 
Entries in e-CRF shall be made complete and correct and in timely manner.  
All data entry and modifications will be stored in an audit’s trail. 
Data Management activities will be performed by Laboratoires THÉA Data Manager and/or the 
CRO in charge of Data Management and will be defined in the Data Management Plan (DMP). 

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Diagnosis for AEs and medical history will be coded using MedDRA. WHODrug Anatomic 
Therapeutic Chemical (ATC) code will be used for previous and concomitants treatment coding. 
Versioning will be specified in the DMP. 
 
8.4 PROCEDURES TO MAINTAIN AND PROTECT PATIENT PRIVACY 
Laboratoires THÉA, as Sponsor of the investigation, acting as data controller and is committed to 
protecting the privacy and security of personal data processed for the purposes of the investigation 
under the conditions define below: 
• Compliance with the General Data Protection Regulation (GDPR) and other 
applicable law or regulation: 
Laboratoires THÉA is committed to comply with the Regulation (EU) 2016/679 of the European 
Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to 
the processing of personal data and on the free movement of such data, and repealing Directive 
95/46/EC (hereinafter the “GDPR”) and any other applicable law or regulation related to the 
protection of personal data.  
It is specified that for the investigation, Laboratoires THÉA also comply with the applicable 
guidelines of the French supervisory authority (“Commission Nationale de l’Informatique et des 
Libertés” hereinafter the “CNIL”) as defined in the deliberation n°2019-153 of 3 May 2019 of the 
CNIL, also called the “MR-001”.  
• Data subjects information on the processing of their personal data 
The data subjects namely the patients and the investigator, including the personnel working with the 
investigator, are informed of the collection and processing of their personal data for the realisation 
of the investigation.  
In particular, the patients are informed by the investigator during the delivery of the ICF where all 
the mandatory information of article 13 of the GDPR are provided.   
• Data subjects exercise of their rights on their data 
The data subjects, namely the patients and the investigator, including the personnel working with 
the investigator, have the right, under the conditions and within the limits provided by the 
regulations, to access, rectify, delete or determine guidelines as to the use of their personal data after 
their death, as well as the right to oppose or request the limitation of processing. 
In addition, and according with article L1111-7 of the French Public Health Code, the patients can 
access to their personal data by asking to the investigator. 
For all requests concerning the rights of the patients regarding their personal data, they are advised 
to contact the investigator who will in turn contact Laboratoires THÉA. Otherwise, Laboratoires 
THÉA named a Data Protection Officer who can be contacted by the patients.  
The data patients, namely the patients and the investigator, including the personnel working with 
the investigator, have the right to bring a complaint with the supervisory authority, namely the CNIL 
in France and/or local equivalent of CNIL. 
8.5 METHODS FOR DATABASE LOCKING AT THE START OF THE ANALYSIS 
AND STORAGE UPON COMPLETION OF THE CLINICAL INVESTIGATION 

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The database lock consists in the removal or changing of user access for database to prevent any 
further changes to the data. The database lock enables data collected to be used for formal analysis 
or submission to a regulatory authority. Database lock occurs following the conduct of the study. 
 
Database will be locked when all data will be entered and clean. CRO Data Management coordinates 
the activities around Database Lock, including completing the Database Lock Checklist managing 
Database Lock Form, and ensuring archival activities are complete. 
8.6 CONFIDENTIALITY 
All information concerning the product as well as any matter concerning the operation of the 
Sponsor, such as clinical indications for the IMD, its formula, methods of manufacture and other 
scientific data relating to it, that have been provided by the Sponsor and are unpublished, are 
confidential and must remain the sole property of the Sponsor. The investigator will agree to use the 
information only for the purposes of carrying out this investigation and for no other purpose unless 
prior written permission from the Sponsor is obtained. 
Laboratoires THÉA has full ownership of the original e-CRFs completed as part of the investigation. 
8.7 DATA RETENTION PROCEDURES AND SPECIFIED RETENTION PRIOD 
The investigator must retain the patient identification codes for at least 10 years after the last device 
has been placed on the market. Patient files and other source data must be kept for the maximum 
period of time permitted by the hospital, institution or private practice, but not less than 10 years 
after the last device has been placed on the market, to meet the Sponsor regulatory local 
requirements. The investigator must produce investigation documentation or supply copies thereof 
to Sponsor, its designee or to CAs upon request, while ensuring patient confidentiality at all times. 
8.8 OTHER ASPECTS OF CLINICAL QUALITY ASSURANCE 
8.8.1 
Monitoring/Data Audits 
Laboratoires THÉA/representatives of Laboratoires THÉA shall be permitted to inspect any 
proposed investigational site prior to commencement and during the course of the investigation to 
ensure that the investigational site is suitable and has the suitable facilities, staff and capacity for 
the conduct of the investigation. 
The e-CRFs should be available for review by the clinical monitor or auditor or national regulatory 
inspectors. The investigator is required to give access to all source documents and investigation 
data. Laboratoires THÉA and CROs will not require the investigator or any member of their staff to 
take any action or be a party to any action which is contrary to the laws of the country in which the 
investigation is being carried out or to medical ethics. 
8.8.2 
On-site Audits/Regulatory Inspection 
CAs, Independent Ethics Committees/ Institutional Review Boards (IECs/IRBs), and/or 
Laboratoires THÉA’s Clinical Quality Assurance Group may carry out on-site audits and/or on-site 
audit inspections. Direct access to source data will be required for these inspections and audits; they 
will be carried out giving due consideration to data protection and medical confidentiality. The 
investigator assures the Sponsor of the necessary support at all times. 

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The investigation may be subjected to auditing by representatives of the Sponsor and/or to 
inspection(s) by authorised representatives of local and/or foreign CAs. In case of an audit or 
inspection, the investigator will be informed in advance. 
 
9. APPROVAL 
OF 
THE 
CLINICAL 
INVESTIGATION 
AND 
AMENDMENTS 
Prior to starting the investigation, the CIP and other relevant documents will be submitted and 
approved by the IEC/IRB and/or CAs, in accordance with regional/local regulatory requirements. 
The Sponsor must ensure that all ethical and legal requirements have been met before the first patient 
is enrolled in the investigation. 
Full compliance with this CIP must be sought. To alter the CIP, amendments must be written, 
approved by the appropriate personnel, and by IEC/IRB/CAs prior to implementation. 
All amendments will be distributed to all CIP recipients, with appropriate instructions. 
By signing the CIP, the investigator confirms that he/she agrees to perform the investigation as 
outlined in the CIP.  
The CIP is the binding document for the investigator, the Sponsor and its designee; modifications 
are only valid if agreed upon by the Sponsor, its designee and the Coordinating investigator. 
Modifications must be documented in a signed amended CIP.  
The Sponsor will promptly report the following for review or information to the Ethics 
Committee(s) and the CA for: 
• Substantial CIP modifications 
• Administrative changes 
• Deviations to the CIP implemented to eliminate immediate hazards to the trial patients 
• New information that may affect adversely the safety of the patients or the conduct of the 
investigation. The EC and the CA must be informed and approve all CIP amendments, 
in accordance with local legal requirements before implementation. Amendments must be 
evaluated to determine whether formal approval must be sought and whether the informed 
consent document should also be revised.  
The written signed approval of the CIP amendment must contain specific identification of the 
document (e.g., the investigator's name and the CIP title and number). 
 
 
10. DEVIATIONS FROM CIP 
The investigator will conduct the investigation in accordance with this CIP, all relevant local 
laws, regulations or guidelines and in accordance with the principles of GCP – ISO 14155 current 
version. The investigator should not initiate the investigation before:  
• The CIP is signed;  

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• Written approval from the appropriate IEC and Clinical Trial Authorization from CA are 
received; 
• The site is initiated by Laboratoires THÉA or the CRO designated by Laboratoires THÉA.  
During the investigation, in case of important deviations observed in an investigational site (such as 
deviations related to inclusion and/or exclusion criteria, deviations that may put a patient at risk), 
the Sponsor could decide to stop the enrolment in this site.  
At the end of the investigation, CIP deviations will be reviewed and classified as minor or major 
during a blind data review meeting that will be held before database lock. The exclusion of patients 
from the analysis sets (see details of analysis sets in Section 7) will be discussed during the blind 
data review meeting. 
 
 

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11. IMD ACCOUNTABILITY 
11.1 
DESCRIPTION OF THE PROCEDURES FOR THE ACCOUNTABILITY OF 
IMD 
Patients will return used and unused IMDs to the site at each visit. 
The unmasked collaborator or pharmacist counts the number of IMDs remaining in the returned 
pack, completes and validates the “Treatment Tracking Form” (used, not used, not returned IMD) 
and the Drug Accountability Module and Return Form in IWRS. 
The masked investigator will remain masked to the IMD. He/she will not retrieve the product from 
any patient. 
All IMDs will be retained for inspection by the study monitor. The monitor will, upon completion 
of drug count and validation of the return section of the “Treatment Tracking Form”, collect 
used/unused/broken containers of the supplied investigational products and these will be returned 
as instructed by Laboratoires THÉA.  
11.2 
PROCEDURES AND PARTICULAR MATERIALS AND INSTRUCTIONS 
FOR THE SAFE RETURN OF IMD, INCLUDING THOSE THAT ARE 
POTENTIALLY HAZARDOUS 
The IMD used and unused will be returned to a depot in the involved country or to the depot in 
France for destruction. 
This return will be prepared by the site team with the help of Monitor. The return request will be 
sent to the CRO of packaging/labelling. An import licence to authorize the return from UK to France 
is mandatory. At receipt, The CRO of packaging and Labelling has to confirm the Good Receipt to 
the site team and monitor.  
All details regarding return of used and unused IMD will be recorded in the Drug accountability 
return module in IRT. 
 
The return will be stored in the depot in waiting the authorization of destruction by the sponsor. 
 
 

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12. STATEMENTS OF COMPLIANCE 
This investigation will be conducted in accordance with the ethical principles of the Declaration of 
Helsinki of October 2013, with GCP as described in the International Standards ISO 14155 current 
version and with the local regulations. 
Prior to commencement of the investigation, the Sponsor or his legal representative in the 
community must submit a valid application, with the same version of the documentation, to the IEC 
and the CA (see Section 9).  
Before the investigation starts, the clinical monitor must ensure that all relevant documents are 
available and that IEC/IRB/CAs authorisation(s) and approval(s) have been obtained. Only then, 
arrangements for shipment of the clinical supplies can be made and start of recruitment can begin. 
The Sponsor or his legal representative will report any amendments (see Section 9) and safety-
related events (see Sections 14.5 and 14.6) according to the local regulations. 
The Sponsor will notify each IEC/IRB/CAs concerned of the end of a clinical investigation in all 
countries in which the clinical investigation has been conducted. That notification will be made 
within 90 days from the end of the investigation in the last country in which the clinical investigation 
has been conducted/in accordance with the local regulations. 
If the investigation has terminated prematurely, the reason for the termination must be given (see 
Section 16) 
When a temporarily halted clinical investigation is resumed the Sponsor will inform all involved 
investigators and must notify IEC/IRB/CA concerned through the EU portal and/or another way 
within 15 days from the restart of the temporarily halted clinical investigation in all country 
concerned.  
The Sponsor will take out reasonable third-party liability insurance cover in accordance with all 
local legal requirements. The civil liability of the investigator, the persons instructed by him/her and 
the hospital, practice or institute in which they are employed and the liability of the Sponsor with 
respect to financial loss due to personal injury and other damage that may arise as a result of the 
carrying out of this investigation are governed by the applicable law. 
The Sponsor will arrange for patients participating in this investigation to be insured against 
financial loss due to personal injury caused by the products being tested or by medical steps taken 
in the course of the investigation. 
When required, a hospital specific indemnity agreement and/or an investigator specific agreement 
will be used. 
13. INFORMED CONSENT PROCESS 
In obtaining and documenting informed consent, the investigator must comply with the applicable 
regulatory requirement(s) and adhere to the International Standards ISO14155 on GCP for medical 
devices and the requirements in the Declaration of Helsinki – October 2013. 
Prior to any investigation-related activity or any discontinuation of current medication, the 
investigator must give the patient (or the patient’s legally authorized representative) oral and written 
information about the aims, methods, anticipated benefits, potential risks and inconveniences of the 
investigation. The measures taken to safeguard the patient’s privacy and the protection of personnel 
data should also be described in the informed consent. The patients must be informed about their 
right to abstain from participating in the investigation and to withdraw their consent at any time 
without affecting their medical care.  

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Before informed consent may be obtained, the investigator should provide the patient ample time 
and opportunity to inquire about details of the investigation and to decide whether or not to 
participate in the investigation. All questions about the investigation should be answered to the 
satisfaction of the patient. The patient must be given the opportunity to ask questions and have 
reasonable time for reflection before giving his/her informed consent. 
The informed consent must be signed prior to initiation of any investigational procedures or any 
discontinuation of current medication. No measures whatsoever described in the CIP shall be 
undertaken without such consent indicating that the patient has been given both verbal and written 
information about the investigation and the IMD.  
 
If the patient is illiterate, oral information regarding the investigation will be provided to the 
patient using the informed consent form (ICF). A witness will be present during the entire informed 
consent discussion. The witness will personally sign and date the ICF to confirm that the information 
was accurately explained to the patient, and apparently understood, and that consent was freely 
given. 
Two original copies of the ICF shall be signed and dated by the patient (or the legally authorized 
representative) and the investigator prior to initiate any investigation related procedures. One 
original consent form will be given to the patient and the other original will be included in the 
investigator's file. 
As soon as the patient has signed the Informed Consent, he/she will receive a patient number.  
The information/consent form may be revised during the investigation whenever important new 
information becomes available. The amended ICF will be submitted for approval to the IEC and/or 
CAs as appropriate (see Section 9). Once approved, informed consent of the already enrolled 
patients will be documented as described above i.e., in the same way as the initial informed consent. 
 
 

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14. ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND DEVICE 
DEFICIENCIES 
14.1 
DEFINITION OF ADVERSE EVENT (AE) AND ADVERSE DEVICE 
EFFECT (ADE) 
Adverse Event (AE): Any untoward medical occurrence, unintended disease or injury or untoward 
clinical signs (including abnormal laboratory finding) in subjects, users or other persons whether or 
not related to the IMD. 
NOTE: 
• 
This definition includes events related to the IMD or the comparator 
• 
This definition includes events related to the procedures involved 
• 
For users or other persons, this definition is restricted to events related to the use of the IMD or 
comparator. 
Adverse device effect (ADE):  AE related to the use of an IMD.  
NOTE: 
• This definition includes AEs resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation or operation, or any malfunction* of the IMD; 
• This definition includes any event resulting from use error or from intentional misuse 
of the IMD. 
• This includes comparator if the comparator is a medical device. 
*Malfunction is defined as a failure of an IMD to perform in accordance with its intended purpose 
when used in accordance with the instructions for use or CIP. 
Treatment-emergent AE (TEAE): AE that occurs or that worsens in severity after at least one 
dose of IMD has been administered/applied.  
14.2 
DEFINITION OF DEVICE DEFICIENCIES 
Device Deficiency (DD) : Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.  
NOTE: 
• DD include malfunctions, use errors, and inadequate labelling. 
• This definition includes DD related to the investigational medical device or the comparator. 
14.3 
DEFINITION OF A SERIOUS ADVERSE EVENT (SAE) OR SERIOUS 
ADVERSE DEVICE EFFECT (SADE) AND UNANTICIPATED SERIOUS 
ADVERSE DEVICE EFFECTS 
Serious Adverse Event (SAE):  AE  that: 
• Led to death 
• Led to serious deterioration in the health of the subject, that either resulted in  
 A life-threatening illness or injury, or  
 A permanent impairment of a body structure or a body function, or  

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 In-patient or prolonged hospitalization, or  
 Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
 Chronic disease 
• Led to foetal distress, foetal death or a congenital abnormality or birth defect. 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the 
CIP, without serious deterioration in health, is not considered a SAE. 
Serious Adverse Device Effect (SADE): ADE that has resulted in any of the consequences 
characteristic of a serious adverse event . 
Unanticipated Serious Adverse Device Effect (USADE): SADE which by its nature, incidence, 
severity or outcome has not been identified in the current risk assessment.  
NOTE: Anticipated SADE (ASADE): an effect which by its nature, incidence, severity or outcome 
has been identified in the risk assessment. 
14.3.1 
Definition of the Severity of an Adverse Event  
The intensity of each AE must be assessed by the investigator using one of the following categories, 
and recorded in the e-CRF: 
1 = MILD: Event results in mild or transient discomfort, not requiring intervention or treatment 
and does not interfere with the patient daily activities; 
2 = MODERATE: Event results in sufficient discomfort, may require an additional treatment, 
but does not interfere with the patient’s daily activities; 
3 = SEVERE: Event results in significant symptoms, may require an additional treatment, or a 
modification of this treatment (or hospitalisation) and may interfere with the patient’s daily 
activities. 
Caution: The term “severe” is used to describe the intensity (severity) of the event. This means it 
is not the same as “serious” used to describe the seriousness of SAE which is based on patient event 
outcome or action criteria usually associated with events that pose a threat to a patient’s life or 
functioning (see section 14.3 for having the definition of a SAE). 
14.3.2 
Causality Relatedness to the IMD  
The investigator will assess the causality/relationship between the IMD and the AE and record that 
assessment in the e-CRF based on the following definitions (only one answer possible): 
Each AE will be classified according to five different levels of causality: 
 
1. Not related 
2. Possible 
3. Probable 
4. Causal relationship 
 
The sponsor and the investigators will use the following definitions to assess the relationship of the 
adverse event to the investigational device or the investigation procedures. 
 
1. Not related: Relationship to the device or procedures can be excluded when: 

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- the event has no temporal relationship with the use of the device or investigation 
procedures; 
- the adverse event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible - and reintroduction of its use (or increase of 
the level of activation/exposure), do not impact on the adverse event; 
- the event involves a body-site or an organ that cannot be affected by the device or 
procedures; 
- the serious adverse event can be attributed to another cause (e.g. an underlying or 
concurrent illness/ clinical condition, an effect of another device, drug, treatment or other 
risk factors); 
In order to establish the non-relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the adverse event. 
 
2. Possible: The relationship with the use of the investigational device or the relationship with 
procedures, is weak but cannot be ruled out completely. Alternative causes are also possible 
(e.g. an underlying or concurrent illness/ clinical condition or/and an effect of another 
device, drug or treatment). Cases where relatedness cannot be assessed, or no information 
has been obtained should also be classified as possible. 
 
3. Probable: The relationship with the use of the investigational device or the relationship with 
procedures, seems relevant and/or the event cannot be reasonably explained by another 
cause. 
 
4. Causal relationship: the adverse event is associated with the investigational device or with 
procedures beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or of similar 
devices and procedures; 
- the event has a temporal relationship with investigational device use/application or 
procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational device or procedures have an effect on; 
- the adverse event follows a known response pattern to the medical device (if the response 
pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the adverse event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and 
an effect of another device, drug or treatment) have been adequately ruled out; 
- harm to the subject is due to error in use; 
 

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In order to establish the relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the adverse event. 
 
The sponsor and the investigators will distinguish between the adverse events related to the 
investigational device and those related to the procedures (any procedure specific to the clinical 
investigation). An adverse event can be related both to procedures and the investigational device.  
 
Complications caused by concomitant treatments, not imposed by the clinical investigation plan, 
are considered not related. If routine procedures are not imposed by the clinical investigation plan, 
complications caused by them are also considered not related. 
 
In some particular cases the event may not be adequately assessed because information is 
insufficient or contradictory and/or the data cannot be verified or supplemented. The sponsor and 
the investigators will make the maximum effort to define and categorize the event and avoid these 
situations. Where an investigator assessment is not available and/or the sponsor remains uncertain 
about classifying the adverse event, the sponsor should not exclude the relatedness; the event should 
be classified as “possible” and the reporting is not delayed. 
 
Particular attention shall be given to the causality evaluation of unanticipated serious adverse events. 
The occurrence of unanticipated events related could suggest that the clinical investigation places 
subjects at increased risk of harm than was to be expected beforehand. 
 
14.4 
RECORDING AES  
AEs  recording and reporting will extend from signing of informed consent until the final visit. If 
the investigator is aware of an AE occurring within one month after final investigation visit and that 
he considers there is a causal relationship with the IMD, the AE should be recorded in the e-CRF.  
The investigator shall: 
a) Record all AEs , regardless of the relationship to IMD, in the e-CRF, together with an 
assessment.  
b) Report to the Sponsor, without unjustified delay, all serious AEs; this information shall be 
promptly followed by detailed written reports. 
c) Supply the Sponsor, upon Sponsor's request, with any additional information related to the 
safety reporting of a particular event. 
All AE reports should contain: a brief description of the event (diagnosis, localisation …) date and 
time of onset (if needed), duration (hours or days), intensity of symptoms (severity), treatment 
required, relationship with IMD and CIP procedure, action taken with the IMD, outcome, date and 
time of resolution and whether the event is classified as serious. 
If there is a worsening of a medical condition that was present before starting the clinical 
investigation, this should be considered as a new AE and a complete evaluation should be recorded. 
14.5 
REPORTING OF SAE  
Reporting by the investigator to the Sponsor 

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14.6 
REPORTING OF DEVICE DEFICIENCIES 
If the investigator observes any abnormality and/or deficiency of T2769 the investigator must report 
to Laboratoires THÉA within 24 hours of being aware of it 
. 
Laboratoires THÉA must  
- 
review all DD and determine and document in writing whether they could have led to a SAE; 
in case of disagreement between the sponsor and the principal investigator(s), the sponsor 
shall communicate both opinions to concerned parties 
- 
report to regulatory authorities/EC/investigators, within the required time period, any 
device deficiencies that might have led to a serious adverse event if appropriate action 
had not been taken, intervention had not occurred, or circumstances had been less 
fortunate.  
 
Once Laboratoires THÉA is made aware of any deficiency with any components of the IMD and in 
function of the type of deficiency, the Laboratoires THÉA will take the appropriate decision to 
maintain the security/safety of patients. 
14.7 
FOLLOW-UP OF PATIENT AFTER AE 
The investigator is responsible for ensuring the follow-up of any patient who experiences an AE 
during the investigation.  
All AEs experienced by a patient, irrespective of the suspected causality, will be monitored until the 
event has resolved, any abnormal laboratory values have returned to baseline or stabilised at a level 
acceptable to the investigator and Medical Expert, until there is a satisfactory explanation for the 
changes observed. 
In case of SAE, the investigator or an appropriate qualified physician must re-examine the patient 
at regular intervals until the event has resolved or stabilised at a level acceptable to the investigator 
and Medical expert and/or until completion of the “Last Patient Last Visit”.  
Further follow up information will be reported to Laboratoires THÉA. 
14.8 
MANAGEMENT OF PREGNANCY  
In case of the investigator or an appropriate qualified physician is informed that a patient becomes 
pregnant while taking IMDs, she will be immediately withdrawn from the investigation and she will 
be followed until the outcome of the birth is available.  
A communication will be sent by the investigator to Laboratoires THÉA as soon as he/she has 
knowledge of the normal outcome. Conversely, if the outcome of the pregnancy meets the criteria 
of SAE (e.g spontaneous or therapeutic abortion, stillbirth, neonatal death, congenital abnormality, 
birth defect), the investigator should follow the procedure for reporting of SAEs. 
Handling of a pregnancy occurring throughout the investigation follows the same reporting 
procedure as per an SAE notification. 
Upon medically confirmed pregnancy during the investigation the investigator must: 
- 
Report immediately (maximum 24 hours) the pregnancy status to Laboratoires THÉA using 
the email 
   
- 
Discontinue the IMD.  

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- 
Perform / ensure assessment until delivery of a thorough investigation of the fetus  
- 
Remain responsible for any medical advice he/she might sought thus making appropriate 
decision upon pregnancy 
- 
Report to Laboratoires THÉA Follow-Up data / update(s) using the SAE form 
14.9 
LIST OF FORESEEABLE AES AND ANTICIPATED ADVERSE DEVICE 
EFFECTS, TOGETHER WITH THEIR LIKELY INCIDENCE, MITIGATION OR 
TREATMENT 
According to the IMD leaflets, the following side effects are known: rare possibility of mild eye 
irritation and ocular redness. 
 
When you use eye drops, you might experience disturbing symptoms such as burning sensation, 
stinging sensation, foreign body sensation in the eye and blurred vision for a short time. 
 
15. VULNERABLE POPULATION 
This clinical investigation will not be conducted in children, or in any other vulnerable populations. 
If the patient is not capable of giving consent, the written consent of the patient’s legal representative 
will be required before participation in the investigation (see Section 13). 
 
 

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16. SUSPENSION OR PREMATURE TERMINATION OF THE 
CLINICAL INVESTIGATION 
16.1 
TEMPORARY HALT OF THE INVESTIGATION 
The Sponsor may suspend the clinical investigation for any safety, ethical or administrative reason 
at any time. The investigator, IEC or CA may suspend or prematurely terminate participation at the 
investigational sites for which they are responsible. 
As required by the Clinical Trials legislation, in the case of temporary halt of the clinical 
investigation: 
- 
For reasons not affecting the benefit-risk balance, the Sponsor shall notify each country 
concerned through the EU portal within 15 days from the temporary halt of the clinical 
investigation 
- 
For reasons of a change of the benefit-risk balance the Sponsor shall notify without undue 
delay but not later than in 15 days of the date of the temporary halt in each country concerned 
through the EU portal of the reasons for such action and, follow-up measures for the patient. 
- 
For an exceptional circumstance (e.g. COVID-19 pandemic), the Sponsor will follow the 
CAs’ recommendations.  
When a temporarily halted clinical investigation is resumed the Sponsor will inform all involved 
investigators. The Sponsor must notify IEC/IRB/CA with the reason(s) for the suspension, as per 
the applicable regulatory requirement(s). 
If a temporarily halted clinical investigation is not resumed within two years, the expiry date of this 
period or the date of the decision of the sponsor not to resume the clinical investigation, whichever 
is earlier, shall be deemed to be the date of the end of the clinical investigation.  
The restart of the clinical investigation following a temporary halt shall be deemed to be a substantial 
modification. 
16.2 
EARLY TERMINATION OF THE INVESTIGATION 
The Sponsor or the investigator has the right to terminate the clinical investigation for any safety, 
ethical or administrative reason at any time. As far as possible, this should occur after mutual 
consultation. 
As required by the Clinical Trials legislation, in the case of early termination of the clinical 
investigation: 
- 
For reasons not affecting the benefit-risk balance, the Sponsor shall notify each country 
concerned through the EU portal of the reasons for such action and, when appropriate, 
follow-up measures for the patient 
- 
For reasons of a change of the benefit-risk balance the Sponsor shall notify without undue 
delay but not later than in 15 days of the date of early termination in each country concerned 
through the EU portal of the reasons for such action and, follow-up measures for the patient. 
The investigator, IEC or CA may prematurely terminate participation at the investigational sites for 
which they are responsible. 
Should the investigation be terminated prematurely, all investigational materials (IMDs, completed, 
partially completed, etc.) must be returned to the Sponsor or the Sponsor’s representative as if the 
investigation had been completed. 

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Laboratoires THÉA shall have the right to terminate the investigation at any time on written notice to 
the investigator. Without in any way limiting this right, Laboratoires THÉA would normally only 
terminate the investigation in the following circumstances:  
- 
Occurrence of  
• new events related to the conduct of a investigation or the development of an IMD likely 
to affect the safety of patient, such as:  
o a SAE which could be associated with the investigation procedures, and 
which could modify the conduct of the investigation 
o a significant hazard to the patient population such as lack of performance of 
an IMD used for the treatment of a life-threatening disease  
o a major safety finding from a newly completed animal study/investigation 
(such as carcinogenicity) 
• a temporary halt of an investigation for safety reasons if the investigation is conducted 
with the same IMDs in another country by the same Sponsor 
- 
If severe and/or serious AEs with the IMD in human or animal studies should indicate 
discontinuation of the investigation.  
- 
If Laboratoires THÉA should wish to discontinue the investigation for commercial reasons.  
- 
If Laboratoires THÉA had reasons to believe that the investigation could not be satisfactorily 
completed, including, but not limited to, the reason that inadequate numbers of patient could 
be enrolled or insufficient centres found within the necessary time.  
In the case of early termination of the clinical investigation, the date of the early termination shall 
be deemed to be the date of the end of the clinical investigation. 
 
16.3 
REQUIREMENTS FOR PATIENT FOLLOW-UP AND CONTINUED CARE 
In the case of temporary halt or early termination of the investigation, the requirements for patient 
follow-up will depend on the circumstance of the temporary halt or early termination: 
- 
For reasons not affecting the benefit-risk balance, according to the Sponsor 
recommendations, the investigator could decide if the patient may continue the clinical 
investigation as planned or if the patient should be withdrawn from the investigation. 
- 
For reasons of a change of the benefit-risk balance, the patient should be withdrawn from 
the investigation and the IMD must be discontinued. 
- 
For an exceptional reason (e.g. COVID-19 pandemic), each investigator has to decide 
whether the patient continued the investigation when able to follow the CIP requirements 
safely or to withdraw the patient from the investigation, based on his/her assessment of the 
benefit/risk ratio regarding the Covid-19 pandemic situation in his/her country/region and 
own investigational site, in accordance with the national/regional recommendations. 
This concerns all patient still on-going in the clinical investigation at the time of temporary halt or 
early termination. 
If a patient is prematurely stopping the IMD or should prematurely withdraw from the investigation, 
the investigator must perform at least one premature discontinuation visit following by one/several 
follow-up visits as decided by the Sponsor and according to the circumstances.  
If possible and depending the circumstance, the premature discontinuation visit will be realized on 
site and the follow-visit(s) could be performed by phone. 

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If it is not possible, the premature discontinuation visit will be performed by phone-call and/or 
online video consultation. In this case and if current circumstances are favorable, at least one of 
follow-up safety visit should be performed onsite. 
During the premature discontinuation visit/phone-call, the investigator has to: 
- 
Collect AE/SAE  
- 
Check the IMD compliance 
- 
Check the number of returned used and unused IMD 
- 
Instruct the patient to stop or to continue the IMD (depending on the reason as described 
above) 
- 
Ensure the continuity of investigational disease medication (if appropriate) 
- 
Perform evaluations described for the premature investigation discontinuation/final visit if 
possible (onsite visit) 
- 
Prescribe to the patient the best appropriate treatment if needed 
- 
Collect information on concomitant medications changes.  
 
If some follow-up visit(s) are required or if the premature discontinuation visit could not be realized 
on site, the investigator will have to schedule these phone-calls/visits. During this/these visit(s), the 
investigator has to: 
- 
Collect AE/SAE  
- 
Collect information on concomitant medications changes 
- 
Check the IMD compliance, if applicable 
- 
Check the number of returned used and unused IMD, if applicable 
- 
Perform evaluations described for the premature investigation discontinuation/final visit if 
not done at the premature discontinuation visit 
- 
Prescribe to the patient the best appropriate treatment if needed. 
 
The role of investigator-masked and Unmasked collaborator will be the same as previous visits. 
 
In any case, the requirements for patient follow-up will be described in more details in specific 
guidelines which will be provided to each involved person (investigators, Investigational team, 
Hospitals etc…) and to Institutions if necessary (IEC, CA etc...). This could be done by submitting 
a notification (in case of emergency) and/or a substantial modification. 
 
 

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17. PUBLICATION POLICY 
By signing the CIP, the investigator agrees that the results of the investigation may be used for the 
purposes of national and international registration, publication, and information for medical and 
pharmaceutical professionals. If necessary, the CAs will be notified of the investigator's name, 
address, qualifications, and extent of involvement. 
The data resulting from this investigation will be the proprietary information of Sponsor. An 
investigator shall not publish any data (poster, abstract, paper, etc.) without having consulted with 
Laboratoires THÉA in advance. 
At the end of the investigation, Laboratoires THÉA will prepare a Clinical Investigation Report. 
The draft reports will be discussed with the coordinating investigator and with Laboratoires THÉA. 
For any manuscript for publication prepared by Laboratoires THÉA, Laboratoires THÉA reserves 
the right to select the investigators who will be the authors to review the manuscript. Laboratoires 
THÉA will allow the selected investigators sufficient time for full review of the manuscript before 
publication.