Conditions: Diabetic Macular Edema
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 25
Healthy volunteers: no

Brief summary:
The purpose of this clinical trial is to evaluate the safety and tolerability of suprachoroidal microcatheterization with the Oxulumis® device for a randomized treatment with two dose levels of Triesence® in subjects with Diabetic Macular Edema.

Detailed description:
Twenty-four (24) week, randomized, two-arm, single-masked, clinical trial to evaluate safety, tolerability, and to explore the efficacy of two dose levels of suprachoroidal triamcinolone acetonide suspension (Triesence®, 2.4 mg, and 4.0mg) administered using the Oxulumis® microcatheterization device in subjects with previously treated Diabetic Macular Edema.

After a screening period, approximately 20 eligible Diabetic Macular Edema subjects will be treated using a 1:1 ratio to receive a single administration of one of two dose levels of triamcinolone acetonide (low dose, 2.4mg. or mid-dose, 4.0mg, respectively). If for any reasons treatment in randomized subjects cannot be completed, additional consecutive subjects will be randomized until the target number of approximately 20 treated subjects is reached.

From Week 4, subjects will be assessed for the need for follow-on treatment. The follow-up period after treatment administration will be up to twenty-four (24) weeks.

Arms:
arm 1: The Oxulumis® device will be used for the administration of Triesence® (Triamcinolone acetonide) via suprachoroidal microcatheterization. A single treatment with 2.4mg/60µl Triesence® will be applied. arm 2: The Oxulumis® device will be used for the administration of Triesence® (Triamcinolone acetonide) via suprachoroidal microcatheterization. A single treatment with 4.0mg/100µl Triesence® will be applied.

Interventions: intervention 1: Triamcinolone Acetonide intervention 2: Semi-automated Suprachoroidal Microcatheter
Intervention descriptions: intervention 1: Single suprachoroidal Administration of Triamcinolone acetonide intervention 2: Ophthalmic Adminstration Device

Protocol document:
Prot_000.pdf: 
OXUCT-103 Clinical Trial Protocol V3.0 17 Feb 2023 
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Oxular Limited 
Clinical Trial Protocol 
Clinical Trial Protocol Title: 
A Multi-Center, Randomized, Two-Arm, Parallel-Group, Single-masked, 24-week, Clinical 
Trial to Evaluate Safety and Tolerability of Two Dose Levels of Suprachoroidal 
Triamcinolone Acetonide Administered with the Oxulumis® Ophthalmic Administration 
Device in Subjects with Diabetic Macular Edema 
Clinical Trial Reference Number: 
OXUCT-103 
ClinicalTrials.gov Identifier: 
NCT05512962 
Investigational Product Name: 
Triamcinolone acetonide via suprachoroidal 
delivery with the Oxulumis® device in DME 
CT Version: 
V3.0 
Date: 
17 Feb 2023 
Sponsor: 
 
Oxular Ltd.  
Magdalen Centre 
1 Robert Robinson Avenue 
Oxford  
OX4 4GA, United Kingdom 
Email: OXUCT-103@oxular.com  
Telephone: +44 (0)1865 636200 
Funding Source: 
Oxular Ltd.  
Author(s): 
 
PD Dr. med. Friedrich Asmus, MD,  
Chief Medical Officer 
 


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Contact Information for Medical Oversight:  
Oxular Medical Monitor - Clinical Development 
Oxular Limited, Magdalen Centre, 1 Robert Robinson Avenue Oxford OX4 4GA, United 
Kingdom 
OXUCT-103@oxular.com 
 
Confidentiality Statement 
This document includes confidential and privileged information and data that contain trade 
secrets that are the property of Oxular Limited. This information shall not be made public 
without prior written permission of Oxular Limited. This document may be disclosed to and 
used by the staff that conducts the clinical trial at a clinical trial site, who are under a 
confidentiality agreement with Oxular Limited and/or the Contract Research Organization 
conducting this clinical trial. 


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Signatures 
I hereby confirm that I approve of this clinical trial protocol and agree to comply with its 
terms as laid out in this document.  
Sponsor signatory: 
PD Dr. med. Friedrich Asmus, MD
Chief Medical Officer 
 
 
 
Name, Function (print) 
Signature 
Date 
I hereby confirm that I approve of this clinical trial protocol and agree to comply with its 
terms as laid out in this document.  
Coordinating Principal Investigator: 
 
 
Name: 
Function: 
Organization: 
Address: 
Telephone: 
 
Signature 
Date 
I hereby confirm that I approve of this clinical trial protocol and agree to comply with its 
terms as laid out in this document.  
Principal Investigator: 
 
 
Name: 
Function: 
Organization: 
Address: 
Telephone: 
 
Signature 
Date 
 
 
 
2/17/2023


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Abbreviations 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
Anti-VEGF 
Anti-Vascular Growth Factor 
AMD 
Age-Related Macular Degeneration 
BCVA 
Best Corrected Visual Acuity 
BM 
Biomicroscopy 
CFP 
Color Fundus Photography 
CNV 
Choroidal Neovascularization 
CRF 
Case Report Form  
CME 
Cystoid Macular Edema 
CRO 
Contract Research Organization 
CST 
Central Subfield Thickness 
CTP 
Clinical Trial Protocol 
DME 
Diabetic Macular Edema 
EDC 
Electronic Data Capture 
EMA 
European Medicines Agency 
EoS 
End of Study 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HR 
High Resolution 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IFU 
Instruction for Use 
IOP 
Intraocular Pressure 
IRB 
Institutional/Independent Review Board 
ISO 
International Organization for Standards 
IVT 
Intravitreal 
MedDRA 
Medical Dictionary for Regulatory Activities 
ME 
Macular Edema 


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OCT-A 
Optical Coherence Tomography Angiography 
OU 
Oculus Uterque – Both Eyes 
PDR 
Proliferative Diabetic Retinopathy 
PRP 
Panretinal Photocoagulation 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SD-OCT 
Spectral Domain Optical Coherence Tomography 
SE 
Study Eye 
SUSAR 
Serious and Unexpected Suspected Adverse Reaction 
TA 
Triamcinolone Acetonide 
TEAE 
Treatment Emergent Non-Serious Adverse Effect 
UADE 
Unanticipated Adverse Device Effect 
US FDA 
United States Food and Drug Administration  
VEGF 
Vascular Endothelial Growth Factor 
 
 


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Table of Contents 
Table of Contents ....................................................................................................................... 6 
List of Figures: ........................................................................................................................... 9 
List of Tables .............................................................................................................................. 9 
1 
Protocol Summary ..................................................................................................... 10 
1.1 
Synopsis ..................................................................................................................... 10 
1.2 
Schema ....................................................................................................................... 26 
1.3 
Schedule of Activities (SoA) ..................................................................................... 27 
2 
Introduction ............................................................................................................... 30 
2.1 
Study Rationale .......................................................................................................... 30 
2.2 
Background ................................................................................................................ 31 
2.3 
Preclinical Testing of the Oxulumis® Ophthalmic Administration Device ............... 32 
2.4 
Previous clinical experience ...................................................................................... 32 
2.4.1 
Diabetic Macular Edema: .......................................................................................... 33 
2.4.2 
Suprachoroidal Administration of TA via Microcatheterization .............................. 34 
2.5 
Benefit/Risk Assessment ........................................................................................... 36 
3 
Objectives and Endpoints .......................................................................................... 38 
3.1 
Objectives .................................................................................................................. 38 
3.1.1 
Primary Objective ..................................................................................................... 38 
3.1.2 
Explorative Objective ................................................................................................ 38 
3.2 
Endpoints ................................................................................................................... 38 
3.2.1 
Primary (Safety) Endpoints ....................................................................................... 38 
3.2.2 
Exploratory Efficacy (and/or Safety) Endpoints ....................................................... 38 
4 
Clinical Trial Design ................................................................................................. 39 
4.1 
Overall Trial Design .................................................................................................. 39 
4.2 
Scientific Rationale for Study Design ....................................................................... 41 
4.2.1 
Target Indication ....................................................................................................... 41 
4.3 
Justification of Dose .................................................................................................. 41 
4.4 
End-of-Study Definition ............................................................................................ 42 
5 
Study Population ....................................................................................................... 42 
5.1 
Inclusion Criteria ....................................................................................................... 42 
5.2 
Exclusion Criteria ...................................................................................................... 43 
5.3 
Lifestyle Considerations ............................................................................................ 45 
5.4 
Screen Failures .......................................................................................................... 46 
6 
Study Intervention and Concomitant Therapies ........................................................ 46 
6.1 
Study Intervention Administered ............................................................................... 46 
6.1.1 
Oxulumis® Ophthalmic Administration Device ........................................................ 46 
6.1.2 
Triamcinolone acetonide (Triesence®) ...................................................................... 47 
6.1.3 
Preparation, Handling, Storage, and Accountability ................................................. 47 
6.1.4 
Assignment to Study Intervention ............................................................................. 48 
6.1.5 
Masking ..................................................................................................................... 48 
6.1.6 
Study Intervention Compliance ................................................................................. 48 
6.1.7 
Dose Modification ..................................................................................................... 48 
6.1.8 
Follow-on Treatment ................................................................................................. 48 
6.1.9 
Treatment for Complications of the Underlying Disease .......................................... 49 
6.1.10 
Continued Access to Study Intervention after the End of the Study ......................... 50 
6.1.11 
Treatment Overdose .................................................................................................. 50 
6.2 
Prior and Concomitant Therapy ................................................................................ 50 
6.2.1 
Permitted Medications and/or Treatments ................................................................ 50 


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6.2.2 
Prohibited Medications and/or Treatments ............................................................... 50 
6.2.3 
Concomitant Medications ......................................................................................... 51 
6.3 
COVID-Related Measures ......................................................................................... 52 
7 
Discontinuation of Study, the Study Intervention and Subject 
Discontinuation/Withdrawal ..................................................................................... 52 
7.1 
Discontinuation of the Trial ....................................................................................... 52 
7.2 
Discontinuation of Study Intervention ...................................................................... 53 
7.3 
Subject Discontinuation/Withdrawal from the Study ................................................ 53 
7.4 
Lost to Follow-up ...................................................................................................... 54 
8 
Study Assessments and Procedures ........................................................................... 54 
8.1 
Evaluations Performed During Investigational Visits ............................................... 55 
8.1.1 
Screening Visit (Visit 1, Days -21 through -2) ......................................................... 55 
8.1.2 
Baseline visit (Visit 2, Day 0) ................................................................................... 55 
8.1.3 
Visits 3 through 9 (Day 1 – Week 20)....................................................................... 58 
8.1.4 
End of study visit (Visit 10, Week 24± 5 days) ........................................................ 59 
8.1.5 
Early termination (ET) visit ...................................................................................... 59 
8.1.6 
Unscheduled visit ...................................................................................................... 59 
8.2 
Administrative and General/Baseline Procedures ..................................................... 59 
8.2.1 
Consent form completion .......................................................................................... 59 
8.2.2 
Demographic information and medical history ......................................................... 60 
8.2.3 
Urine pregnancy test .................................................................................................. 60 
8.2.4 
Concomitant medication review ................................................................................ 60 
8.2.5 
Weight, Height, Vital Signs ...................................................................................... 60 
8.2.6 
Oxulumis® use to administer Triesence®................................................................... 60 
8.2.7 
Subject Experience Assessment ................................................................................ 61 
8.2.8 
Retinal physician’s Documentation and Assessment of the Administration procedure
 
61 
8.2.9 
Follow-on Treatment ................................................................................................. 61 
8.2.10 
Disposition of samples .............................................................................................. 61 
8.3 
Ocular Assessments ................................................................................................... 61 
8.3.1 
Best Corrected Visual Acuity (BCVA) ..................................................................... 61 
8.3.2 
Axial length measurement ......................................................................................... 62 
8.3.3 
Slit-lamp biomicroscopy ........................................................................................... 62 
8.3.4 
IOP measurement ...................................................................................................... 62 
8.3.5 
Dilated indirect ophthalmoscopy .............................................................................. 62 
8.3.6 
SD-OCT, and Peripheral OCT assessments .............................................................. 63 
8.3.7 
OCT-Angiography .................................................................................................... 64 
8.3.8 
Color fundus photography ......................................................................................... 64 
8.4 
Safety Assessments .................................................................................................... 65 
8.4.1 
Adverse Events and Adverse Device Effect collection ............................................. 65 
8.4.2 
Safety laboratory tests ............................................................................................... 65 
8.4.3 
Height, Weight, Vital Signs, and Blood Pressure ..................................................... 66 
8.5 
Safety Reporting, Adverse Events (AEs), and Serious Adverse Events (SAEs)....... 66 
8.5.1 
Time Period and Frequency for Collecting AE and SAE Information ..................... 67 
8.5.2 
Method of Detecting AEs and SAEs ......................................................................... 68 
8.5.3 
Follow-up of AEs and SAEs ..................................................................................... 68 
8.5.4 
Disease-related events and/or Disease-related outcomes not qualifying as AEs or 
SAEs .......................................................................................................................... 68 
8.5.5 
Regulatory Reporting Requirements for Serious Safety Events ............................... 68 
8.5.6 
Adverse Events of Special Interest ............................................................................ 69 


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8.5.7 
Device Deficiencies ................................................................................................... 69 
8.5.8 
Contraception Guidance ............................................................................................ 70 
8.5.9 
Pregnancy .................................................................................................................. 71 
9 
Statistical Considerations .......................................................................................... 72 
9.1 
Statistical Hypothesis ................................................................................................ 72 
9.2 
Sample Size Determination ....................................................................................... 72 
9.3 
Analysis Sets .............................................................................................................. 72 
9.3.1 
Safety Population ...................................................................................................... 72 
9.3.2 
Efficacy Evaluable Population .................................................................................. 73 
9.3.3 
Per Protocol Efficacy Population .............................................................................. 73 
9.4 
Statistical Analyses .................................................................................................... 73 
9.4.1 
General Considerations ............................................................................................. 73 
9.4.2 
Safety Analyses ......................................................................................................... 73 
9.4.3 
Exploratory Efficacy and Safety Endpoint Analysis ................................................. 74 
9.4.4 
Important Protocol Violations ................................................................................... 74 
9.4.5 
Other Analyses .......................................................................................................... 75 
9.4.6 
Missing Data and Imputation Methods ..................................................................... 75 
9.5 
Deviations from the clinical study protocol .............................................................. 75 
9.6 
Interim Analysis ........................................................................................................ 76 
10 
Supporting Documentation and Operational Considerations. ................................... 77 
10.1 Regulatory and Ethical Considerations ..................................................................... 77 
10.2 Financial Disclosure .................................................................................................. 77 
10.3 Informed Consent Process ......................................................................................... 78 
10.4 Recruitment strategy .................................................................................................. 78 
10.5 Data Protection .......................................................................................................... 79 
10.5.1 
Committee Structure ................................................................................................. 80 
10.5.2 
Dissemination of Clinical Trial Data ........................................................................ 80 
10.5.3 
Data Quality Assurance ............................................................................................. 81 
10.5.4 
Source Documents ..................................................................................................... 82 
10.6 Publication Policy ...................................................................................................... 83 
10.7 Study and Site Start up and Closure .......................................................................... 83 
10.7.1 
First Act of Recruitment ............................................................................................ 83 
10.7.2 
Study/Site Termination ............................................................................................. 83 
11 
Safety: Events, Definitions and Procedures .............................................................. 84 
11.1 Emergency Contacts for Investigator Reporting of Safety Events ............................ 84 
11.2 Adverse Event (AE) ................................................................................................... 84 
11.3 Device Adverse Event (AE) and Adverse Device Effect (ADE) .............................. 85 
11.4 Device Deficiency ..................................................................................................... 85 
11.4.1 
Time Period for Detecting Device Deficiencies ....................................................... 85 
11.4.2 
Follow-up of Device Deficiencies ............................................................................. 85 
11.4.3 
Regulatory Reporting Requirements of for Device Deficiencies .............................. 86 
11.5 Serious Adverse Event (SAE) ................................................................................... 86 
11.6 Device SAE, SADE and USADE .............................................................................. 88 
11.7 AE and SAE Recording ............................................................................................. 89 
11.7.1 
Assessment of Intensity ............................................................................................. 90 
11.7.2 
Assessment of Causality ............................................................................................ 91 
11.7.3 
Assessment of the Outcome of Adverse Events ........................................................ 91 
11.7.4 
Follow-up of AEs and SAEs ..................................................................................... 92 
12 
Regulatory Reporting Requirements (Serious Safety Events, Safety Reporting in 
Clinical Investigations of Medical Devices, and DSUR) .......................................... 92 


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12.1 Suspected Unexpected Serious Adverse Reaction (SUSAR) .................................... 93 
13 
Outcome Assessments and Questionnaires ............................................................... 94 
13.1 Subject’s Experience Assessment – Day 0, Visit 2 ................................................... 94 
Instructions for the site interviewer: ......................................................................................... 94 
Instructions for the subject (to be read to the subject by the interviewer): .............................. 94 
13.2 Subject’s Experience Assessment – Day 1, Visit 3 through Week 4, Visit 5 ........... 97 
Instructions for site interviewer: .............................................................................................. 97 
Instructions for study subject (to be read to the subject by the interviewer): .......................... 97 
13.3 Retinal physician’s documentation and assessment of administration procedure ..... 99 
13.4 Guidance on Factors to Consider for Expected Assessment of Procedural 
Complexity ......................................................................................................................... 107 
14 
References ............................................................................................................... 110 
 
List of Figures: 
Figure 1: Study Flow Diagram ................................................................................................. 26 
 
List of Tables: 
 
Table 1 Schedule of Activities ............................................................................................... 27 
Table 2 Treatment groups of two dose levels of triamcinolone acetonide suspension. ......... 39 
Table 3 Time Intervals of ME Medication before Screening and Qualification as Follow-on 
Treatment .................................................................................................................. 51 
Table 4  Overview of Imaging Systems and Required Field of View for Wide-Field Color 
Funds Photographs .................................................................................................... 65 
 


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1 
Protocol Summary 
1.1 
Synopsis 
Title 
A 24-week, Randomized, Two-Arm, Parallel-Group, Single-masked, 
Clinical Trial to Evaluate Safety and Tolerability of Two Dose Levels 
of Suprachoroidal Triamcinolone Acetonide Administered with the 
Oxulumis® Ophthalmic Administration in Subjects with Diabetic 
Macular Edema 
Sponsor  
Protocol #: 
OXUCT-103 
Phase: 
Exploratory Clinical Trial – Phase 2 
Background and 
Rationale: 
There remains a high unmet need for a safe and efficacious treatment 
for DME in selected patients. Currently approved treatments 
including intravitreal (IVT) steroid implants or IVT anti-VEGF 
treatments in DME may not show satisfactory and/or sustained 
enough improvement of the macular edema and of vision. With 
existing ophthalmic steroid treatments, visual benefits may be 
compromised by meaningful side effects, which often trigger 
additional drug treatments or even ocular surgeries, e.g., intraocular 
lens replacement surgery. Accordingly, there continue to be 
significant treatment challenges for the heterogenous population of 
patients with DME. 
The current clinical trial evaluates a novel microcatheterization 
approach for suprachoroidal steroid administration that has the 
potential to address challenges with respect to critical adverse events, 
efficacy, and durability of treatment compared to other currently 
applied treatment options, e.g., subtenon, or IVT administration of the 
same ophthalmic steroid suspension. 
The proposed ophthalmic administration device (Oxulumis®) deploys 
an integrated, highly flexible, soft (atraumatic) microcatheter in the 
suprachoroidal space through a minimally invasive, short (27G) 
insertion needle in the region of the pars plana, typically 4-7mm post 


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limbus corneae. The soft microcatheter incorporates an illuminated 
shaft. Before administration of the drug product, the illumination 
allows confirmation of microcatheter positioning in the 
suprachoroidal space. Drug delivery is achieved via a low-volume 
administration of the triamcinolone acetonide suspension 
(Triesence®). The current trial evaluates two different dose levels to 
initially explore the safety of different administration volumes. The 
low dose is 2.4mg triamcinolone acetonide (TA, 60µl of a 40mg/ml 
suspension). The mid-dose is 4.0mg TA (100µl of a 40mg/ml 
suspension). 
In a compassionate use program in Switzerland, both dose levels of 
2.4mg and 4.0mg were applied in patients with cystoid macular 
edema (CME) or post-surgical inflammatory edema refractory to 
standard treatments. In this limited number of treatments so far, no 
safety concerns were observed. 
The current trial OXUCT-103 is expected to deliver first exploratory 
data for two randomized dose groups, that both dose levels are safe, 
and may explore first trends of potential differences in peak efficacy 
and duration of effect. 
It is anticipated that posterior deployment of the drug in the 
suprachoroidal space will lead to a safer, more tolerable, and effective 
treatment compared to IVT or subtenon administration. An important 
success factor for a completed Oxulumis® procedure is a controlled 
scleral engagement of the insertion needle of the ophthalmic 
administration device. In a subset of subjects with more limited 
access to the orbita, enophthalmus, and/or a thick, opaque, 
hypermobile conjunctivas a small incision of the conjunctiva may be 
needed to ensure facilitated access and full visibility through the 
scleral engagement phase of the Oxulumis microcatheterization 
procedure. Depending on the expert assessment of the investigator at 
the screening visit, the procedure can either be performed,  


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a) in an in-clinic setting first. In case the study treatment cannot be 
administered in this setting, the investigator can perform the 
procedural variant with a conjunctival/tenon incision. Activities for 
Visit 2 need to be completed within 14 days (for details on scheduling 
see Section 1.3). 
b) at the discretion of the investigator, the procedure can be 
performed directly in an operating/procedure room, if the procedural 
variant with the conjunctival/tenon incision is likely to be needed. 
An operating/procedure room will allow for the setting for a 
conjunctival/tenon incision, which is typically not performed in an in-
office setting. 
As eligibility for this trial is based on limited or no response to 
standard treatments, this trial uses another dose level of TA 
suspension as a control rather than exposing subjects the same or a 
similar treatment that they already had failed to respond. 
The standard dose for IVT injection is 4.0mg. This dose level will be 
administered in the current trial in the mid-dose group. In addition, 
2.4mg TA will be used in the low dose group. In both dose groups, 
TA is expected to be administered closer to the location of the disease 
activity compared to other treatment approaches. Local 
concentrations of TA in the retinal tissues are expected to be higher 
compared to the same doses administered by IVT or subtenon 
injection. 
Overall Design 
Twenty-four (24) week, randomized, two-arm, single-masked, 
clinical trial to evaluate safety, tolerability, and to explore the 
efficacy of two dose levels of suprachoroidal triamcinolone acetonide 
(TA) suspension (Triesence®, 2.4 mg, and 4.0mg) administered using 
the Oxulumis® ophthalmic administration device in subjects with pre-
treated Diabetic Macular Edema. 


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A focus of this trial is to evaluate the feasibility, safety, and 
tolerability of the ophthalmic administration of a low and a mid-dose 
of suprachoroidal triamcinolone acetonide suspension (Triesence®) 
with the Oxulumis® in DME. In addition, for the two dose groups of 
the trial, efficacy data on visual and anatomic changes will be 
collected. 
To support the main objectives of this trial, a sample size of 
20 treated subjects is estimated to be sufficient to detect common and 
very common adverse events. This safety information is relevant to 
inform further trials in the Oxulumis development program with 
respect to safety considerations including initial safety and feasibility 
experience with suprachoroidal administration procedure. 
After a screening period, approximately 20 eligible DME subjects 
will be randomized and treated using a 1:1 ratio to receive a single 
administration of one of two dose levels of TA (low dose, 2.4mg. or 
mid-dose, 4.0mg, respectively). Subjects in whom the procedure 
could not be completed, and TA is not injected, will be replaced in 
order to reach approximately 20 treated subjects. 
The follow-up period after treatment administration will be up to 
twenty-four (24) weeks. 
Clinical visits will occur on Day 0, Day 1, Week 1, Week 4, and then 
every four (4) weeks thereafter for a total of twenty-four (24) weeks. 
From Week 4 on, subjects will be assessed for their need for 
follow-on treatment to determine the length of the treatment interval. 
Treatment 
Arm 
Intervention 
Subjects 
1 
One treatment with suprachoroidal low 
dose (2.4mg) triamcinolone acetonide  
N=10 
2 
One treatment with suprachoroidal 
mid-dose (4.0mg) triamcinolone 
acetonide  
N=10 


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If subjects show a need for the next treatment of DME according to 
pre-specified criteria, participation in this clinical investigation will 
end, and an early termination/end of the study visit will be conducted 
at the respective visit date. In this case, the follow-up period will be 
shorter than 24 weeks. 
After completion of participation in this clinical trial, patients will 
continue treatment with therapeutic options determined by the 
treating retinal specialists in accordance with current medical practice 
for their DME. 
Periodically, the coordinating investigator together with the medical 
monitor will review individual patient data as well as the totality of 
the safety data to recommend if the investigation should continue as 
is, continue with changes, or be terminated. This review can also be 
performed by a Safety Review Committee, which includes all active 
investigators in this trial. 
Objective(s): 
Primary Objective: 
• To evaluate the safety and tolerability of two dose levels of 
triamcinolone acetonide administered with the Oxulumis® to the 
suprachoroidal space in subjects with DME. 
Exploratory Objective: 
• To explore the efficacy of two dose levels of triamcinolone 
acetonide with respect to VA changes, edema control, and 
durability of the treatment effect of suprachoroidal triamcinolone 
acetonide suspension (Triesence®) in subjects with DME. 
Endpoint(s): 
Safety endpoint: 
The primary endpoint of this study is safety and tolerability as 
assessed by: 
1. Frequency of ocular and systemic adverse events (treatment-
emergent serious adverse events [SAEs] and treatment-
emergent non-serious adverse events [TEAEs]) 


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2. Frequency of adverse device effects (ADEs, serious ADEs 
[SADEs]) 
Exploratory efficacy (and/or safety) endpoints: 
1. Mean Change in BCVA (ETDRS) at all study visits through 
Week 24 compared to baseline 
2. Percentage of subjects with vision gain and vision loss of at 
least 5, at least 10, and at least 15 letters at all study visits 
through Week 24 compared to baseline 
3. Time to subjects requiring follow-on treatment 
4. Mean Change in Central subfield thickness (CST) at all study 
visits through Week 24 compared to baseline. 
5. Mean Change in IOP at all study visits through Week 24 
compared to baseline 
Population 
Studied: 
This study population will consist of adult male and female subjects 
who: 
• Have been diagnosed with Type 1 or Type 2 diabetes mellitus. 
• Have DME involving the center of the fovea with central 
subfield thickness (CST) in the study eye of: 
≥ 320 for males or ≥ 305 for females on Spectralis 
(Heidelberg) or  
≥ 305 for males or ≥ 290 for females with Cirrus (Zeiss) by 
SD-OCT. 
• Have BCVA of ≤73 letters (ETDRS, approximate Snellen 
equivalent of 20/40 or worse) at the screening in the study 
eye. 
• Have shown short-lived, limited, or no response to prior 
therapy with ocular (e.g., IVT, or subtenon) injections of 
steroids and/ or anti-VEGF agents. Short-lived in the context 
of this trial is defined as less than 4 weeks. 


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• Have no structural deficit of the retina likely correlated to 
short-lived, limited, or absent therapeutic response. 
• Study eye suitable for suprachoroidal injection, i.e., no 
relevant structural abnormalities can be observed like 
choroidal coloboma, chorioretinal anastomosis, and extreme 
scleral thinning, or hypotony, amongst others. 
The study is planned to be conducted in the United States. 
Duration of Study: 
There will be up to ten (10) clinic visits over 24 weeks (in addition to 
up to three [3] weeks of Screening, plus up to 14 days to complete the 
baseline visit activities). 
Subjects who meet the criteria for follow-on treatment will end study 
participation with an earlier EoS Visit before week 24. 
Number of 
Subjects: 
Approximately 20 subjects will be randomized and treated using a 1:1 
ratio to two treatment arms receiving either 2.4mg TA (low dose arm) 
or 4.0mg TA (mid-dose arm) as a single treatment with triamcinolone 
acetonide (Triesence®) administered with the Oxulumis® to the 
suprachoroidal space of one eye, the study eye. Subjects in whom the 
procedural attempts do not result in administration of TA will be 
replaced to reach a total of approximately 20 treated subjects. 
Eligibility: 
Inclusion Criteria: 
Subjects will be eligible if they meet all the following inclusion 
criteria: 
1. Able to understand and sign an informed consent form. 
2. At least 18 years of age. 
3. Have been diagnosed with Type 1 or Type 2 diabetes mellitus. 
4. Have DME involving the center of the fovea in the study eye 
with a central subfield thickness (CST) on SD-OCT of: 
≥ 320 for males or ≥ 305 for females on Spectralis 
(Heidelberg)  or  
≥ 305 for males or ≥ 290 for females with Cirrus (Zeiss). 


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5. Have BCVA in the study eye of ≤73 ETDRS letters 
(approximate Snellen equivalent of 20/40 or worse) at the 
screening visit. The eligibility will be assessed based on the 
ETDRS BCVA letter score. 
6. Short-lived, limited, or no response to prior ocular injection 
therapy (e.g., IVT or subtenon) of steroids and/or anti-VEGF 
agents based on the investigator’s assessment. Short-lived in 
this trial is defined as less than 4 weeks. 
7. For women who are not postmenopausal (i.e., at least12 
months of non-therapy-induced amenorrhea or surgically 
sterile (absence of ovaries and/or uterus) agreement to remain 
abstinent or use combined contraceptive methods that result in 
a failure rate of less than 1% per year from the treatment visit 
(Day 0) until the end of trial participation, or for at least 
12 weeks from the treatment visit (D0), if study participation 
ends before Visit 7, Week 12. Examples of contraceptive 
methods with an expected failure rate of less than 1% per year 
include male sterilization, hormonal implants, proper use of 
combined oral or injected hormonal contraceptives, and 
certain intrauterine devices. Alternatively, two methods (e.g., 
two barrier methods such as a condom and a cervical cap) 
may be combined to achieve a failure rate of less than 1% per 
year, barrier methods must always be supplemented with the 
use of a spermicide. 
8. Males must agree to use a barrier method of contraception 
from the treatment visit (Day 0) until the end of trial 
participation, or for at least 12 weeks from the treatment visit 
(D0), if study participation ends before Visit 7, Week 12. 
9. Subject must be willing not to participate in any other clinical 
trial including an investigational medicinal product (IMP) or 
an investigational device until the end of the participation in 
this trial. 


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Main Exclusion Criteria: 
Subjects will be eligible if they do not meet any of the following 
exclusion criteria: 
1. Presence of any significant ocular or non-ocular 
disease/disorder (or medication and/or laboratory test 
abnormalities) which, in the opinion of the Investigator and 
with concurrence of the Oxular Medical Monitor, may either 
put the subject at risk because of participation in the trial, may 
influence the results of the trial, or the subject’s ability to 
participate in the trial. 
2. Macular edema considered due to a cause other than diabetes 
mellitus in the study eye. 
3. Condition, in the study eye, in which visual acuity is not 
expected to improve from the resolution of macular edema 
(e.g., foveal atrophy, clinically relevant loss of ellipsoid zone, 
pigment abnormalities, vitreomacular traction, or nonretinal 
causes). 
4. Conditions, in the study eye, that may render the 
suprachoroidal microcatheter insertion and deployment 
difficult or subject the patient to excessive risk of 
complications. Examples include but are not limited to ocular 
surface disease with significant conjunctival edema and/or 
inflammation, ocular hypotony, scleral staphylomas, 
necrotizing scleritis, scleral melting, excessive choroidal 
scarring e.g., associated with pan-retinal photocoagulation, 
amongst others. 
5. Macular laser photocoagulation or panretinal laser 
photocoagulation (PRP) in the study eye performed within 
sixteen (16) weeks prior to screening. 
6. Active proliferative diabetic retinopathy (PDR) or sequelae of 
PDR (including iris neovascularization, vitreous hemorrhage, 


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tractional retinal detachment, extensive scarring following 
PRP) at screening in the study eye. 
7. History of recurrent or active intraocular inflammation in 
either eye (e.g., uveitis) within 12 weeks prior to screening. 
8. Infectious eye disease like infectious blepharitis, keratitis, or 
conjunctivitis in either eye within four (4) weeks of screening. 
9. IOP ≥ 22 mmHg, or glaucomatous disc changes (i.e., a cup 
disc ratio greater than 0.8) in the study eye at screening. 
10. History of glaucoma surgery, and or anti-glaucoma therapy 
with more than two active substances (in separate or a 
combination preparation) at the screening visit are 
exclusionary. 
11. History of closed-angle glaucoma. 
12. IOP <6mmHg (hypotony) in the study eye at screening. 
13. Spherical equivalent of the refractive error of −6 diopters of 
myopia or worse (prior to cataract or refractive surgery) at 
screening. 
14. Cataract or other media opacity that limits the ability to obtain 
the planned imaging assessments. 
15. History of retinal detachment. 
16. Subjects who were previously treated for DME in the study 
eye must not have received:  
a.) an intravitreal anti-VEGF treatment within four (4) weeks 
before screening. The 4 week interval before screening is 
used for IVT bevacizumab, ranibizumab, aflibercept, 
brolucizumab, or faricimab (i.e., a combined Anti-
VEGF/anti-Ang2 agent), as also inclusion criterion No. 6 
on therapeutic response must be met. 
b.) Prior treatment with SUSVIMO® (Port Delivery System) 
implant at any time is exclusionary. 


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c.) Intra- or periocular/subtenon triamcinolone acetonide 
suspension within 12 weeks before screening.  
d.) Intravitreal dexamethasone implant (Ozurdex®) within 
24 weeks before screening. 
e.) Prior treatment with longer duration implants (e.g., 
fluocinolone acetonide IVT implant, e.g., Iluvien®) at any 
time is exclusionary. 
f.) Prior treatment with suprachoroidal steroids (commercial, 
investigational, or off-label) at any time is exclusionary. 
17. Concurrent use of systemic glucocorticoid medications or 
systemic steroids within twelve (12) weeks before screening is 
exclusionary. 
Intranasal, inhaled, and extra-ocular topical corticosteroids are 
allowed. 
18. Treatment with ocriplasmin (Jetrea®) at any time. 
19. History of vitreoretinal surgery (including surgery for retinal 
detachment or scleral buckle) in the study eye. Vitrectomy is 
only exclusionary, if within 12 weeks prior to screening. 
20. Any other previous ophthalmic surgeries, uncomplicated 
cataract surgery, or uncomplicated trauma in the study eye 
within twelve (12) weeks prior to screening. Complicated 
cataract surgery or trauma that may impact access and/or drug 
delivery to the suprachoroidal space is exclusionary. 
21. Hypersensitivity to triamcinolone acetonide, or any of the 
excipients in the Triesence® formulation or Oxulumis® device 
components. 
22. Active malignancy or history of malignancy within the past 
five (5) years. 
23. Uncontrolled diabetes with a hemoglobin A1c (HbA1c) 
> 12% or any other uncontrolled systemic disease at 
screening. 


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24. Uncontrolled hypertension, defined as blood pressure with a 
systolic value of ≥ 160mmHg or a diastolic value of ≥ 100 
mmHg upon repeat assessment at screening. 
25. History of myocardial infarction, stroke, transient ischemic 
attack, acute congestive heart failure, or any acute coronary 
event within 90 days before screening. 
26. Subjects who are pregnant or breastfeeding at the screening 
visit, or who test positive for pregnancy at the screening visit 
or are unwilling to use adequate birth control methods to 
prevent pregnancy throughout the study. 
27. Subjects who were previously randomized in this trial, but in 
whom administration of study treatment could not be 
completed. 
 
Investigational 
Product: 
Triamcinolone acetonide injectable suspension 40 mg/mL 
(Triesence®) administered with the Oxulumis® ophthalmic 
administration device to the suprachoroidal space. 
The trial will investigate two dose levels of TA: 
1. Low dose arm: the target dose of triamcinolone acetonide 
suspension is 2.4 mg (i.e., 60µl).  
2. Mid dose arm: the target dose of triamcinolone suspension is 
4.0mg (i.e., 100µl)  
The Oxulumis® is a sterile, semi-automatically operated, minimally 
invasive, single-use device designed to deploy a therapeutic drug via 
a delivery-guiding illuminated ophthalmic microcatheter into the 
suprachoroidal space. The illumination confirms that the 
microcatheter is deployed correctly, prior to administration of the 
therapeutic drug. 
Subjects will receive topical anesthetics and/or local injection 
anesthesia (typically subtenon injections) at the discretion of the 
investigator to reduce potential pain and discomfort during the 


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procedure. The investigator will assess at the baseline visit the 
expected procedural complexity in categories of low, medium, or 
high. If subject characteristics (e.g., enophthalmos, and/or thick, 
opaque conjunctiva or similar features) suggest an increased 
complexity for engaging the Oxulumis® insertion needle into the 
sclera, a variant of the Oxulumis® procedure may be used with an 
incision of the conjunctiva/tenon. This procedural variant is expected 
to be carried out after local injection anesthesia in an operating/ 
procedure room. Locally established procedural practices for 
conjunctival/tenon incision and closure will be used at the discretion 
of the investigator. 
The treatment visit V2, Day 0, can be split to allow for collection of 
baseline assessments on a different day than the administration of the 
study drug. If a first attempt of study treatment is made in-clinic and 
treatment cannot be administered, a second attempt in an 
operating/procedure room is allowed. Only assessments feasible in an 
operating/procedure room setting need to be performed on this 
treatment day (for details see 1.3)  The maximum time interval from 
starting activities of V2 to completion is 14 days. 
Antiseptic conditions according to global IVT treatment standards 
and following the current practice at the investigational site must be 
applied before the Oxulumis® procedure. 
Dosing Regimen: 
A single suprachoroidal administration of triamcinolone acetonide 
suspension (Triesence®) (at two different dose levels per treatment 
arm, 2.4mg and 4.0mg, respectively) will be given at the baseline 
visit (Visit 2, Day 0) in the study eye. 
Reference/Compar
ator Therapy: 
This trial will assess in two randomized parallel groups the safety and 
exploratory efficacy of triamcinolone acetonide suspension 40mg/ml 
at dose levels of 2.4mg and 4.0mg. 


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Need for Follow-
On Treatment.  
End-of-Study 
Subjects will be followed with regular visits (from Week 4 on, at 
monthly intervals) to assess the safety and the course of visual and 
anatomic outcomes. 
From Week 4 on, subjects will be evaluated against prespecified 
criteria indicating the need for follow-on treatment (i.e., indicating 
the end of the current treatment interval). Criteria are as follows: 
• At least 75 μm increase in CST on SD-OCT compared to the 
best-achieved CST value since the baseline visit [Visit 2, 
day 0]. 
• A decrease in BCVA of at least 10 ETDRS letters from the 
best achieved BCVA since the baseline visit [Visit 2, day 0], 
that in the opinion of the investigator, is due to worsening of 
DME. 
For subjects showing no reduction of edema or no improvement of 
BCVA, the baseline visit will be considered the best CST or BCVA 
value. 
If one or both above criteria are met, the subject will be eligible for 
follow-on treatment and will be managed according to the local 
standard of care after ending participation in this clinical trial. 
If the investigator decides that the subject requires follow-on 
treatment during a study visit, the respective visit-day procedures will 
be extended to include the assessments foreseen for the EoS visit. 
This visit will then be an early termination/EoS visit. 
For subjects who decide to discontinue study participation for any 
reason, the respective visit-day procedures will be extended to 
include the assessments scheduled for the EoS visit (or an EoS visit 
will be scheduled for the subject if notification of discontinuation is 
received outside of a scheduled study visit). This visit will then be an 
early termination/EoS visit. 
If the non-study eye requires management for ME, this shall be 
carried out according to the local standard of care. 


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Assessments/Evalu
ations: 
Safety: 
• Adverse events (AE) and Adverse Device Effects (ADE) will 
be coded to system organ classes (SOCs) and preferred terms 
(PTs) using the Medical Dictionary for Regulatory Activities 
(MedDRA). 
o Subjects will be monitored for safety throughout the study. 
o On the injection day, Day 0, Visit 2, subjects will be 
monitored for at least sixty (60) minutes immediately 
following the suprachoroidal administration of TA. 
Additional assessments including efficacy endpoints: 
• Best-corrected visual acuity (BCVA) using the ETDRS 
methodology 
• IOP measurement 
• Slit-lamp biomicroscopy 
• Dilated indirect ophthalmoscopy 
• SD-OCT 
• OCT Angiography (OCT-A) 
• Color fundus photography using (UWF) imaging or  
4 wide-field (4WF) imaging 
• (if available at site:) Swept-Source (SS)-OCT or 
Ultra-widefield (UWF) SD-OCT 
Selection of Study 
Eye: 
Only one (1) eye will be determined as the study eye and only the 
study eye will receive a single administration of study drug at Visit 2, 
Day 0. 
Study eyes need to meet all inclusion criteria and none of the 
exclusion criteria. If both eyes meet the relevant criteria, the eye with 
the worse BCVA will be selected as the study eye; if both eyes meet 


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the relevant criteria and have the same BCVA, the investigator can 
select the study eye. 
Subjects’ fellow eyes may continue to receive non-study treatment 
following guidelines and standards at the investigational site. 
Treatment of the fellow eye is not considered part of the study 
treatment. 
Statistical 
Methods: 
Analyses will generally be descriptive in nature. The incidence of 
AEs and ADEs will be summarized for the study population. Ocular 
AEs will be summarized for all subjects using descriptive statistics 
for each eye and per treatment arm. Efficacy endpoints will be 
summarized for all subjects using descriptive statistics for each eye 
and per treatment arm. Summary statistics for other safety and 
efficacy outcomes will be presented. Further details will be provided 
in a Statistical Analysis Plan (SAP). Descriptive subgroup analysis 
will be performed and will be defined in a statistical analysis plan 
(SAP). 


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1.2 
Schema 
The study flow diagram is displayed in Figure 1. 
Figure 1: 
Study Flow Diagram 
 
⧫ = Suprachoroidal Triamcinolone Administration; all baseline visit activities, e.g., a 2nd 
treatment attempt in an operating/procedure room, need to be completed within 14 days, 
Q4W = monthly 


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1.3 
Schedule of Activities (SoA) 
Table 1 Schedule of Activities  
 
Study Period 
Screening 
Baseline 
Post-Baseline Follow-Up 
Study Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Days/Week 
Day 
-21 to-2 
D0 
To be completed within 14 days 
D1 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
ET/EoS 
Visit Window (days) a 
 
  
in-clinic b 
variant with 
conj./tenon 
incision j 
+ 1 
± 3 
± 5 
± 5 
± 5 
± 5 
± 5 
± 5 
ICF 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility 
X 
X* 
X* 
 
 
 
 
 
 
 
 
Randomization 
 
X* 
Xk 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication 
X 
X* 
X* 
X 
X 
X 
X 
X 
X 
X 
X 
AEs and ADE 
X 
X** 
X** 
X 
X 
X 
X 
X 
X 
X 
X 
Height, Weight,  
Vital Signs 
X 
 
 
 
 
 
 
 
 
 
 
Lab Assessment 
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test d 
X 
X* 
X* 
- 
X 
X 
X 
X 
X 
X 
X 
Slit-lamp BM 
OU 
OU* 
OUk 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
IOP 
OU 
OU*/SE***,i 
OU*,k/SE** 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
BCVAe, f 
OU 
OU* 
OU*,k 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
Dilated Ophthalmoscopy 
OU 
OU*/SE** 
OU*,k/ SE** 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 


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AEs = adverse events; ADEs = adverse device effects; BCVA = best corrected visual acuity; BM = biomicroscopy; CFP = color fundus photography, CMs = concomitant 
medications; EoS = end of study; ET = early termination; ETDRS = Early Treatment Diabetic Retinopathy Study; ICF = informed consent form; OCT-A (Ocular Coherence 
Tomography Angiography); OU = both eyes; SD-OCT = Spectral-Domain Ocular Coherence Tomography; SE = study eye; Tx = treatment. (*) Pre-treatment, (**) Post-
Attempt or Post-treatment, (***) Post Treatment. 
a. 
Visit dates and visit windows are calculated for the screening visit from the day of the first procedural attempt and for post baseline visits from the date of the completed 
study treatment administration. Between the maximum interval from start of activities for Visit 2 and the completion is 14 days including a potential 2nd treatment attempt 
in an operating/procedure room, see also footnote b. and c. 
Study Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Days/Week 
Day 
-21 to-2 
D0 
To be completed within 14 days 
D1 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
ET/EoS 
Visit Window (days) a 
 
  
in-clinic b 
variant with 
conj./tenon 
incision j 
+ 1 
± 3 
± 5 
± 5 
± 5 
± 5 
± 5 
± 5 
Axial Lengthg 
OU 
 
 
 
 
 
 
 
 
 
 
SD-OCT 
OU 
SE*/SE** 
SE*,k 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
OCT-A 
OU 
 
 
 
 
 
 
OU 
 
 
OU 
Swept-Source or  
UWF OCT h 
OU 
SE*** 
 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
Color Fundus Photog. 
OU 
SE** 
SE*,k 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
Overall Assessment of 
Expected Procedural 
Complexity 
X 
 
 
 
 
 
 
 
 
 
 
Study Medication 
Administration 
 
SE 
SE 
 
 
 
 
 
 
 
 
Procedure 
Documentation and 
Assessment 
 
X** 
X** 
 
 
 
 
 
 
 
 
Subject’s Experience 
Assessmentj 
 
X*** 
X*** 
X 
X 
X 
 
 
 
 
 
Assessment of need for 
follow-on treatment 
 
 
 
 
 
SE 
SE 
SE 
SE 
SE 
SE 


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b. Column shows the schedule of assessments for a study treatment carried out in a setting with access to devices for ophthalmic assessment or imaging. 
c. 
The treatment day can be primarily performed in an operating/procedure room or be split between a first in-clinic attempt followed by another attempt in an 
operating/procedure room in case of non-completion of administration of the study treatment in the clinic. If the operating/procedure room is not fully equipped with 
ophthalmic assessment and imaging devices, this assessment schedule is the minimum to be performed.  
d. Females of childbearing potential only. A urine pregnancy test will be performed at screening. A pregnancy test on D0 (urine) shall be negative for the subject to receive 
study treatment. Additional pregnancy tests will be performed at monthly intervals throughout study participation. 
e. 
BCVA assessments need to be performed in duplicates for the eyes that should be assessed at visits. 
f. 
BCVA eligibility will be assessed at the screening visit. 
g. Axial length measurement to assess the axial dimensions of the eye to support exploratory imaging of the location of the deployment of study drug in equipped sites only. 
h. SS-OCT or UWF SD-OCT to visualize the site of deployment will be obtained at sites in which the equipment is available. 
i. 
On Day 0, subjects will be monitored for at least sixty (60) minutes immediately following study treatment with at least 2 IOP measurements. 
j. 
If the Oxulumis® procedure is attempted first in-clinic and then another procedural attempt in an operating/procedure room, the subject’s experience questionnaire will 
only be completed for the completed procedure, i.e., the procedure when study drug is administered. 
k. In case the study procedure is only performed in an operating/procedure room setting, the mandatory baseline assessments would have to be performed still at the 
investigational site, if not available in the operating/procedure room facility. This may be done prior to or on the same day of treatment administration. All baseline visit 
activities have to be completed within 14 days after their start. 


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2 
Introduction 
2.1 
Study Rationale 
Oxular Limited is developing a novel investigational ophthalmic administration device, called 
the Oxulumis®, which can be used for semi-automated microcatheterization of the 
suprachoroidal space. 
The Oxulumis® deploys an integrated, highly flexible, atraumatic 7mm microcatheter in the 
suprachoroidal space through a minimally invasive, short (27G) needle insertion in the area of 
the pars plana. The typical distance of the insertion site to the limbus cornea is between 
4--7mm. Through the microcatheter of 7mm length, triamcinolone acetonide suspension 
(Triesence®) can be delivered in proximity to the posterior retina. The soft microcatheter 
incorporates an illuminated shaft. The illumination is used to visualize the catheter and to 
confirm positioning of the microcatheter and the atraumatic tip in the posterior region before 
administration of the drug product. Drug delivery is performed as low-volume administration. 
Triamcinolone acetonide suspension (Triesence®) disperses slowly in the suprachoroidal 
space following deployment. It is anticipated that the posterior positioning of the drug will 
reduce diffusion of Triesence® and steroid exposure of anterior ocular tissues, including the 
ciliary body and the lens, which are relevant structures for main adverse effects of ocular 
steroid treatment. 
Another clinical advantage of suprachoroidal administration compared to IVT injections is the 
absence of penetration of the vitreous cavity. The risk of IVT bacterial contamination leading 
to e.g., endophthalmitis is expected to be reduced. 
Overall, a combination of the Oxulumis® with a US FDA approved ophthalmic steroid such 
as triamcinolone acetonide suspension (Triesence®) is expected to have the following 
benefits: 
1. Reduction of the risk of steroid-induced complications and adverse events 
2. Enhanced efficacy of triamcinolone acetonide suspension compared to IVT and other 
forms of steroid delivery due to an expected higher steroid concentration in the 
posterior choroid and retina. 
3. Prolonged efficacy compared to IVT delivery of triamcinolone acetonide suspension 
4. No penetration of the vitreous cavity with the suprachoroidal administration procedure 
of triamcinolone acetonide suspension 


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Oxular Limited is conducting the OXUCT-103 clinical trial as a 24-week randomized, two-
arm, parallel-Group, single-masked, clinical trial to evaluate safety and tolerability of two 
dose levels of suprachoroidal triamcinolone acetonide administered with the Oxulumis® 
ophthalmic administration in approximately 20 subjects with diabetic macular edema. 
2.2 
Background 
There remains a high unmet need for a safe and efficacious treatment for DME in selected 
patients. Currently approved treatments may neither show satisfactory peak efficacy nor 
sustained improvement of vision (Wilkins et al., 2021; Ehlers et al. 2022). In addition, steroid 
treatment-related side effects occur frequently and may trigger additional drug treatments or 
even ocular surgeries The major treatment challenges are summarized below: 
For DME, registered intravitreal (IVT) anti-VEGF treatments (e.g., Lucentis® or Eylea®) are 
the current standard of care (Ehlers et al., 2022). However, a sizeable proportion of DME 
patients experiences very limited vision gains and short-lived or insufficient edema control 
due to additional inflammatory factors contributing to chronic DME (Udaondo et al., 2021; 
Zur, Iglicki, and Loewenstein, 2019). Administration of ocular steroids in DME may result in 
adequate disease control, however current formulations and their side effect profiles remain 
challenging. For topical or subtenon steroid administration, treatment effects may not last 
sufficiently long with need for early re-treatment (Shah et al., 2020; Qi et al., 2012). For both 
subtenon and IVT administration, a high incidence of steroid-related adverse events, such as 
cataract formation and increased intraocular pressure (IOP), substantially complicate 
treatment and thereby even limit the use of ocular steroids in a relevant number of patients 
(Boyer et al., 2014; Ehlers et al., 2022). 
To overcome these therapeutic challenges, an innovative approach for ophthalmic drug 
administration is needed, which has the potential to reduce the rate and extent of 
complications with IVT steroid administration and maximizes the benefit/risk ratio by 
providing sufficiently high, local steroid concentrations to control DME. 
In recent clinical trials assessing a device with a microinjection needle for suprachoroidal 
steroid administration, first trends of reducing side effects could be observed (Barakat et al., 
2021; Campochiaro et al., 2018; Yeh et al., 2020). However, the microneedle device typically 
punctures the eyewall at the pars plana and injects the steroid at this anterior location. A more 
posterior administration of steroids using an insertion point at 4-7mm post the limbus corneae 
in combination with deployment of a7mm- microcatheter is expected to further reduce the risk 
for IOP increases by reducing exposure to steroids of the more anterior parts of the eye. In 


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addition, by steroid administration to the posterior suprachoroidal space, higher local 
concentrations of steroids in the targeted macular region are expected. 
2.3 
Preclinical Testing of the Oxulumis® Ophthalmic Administration Device 
The tissue contact portion of the Oxulumis® was tested per the requirements of ISO 10993 for 
devices with limited use (<24 hrs.), and the results of this testing demonstrated 
biocompatibility suitable for transient tissue contact with breached or compromised tissue. All 
testing was conducted in accordance with FDA 21 CFR Part 58 Good Laboratory Practice 
(GLP) Regulations. The results of testing showed that the patient-contacting materials used in 
the Oxulumis® passed all the applicable biocompatibility requirements contained in 
ISO 10993-1. Results of the toxicological risk assessment indicate that the patient contacting, 
and fluid pathway materials do not pose an unacceptable level of risk to the target patient 
population. Additionally, extractable and leaching testing to evaluate impurities that could 
potentially be conferred to the drug product resulted in levels of extracted elements that were 
safe based on their relationship with ICH Q3D guidelines for elemental impurities (parenteral 
route of administration). 
The Oxulumis® has also undergone a battery of testing in acute pig and rabbit studies for the 
purpose of evaluating the device design with regard to the microcatheter formulation, 
structure, and length. In addition, in these studies, the feasibility of dose volumes and the 
effectiveness of training procedures for ocular disease specialists were evaluated. The current 
Oxulumis® design has been optimized for safety and efficacy of delivery to the suprachoroidal 
space based on outcomes from these preclinical animal studies. 
2.4 
Previous clinical experience 
The efficacy and safety of IVT steroids in the management of DME is well documented.  
In their recent Cochrane review, Rittiphairoj et al. reported findings from 10 clinical trials 
involving 4505 eyes with DME of 4348 subjects treated with IVT steroids compared to other 
treatments (Rittiphairoj et al., 2020).  Despite potential efficacy on visual acuity (VA) and 
reduction of ME, the authors concluded that benefits from IVT steroids should be weighed 
against IOP elevation, the use of IOP‐lowering medication, and in phakic patients, the 
progression of cataracts. 
To overcome these potential side effects (IOP elevation and cataract progression), several 
groups have tried to deliver TA via the suprachoroidal space. By changing the site of 
administration from the vitreous cavity to the suprachoroidal space, target tissues associated 


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with these complications (i.e., lens and anterior segment of the eye) are expected to be 
exposed to lower concentrations of steroids and hence, may be less prone to develop these 
side effects. 
Suprachoroidal drug administration has been proposed as an approach to ophthalmic drug 
administration resulting in higher concentrations of medication to target tissues (i.e., in 
choroid, and retina) and lower concentrations of medication to anterior segment structures 
(Pearce, Hsu, and Yeh, 2015). Although already proposed in the late 1970s by Russian 
ophthalmic surgeons, suprachoroidal drug administration was only picked up again three 
decades later with technical advances in microsurgical techniques including the use of a 
microsurgical cannula (Olsen et al., 2006) or a hollow microneedle (Patel et al., 2012) to 
target the suprachoroidal space. These animal studies in non-human primates and rabbits 
demonstrated detailed drug distribution following suprachoroidal delivery. 
2.4.1 Diabetic Macular Edema: 
Experience with subtenon TA treatment 
For the subtenon treatment of DME with TA, clinical data are summarized in a review and 
meta-analysis (Qi et al., 2012). 
The review compared IVT administration of TA and subtenon TA injections. Overall, these 
clinical data demonstrate that both administration methods may initially improve VA and 
reduce ME. However, the subtenon administration of TA in DME has a significantly shorter 
duration, as visual and anatomic benefits already decline at the 3 months follow-up 
assessments. As expected, the IOP increase with subtenon TA was lower at 3 months 
compared to IVT TA. These systematic review data also suggest that subtenon TA in DME 
has limitations in respect to maximum efficacy, durability, and steroid-induced IOP increases. 
Of note, the subtenon dose of TA is generally substantially higher (40 mg, 1.0 mL) compared 
to the IVT administered dose (4.0 mg, 100 µl) (Qamar, Saleem, and Saleem, 2013). Also, the 
posterior subtenon administration may have some relevant safety complications like an 
accidental direct injection of TA into the choroidal or retinal circulation, perforation of the 
globe, occlusion of the central retinal artery, cataract formation, orbital fat atrophy, 
strabismus, and conjunctival necrosis. 


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Experience with suprachoroidal microneedle TA injections 
Recently, clinical trials (Wykoff et al., 2018; Barakat et al., 2021) investigating 
microinjection techniques in the area of the pars plana, suggested the clinical feasibility of 
suprachoroidal administration with an acceptable safety profile and meaningful clinical 
efficacy. 
In the HULK trial (Wykoff et al., 2018), an open-label, 20 subjects study evaluating the use of 
TA applied to the suprachoroidal space with a microinjector in the management of DME, 
treatment naïve subjects (n=10) had 8.5 ETDRS letters improvement at month 6, while those 
previously treated (n=10) improved only by 1.1 letters. Ten percent (10%) of the subjects 
(n=2 of 20) experienced a ≥ 10 mmHg increase in IOP during the trial. There were three cases 
of cataract progression. Notably, there was injection site pain (1 of 20 subjects) and 
inadvertent IVT drug deposit (1 of 20 subjects). 
In the TYBEE Phase 2 trial, 71 subjects with DME were randomized to receive either: 
i) 4 monthly doses of aflibercept (Day 0, Weeks 4, 8, and 12) with additional as-needed 
aflibercept doses at Weeks 16 and/or 20), or ii) 2 TA injections (4 mg) administered to the 
suprachoroidal space (Day 0 and week 12) with the option for aflibercept at weeks 4, 8, 16 
and 20 as needed (Barakat et al., 2021). The primary endpoint was the mean change in BCVA 
from baseline at Week 24. Despite anatomical improvement in terms of CST (226.5 µm mean 
change at week 24) for the combination arm compared to the aflibercept mono arm 
(-176.1 µm), the mean change in BCVA at week 24 for the combination arm (12.3 ETDRS 
letters) was not statistically different from the aflibercept arm (13.5 ETDRS letters, logrank 
test, two-sided significance level of 0.10). An IOP increase of more than 30mmHg occurred in 
3 subjects in the active group and 0 subjects in the control group. Intraocular pressure 
increases of more than 10mmHg occurred in 5 and 0 subjects in the active and control groups, 
respectively (Barakat et al., 2021). 
2.4.2 Suprachoroidal Administration of TA via Microcatheterization 
There has been rapid and substantial progress in medical technology since Penkov’s 
conceptualization of suprachoroidal drug administration in the 1960s. This has resulted in the 
technical development and exploration of the feasibility of medical devices that use 
microcatheters to administer drugs to the suprachoroidal space. 
For the use of microcatheters to reach the suprachoroidal space, more recent smaller studies 
showed substantial progress of the device technique resulting in therapeutic benefits in 
advanced retinal disease unresponsive to conventional treatments. 


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The subsequent publications demonstrate the feasibility and principal safety of suprachoroidal 
administration via microcatheterization. The knowledge around the choice of agents for the 
respective forms of ME, specifically for neovascular AMD, has further matured over the last 
decade. 
The use of microcatheter drug administration to the suprachoroidal space was reported in 
11 subjects (eyes) with advanced neovascular AMD that failed to respond to conventional 
therapy (Chang, 2009).  Treatment consisted of a single dose of bevacizumab (Avastin) and/or 
TA administered by suprachoroidal catheterization. The average preoperative BCVA was 
1.78 ± 0.41 logMAR units, which increased to 1.40 ± 0.60 at three months and was 
1.63 ± 0.71 at 12 months. Overall, BCVA showed a trend towards improvement but in this 
small group of subjects did not reach statistical significance. After three months, the BCVA 
appeared to regress towards preoperative levels. The average central subfield foveal thickness 
appeared to decrease after surgery at all time points. Total macular volume significantly 
decreased from baseline levels at six months. Only two of 11 eyes had an elevation of IOP 
above 21 mmHg at any postoperative visit beyond one week, with both eyes reaching an IOP 
of 24 mmHg and resolving without treatment. Of the six eyes that were phakic at baseline, 
one eye with a pre-existing grade 2+ nuclear sclerotic cataract developed a 1+ posterior 
subcapsular cataract during the follow-up period. 
Tetz and co-workers (Tetz, Rizzo, and Augustin, 2012) investigated the suprachoroidal 
administration of a combination of bevacizumab and TA to the submacular suprachoroidal 
space, via a microcatheter, in eyes with advanced neovascular AMD that failed to respond to 
conventional therapy. A slight improvement in the average BCVA at one month and six 
months was observed, but statistical significance was not reached at any time point compared 
with baseline.  Initial CSFT was 407.2 μm (SD=229.8), decreasing at one month to 
333.3 μm (SD=179.4), remaining stable at three months and trending towards initial levels at 
six months (384.8 μm, SD=265.7). No serious complications were encountered during the 
administration of therapy.  Only one of 21 eyes included in the study experienced a transient 
elevation in IOP at three months, which was medically controlled. In two eyes, an increase in 
nuclear sclerotic cataracts was noted. 
Rizzo and co-workers (Rizzo et al., 2012) evaluated 6 eyes with RVO, or diffuse DME 
accompanied by massive subfoveal hard exudates that were unresponsive to multiple IVT 
injections. The eyes underwent a single treatment in which a combination of bevacizumab and 
triamcinolone was administered to the submacular suprachoroidal space via a microcatheter. 


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BCVA improved by 2+ lines in 4 eyes and remained stable in 2 eyes.  At 1 to 2 months, the 
hard exudates had almost completely resolved in all eyes.  There were no complications 
observed. 
In compassionate use cases in Switzerland, as of December 2021, Oxulumis® was used to 
deliver Triesence® in a total of 4 patients with 6 treatments (2 repeat treatments of the initially 
treated eye) with refractory ME of different etiologies (post-surgical ME, and non-infectious 
inflammatory cystoid ME). In contrast to their pre-treatment, these patients showed, after 
suprachoroidal administration of TA, a robust anatomical response with a quick onset, as well 
as visual improvements. No device-related AEs were described and no challenges with IOP 
rises after TA administration were encountered. 
Compared to the administration of TA using a microneedle device at the pars plana, 
Oxulumis® is specifically designed to administer the drug via microcatheterization more 
posteriorly, potentially allowing for effective, higher concentrations of drug in the macular 
region and lower exposure of the anterior segment tissues to TA. This is expected to translate 
into better benefit/risk based on greater efficacy and a better safety profile for triamcinolone 
acetonide suspension (Triesence®) delivered to the suprachoroidal space using the Oxulumis®. 
2.5 
Benefit/Risk Assessment 
To date, only a limited number of patients with ME have been treated with Triesence® 
administered with the Oxulumis®, limiting the ability to establish a robust benefit/risk profile. 
However, so far, no severe, serious adverse events or serious adverse device effects have been 
reported. 
Suprachoroidal administration of triamcinolone acetonide suspension with Oxulumis®, in 
contrast to IVT injection, does not penetrate the vitreous cavity, and reaches more posterior 
sections of the retina, towards the macula, through the suprachoroidal space. The 
suprachoroidal route of administration is, therefore, expected to result in improved safety and 
tolerability, particularly with regard to complications, such as increased IOP in addition to 
potential improvement in efficacy due to the expected higher concentration of triamcinolone 
acetonide suspension in the retina and choroid. For repeat treatments over a longer period of 
time, the cataract risk would be expected to be smaller, although the duration of the current 
clinical trial with a single administration and follow-up of up to 24 weeks may not be long 
enough to provide definitive data on cataract progression. 


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Similarly, two recent 24-week studies with suprachoroidal TA and a microinjection device for 
the suprachoroidal space could not detect differences in cataract progression in DME (TYBEE 
trial) and ME due to non-infectious uveitis (PEACHTREE trial) (Price, Albini, and Yeh, 
2020; Barakat et al., 2021).  
The combination of the Oxulumis® plus triamcinolone acetonide suspension (Triesence®) 
used in the current trial is expected to satisfy an unmet medical need to: 
1. Reduce the risk of steroid-induced complications and adverse events 
2. Enhance the efficacy of triamcinolone acetonide suspension compared to IVT 
administration 
3. Prolong the efficacy of triamcinolone acetonide suspension compared to IVT 
administration 
4. Ensure non-penetration of the vitreous cavity with the suprachoroidal 
administration. 
Theoretical class risks associated with the suprachoroidal administration procedure include: 
endophthalmitis, choroidal hemorrhages, choroidal effusion, retinal penetration, and retinal 
detachment, amongst others. In addition, the eligibility criteria of this trial exclude subjects 
with structural lesions of the eyewall (e.g., subjects with scleral ectasia or scleral defect, 
which may have a risk of scleral perforation) to further reduce any potential procedural risks. 
The atraumatic design, a tangential angle of approach for device insertion (not perpendicular 
to the sclera once the sclera is reached in the insertion phase and not pointing to the vitreous 
cavity), and the 7mm length of the microcatheter, together with the rounded ball-like catheter 
tip, as well as control over the speed of the microcatheter deployment by adjustment of the 
Oxulumis® are design elements expected to prevent or substantially limit the risk of the 
adverse events summarized above. Still, as the Oxulumis® procedure is relatively novel, non-
completion of microcatheter placement may happen in an in-clinic setting, requiring the use of 
a procedural variant that uses an incision of the conjunctiva and/or tenon to increase visibility 
of the scleral engagement in the insertion phase of the Oxulumis® procedure. 
To optimize detection of any adverse events and other unforeseen risks and to potentially 
initiate countermeasures in a timely fashion, subjects will be monitored closely for at least 
60 minutes after administration of triamcinolone acetonide suspension (Triesence®) to the 
suprachoroidal space. This monitoring includes an ophthalmoscopy, IOP measurements, and 
post-treatment retinal imaging. Additionally, visits following treatment, on day 1, week 1, 


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week 4, and every 4 weeks thereafter, will include multiple safety evaluations to ensure the 
detection and management of any emerging adverse events. 
3 
Objectives and Endpoints 
3.1 
Objectives 
The objectives of this exploratory clinical trial are summarized in detail below. 
3.1.1 Primary Objective 
• To evaluate the safety and tolerability of two dose levels of triamcinolone acetonide 
administered with the Oxulumis® to the suprachoroidal space in subjects with DME. 
3.1.2 Explorative Objective 
• To explore the efficacy of two dose levels of triamcinolone acetonide with respect to VA 
changes, edema control, and durability of the treatment effect of suprachoroidal 
triamcinolone acetonide suspension (Triesence®) in subjects with DME. 
3.2 
Endpoints 
3.2.1 Primary (Safety) Endpoints 
The primary endpoint of this study is safety and tolerability as assessed by: 
1. Frequency of ocular and systemic adverse events (treatment-emergent serious adverse 
events [SAEs] and treatment-emergent non-serious adverse events [TEAEs]) 
2. Frequency of adverse device effects (ADEs, serious ADEs [SADEs]) 
3.2.2 Exploratory Efficacy (and/or Safety) Endpoints 
1. Mean Change in BCVA (ETDRS) at all study visits through Week 24 compared to 
baseline. 
2. Percentage of subjects with vision gain and vision loss of at least 5, at least 10, and at 
least 15 letters at all study visits through Week 24 compared to baseline. 
3. Time to subjects meeting criteria for follow-on treatment (per pre-specified criteria). 
4. Mean Change in Central subfield thickness (CST) at study visits through Week 24 
compared to baseline. 
5. Mean Change in IOP at all study visits through Week 24 compared to baseline. 


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4 
Clinical Trial Design 
4.1 
Overall Trial Design 
This is a 24-week, randomized, two-arm, parallel-group, single-masked, clinical trial to 
evaluate safety and tolerability of two dose levels of suprachoroidal triamcinolone acetonide 
administered with the Oxulumis® ophthalmic administration in 20 subjects with DME.  
Triamcinolone acetonide suspension (Triesence®) will be administered to the suprachoroidal 
space in subjects with DME showing short-lived, limited, or no response to prior anti-VEGF 
or steroid therapy. 
A focus of this trial is to evaluate the feasibility, safety, and tolerability of the ophthalmic 
administration of a low and a mid-dose of suprachoroidal triamcinolone acetonide suspension 
(Triesence®) with the Oxulumis® in DME. In addition, for the two dose groups of the trial, 
efficacy data on visual and anatomic changes will be collected. 
To support the main objectives of this trial, a sample size of 20 treated subjects is estimated to 
be sufficient to detect common and very common adverse events. This safety information is 
relevant to inform further trials in the Oxulumis development program with respect to safety 
considerations including initial safety and feasibility experience with suprachoroidal 
administration procedure. 
After a screening period, approximately 20 eligible DME subjects will be randomized using a 
1:1 ratio to receive a single administration of one of two dose levels of TA (low dose, 2.4mg. 
or mid-dose, 4.0mg, respectively). Subjects in whom the study treatment cannot be 
administered will be replaced. Randomization will limit bias in assignment to one of the two 
dose levels. 
The study will be conducted by retinal specialists in clinics or academic hospitals in the 
United States at up to 10 investigational sites. 
Table 2 
Treatment groups of two dose levels of triamcinolone acetonide suspension 
Treatment 
Arm 
Intervention 
Subjects 
1 
One treatment with suprachoroidal low dose (2.4mg) 
triamcinolone acetonide  
N=10 
2 
One treatment with suprachoroidal mid-dose (4.0mg) 
triamcinolone acetonide  
N=10 


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Clinical visits will occur on Screening Day, Day 0, Day 1, Week 1, Week 4, and then every 
four (4) weeks thereafter for a total of twenty-four (24) weeks. From Week 4 on, subjects will 
be assessed for their need for follow-on treatment to determine the length of the treatment 
interval. The treatment visit V2, Day 0, can be split to allow for collection of baseline 
assessments on a different day than the administration of the study treatment. If a first attempt 
of study treatment is made in-clinic and treatment cannot be administered, a second attempt in 
an operating/procedure room is allowed. Only assessments feasible in an operating/procedure 
room setting need to be performed for this 2nd treatment attempt (for details see 1.3). The 
maximum time interval from starting activities of V2 to completion is 14 days. If the 
investigator decides to perform the Oxulumis procedure directly in an operating/procedure 
room, some assessments, as indicated in Section 1.3, need to be performed before the 
administration of study treatment. The follow-up period after a completed treatment 
administration will be up to twenty-four (24) weeks. 
If subjects show a need for the next treatment of DME according to pre-specified criteria (for 
details see Section 6.1.8), participation in this clinical investigation will end, and an early 
termination/end of the study visit will be conducted at the respective visit date. In this case, 
the follow-up period will be shorter than 24 weeks. 
For subjects who decide to discontinue study participation for any reason, the respective visit-
day procedures will be extended to include the assessments scheduled for the EoS visit (or an 
EoS visit will be scheduled for the subject if notification of discontinuation is received outside 
of a scheduled study visit). For subjects in whom the treatment administration could not be 
completed on the respective treatment day(s), only a CFP and a SD-OCT need to be acquired. 
This visit will then be an early termination/end-of-study visit. 
After completion of participation in this clinical trial, patients will continue treatment with 
therapeutic options determined by the treating retinal specialists in accordance with current 
medical practice for their DME. 
Periodically, the coordinating investigator together with the medical monitor will review 
individual patient data as well as the totality of the safety data to recommend if the 
investigation should continue as is, continue with changes, or be terminated. 
Study eyes shall meet all inclusion criteria and none of the exclusion criteria. If both eyes 
meet the relevant criteria, the eye with the worse BCVA will be selected as the study eye; if 
both eyes meet the relevant criteria and have the same BCVA, the investigator can select the 
study eye. 


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Subjects’ fellow eyes may continue to receive non-study treatment following guidelines and 
standards at the investigational site. Treatment of the fellow eye is not considered a study 
treatment. If the non-study eye requires management for DME, this should be carried out 
according to the local standards of care. Treatment of non-study eyes is not considered a study 
treatment. 
4.2 
Scientific Rationale for Study Design 
4.2.1 Target Indication 
The OXUCT-103 exploratory clinical trial will evaluate safety, tolerability, and the efficacy 
of administering Triesence® (2.4 mg) to the suprachoroidal space using the Oxulumis® in 
subjects with DME with short-lived, limited or no therapeutic response with prior therapy 
with ocular injections of steroids and/ or anti-VEGF agents. For details on the eligibility 
criteria see Section 5.1 and Section 5.2. 
4.3 
Justification of Dose 
The current trial evaluates two different dose levels. The low dose is 2.4mg TA (60µl of a 
40mg/ml TA suspension). The mid dose is 4.0mg TA (100µl of a 40mg/ml TA suspension). 
In a compassionate use program in Switzerland, both dose levels, 2.4mg and 4.0mg, were 
applied in patients with cystoid macular edema (CME) or post-surgical inflammatory edema 
refractory to standard treatments. 
The current trial OXUCT-103 is expected to deliver safety and first exploratory data for two 
randomized dose groups. Trends for potential differences of the dose levels in peak efficacy 
and duration of effect will be explored. 
It is anticipated that posterior deployment of the drug in the suprachoroidal space will lead to 
a safer, more tolerable, and effective treatment compared to IVT or subtenon administration. 
As eligibility for this trial is based on limited or no response to standard treatments, this trial 
uses another dose level of TA suspension as a control rather than exposing subjects the same 
or a similar treatment that they already had failed to respond.  
The standard dose for IVT injection is 4.0mg. This dose level will be administered in the 
current trial in the mid dose group. In addition, 2.4mg TA will be used in the low dose group, 
Using the Oxulumis® device in both treatment groups, TA is expected to be administered 
closer to the location of the disease activity compared to other treatment approaches. Local 
concentrations of TA in the retinal tissues are expected to be higher compared to the same 
doses administered by IVT or subtenon injection. 


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4.4 
End-of-Study Definition 
The end of the study is defined as the time at which all subjects have either: 
• Received the study drug and have been followed for 24 weeks; or  
• Met criteria for follow-on treatment, or  
• Have withdrawn consent, or 
• Are lost to follow-up 
A subject is considered to have completed the study if the subject has received the study drug 
and has completed the 8 study visits over the 24-week follow-up period, which includes the 
final EoS visit. 
5 
Study Population 
5.1 
Inclusion Criteria 
Subjects will be eligible if they meet all the following inclusion criteria: 
1. Able to understand and sign an informed consent form. 
2. At least 18 years of age. 
3. Have been diagnosed with Type 1 or Type 2 diabetes mellitus. 
4. Have DME involving the center of the fovea in the study eye with central subfield 
thickness (CST) on SD-OCT of:  
≥ 320 for males or ≥ 305 for females on Spectralis (Heidelberg) or  
≥ 305 for males or ≥ 290 for females with Cirrus (Zeiss). 
5. Have BCVA in the study eye of ≤73 ETDRS letters (approximate Snellen equivalent of 
20/40 or worse) at the screening visit. The eligibility will be assessed based on the 
ETDRS BCVA letter score. 
6. Short-lived, limited, or no response to prior ocular injection therapy (e.g., IVT or 
subtenon) of steroids and/or anti-VEGF agents based on the investigator’s assessment. 
Short-lived in this trial is defined as less than 4 weeks. 
7. For women who are not postmenopausal (i.e., at least12 months of non-therapy-
induced amenorrhea or surgically sterile (absence of ovaries and/or uterus) agreement 
to remain abstinent or use combined contraceptive methods that result in a failure rate 
of less than 1% per year from the treatment visit (Day 0) until the end of trial 
participation, or for at least 12 weeks from the treatment  visit (Day 0), if study 


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participation ends before visit 7, Week 12. Examples of contraceptive methods with an 
expected failure rate of less than 1% per year include male sterilization, hormonal 
implants, proper use of combined oral or injected hormonal contraceptives, and certain 
intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a 
condom and a cervical cap) may be combined to achieve a failure rate of less than 1% 
per year; barrier methods must always be supplemented with the use of a spermicide. 
8. Males must agree to use a barrier method of contraception from the treatment visit 
(Day 0) until the end of trial participation, or for at least 12 weeks from the treatment 
visit (Day 0), if study participation ends before visit 7, Week 12. 
9. Subject must be willing not to participate in any other clinical trial including an 
investigational medicinal product (IMP) or an investigational device until the end of 
the participation in this trial. 
5.2 
Exclusion Criteria 
Subjects will be eligible if they do not meet any of the following exclusion criteria: 
1. Presence of any significant ocular or non-ocular disease/disorder (or medication and/or 
laboratory test abnormalities) which, in the opinion of the Investigator and with 
concurrence of the Oxular Medical Monitor, may either put the subject at risk because 
of participation in the trial, may influence the results of the trial, or the subject’s 
ability to participate in the trial. 
2. Macular edema considered due to a cause other than diabetes mellitus in the study eye. 
3. Condition, in the study eye, in which visual acuity is not expected to improve from the 
resolution of macular edema (e.g., foveal atrophy, clinically relevant loss of ellipsoid 
zone, pigment abnormalities, vitreomacular traction, or nonretinal causes). 
4. Conditions, in the study eye, that may render the suprachoroidal microcatheter 
insertion and deployment difficult or subject the patient to excessive risk of 
complications. Examples include but are not limited to ocular surface diseases with 
significant conjunctival edema and/or inflammation, ocular hypotony, scleral 
staphylomas, necrotizing scleritis, scleral melting, excessive choroidal scarring e.g., 
associated with pan-retinal photocoagulation, amongst others. 
5. Macular laser photocoagulation or panretinal laser photocoagulation (PRP) in the 
study eye performed within sixteen (16) weeks prior to screening. 


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6. Active proliferative diabetic retinopathy (PDR) or sequelae of PDR (including iris 
neovascularization, vitreous hemorrhage, tractional retinal detachment, extensive 
scarring following PRP) at screening in the study eye. 
7. History of recurrent or active intraocular inflammation in either eye (e.g., uveitis) 
within 12 weeks prior to screening. 
8. Infectious eye diseases like infectious blepharitis, keratitis, or conjunctivitis in either 
eye within four (4) weeks of screening. 
9. IOP ≥ 22 mmHg, or glaucomatous disc changes (i.e., a cup disc ratio greater than 0.8) 
in the study eye at screening.  
10. History of glaucoma surgery, and or anti-glaucoma therapy with more than two active 
substances (in separate or a combination preparation) at the screening visit are 
exclusionary. 
11. History of closed-angle glaucoma. 
12. IOP <6mmHg (hypotony) in the study eye at screening. 
13. Spherical equivalent of the refractive error of −6 diopters of myopia or worse (prior to 
cataract or refractive surgery) at screening. 
14. Cataract or other media opacity that limits the ability to obtain the planned imaging 
assessments. 
15. History of retinal detachment. 
16. Subjects who were previously treated for DME in the study eye must not have 
received:  
a.) an intravitreal anti-VEGF treatment within four (4) weeks before screening. The 4-
week interval before screening is used for IVT bevacizumab, ranibizumab, 
aflibercept, brolucizumab, or faricimab (i.e., a combined Anti-VEGF/anti-Ang2 
agent), as also inclusion criterion No. 6 on therapeutic response must be met. 
b.) Prior treatment with SUSVIMO® (Port Delivery System) implant at any time is 
exclusionary. 
c.) Intra- or periocular/subtenon triamcinolone acetonide suspension within 12 weeks 
before screening.  
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e.) Prior treatment with longer duration implants (e.g., fluocinolone acetonide IVT 
implant, e.g., Iluvien®) at any time is exclusionary. 
f.) Prior treatment with suprachoroidal steroids (commercial, investigational, or off-
label) at any time is exclusionary. 
17. Concurrent use of systemic glucocorticoid medications or systemic steroids within 
twelve (12) weeks before screening is exclusionary. 
Intranasal, inhaled, and extra-ocular topical corticosteroids are allowed. 
18. Treatment with ocriplasmin (Jetrea®) at any time. 
19. History of vitreoretinal surgery (including surgery for retinal detachment or scleral 
buckle) in the study eye. Vitrectomy is only exclusionary, if within 12 weeks prior to 
screening. 
20. Any other previous ophthalmic surgeries, uncomplicated cataract surgery, or 
uncomplicated trauma in the study eye within twelve (12) weeks prior to screening. 
Complicated cataract surgery or trauma that may impact access and/or drug delivery to 
the suprachoroidal space are exclusionary. 
21. Hypersensitivity to triamcinolone acetonide, or any of the excipients in the Triesence® 
formulation or Oxulumis® device components. 
22. Active malignancy or history of malignancy within the past five (5) years. 
23. Uncontrolled diabetes with a hemoglobin A1c (HbA1c) > 12% or any other 
uncontrolled systemic disease at screening. 
24. Uncontrolled hypertension, defined as blood pressure with a systolic value of ≥ 
160mmHg or a diastolic value of ≥ 100 mmHg upon repeat assessment at screening. 
25. History of myocardial infarction, stroke, transient ischemic attack, acute congestive 
heart failure, or any acute coronary event within 90 days before screening. 
26. Subjects who are pregnant or breastfeeding at the screening visit, or who test positive 
for pregnancy at the screening visit or are unwilling to use adequate birth control 
methods to prevent pregnancy throughout the study. 
27. Subjects who were previously randomized in this trial, but in whom administration of 
study treatment could not be completed. 
5.3 
Lifestyle Considerations 
No special lifestyle considerations or restrictions are required for participation in this study. 


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5.4 
Screen Failures 
A screen failure occurs when a subject who has consented to participate in the clinical study is 
not subsequently enrolled in the study. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure subjects to meet the CONSORT publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once after failing the initial screening. The rescreening can occur at any time after 
the reason for screen failure is addressed. Rescreened subjects shall be assigned a new subject 
number and sign a new ICF for each screening/rescreening event. 
6 
Study Intervention and Concomitant Therapies 
6.1 
Study Intervention Administered 
In the OXUCT-103 clinical trial, Triesence® will be administered with the Oxulumis® 
Ophthalmic Administration Device to the suprachoroidal space of study eyes. 
6.1.1 Oxulumis® Ophthalmic Administration Device 
The Oxulumis® ophthalmic administration device is a sterile, semi-automatically operated, 
minimally invasive, single-use device. It is designed to deploy a therapeutic drug via 
a delivery-guiding illuminated ophthalmic microcatheter to ophthalmic compartments, e.g., to 
the suprachoroidal space. The illumination provides confirmation that the microcatheter is 
inserted and deployed correctly, prior to administration of the therapeutic drug. With a 27G 
insertion needle and an 7mm microcatheter, the Oxulumis® administration device is well 
suited to administer suspensions of drugs like Triesence® to the posterior retina. 
For the Oxulumis® administration procedure, subjects may receive topical anesthetics (e.g., 
anesthetic eye drops, gels, local subconjunctival, or anesthetic injections, typically subtenon 
administrations) to reduce potential pain and discomfort during the procedure. 
As for IVT injections, antiseptic conditions shall be applied following the standard procedures 
at the investigational site. Colorless disinfectants for ophthalmic use, e.g., chlorhexidine or 
application of PVP iodine followed by sterile rinsing with saline, are recommended. Details 
about the Oxulumis® device and the ophthalmic administration are available in the Instruction 
for Use (IFU) manual. 
The materials used in the Oxulumis® were selected for appropriate mechanical properties, 
optical properties, and biocompatibility of the tissue and fluid contact components.  The tissue 


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and drug fluid pathway contacting portions of the Oxulumis® have been tested to ISO 10993 
for biocompatibility assurance, however, subject-specific sensitivity may occur to the 
following tissue and drug fluid pathway contacting components of the device: 
 
 
6.1.2 Triamcinolone acetonide (Triesence®) 
Triesence® (Triamcinolone acetonide [TA] 40 mg/mL; Novartis Pharmaceutical Corporation 
[former subsidiary: Alcon Laboratories, Inc.]) is a synthetic corticosteroid with anti-
inflammatory action approved by the United States Food and Drug Administration (US FDA) 
for IVT administration for the treatment of ophthalmic diseases including sympathetic 
ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions unresponsive to 
topical corticosteroids. The suprachoroidal microcatheterization with the Oxulumis® is an 
investigational route of administration for Triesence®. In the context of other development 
programs, clinical data on the generally favorable safety of other forms of suprachoroidal 
administration of TA have been generated (see Section 2.4.2). 
Hypersensitivity reactions may occur to triamcinolone acetonide or any of the excipients in 
the Triesence® formulation. Per the US prescribing information of Triesence®, each mL of the 
sterile, aqueous suspension provides 40 mg of triamcinolone acetonide, with sodium chloride 
for isotonicity, 0.5% (w/v) carboxymethylcellulose sodium and 0.015% polysorbate 80. It also 
contains potassium chloride, calcium chloride (dihydrate), magnesium chloride (hexahydrate), 
sodium acetate (trihydrate), sodium citrate (dihydrate) and water for injection. Sodium 
hydroxide and hydrochloric acid may be present to adjust pH to a target value 6 – 7.5. 
6.1.3 Preparation, Handling, Storage, and Accountability 
1. The investigator or designee must confirm appropriate conditions (e.g., temperature) 
have been maintained during transit for all study interventions received, and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only subjects enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention.  
3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. 


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4. The investigator is responsible for study intervention accountability, reconciliation, 
and record maintenance (i.e., receipt, reconciliation, and final disposition records). 
5. Unused products are accounted for and returned to the Sponsor or their designee for 
destruction or destroyed locally upon agreement with and approval from the sponsor 
or their designee. 
6.1.4 Assignment to Study Intervention 
This is a double-arm study in which all enrolled subjects will be randomized at a 1:1 ratio to 
receive either low (2.4mg) or mid (4mg) dose of TA in a single-masked manner. Accordingly, 
approximately 10 subjects will be treated at each of the two dose levels. A central 
randomization scheme provided by an interactive voice response system (IVRS)/interactive 
web response system (IWRS) to the designated study pharmacist (or qualified designee). If 
subjects are randomized but the study treatment cannot be administered, these subjects will be 
replaced, targeting approximately 20 treated subjects total. 
6.1.5 Masking 
This is a single masked study. The study subjects will be masked for the treatment dose 
allocation. No masking of treatment assignment nor the dose is foreseen for the Investigator, 
the site staff nor the Sponsor team involved in the trial. Subjects will only be able to receive 
information about their treatment assignment after the end of the study. No impact on 
masking is expected from the potential repeat of procedural attempts in an 
operating/procedure room. In case of any emergency, the treating site investigator can share 
the dose level upon request and needs to document all details regarding this procedure. 
6.1.6 Study Intervention Compliance 
The investigator will administer the study intervention after the subject had been randomized 
to one of the two treatment arms. The date and time of each dose administered will be 
recorded in the source documents. The study intervention, the allocated treatment dose and 
study subject identification will be confirmed at the time of dosing by a member of the study 
site staff taking all the necessary measures to maintain subject’s masking.  
6.1.7 Dose Modification 
There is no planned dose modification in this study. 
6.1.8 Follow-on Treatment 
Subjects will be followed with regular visits (from Week 4 on with monthly intervals) to 
assess the safety and the course of visual and anatomic outcomes. From Week 4 on, subjects 


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will be evaluated against prespecified criteria indicating the need for follow-on treatment (i.e., 
indicating the end of the current treatment interval).  
Criteria are as follows: 
• 
At least 75 μm increase in CSFT on SD-OCT compared to the best-achieved CST 
value since the baseline visit [Visit 2, day 0]. 
• 
A decrease in BCVA of at least 10 ETDRS letters from the best achieved BCVA 
since the baseline visit [Visit 2, day 0], that in the opinion of the investigator, is due 
to worsening of DME. 
For subjects showing no reduction of edema or no improvement of BCVA, the baseline visit 
will be considered the best CST or BCVA value. 
If one or both of the above criteria are met, the subject will be eligible for follow-on treatment 
and will be managed according to local standard of care. 
If subjects meet the criteria for follow-on treatment in the study, the visit will be considered 
EoS visit, and the assessment scheduled for EoS visit will be performed. 
If the non-study eye requires management for DME, this should be carried out according to 
the local standard of care. Treatment of non-study eyes is not considered a study treatment. 
6.1.9 Treatment for Complications of the Underlying Disease 
A subject may receive other treatment for complications of the underlying diseases at any 
time if they experience any complications other than recurrence or progression of ME that 
require urgent management (e.g., progression to high-risk PDR, intraocular lens replacement 
for visually significant cataract, neovascularization, etc.). 
Any ocular or systemic treatments already clinically indicated or planned at the time of patient 
referral to this study, should be performed before further consideration of study participation. 
After such treatments, the post intervention intervals defined in the exclusion criteria must be 
met to consider participation or rescreening, respectively. The date and time of medication 
administered to treat complications as well as the name and dosage regimen of the medication 
shall be recorded. If the treatment administered has an effect on DME, e.g., intravitreal anti-
VEGF injections, the study participation for this subject ends with the visit, where the 
decision on the need for the treatment of a complication has been recorded and an early 
termination/end-of-study visit will be performed. 


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6.1.10 Continued Access to Study Intervention after the End of the Study 
There will be no continued access to the study intervention, specifically not to the 
investigational Oxulumis® ophthalmic administration device after the end of the study. 
6.1.11 Treatment Overdose 
The study includes a single administration of one of two dose levels of the study drug 
assigned by a central randomization procedure. The risk of overdose from receiving study 
intervention is very low, with overdose defined as administration of a dose greater than 4.0mg 
TA. Overdose resulting from a device malfunction will be captured as an Adverse Device 
Effect (ADE). In the event of an accidental overdose of triamcinolone acetonide suspension 
(Triesence®), subjects will be monitored closely for the emergence of side effects such as 
increased IOP and cataract formation. Any emerging side effects will be managed based on 
the clinical discretion of the investigator and consultation with the sponsor. 
6.2 
Prior and Concomitant Therapy 
6.2.1 Permitted Medications and/or Treatments 
Any treatment that the subject receives at the time of enrollment or receives during the 
investigation shall be recorded along with: 
• Reason for use 
• Dates of administration including start and stop dates 
• Start and stop dates for changes in medications and changes in dose 
• Dosage information including dose and frequency 
Intranasal, inhaled, and topical glucocorticoid medications or stable systemic steroids are 
allowed. For further guidance see also Table 3. 
The medical monitor shall be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.2.2 Prohibited Medications and/or Treatments 
Subjects should not receive any medications (approved or investigational) for their DME in 
the study eye other than the study drug administered with the Oxulumis® prior to screening 
(see the exclusion criteria in Section 5.2 or during the trial as specified in Table 3 in this 
section. This includes medications for DME administered locally (e.g., IVT, suprachoroidal, 
topical, juxtascleral, or periorbital routes). 
If the investigator determines that any of these treatments is needed because of worsening of 
DME, based on follow-on criteria ins Section 6.1.8, the procedures foreseen for the respective 


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visit-day will be extended to include the assessments mandatory for an EoS visit. This visit 
will then be an early termination/end-of-study visit. 
The treatments in Table 3 render a subject not eligible for this study and are considered a 
“follow-on” treatment triggering the end of study participation when intended to be 
administered to a subject participating in this trial. 
Table 3 Time Intervals of ME Medication before Screening and Qualification as 
Follow-on Treatment 
Therapy 
Forbidden interval 
before screening 
Qualifies as Follow-on 
Treatment  
Ranibizumab or bevacizumab (IVT) 
 4 weeks  
Yes 
Aflibercept (IVT) 
 4 weeks  
Yes 
Faricimab or brolucizumab (IVT) 
 4 weeks  
Yes 
Intra- or periocular/subtenon 
injection of triamcinolone acetonide 
 12 weeks  
Yes 
IVT dexamethasone implant 
(Ozurdex®)  
 24 weeks 
Yes 
IVT fluocinolone implant 
At any time 
Yes 
IVT Port Delivery System 
At any time 
Yes 
Suprachoroidal Steroids 
At any time 
Yes 
Vitrectomy 
 12 weeks  
Yes 
Focal (Macular) Laser 
Photocoagulation 
 16 weeks  
Yes 
Panretinal Laser Photocoagulation 
(PRP) 
 16 weeks  
Yes 
Investigational Therapies for ME 
(agents with anti-VEGF activity, or 
combined pharmacologic activity, 
gene therapies, cell therapies, or any 
other therapeutic medicinal product) 
At any time 
Yes 
6.2.3 Concomitant Medications 
For previous and concomitant medications, the original terms will be recorded on the Study 
Subjects’ eCRF by the investigator. Previous and concomitant medications will not be coded, 
and verbatim original terms recorded on the eCRF will be presented as data listings. 


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6.3 
COVID-Related Measures 
Appropriate precautions to limit the spread of COVID-19, in accordance with the 
investigational site’s standard procedures, should be taken. 
The US FDA guidance on the management of clinical trials during the COVID-19 pandemic 
(FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 
Public Health Emergency, August 2021) will be implemented in this study as applicable. A 
more limited impact on treatment is expected as this clinical trial evaluates a single 
suprachoroidal administration of TA in ME. The following measures will be taken: 
• Assessment of feasibility of starting the clinical trial at the chosen sites in close 
collaboration with the sites and factoring in potential risk with repeat travel to the sites 
for study visits. 
• As this clinical trial was designed during the ongoing pandemic, no design changes 
related to the COVID-19 pandemic are expected, but a periodic risk assessment may 
result in adaptations necessitating an amendment. 
• If restrictions would not allow travel of treated subjects to the investigation site, safety 
follow-ups could be performed by a local ophthalmologist. 
7 
Discontinuation of Study, the Study Intervention and Subject 
Discontinuation/Withdrawal 
7.1 
Discontinuation of the Trial 
This trial will be subject to continuous safety assessment by the investigators and the Medical 
Monitor with periodic, at least monthly meetings or distribution of safety update 
communications, to discuss individual and aggregate subject data. If any important safety 
concerns (e.g., SAEs, SADE, AESIs) arise, dosing of further subjects could be temporarily 
halted or stopped. If further dosing is stopped, study visits of enrolled subjects with e.g., 
follow-up visits including safety evaluations will still be performed as foreseen. If the 
Sponsor, Medical Monitor or designee, study center monitor, or appropriate regulatory 
officials discover conditions arising during the trial that indicate that the study should be 
halted, this action may be taken after appropriate consultation. 
In addition, both the Sponsor and the Investigator reserve the right to terminate the study 
according to the study contract. The Sponsor will timely notify the US FDA and respective 
IRB following applicable regulations, e.g., 21 CFR 312.56(d) (drugs); 21 CFR 812.150 
(devices), and other regulatory authorities as applicable in writing of the trial’s early 
termination. 


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Study termination and follow-up will be performed in compliance with the conditions set 
forth in the International Conference on Harmonization (ICH) guidelines (ICHE6 R2), and 
local regulatory requirements. 
7.2 
Discontinuation of Study Intervention 
Discontinuation of the study intervention is not foreseen, as this is a one-time ophthalmic 
administration 2.4 mg or 4mg dose of Triesence® to the suprachoroidal space at the baseline 
visit. See Section 7.3 below for discontinuation in case of inability to administer the study 
medication. 
7.3 
Subject Discontinuation/Withdrawal from the Study 
Each subject should remain in the clinical trial until completion of the required follow-up 
period; however, a subject’s participation in the trial may be discontinued at any time. Should 
this occur, the reason for discontinuation shall be documented in the withdrawal form. 
Reasons for discontinuation include the inability to administer trial medication with the 
Oxulumis® device. 
Subjects shall be informed about their right to withdraw from the trial at any time and for any 
reason without sanction, penalty, or loss of benefits to which the subject is otherwise entitled. 
Withdrawal from the clinical trial will not jeopardize the subject’s future medical care or 
relationship with the investigator. 
Subjects will be asked to specify the reason for the termination but have the right not to 
answer. In this case, only potentially ongoing adverse events or adverse device defects will be 
followed-up, if the subject agrees. 
The investigator may decide to withdraw a subject from the study at any time with reasonable 
rationale, e.g., lack of improvement or clinically meaningful deterioration of DME after 
administration of Triesence® with the Oxulumis® device. 
The subject’s future care will not be influenced by a decision, voluntary or otherwise, to 
withdraw from the study. All reasonable efforts should be made to retain the subject in the 
clinical trial until the completion of the trial. 
Reasons for the subject’s withdrawal include, but are not limited to:  
• Subject refuses to continue participating in the trial 
• Subject’s non-compliance 


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• Subject’s participation is terminated by the PI or investigator, although the subject 
consented since participation is no longer medically appropriate 
• Subject is ‘lost to follow up’ (for details see Section 7.4). 
If a subject withdraws from the clinical trial, the site will record the subject’s reasons for 
withdrawal on a Withdrawal Case Report Form (CRF). When subject withdrawal from the 
clinical trial is due to an adverse event the subject will be followed until resolution of that 
adverse event or determination that the subject’s condition is stable for a maximum duration 
of six (6) months. The status of the subject’s condition should be documented at the time of 
withdrawal. 
7.4 
Lost to Follow-up 
A subject is considered “lost-to-follow-up” if the subject does not adhere to the scheduled 
follow-up visits but has not explicitly requested to be withdrawn from the clinical trial (this 
does not apply to missed visits). Site personnel should at all times make all reasonable efforts 
to locate and communicate with the subject in order to achieve subject compliance to the 
scheduled follow up visits:  
1. A subject will be considered ‘Lost to Follow Up’ after a minimum of two phone calls 
of a physician or delegate at the investigational site to the subject or contact. These 
two phone calls need to be documented in the subject’s records. 
2. If these attempts are unsuccessful, a letter should be sent to the subject’s last known 
address or general practitioner and a copy of this letter should be maintained in the 
subject’s records.  
Note: If a subject misses one or more of the scheduled follow-up visits (inclusive of the 
assigned visit windows), this will be considered as a missed visit. The subject may therefore 
still return for subsequent visits and will not be excluded from the investigation. 
8 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the schedule of activities (SoA, see 
Section 1.3). Adherence to the study design requirements, including those specified in the 
SoA in Section 1.3, is essential and required for study conduct. Protocol waivers or 
exemptions are not allowed. 
All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The investigator will maintain a screening log to record details of 


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all subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
In the event of a significant study-continuity issue (e.g., caused by a pandemic), alternate 
strategies for subject visits, assessments, medication distribution, and monitoring may be 
implemented by the sponsor or the investigator, as per local health authority/ethics 
requirements. 
8.1 
Evaluations Performed During Investigational Visits 
8.1.1 Screening Visit (Visit 1, Days -21 through -2) 
• (Informed) Consenting 
• Eligibility criteria review 
• Obtaining demographic data and medical history 
• Concomitant medication review 
• AEs and ADEs collection 
• Height, weight, vital signs (body temperature, blood pressure, and heart rate) 
• Lab assessment 
• Urine pregnancy test for females of childbearing potential 
• Slit-lamp BM (OU) 
• IOP measurement (OU) 
• Best-corrected visual acuity using ETDRS protocol (OU), duplicate assessments for 
either eye 
• Dilated indirect ophthalmoscopy (OU) 
• Overall assessment of expected procedural complexity (Categories: Low, Medium, 
High) 
• Axial length measurement when available (OU) 
• SD-OCT (OU) 
• OCT-A (OU) 
• Peripheral SS-OCT or UWF SD-OCT when available (OU) 
• Color fundus photographs (OU) 
8.1.2 Baseline visit (Visit 2, Day 0) 
Activities of the baseline visit can spread over up to  14 days. As facilities with the 
operating/procedure room may not have the full spectrum of ophthalmic assessment or 
imaging devices, the visit schedule varies for an in-clinic baseline visit and a baseline visit in 


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an operating/procedure room. If treatment administration in an operating/procedure room is 
intended, some assessments need to be performed before, as the respective equipment may not 
be present in an operating/procedure room. If the investigator decides for a 2nd treatment 
attempt in an operating/procedure room only a selected number of assessments need to be 
repeated. 
The date for calculation of visits following Visit 2, Day 0 will be the date of completion of 
administration of study treatment, i.e., it can be the date of the 2nd attempt for treatment 
administration. 
8.1.2.1 In-Clinic baseline visit (Visit 2, Day 0) 
Some assessments only need to be completed after administration of study treatment  (denoted 
as “only post treatment) but not after an unsuccessful treatment attempt as indicated in 
brackets below (“post attempt”) 
 
Pre-treatment: 
• Eligibility criteria review, partial: only lab results and updates since screening visit 
• Randomization 
• Concomitant medication review 
• AEs and ADEs collection 
• Urine pregnancy test for females of childbearing age 
• Slit-lamp BM in both eyes (OU) 
• IOP measurement in both eyes (OU) 
• Best-corrected visual acuity using ETDRS protocol (OU) 
• Dilated indirect ophthalmoscopy (OU) 
• SD-OCT (SE) 
Treatment 
• Administration of study medication in study eye (SE) 
Post-treatment: 
• AEs and ADEs collection (post attempt and post-treatment) 
• IOP measurement in the SE (repeat measurements, at least 2 over a period of 60min, 
only post-treatment) 
• Dilated indirect ophthalmoscopy (SE) (post attempt and post treatment) 


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• SD-OCT (SE) (post attempt and post treatment) 
• Peripheral SS-OCT or UWF SD-OCT when available (SE) (only post treatment) 
• Color fundus photographs (SE) (post attempt and post treatment) 
• Retinal Physician’s documentation and assessment of administration procedure (post 
treatment attempt partially filled in). 
• Subject’s experience assessment (only post treatment) 
8.1.2.2 Operating/Procedure Room baseline visit (Visit 2, time window for start of V2 
activities to completion: 14 days) 
All listed assessments need to be completed. 
This visit variant will be used in case the investigator: 
• Decides directly to perform the treatment in an operating/procedure room (“direct to 
OR/PR”) 
• Decides for a 2nd treatment attempt in an operating/procedure room after a first in-
clinic Visit 2, which did not result in administration of study treatment. In this case, 
some assessment do not need to be repeated as indicated in brackets below) 
The day of completion of administration of study treatment will be used for calculation of 
further visit dates and windows. 
Pre-treatment: 
• Eligibility criteria review, partial: (for direct to OR/PR: only lab results and updates 
since screening visit), for 2nd treatment attempt: only updates since first attempt) 
• Randomization (for direct to OR/PR mandatory, may be done prior to OR/PR session) 
• Concomitant medication review (mandatory, may be done prior to OR/PR session) 
• AEs and ADEs collection (mandatory) 
• Urine pregnancy test for females of childbearing age (to be performed 1x on the day of 
the treatment attempt) 
• Slit-lamp BM in both eyes (OU, for direct to OR/PR mandatory; may be done prior to 
OR/PR session; no repeat for 2nd treatment attempt) 
• IOP measurement in both eyes (OU, mandatory) 
• Best-corrected visual acuity using ETDRS protocol (OU, for direct to OR/PR 
mandatory, may be done prior to OR/PR session; no repeat for 2nd treatment attempt) 
• Dilated indirect ophthalmoscopy (OU, mandatory) 


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• SD-OCT (SE, for direct to OR/PR mandatory, may be done prior to OR/PR session, 
no repeat for 2nd treatment attempt) 
Treatment 
• Administration of study medication in study eye (SE) 
Post-treatment: 
• AEs and ADEs collection (mandatory) 
• IOP measurement in the SE (repeat measurements, at least 2 over a period of 60min 
post-treatment, mandatory) 
• Dilated indirect ophthalmoscopy (SE, mandatory)  
• Retinal Physician’s documentation and assessment of administration procedure (for 
direct to OR/PR to be completely filled; completion of previously started version, if 
2nd treatment attempt, mandatory). 
• Subject’s experience assessment (post treatment, mandatory) 
8.1.3 Visits 3 through 9 (Day 1 – Week 20) 
The following visits have evaluations to be performed as listed below: Visit 3 (Day 1 +1), 
Visit 4 (Week 1 ± 3 days), Visit 5 (Week 4 ± 5 days), Visit 6 (Week 8 ± 5 days), Visit 7 
(Week 12 ± 5 days), Visit 8 (Week 16 ± 5 days), and Visit 9 (Week 20 ± 5 days) 
• Concomitant medication review 
• AEs and ADEs collection 
• Urine pregnancy test for females of childbearing age (except for visit 2, Day1). 
• Slit-lamp BM (SE), for both eyes (OU) on visit 7 (Week 12 ± 5 days) 
• IOP measurement (SE), for both eyes (OU) on visit 7 (Week 12 ± 5 days) 
• Best-corrected visual acuity using ETDRS protocol (SE), for both eyes (OU) on visit 7 
(Week 12 ± 5 days) 
• Dilated indirect ophthalmoscopy (SE), for both eyes (OU) on visit 7 (Week 12 ± 5 
days) 
• SD-OCT (SE), for both eyes (OU) on visit 7 (Week 12 ± 5 days) 
• OCT-A (OU) on Visit 7 (Week 12 ± 5 days) 
• Peripheral SS-OCT or UWF SD-OCT when available (SE) 
• Color fundus photographs (SE), for both eyes (OU) on visit 7 (Week 12 ± 5 days) 


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• Subject experience assessment on visits 3 (Day 1 + 1 day), 4 (Week 1 ± 3 days), and 5 
(Week 4 ± 5 days) 
• Follow-on treatment administration if prespecified criteria are met from Visit 5, 
Week 4 onward 
8.1.4 End of study visit (Visit 10, Week 24± 5 days) 
• Concomitant medication review 
• AEs and ADEs collection 
• Urine pregnancy test for females of childbearing age. 
• Slit-lamp BM (OU) 
• IOP measurement (OU) 
• Best-corrected visual acuity using ETDRS protocol (OU) 
• Dilated indirect ophthalmoscopy (OU) 
• SD-OCT (OU) 
• OCT-A (OU) 
• Peripheral SS-OCT or UWF SD-OCT using accessory lenses (SE) 
• Color fundus photographs (OU) 
• Follow-on treatment administration if prespecified criteria are met 
8.1.5 Early termination (ET) visit  
Visits in which subjects meet follow-on treatment criteria as defined in Section 6.1.8  will be 
considered early termination (ET) visits. The actual visit schedule will be extended by the 
assessments foreseen for the end of study (EoS)/Week 24 visit as defined in Section 8.1.4. 
8.1.6 Unscheduled visit 
All attempts should be made to keep subjects on the study schedule. However, unscheduled 
visits may be necessary if abnormal findings or AEs occur to evaluate further or repeat testing 
following abnormal findings, or for any other reason, as warranted. 
8.2 
Administrative and General/Baseline Procedures 
8.2.1 Consent form completion 
Following Institutional Review Board (IRB) approval and before any study-related procedure, 
potential subjects will be asked to sign a written informed consent form (ICF) by the 
investigator or the study staff. The subjects will be given sufficient time for the information to 
be read and understood. The subject will be approached and given the chance to ask any 


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questions that have arisen after reading the ICF. Additional guidance on the informed consent 
process can be found in Section 10.3. 
8.2.2 Demographic information and medical history  
The screening visit will obtain information about the subject’s demographics, 
medical/surgical history, and factors pertaining to the use of Oxulumis® to administer 
Triesence® to the suprachoroidal space. 
8.2.3 Urine pregnancy test 
For women of childbearing potential, a negative urine pregnancy test at screening and 
baseline visits is required for eligibility, and then every 4 weeks through the end of study 
participation (Visit 5-9). 
8.2.4 Concomitant medication review 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the subject receives at the time of enrollment or receives 
during the study shall be recorded at each visit along with: 
• Reason for use 
• Dates of administration including start and stop dates 
• Start and stop dates for changes in medications and changes in dose 
• Dosage information including dose and frequency 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
8.2.5 Weight, Height, Vital Signs 
At the screening visits the subject’s weight, height, and vital signs will be assessed. Vital 
signs include measuring of body temperature, of blood pressure after 5min of sitting in a 
relaxed position, and of heart rate. If blood pressure values would render subjects not eligible 
per exclusion criterion No. 24, at the same visit, repeat assessments could be performed to 
exclude temporarily exaggerated values. Subjects are asked to refrain from consuming any 
caffeinated beverages at least 30 minutes prior to blood pressure and pulse measurements. 
8.2.6 Oxulumis® use to administer Triesence® 
Details about the use of Oxulumis® to administer Triesence® are available in the Oxulumis® 
IFU manual. 


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8.2.7 Subject Experience Assessment 
Details about the subject's experience during and after the procedure will be collected in 
interview form (for details see Section 13.1 for the questionnaire for Visit 2, Day 0, and 
Section 13.2 for Visits 3 through 5). 
If the Oxulumis® procedure is repeated after a first in-clinic attempt with an attempt in an 
operating/procedure room, the subject’s experience questionnaire will only be completed on 
with completion of administration of the study treatment. 
8.2.8 Retinal physician’s Documentation and Assessment of the 
Administration procedure 
The retinal physician will document the procedure details and complete the procedure 
assessment questions in the source data using the questionnaire provided in Section 13.3. 
If the treatment administration attempts are repeated after a first unsuccessful in-clinic attempt 
followed by performance of the Oxulumis® procedure in an operating/procedure room setting, 
only one “Retinal Physician’s Documentation and Assessment of the Administration 
Procedure” will be completed with the final procedure reflecting experiences for all 
procedural attempts and treatment. 
8.2.9 Follow-on Treatment 
For details on the assessment of the need for follow-on treatment see Section 6.1.8. 
8.2.10 Disposition of samples 
Any remaining blood, plasma, serum, or urine samples collected for laboratory testing in the 
local laboratories will be destroyed. 
8.3 
Ocular Assessments 
8.3.1 Best Corrected Visual Acuity (BCVA) 
Manifest refraction will be conducted prior to BCVA assessment at every visit. 
The BCVA assessment will be conducted prior to dilating pupils, using the standard ETDRS 
protocol at 4 meters with back-illuminated eye charts and before any other ocular 
procedures/assessments requiring contact with the eye are performed. 
BCVA in the study eye will be assessed at all visits, as specified in the Schedule of Activities, 
(Section 1.3). All BCVA assessments need to be performed in duplicate. Both measurements 
will be entered in the CRF. For eligibility determination at the screening visit the mean of 
both BCVA assessments will be calculated, if both ETDRS letters scores do not differ by 


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more than 5 letters. If the differences are greater than 5 letters, the better (higher) ETDRS 
letter score will be used. Further details on handling duplicate BCVA assessments will be 
described in the SAP. Refraction only needs to be performed a single time per visit, if 
duplicate BCVA assessments are performed sequentially, i.e., no other study assessment in 
between the 1st and the 2nd BCVA assessment. 
BCVA assessment will be performed by a certified VA examiner. 
8.3.2 Axial length measurement 
Axial length will be measured at the screening visit using a non-contact optical biometry 
device (e.g., partial coherence interferometry (PCI) using the IOL Master (Carl Zeiss Meditec 
AG), LensStar (Haag-Streit, Switzerland), Pentacam AXL (Oculus Optikgeräte GmbH, 
Germany). Axial length measurement will assess the axial dimensions of the eye to support 
exploratory imaging of the location of the deployment of study drug in equipped sites only. 
8.3.3 Slit-lamp biomicroscopy 
Subjects’ anterior ocular structure (including the assessment and grading of the lens opacities) 
and ocular adnexa will be examined in the study eye at each study visit using a slit lamp, as 
specified in the SoA (Section 1.3).  Slit-lamp biomicroscopy in the fellow eye will be 
performed at screening, baseline, Week 12, and Week 24/ET, as specified in the SoA (Section 
1.3). The exact method for assessing and grading lens opacities/cataracts is described in the 
study procedure manual. 
8.3.4 IOP measurement 
Intraocular pressure (IOP) of the study eye will be measured at every visit using Goldmann 
applanation tonometry or Tono-pen™, as specified in the SoA (Section 1.3). The same 
method of IOP measurement as chosen at the screening visit must be used throughout the 
study for each individual subject to allow for comparability of assessments. After the 
treatment intervention on the baseline visit, IOP measurement in the study eye must be 
repeated at least twice over a period of 60 minutes after treatment. 
IOP measurement in the fellow eye will be measured at screening, baseline, Week 12, and 
Week 24/ET, as specified in the SoA (Section 1.3). 
8.3.5 Dilated indirect ophthalmoscopy 
Subjects’ posterior pole and peripheral retina will be examined by dilated indirect 
ophthalmoscopy at each study visit in the study eye, as specified in the SoA (Section 1.3). A 


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post-dose evaluation shall be performed immediately after the administration of the study 
treatment. 
Dilated indirect ophthalmoscopy in the fellow eye will be performed at screening, baseline, 
Week 12, and Week 24/ET, as specified in the SoA (Section 1.3). 
8.3.6 SD-OCT, and Peripheral OCT assessments 
Retinal characteristics will be evaluated at every visit using SD-OCT. Key imaging 
parameters are described below but may be adapted and if necessary extended to fulfill the 
objectives of this trial. More details will be described in more detail in the trial’s imaging 
manual. All OCT images will be captured and uploaded to a central repository at a central 
reading center (CRC) via an encrypted secure website. All OCTs images will be electronically 
archived at the investigational sites as part of the source documentation. 
Acceptable SD-OCT machines are Spectralis (Heidelberg Engineering GmbH) and Cirrus 
(Carl Zeiss Meditec AG). Other devices would need to be approved by the sponsor upon 
request. In this case, device specific CST values for eligibility assessment will be provided as 
for the devices mentioned in inclusion criterion No.4. The same device should be used for 
screening and the subsequent follow-up assessments for each subject. 
For Spectralis devices the below parameters should be used to acquire two scans: 
• Volume Scan (centered on the fovea): 20° x 20°, 97 Section with ART set to 16 and 
High-Resolution mode (HR) 
•  Volume Scan (centered on the fovea): 30° x 5°, 7 Section with ART set to 25 and HR) 
For Cirrus devices the below parameters should be used to acquire two scans: 
• 512x128 Macular Cube  
• HD 5 Line Raster 
Peripheral SS-OCT (will be assessed in sites with available capabilities using appropriate 
imaging parameters). 
OCT imaging, i.e., SD-OCT and, when available peripheral OCT, will be performed at each 
visit for the study eye. Exceptions are: 
• If the Oxulumis® procedure is not completed, only a post treatment attempt SD-OCT 
is required. The optional peripheral OCT is not assessed, as its main purpose is to 
visualize the suprachoroidal drug bleb post study treatment. 


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• If the Oxulumis® procedure is completed in an operating/procedure room with neither 
access to an SD-OCT nor Peripheral OCT in this facility on Day 0, Visit 2, these are 
not required to be performed post treatment. Assessments on Day 1 will be sufficient. 
For the non-study eye, SD-OCT and, when available. 
8.3.7 OCT-Angiography 
The anatomical state of the retinal vasculature will be evaluated by optical coherence 
tomography angiography (OCT-A). Key imaging parameters are described below but may be 
adapted and if necessary extended to fulfill the objectives of this trial. More details will be 
described in more detail in the trial’s imaging manual. OCT-A images will be captured and 
uploaded to a central repository at a CRC via an encrypted secure website. All OCT-As will be 
electronically archived at the investigational sites as part of the source documentation. 
The preferred OCT-A machine for retinal vascular diseases is the ZEISS PlexElite.  The 
Optovue can also be used but may have fewer wide-angle choices. The same device should be 
used for screening and the subsequent follow-up assessments for each patient. The preferred 
scan acquisition protocols for retinal vasculopathies are 3x3 and 9x9 scans. 
OCT-A imaging, will be performed at screening, Week 12, and Week 24/EOS visits, as 
specified in the SoA (Section 1.3). 
8.3.8 Color fundus photography 
Retinal anatomy will be evaluated by Color Fundus Photography (CFP). In case of non-
completion of the procedure in the clinic, a CFP is required to be acquired in the study eye. 
Key imaging parameters are described below but may be adapted and if necessary extended to 
fulfill the objectives of this trial. More details will be described in more detail in the trial’s 
imaging manual. Fundus photography will be captured and uploaded to a central repository at 
a CRC via an encrypted secure website. All CFPs will be archived at the site as part of the 
source documentation. 
CFP in the study eye will be captured at all visits, as specified in the SoA (Section 1.3). If the 
Oxulumis® procedure is completed in an operating/procedure room with no access to a CFP in 
this facility on Day 0, Visit 2, it is sufficient to perform the CFP foreseen for Day 1, Visit 3. 
CFP in the fellow eye will be captured at screening, Week 12, and Week 24/ET, as specified 
in the SoA (Section 1.3). 


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A CFP shall be performed once a subject has met follow-on treatment criteria in the study eye 
and before follow-on treatment is given. 
CFP will be captured using either 4WF or UWF imaging methods (see Table 4). Additional 
images to document the site of drug deployment using infra-red imaging will be taken. 
4 Wide Field imaging (4WF):  Take one FR (Fundus Reflex) and stereo pairs of F1W and 
F2W, and single images F4W and F5W of each eye for a minimum of 7 images per eye, 14 
total images OU. In addition, infra-red images of the site of deployment will be taken. 
Ultrawide Field (UWF) imaging: Perform 2 Central Wide Field single images. In addition, 
infra-red images of the site of deployment will be taken. 
Table 4  Overview of Imaging Systems and Required Field of View for Wide-Field 
Color Funds Photographs 
Imaging System 
Required Image Field of View (FOV) 
Clarus 
Take all images at 133-degree capture mode 
Optos 
Take all images at 200-degree capture mode 
Spectralis 
Take all images using a 102-degree lens using ART 15 
8.4 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoAs in Section 1.3. 
The following assessments will also provide safety-relevant information but are discussed in 
other sections: IOP assessment (Section 8.3.4), slit-lamp biomicroscopy (Section 8.3.3), 
dilated indirect ophthalmoscopy (Section 8.3.5), SD-OCT (Section 8.3.6). and pregnancy test 
(Section 8.2.3). 
8.4.1 Adverse Events and Adverse Device Effect collection 
At every visit, the investigator (or designee) will assess for and record all adverse events 
(AEs) and adverse device effects (ADEs) that occur from the time the informed consent is 
signed until the end of the study. 
8.4.2 Safety laboratory tests  
Blood samples for routine clinical laboratory tests will be collected at the screening visit 
(Visit 1, D -21 to -2). Screening laboratory tests will be performed in local CLIA certified 
laboratories. Tests may be repeated once at the discretion of the investigator. The minimum 
tests to be performed include the following: 


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• Non-fasting chemistry (blood): sodium, potassium, chloride, bicarbonate, albumin, 
alkaline phosphatase, aspartate amino transferase, alanine amino transferase, bilirubin 
direct, bilirubin indirect, total bilirubin, creatinine, blood urea nitrogen, total protein, 
calcium, phosphorus, and hemoglobin A1c 
• Hematology (complete blood count with differential): white blood cell count, red 
blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean 
corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell 
distribution width, platelet count, and mean platelet volume 
• Thyroid: thyroid-stimulating hormone 
The investigator shall review the laboratory report, document the review, and record any 
clinically significantly abnormal findings. Clinically significant abnormal findings from the 
screening laboratory testing that are explained by known diseases or conditions will be 
considered medical history and recorded as such on the medical history page of the case report 
form (CRF). If the screening laboratory assessments detect new, clinically significant 
abnormal findings, that are not explained by known diseases or conditions, such findings 
should be recorded as non-treatment-emergent AE. The laboratory reports shall be filed with 
the source documents.  
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered 
clinically significant by the investigator, then the results shall be recorded in the CRF. 
8.4.3 Height, Weight, Vital Signs, and Blood Pressure 
Blood pressure and heart rate will be measured after 5min of sitting in a relaxed position. If 
blood pressure values would render subjects not eligible per exclusion criterion No. 24, at the 
same visit, repeat assessments could be performed to exclude temporarily exaggerated values. 
Subjects are asked to refrain from consuming any caffeinated beverages at least 30 minutes 
prior to blood pressure and pulse measurements. Height and Weight will be used calculate the 
BMI (kg/m²). 
8.5 
Safety Reporting, Adverse Events (AEs), and Serious Adverse Events (SAEs) 
All subjects enrolled to the study treatment will be assessed for safety. 
Investigators are responsible for monitoring the safety of subjects who have entered this study 
and for alerting the Sponsor regarding any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the subject. The Investigator is responsible for 
appropriate medical care of subjects during the study. 


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The definitions of adverse events (AEs) and serious adverse events (SAEs) considering the 
definitions also of 21 CFR 312.31(a) can be found in Section 11. 
The definitions of device-related safety events including adverse device effects (ADEs), 
device deficiencies, and serious adverse device effects (SADEs) can be found in Section 11.3, 
Section 11.4, and Section 11.6. 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up all AEs OR AEs that are serious, considered related to the study intervention or 
study procedures, or that caused the subject to discontinue the study (see Section 7). This 
includes events reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject’s legally authorized representative). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 11.7. 
8.5.1 Time Period and Frequency for Collecting AE and SAE Information 
All AEs/SAEs will be collected from the signing the ICF until EoS/ET visit (Week 24) at the 
timepoints specified in the SoA (see Section 1.3). 
A preexisting medical condition is one that had been already present at the start of the study 
(at the time of the signature of the ICF). Such conditions should be recorded on the Medical 
and Surgical History eCRF.  The AEs and SAEs that begin between obtaining the signed ICF 
and the start of study intervention will be categorized as non-treatment emergent AEs/SAEs. 
This also includes AEs/SAEs, which continue after the start of study intervention but do not 
worsen in severity. 
The AEs and SAEs that begin after start of the study intervention, and those existing pre-dose 
that worsened in severity post-dose will be considered treatment-emergent AEs and SAEs. 
A pre-existing medical condition should be recorded as an AE or SAE only if the frequency, 
severity, or character of the condition worsens during the study. When recording such events 
on an AE eCRF and SAE form (if applicable), it is important to convey the concept that the 
preexisting condition has changed by including applicable descriptors (e.g., “more frequent 
headaches”). 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours. The investigator will submit any updated SAE data 


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to the sponsor within 24 hours of it being available. For timelines of reporting to regulatory 
authorities or IRBs see Section 12. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion 
of study participation. However, if the investigator learns of any SAE, including death, at any 
time after a subject has been discharged from the study, and the investigator considers the 
event to be reasonably related to the study intervention or study participation, the investigator 
must promptly notify the sponsor. 
8.5.2 Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about AE 
occurrences. To limit bias in safety reporting, subjects are masked to their dose level. The 
study team must not disclose the dose level received until after the end of the study except for 
emergency situations. 
8.5.3 Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each subject 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the 
event is otherwise explained, or the subject is lost to follow-up (as defined in Section 7.4). 
Further information on follow-up procedures is provided in Section 11.7.4. 
8.5.4 Disease-related events and/or Disease-related outcomes not qualifying 
as AEs or SAEs 
No specific disease-related events not qualifying as AEs or SAEs are defined for this clinical 
trial. Significant and unexpected loss in VA or parameters indicating an increase of macular 
edema may be reported as AE if the extent is significant or unexpected in the opinion of the 
investigator or sponsor. Non-improvement or worsening of disease leading to need for follow-
on treatment (as defined in Section 6.1.8) would only qualify as an AE, if significant or 
unexpected in the opinion of the investigator. 
8.5.5 Regulatory Reporting Requirements for Serious Safety Events 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting 
to the regulatory authority, IRBs/IECs, and investigators. 


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Safety reporting to the regulatory authorities will be performed according to the following 
regulations applicable to the US: 
• IND safety reporting Guidance for Industry and Investigators - Safety Reporting 
Requirements for INDs and BA/BE Studies (US FDA, 2012) 
• Guidance Sponsor Responsibilities - Safety Reporting Requirements and Safety 
Assessment for IND and Bioavailability/Bioequivalence Studies for Investigators (US 
FDA, 2021a) and Sponsors (US FDA 2021b) 
The detailed information on safety reporting timelines and processes according to the above 
regulations will be outlined in the Safety Monitoring Plan. 
8.5.6 Adverse Events of Special Interest 
In this trial, adverse events of special interest (AESIs) are defined and monitored following 
the same expedited reporting as used for SAEs (see Section 8.5.1). AESIs comprise the 
following prespecified terms based on general considerations on potential safety risks with 
suprachoroidal device deployment and treatment. 
• Suprachoroidal hemorrhage 
• Sterile intraocular inflammation 
• Endophthalmitis 
• Choroidal bacterial infection 
• Retinal detachment 
• Retinal perforation 
• Rise of intraocular pressure above 30 mmHg 
• Rise of at least 10 mmHg from baseline IOP 
• Severe pain or discomfort after administration of IP 
To consider an acute IOP rise after the treatment administration procedure as an AESI, the 
rise must continue beyond the 60min observation period on Day 0, Visit 2, or require medical 
intervention, e.g., a paracentesis to lower IOP.  For a persistent rise of the IOP detected upon 
the follow-up visits, to consider it as meeting AESI criteria, the rise must be maintained over 
2 successive visits. 
8.5.7 Device Deficiencies 
Oxulumis® devices are being provided for use in this study to administer Triesence® as part of 
the study intervention. To fulfill regulatory reporting obligations worldwide, the investigator 


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is responsible for the detection and documentation of events meeting the definitions of device 
deficiency that occur during the study with such devices. 
The definition of a medical device deficiency as well as processes and time periods for 
detection, notification, reporting, and follow-up of the medical device deficiencies can be 
found in Section 11.4. 
NOTE: Deficiencies fulfilling the definition of an AE/SAE will follow the processes outlined 
in Sections 8.5 of this protocol. 
8.5.8 Contraception Guidance 
According to the USPI for Triesence®, (Alcon Laboratories Inc., 2007), administration in 
pregnancy can cause fetal harm with first trimester use. Multiple cohorts and case-control 
studies in humans suggest that maternal corticosteroid use during the first trimester increases 
the rate of cleft lip with or without cleft palate from about 1/1000 infants to 3- 5/1000 infants. 
Two prospective case control studies showed decreased birth weight in infants exposed to 
maternal corticosteroids in utero. Human and animal studies suggest an increased risk for 
intrauterine growth restriction and decreased birth weight. An independent overview and 
discussion of these effects were recently compiled also by Bandoli et al. (Bandoli et al., 
2017). 
Accordingly, and following the guidance on contraception of the Clinical Trial Facilitation 
Group (Clinical Trials Facilitation and Coordination Group, 2020), the following 
contraception guidance needs to be implemented in this study and is also mentioned in the 
inclusion criteria in Section 5.1. 
The following methods are considered highly effective as they can achieve a failure rate of 
less than 1% per year when used consistently and correctly.  
• combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation 
o oral 
o intravaginal  
o transdermal 
• progestogen-only hormonal contraception associated with inhibition of ovulation 
o oral 
o injectable 
• implantable 
• intrauterine device 


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• intrauterine hormone-releasing system 
• bilateral tubal occlusion 
• vasectomised partner 
• sexual abstinence 
Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) 
may be combined to achieve a failure rate of less than 1% per year; barrier methods must 
always be supplemented with the use of a spermicide. 
Women who are not postmenopausal, i.e., at least 12 months of non-therapy-induced 
amenorrhea or surgically sterile (absence of ovaries and/or uterus), must agree to remain 
abstinent or use combined contraceptive methods that result in a failure rate of less than 1% 
per year from the treatment visit (Day 0) until the end of trial participation, or for at least 12 
weeks from the treatment visit (Day 0), if study participation ends before visit 7, Week 12. 
Some forms of contraception, e.g., hormonal contraception, need to be started before the 
treatment visit (Day 0) to have full effect from the time of exposure on. 
Male participants must agree to use a barrier method of contraception from the treatment visit 
(Day 0) until the end of trial participation, or for at least 12 weeks from the treatment visit 
Day 0, if study participation ends before visit 7, Week 12. 
8.5.9 Pregnancy 
Details of all pregnancies in female subjects and female partners of male subjects will be 
collected after the start of the study intervention and until the completion of the study. 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the pregnancy. 
This includes the female subject or female partner of a male subject (after obtaining the 
necessary signed ICF from the female partner. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. Any post 
study pregnancy-related SAE considered reasonably related to the study intervention by the 
investigator will be reported to the sponsor as described in Section 8.5 and Section 8.5.1. 
The subject/pregnant female partner will be followed to determine the outcome of the 
pregnancy. The investigator will collect follow-up information on the subject/pregnant female 


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partner and the neonate (after obtaining a signature of pregnancy follow-up specific ICF) and 
the information will be forwarded to the sponsor. 
Any female subject who becomes pregnant while participating in the study will not be treated 
with the study intervention when the pregnancy becomes apparent before treatment 
administration at Visit 2. If the pregnancy is detected after administration of study treatment, 
the patient will be offered to attend study visits for a safety follow-up with non-invasive 
assessments only (as standard at the relevant site for the assessment of pregnant patients). 
9 
Statistical Considerations 
This is a 24-week, randomized, two-arm, parallel-group, single-masked, clinical trial to 
evaluate safety and tolerability of two dose levels of suprachoroidal triamcinolone Acetonide 
Administered with the Oxulumis® ophthalmic administration in subjects with Diabetic 
Macular Edema. 
9.1 
Statistical Hypothesis 
The present clinical trial is a single-masked, two-arm study to evaluate safety and tolerability 
of two dose levels, therefore no formal statistical hypothesis was developed. 
9.2 
Sample Size Determination 
A total of approximately 20 subjects will receive a single treatment with Triesence® 
administered with the Oxulumis® to one eye, the study eye. Subjects in whom study treatment 
cannot be administered will be replaced. 
The sample size is not based on power calculations. It is chosen based on clinical experience 
and considered to be adequate to fulfill the objectives of the clinical trial. A sample size of 20 
subjects is estimated to detect common and very common adverse events, which is key to 
inform further trials in the Oxulumis® development program in respect to safety 
considerations. 
9.3 
Analysis Sets 
In this clinical trial, the following definitions for analysis sets will apply. 
9.3.1 Safety Population 
The safety population (SAF) will include all subjects in whom the administration of study 
treatment was started. 


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9.3.2 Efficacy Evaluable Population 
The efficacy evaluable population will include all subjects who received the study treatment 
and have at least one post baseline efficacy observation or measurement in the study eye (i.e., 
either BCVA or CST). 
9.3.3 Per Protocol Efficacy Population 
The per protocol efficacy population (PP) consists of the Efficacy Evaluable Population with 
the exception of subjects with important protocol violations. 
9.4 
Statistical Analyses 
9.4.1 General Considerations 
All statistical analyses will be outlined in detail in a Statistical Analysis Plan (SAP) which 
will be prepared and signed prior to database lock or any study-specific analyses. Summary 
statistics from investigator findings will be tabulated and summarized descriptively. Where 
applicable, treatment arms of 2.4mg and 4.0mg will be compared with descriptive statistics. 
All continuous measures will be summarized descriptively, including the number of available 
values, minimum, 1st quartile, median, mean, standard deviation, 3rd quartile, maximum, and 
95% confidence interval for the mean, if appropriate. Categorical data will be presented by 
frequency and percentage. Ordinal ratings may be handled as continuous data if appropriate or 
presented as categorical if the number of categories is small. 
9.4.2 Safety Analyses 
All safety analyses will be performed on the SAF population.  
The treatment-emergent AEs/ADEs (defined as any AE occurring or worsening with the same 
date or later than that of the first application of study treatment) will be encoded using the 
MedDRA version 24.1. This version will be used throughout the entire study. If available, 
updates of the MedDRA dictionary will not be applied afterwards. 
The treatment-emergent AEs or ADEs will use the system organ class (SOC) and preferred 
term (PT) codes.  
TEAEs, study drug-related AEs, AEs of Special Interest (AESIS), AEs leading to withdrawal 
from the study and SAEs will be summarized in a similar manner. AEs will be presented 
categorized as ocular and non-ocular AEs. Ocular AEs will be presented separately for the 
study eye and the non-study eye. 


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9.4.3 Exploratory Efficacy and Safety Endpoint Analysis 
The following main exploratory endpoints will be described on efficacy evaluable population 
and per protocol efficacy population (if different): 
1. Mean Change in BCVA (ETDRS) at all study visits through Week 24 compared to 
baseline 
2. Percentage of subjects with vision gain and vision loss of at least 5, at least 10, and at 
least 15 letters at all study visits through Week 24 compared to baseline 
3. Time to subjects requiring follow-on treatment 
4. Mean Change in Central subfield thickness (CST) at all study visits through Week 24 
compared to baseline. 
5. Mean Change in IOP at all study visits through Week 24 compared to baseline 
Further exploratory endpoints derived from the assessments of this trial will be summarized in 
detail in the SAP. 
All continuous measures will be summarized descriptively, including the number of available 
values, minimum, 1st quartile, median, mean, standard deviation, 3rd quartile, maximum, and 
95% confidence interval for the mean, if appropriate. Categorical data will be presented by 
frequency and percentage. Ordinal ratings may be handled as continuous data if appropriate or 
presented as categorical if the number of categories is small. 
9.4.4 Important Protocol Violations 
Protocol violations will be collected and reviewed during the trial. 
Important protocol violations are defined as those violations from the protocol likely to have 
an impact on the perceived efficacy and/or safety of study treatments. 
As important protocol violations are considered: 
• Not meeting the inclusion criteria or meeting the exclusion criteria, respectively 
• Missing study visits or out of window study visits (depending on type of visit and on 
the time interval). 
• Intake of non-authorized concomitant treatment 
• Missing important safety data points (IOP measurements, dilated fundus examinations, 
BCVA measurement, SD-OCT measurement, etc.) 


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9.4.5 Other Analyses 
9.4.5.1 Subject Disposition and Baseline Characteristics 
Subject disposition will include the number of subjects who enroll in the study and the 
number and percentage of subjects included in each analysis population. The frequency and 
percentage of subjects who discontinue from the study, along with the reason for 
discontinuation, will be summarized. Demographics and baseline characteristics, including 
age, gender, and race will be summarized using descriptive statistics for the SAF population. 
9.4.5.2 Concomitant Medications 
For previous and concomitant medications, the original terms will be recorded on the Study 
Subjects’ eCRF by the investigator. Previous and concomitant medications will not be coded, 
and verbatim original terms recorded on the eCRF will be presented as data listings. 
9.4.5.3 Physician Procedure Assessment 
Physician procedure assessment will be described on the Safety Population (SAF). 
9.4.5.4 Patient Experience Assessment 
Patient experience assessment will be described on the Safety Population (SAF) at study 
visits. 
9.4.6 Missing Data and Imputation Methods 
No imputation of missing data will be performed. 
In case the start date for an AE/ADE is missing or incomplete, so that it is not possible to 
evaluate if it has occurred pre- or post-treatment, this AE/ADE will be classified 
conservatively as treatment-emergent. 
9.5 
Deviations from the clinical study protocol 
The investigator is not allowed to deviate from the clinical trial protocol, except under 
emergency circumstances.  
In some cases, failure to comply with the protocol may be considered a failure to protect the 
rights, safety, and well-being of subjects, since non-compliance exposes subjects to 
unreasonable risks. Investigators should seek minimization of such risks by adhering to the 
protocol. Simultaneously, if adhering to the protocol might expose the subject to unreasonable 
risks, the investigator is also required to protect the rights, safety, and well-being of the 
subject by intentionally deviating from the requirements of the clinical trial protocol, so that 
subjects are not exposed to unreasonable risks. 


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Observable and data-driven protocol deviations will be recorded and categorized in a central 
protocol deviation log. 
Relevant information for each protocol deviation will be documented on a deviation form. 
Protocol deviations shall be reported to regulatory authorities in specified timelines as 
appropriate. 
9.6 
Interim Analysis 
To compile data on the safety of the Oxulumis® device, Oxular Ltd. intends to perform an 
analysis on clinical data up to Week 4 of the trial. The focus will be on safety events and 
feedback on administration from the investigator and the subjects. The exact details of this 
analysis will be laid out in the SAP. 
 


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10 Supporting Documentation and Operational Considerations. 
10.1 Regulatory and Ethical Considerations 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP and applicable regulatory 
requirements. The sponsor or the sponsor’s representatives will obtain regulatory approval 
from the competent authority prior to the clinical trial start.  The sponsor will provide all 
necessary documents to obtain such approval. 
If any of the documents relevant to obtaining approval are amended, the sponsor or the 
sponsor’s representatives will submit these documents for review and subsequent approval to 
the competent authority. 
An annual safety/progress report will be provided by the sponsor or the sponsor’s 
representatives to the competent regulatory authority as required by applicable regulations. 
The sponsor or the sponsor’s representatives will obtain ethical approval from the Institutional 
Review Board (IRB) prior to the clinical trial start. The sponsor will provide all necessary 
documents to obtain such approval. 
If any of the documents relevant to obtaining approval are amended, the sponsor or the 
sponsor’s representatives will submit these documents for review and subsequent approval to 
the IRB. 
The investigator is responsible for accuracy and completeness of all data recorded in patient 
medical charts and CRFs.  All data recorded in the CRF are derived from source data unless 
specifically exempted. Source data will be defined prior to the start of the clinical trial but 
consists in general of the information documented in the patient medical chart.  Corrections to 
data should be made in a way so that the originally recorded data is still legible and traceable. 
Any changes should be initialed and dated by the person making the correction. The 
investigator will maintain a file of essential documents of the trial as defined by the regulatory 
requirements, ICH, and the sponsor. 
10.2 Financial Disclosure 
Financial compensation of the investigator and/or his/her institution will be regulated in a 
financial agreement established between the sponsor or the sponsor’s representative and the 
investigator and/or his/her institution. 


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10.3 Informed Consent Process 
Following IRB approval and before any investigation-related procedure, potential subjects 
will be asked to sign a written ICF. The subjects will be given sufficient time for the 
information to be read and understood. The subject will be approached and given the chance 
to ask any questions that have arisen after reading the ICF.  
The sponsor’s sample ICF will be provided to each site. If applicable, it will be provided in a 
certified translation of the local language. The sponsor or its designee must review and 
approve any proposed deviations from the sponsor's sample ICFs before IRB submission. The 
final IRB approved Consent Forms must be provided to the sponsor for health authority 
submission purposes according to local requirements. 
The Consent Forms must be signed and dated by the patient before his or her participation in 
the study. The case history or clinical records for each patient shall document the ICF process 
and that written ICF was obtained prior to participation in the study. 
Patients unable to give consent personally will only be consented in those countries where 
national law/regulations permit. 
The Consent Forms should be revised whenever there are changes to study procedures or 
when new information becomes available that may affect the willingness of the patient to 
participate. The final revised IRB-approved Consent Forms must be provided to the sponsor 
for health authority submission purposes. 
Patients must be re-consented to the most current version of the Consent Forms (or to a 
significant new information/findings addendum in accordance with applicable laws and IRB 
policy) during their participation in the study. For any updated or revised Consent Forms, the 
case history or clinical records for each patient shall document the ICF process and that 
written ICF was obtained using the updated/revised Consent Forms for continued 
participation in the study. 
A copy of each signed Consent Form must be provided to the patient. All signed and dated 
Consent Forms must remain in each patient’s study file or in the site file and must be 
available for verification by study monitors at any time. 
10.4 Recruitment strategy 
Subjects in this clinical trial will be recruited from the pool of patients at the participating 
investigational sites and by referrals from general ophthalmologists or optometrists to the 


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investigational centers. Recruitment is expected to be completed in 9 months after the 
initiation of the clinical trial. 
10.5 Data Protection 
The sponsor maintains confidentiality standards by coding each patient enrolled in the study 
through the assignment of a unique patient identification number. This means that patient 
names are not included in data sets that are transmitted to any sponsor location. 
Patient medical information obtained by this study is confidential and may only be disclosed 
to third parties as permitted by the ICF (or separate authorization for use and disclosure of 
personal health information) signed by the patient unless permitted or required by law. 
Medical information may be given to a patient’s personal physician or other appropriate 
medical personnel responsible for the patient’s welfare for treatment purposes. 
Data generated by this study must be available for inspection upon request by representatives 
of applicable national and local health authorities, sponsor monitors, representatives, and 
collaborators, and the IRB for each study site, as appropriate. 
All reasonable precautions within the constraints of the applicable regulatory requirement(s) 
will be taken to maintain the confidentiality of subjects' identities and sponsor’s proprietary 
information by any party (e.g., domestic and foreign regulatory authorities, sponsor's 
monitors, and auditors) with direct access to patient medical information. 
The data protection officer of the clinical study site and the sponsor must be informed about 
the project before the start of a clinical study. The data protection officer is obligated to 
monitor compliance with the requirements of all data protection regulations. The data 
protection officer must, therefore, not only be informed but all necessary information must be 
provided so that the data protection officer can fulfill his or her inspection obligations.  
In case of a data security breach, the data protection officer needs to be informed. The data 
protection officer is required to report the breach immediately (within 72h) to the responsible 
data protection supervisory authority. Subjects who are personally concerned and potentially 
endangered by a data protection breach will be informed immediately. Any possible measure 
to remedy the data protection breach will be arranged. Appropriate technical and 
organizational measures are implemented to protect information and personal data processed 
against unauthorized or unlawful access, disclosure, dissemination, alteration, destruction, or 
accidental loss, in particular where the processing involves the transmission. 


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Subjects will be assigned a unique identifier by the sponsor. Any subject records or datasets 
that are transferred to the sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. 
The subject must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject who will be required to give consent for their data to be used as 
described in the informed consent.  
The subject must be informed that their medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
10.5.1 Committee Structure 
10.5.1.1 Safety Committee 
Periodically, the coordinating investigator together with the medical monitor will review 
individual patient data as well as the totality of the safety data to recommend if the 
investigation should continue as is, continue with changes, or be terminated. 
10.5.1.2 Study Steering Committee 
The study will use the services of a study steering committee (SSC). The composition, roles, 
responsibilities, and rules governing the SSC are available in the SSC Charter. 
10.5.2 Dissemination of Clinical Trial Data 
Investigators and their staff shall hold confidential and not disclose directly or indirectly to a 
third party other than those persons involved in the study who have a need to know, the 
protocol, the data arising out of the study, and any other information related to the study or to 
Sponsor’s products or research programs that is provided to the Investigator. All such persons 
must be instructed not to further disseminate this information to others. Investigators shall not 
use the confidential information for any purpose other than the study. The foregoing 
obligations of confidence and non-use assumed by the Investigator shall not apply to: 
a. information which at the time of disclosure is in the public domain; 
b. information which thereafter lawfully becomes part of the public domain other than 
disclosure by or through the Investigator;  
c. information which, as evidenced by the Investigator’s written records, was known 
by the Investigator prior to Oxular Limited’s disclosure;  


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d. information which is lawfully disclosed to the Investigator by a third party not under 
any obligation of confidence to Oxular Limited; or 
e. information which is required to be disclosed by law or a government regulatory 
agency, provided reasonable advance notice of such disclosure is given to Oxular 
Limited. 
All data and discoveries arising out of the study, patentable or non-patentable, shall be the 
sole property of Oxular Limited. Oxular Limited reserves the right to prior review of any 
publication or presentation of information related to the study. Oxular Limited reserves the 
right to prior review of any publication or presentation of information related to this study. 
Oxular Limited may use these data now or in the future for presentation or publication at 
Oxular Limited’s discretion or for submission to Regulatory Authorities. 
10.5.3 Data Quality Assurance 
All subject data relating to the study will be recorded on electronic CRFs. The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
The sponsor is responsible for the data management compliance of this study, including 
quality checking of the data, and assumes accountability for actions delegated to other 
individuals. Authorized representatives of the sponsor may perform audits or inspections, 
including source data verification. The purpose of an audit or inspection is to systematically 
and independently examine all study-related activities and documents to determine whether 
these activities were conducted, and data were recorded, analyzed, and accurately reported 
according to the protocol, GCP guidelines of the ICH, and any applicable local regulatory 
requirements. The Investigator agrees to accommodate and participate in audits conducted at a 
reasonable time and in a reasonable manner. The Sponsor’s clinical quality assurance group 
may request access to all source documents, eCRFs, and other study documentation for on-
site audit or inspection.  
Direct access to these documents must be guaranteed by the Investigator, who must provide 
support at all times for these activities. Additionally, the investigational site shall provide 
direct access to all trial-related sites, source data/documents, and reports for the purpose of 
inspection by local and regulatory authorities. In the event of this latter, the Investigator shall 
contact the sponsor immediately if contacted by a regulatory agency about an inspection. 
QC procedures shall be implemented beginning with the data entry system, and data QC 
checks that will be run on the database shall be generated. Any missing data or data anomalies 


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shall be communicated to the site(s) for clarification/resolution. Following written SOPs, the 
monitors will verify that the clinical trial is conducted, and data are generated, documented 
(recorded), and reported in compliance with the protocol, GCP and applicable regulatory 
requirements. 
Clinical study records shall be retained according to the following requirements, unless local 
regulations or institutional policies require a longer retention period than summarized:  
• US regulations (21 CFR Part 312.62) require that records and documents pertaining to 
the conduct of this study and the distribution of investigational products (including 
medical records, eCRFs, ICFs, test results, and investigational product records) be 
kept on file by the Investigator for 2 years after a marketing application is approved 
for the investigational product for the indication for which it is being studied. If no 
application is filed or approved, these records must be kept for 2 years after the 
investigation has been discontinued and the FDA has been notified. 
• ICH-GCP requires that documents should be retained until at least 2 years after the 
last approval of a marketing application in an ICH region and are no pending or 
contemplated marketing applications in an ICH region or until at least 2 years have 
elapsed since the formal discontinuation of clinical development of the investigational 
product. 
No clinical trial records shall be destroyed or transferred to another location or party without 
prior notification and authorization from the Sponsor. 
10.5.4 Source Documents 
The Investigator is required to prepare and maintain adequate and accurate case histories that 
record all observations and other data pertinent to the clinical trial on each subject enrolled. 
Case histories include the CRFs and supporting source documents. Source documents include 
subject signed ICFs, subject medical records with dates and details of the trial procedures 
(screening, laboratory and other test results, study treatments, AEs, and subject status, etc.). 
The source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. These source documents shall be filed at the investigator’s site.  
The sponsor will provide the study sites with eCRFs that will be completed for each study 
subject based on the source documentation. It is the Investigator’s responsibility to ensure the 
accuracy, completeness, legibility, and timeliness of the data reported in the subject’s eCRF.  
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 


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shall be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records shall be available. 
The Investigator, or designated representative, shall complete the eCRF pages as soon as 
possible after information is collected during an examination, treatment, or any other clinical 
trial procedure. Any outstanding entries shall be completed immediately after each subject 
completes the clinical trial. An explanation shall be provided for all missing data. 
The sponsor’s representative will perform monitoring to confirm that data entered into the 
CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents, that the safety and rights of subjects are being protected, and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.6  
Publication Policy 
The data resulting from this clinical trial will be proprietary information of the sponsor. None 
of the data resulting from this clinical trial will be allowed to be presented or published in any 
form, by the investigator or any other person, without the prior approval of the sponsor. The 
sponsor shall not unreasonably refuse, or delay publications based on the trial. 
The sponsor may request, and the investigators shall not unreasonably refuse, the deletion of 
confidential information from a proposed publication. The parties will use their best efforts to 
provide scientifically meaningful equivalent information for such deleted confidential 
information. 
10.7 Study and Site Start up and Closure 
10.7.1 First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
subjects. 
The first act of recruitment is the first site open and will be the study start date.  
10.7.2 Study/Site Termination 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 


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Further to regulations outlined in Section 7, reasons for the early closure of a study site by the 
sponsor or investigator may include but are not limited to: 
For study termination: 
• Discontinuation of further study intervention development 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB or 
local health authorities, the sponsor’s procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of subjects 
by the investigator 
• Total number of subjects included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the subject and shall assure 
appropriate subject therapy and/or follow-up. 
11 Safety: Events, Definitions and Procedures 
11.1 Emergency Contacts for Investigator Reporting of Safety Events 
The primary mechanism for reporting an SAE/SADE/AESI to Sponsor will be the electronic 
data capture system (EDC). The site will enter the SAE/SADE/AESI data into the electronic 
system as soon as it becomes available. If the EDC system is unavailable for a period of time 
which will not allow reporting within 24 hours, the (paper) SAE/SADE/AESI forms will be 
sent by fax to report the event within 24 hours. Contacts for SAE reporting can be found in 
the Investigator Site File. 
11.2 Adverse Event (AE)  
Adverse event means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug-related. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study intervention and does not imply any judgment of causality. 


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11.3 Device Adverse Event (AE) and Adverse Device Effect (ADE) 
The AE definition provided in Section 11.2 includes Medical Device AEs. In addition, AEs 
will be assessed, if they qualify as adverse device effects (ADE), which is defined as an AE 
related to the use of an investigational medical device. This definition includes any AE 
resulting from insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device as well as 
any event resulting from use error or from intentional misuse of the investigational medical 
device. 
11.4 Device Deficiency 
Device deficiency is defined in ISO 14155:2020 as any inadequacy in the identity, quality, 
durability, reliability, safety, or performance of an investigational device, including 
malfunction, use errors, or inadequacy in the information supplied by the manufacturer. Any 
device deficiencies observed during the drug administration procedure to clinical trial subjects 
will be documented by the sponsor, followed-up for root-cause, and included in the device 
risk assessment with an evaluation for the need to implement additional risk mitigations. 
Device deficiencies resulting in SAEs or SADEs will be reported according to regulatory 
reporting requirements described in Section 11.4.3.  
11.4.1 Time Period for Detecting Device Deficiencies 
Medical device deficiencies that result in an incident will be detected and documented, during  
the period of the study in which the medical device is used.  
Thereafter, if the investigator learns of any device deficiency at any time after a subject has 
received drug administration with the device or has been discharged from the study, and such 
a deficiency is considered reasonably related to a medical device provided for the study, the 
investigator will promptly notify the sponsor. 
11.4.2 Follow-up of Device Deficiencies 
The following principles for follow-up will be applied for device deficiencies: 
• Follow-up applies to all subjects, including those who discontinue study intervention. 
• The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
• New or updated information will be recorded on the originally completed form with 
all changes signed and dated by the investigator. 


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11.4.3 Regulatory Reporting Requirements of for Device Deficiencies  
The sponsor will report: 
1. 
Device deficiency-related SAEs and SADEs, observed either during the drug 
administration procedure or subsequently reported by investigators (see below) as 
expedited safety reports following the guidelines in Section 8.5.5. 
2. 
Non-serious AEs due to device deficiencies (including but not limited to “failure to 
treat” with the device) will be reported in the annual DSUR as part of the IND annual 
reporting requirements of 21 CFR 312.33. 
The following regulations apply for reporting of Device Deficiencies to the Sponsor: 
1. 
Any device deficiencies will be reported to the sponsor within 24 hours after the 
investigator determines that the event meets the protocol definition of a medical 
device deficiency. 
2. 
The medical device deficiency without any related AE or related to non-serious AE 
will be recorded in the corresponding EDC chapters. The investigator has to notify the 
Sponsor about a newly recorded medical device deficiency  via email or a telephone 
call. The medical device deficiencies related to SAEs, SADEs and AESIs will be 
recorded in the EDC based SAE form.  . If the EDC is unavailable, then the procedure 
described in Section 11.1 must be applied. 
3. 
The sponsor will be the contact for the receipt of device deficiency reports. 
The investigator will promptly report all SAEs or AEs suspected to be device deficiency-
related occurring post-treatment,  with any medical device provided for use in the study for 
the sponsor to fulfill the legal responsibility to notify appropriate regulatory authorities and 
other entities about certain safety information relating to medical devices being used in 
clinical studies. 
The investigator, or responsible person according to local requirements, will comply with the 
applicable local regulatory requirements relating to the reporting of SAEs or SADEs 
determined to be device deficiency-related to the IRB/IEC. 
11.5 Serious Adverse Event (SAE) 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more 
of the criteria listed (for the US CFR 312.32(a) applies): 
a. Results in death 
b. Is life-threatening 


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The term life-threatening in the definition of serious refers to an event in which the subject 
was at (immediate) risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been admitted (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as to 
whether hospitalization occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other important medical events: 
Medical or scientific judgment should be exercised by the investigator in deciding whether 
SAE reporting is appropriate in other situations such as important medical events that that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition. These events should usually be considered 
serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not 
resulting in hospitalization, or development of intervention dependency or intervention abuse. 


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According to the US FDA guidance, the determination of the categorization of an event, e.g., 
as serious or life-threatening, can be based on the opinion of either the investigator or sponsor 
(US FDA, 2012). 
11.6 Device SAE, SADE and USADE 
To allow for comparability of safety reporting across trials in the development program of 
Oxular on the Oxulumis device, also a categorization of Device SAEs following the European 
MDR will be performed (European Parliament/Council (EC) 2017). The seriousness criteria 
here are slightly different from the SAE criteria outlined in Section 11.5. 
A Medical Device SAE is any serious adverse event that led to 
a. death  
b. serious deterioration in the health of the subject, that either resulted in: 
• A life-threatening illness or injury. 
• A permanent impairment of a body structure or a body function. 
• Hospitalization or prolonged hospitalization. Planned hospitalization for a pre-existing 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE. 
• Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
• Chronic disease (European Parliament/Council (EC) 2017). 
c. Led to fetal distress, fetal death, or a congenital abnormality or birth defect 
A serious adverse device effect (SADE) is defined as an adverse device effect that has 
resulted in any of the consequences characteristic of an SAE. 
Any device deficiency that might have led to an SAE if appropriate action had not been taken, 
the intervention had not occurred, or circumstances had been less fortunate. 
An unexpected serious adverse device effect USADE (also identified as UADE in US 
Regulations 21 CFR 813.3), is defined as a serious adverse device effect that by its nature, 
incidence, severity, or outcome has not been identified in the current version of the risk 
analysis report for the device. 


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11.7  
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. The investigator will then record all relevant AE/SAE information. 
It is not acceptable for the investigator to send photocopies/digital copies of the subject’s 
medical records to Oxular Ltd. or its delegates in lieu of completion of the SAE report form. 
There may be instances when copies of medical records for certain cases are requested by 
Oxular Ltd or its delegates. In this case, all subject identifiers, except for the subject number, 
must be redacted on the copies of the medical records before sharing with Oxular Ltd. or its 
delegates. 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Investigators should use correct medical terminology/concepts when recording AEs or SAEs 
on the eCRF and/or SAE form. Colloquialisms and abbreviations should be avoided. Serious 
AEs must also be recorded on the AE eCRF. Only 1 medical concept should be recorded in 
the event field on the AE eCRF and SAE form (if applicable). 
Adverse Events Occurring Secondary to Other Events 
In general, AEs occurring secondary to other events (e.g., cascade events or clinical sequelae) 
should also be entered as separate AEs. For example, if severe diarrhea is known to have 
resulted in dehydration, both diarrhea and dehydration should be entered as AEs on the eCRF, 
and if also serious, on the SAE form.  
Persistent or Recurrent Adverse Events 
A persistent AE extends continuously, without resolution between subject evaluation time 
points. Such events should only be recorded once in the eCRF unless their severity increases. 
If a persistent AE becomes more severe or its sign or symptoms occur more frequently, the 
change in the severity grading, the date when the severity change was reported, and any new 
action taken shall be recorded in the eCRF. 
A recurrent AE occurs and resolves between subject evaluation time points and subsequently 
recurs. All recurrent AEs should be recorded individually on the AE eCRF. 
Abnormal Laboratory Values 


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Only clinically significant laboratory abnormalities will be recorded as AEs on the eCRF and 
SAE form (if applicable).  
If the laboratory abnormality can be characterized by a precise clinical term, the clinical term 
should be recorded as the AE or SAE. For example, an elevated serum potassium level of 
7.0 mEq/L should be recorded as “hyperkalemia”. 
Observations of the same clinically significant laboratory abnormality from visit to visit 
should not be repeatedly recorded as AEs on the eCRF and SAE form (if applicable), unless 
their severity, seriousness, or etiology changes.  
Deaths 
All deaths that occur during the protocol-specified AE reporting period (see Section 8.5.1), 
regardless of attribution, will be recorded on the AE eCRF and SAE form and reported to the 
Sponsor within 24 hours of event knowledge.  
When recording a death, the event or condition that caused or contributed to the fatal outcome 
should be recorded as a single medical concept. For example, if death resulted from 
respiratory failure, the AE recorded should be “Respiratory Failure”, and the outcome of the 
AE would be “Death”. If the cause of death is unknown and cannot be ascertained at the time 
of reporting, record “unexplained death” on the AE eCRF and SAE form. 
Special Situations Reporting 
Medication errors and uses outside what is foreseen in the protocol, including overdose and 
occupational exposure must be reported to the Sponsor on an AE eCRF and an SAE form for 
tracking purposes and will be considered a protocol deviation. Additional instructions 
for reporting special situation information will be provided by the Sponsor at the time of 
notification. 
11.7.1 Assessment of Intensity 
The investigator will assess the intensity (severity) for each AE and SAE reported during the 
study and assign it to one of the following categories:  
• Mild: 
A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 


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• Moderate:  
A type of adverse event that is usually alleviated with additional specific therapeutic 
intervention.  The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research subject. 
• Severe:  
A type of adverse event that interrupts usual activities of daily living, or significantly 
affects clinical status or may require intensive therapeutic intervention.   
11.7.2 Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE/device deficiency. The investigator will use clinical 
judgment to determine the relationship. 
The relationship will be determined by the Investigator according to the following criteria 
(Medical Device Coordination Group (MDCG), 2020): 
• Not related: The relationship to the intervention can be excluded. 
• Possibly related: The relationship with the intervention is weak but cannot be ruled 
out completely. Alternative causes are also possible. 
• Probably related: The relationship with the intervention seems relevant and/or the 
event cannot reasonably be explained by another cause. 
• Causally related: The serious event is associated with the intervention beyond 
reasonable doubt. 
11.7.3 Assessment of the Outcome of Adverse Events 
The Investigator will record the outcome of AEs and SAEs using the following criteria: 
 
Recovered/resolved: The subject has fully recovered from the event, with no residual 
effects observable. 
Recovered/resolved with sequelae: The subject has recovered from the event, but 
with residual sequelae effects observable. 
Not recovered/resolved: Effects of the event are still present. 
Recovering/resolving: The subject has improved but has not fully recovered from the 
event. 
Fatal: The death is related to the event. 


OXUCT-103 Clinical Trial Protocol V3.0 17-Feb-2023 
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Unknown: The outcome of the event is unknown to the reporter (e.g., the subject was 
lost to follow up). 
11.7.4 Follow-up of AEs and SAEs 
The investigator is obligated to perform or arrange for the conduct of supplemental 
assessments and/or evaluations as medically indicated or as requested by the sponsor or 
sponsor’s designee to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
SAEs unrelated to study treatment and non-serious AEs are to be followed until the last 
scheduled study visit (EOS visit), with the outcome at that point of time to be recorded in 
the eCRF. SAEs related to study treatment are to be followed up until resolution or until 
they return to baseline, stabilize, or the subject is lost to follow-up. Resolution of AEs and 
SAEs (with dates) should be documented on the AE eCRF and SAE form (if applicable) 
and in the subject’s medical record to facilitate source data verification. For some SAEs, 
the Sponsor or its designee may follow up by telephone, facsimile, electronic mail, and/or 
a monitoring visit to obtain additional case details deemed necessary to appropriately 
evaluate the SAE report (e.g., hospital discharge summary, consultant report, or autopsy 
report).  
If a subject dies during participation in the study or during a recognized follow-up period, 
the investigator will provide the sponsor or sponsor’s designee with a copy of any 
postmortem findings including histopathology.  
12 Regulatory Reporting Requirements (Serious Safety Events, Safety Reporting in 
Clinical Investigations of Medical Devices, and DSUR)  
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies (as applicable) about the safety of a study treatment under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements related 
to safety reporting to the regulatory authority, IRBs, and investigators according to the 
regulations listed in Section 8.5.5. The specific reportability criteria, reporting timelines and 
procedures for expedited reporting, cross-reporting for the investigational medicinal product 
and medical device, and submission of the Drug Safety Update Report (DSUR) will be 
outlined in the Safety Management Plan and in accordance with the regulations listed in the 
Section 8.5.5. 


OXUCT-103 Clinical Trial Protocol V3.0 17-Feb-2023 
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12.1 Suspected Unexpected Serious Adverse Reaction (SUSAR) 
For an event to be qualified as a suspected unexpected serious adverse reaction (SUSAR), the 
AE must meet three (3) criteria:  
• the event is serious,  
• there is a reasonable possibility for the event to establish a causal relationship to the 
study drug being researched (i.e., it qualifies adverse reaction), and  
• the nature and severity of the reaction are not in agreement with the product 
information and the safety information in the IB (i.e., the reaction is unexpected as per 
the reference safety information, i.e., the event is unexpected). 
All SUSARs will be reported as required to the Competent Authorities and to the Institutional 
Review Boards (IRBs). In the US, this follows the requirements laid out in the US FDA 
guidance on safety reporting (US FDA, 2012). 
Following the definitions in 21 CFR 312.32(a), an adverse event or suspected adverse reaction 
is considered “unexpected” if it is not listed in the investigator brochure, or the SmPC of 
Triesence (US Version; (Alcon Laboratories Inc., 2007) or is not listed at the specificity or 
severity that has been observed. "Unexpected," as used in this definition, also refers to 
adverse events or suspected adverse reactions that are mentioned in the investigator brochure 
as occurring with a class of drugs or as anticipated from the pharmacological properties of the 
drug but are not specifically mentioned as occurring with the particular drug under 
investigation.


OXUCT-103 Clinical Trial Protocol V3.0 15 Feb 2023 
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13 Outcome Assessments and Questionnaires 
13.1 Subject’s Experience Assessment – Day 0, Visit 2 
Subject’s Experience Assessment: 
Current and Procedure Pain & Discomfort 
 
To be completed by the Site Interviewer 
 
Site Number 
 
Subject number 
 
Date 
 
Visit number  
Day 0 / Visit 2 
Interviewer / completed by 
(print name) 
 
 
Instructions for the site interviewer: Ask the study to subject the questions below after the 
60 minutes post-procedure observation period.  
Questions should be asked at any time after the 60 minutes post-procedure observation period 
and separated by at least five minutes from the completion of any post treatment measurement 
(e.g., OCT, IOP, etc.). Indicate the study subject’s response by checking one response for 
each question. 
Instructions for the subject (to be read to the subject by the interviewer): Please answer the 
following questions about your experience of the procedure with the Oxulumis® device.   
 
Question 1: Are you currently experiencing pain in the procedure eye?  
☐ Yes 
☐ No  
Question 2: Rate your current level of pain in your procedure eye on a scale of 1 – 5 
☐ (1) No Pain 
☐ (2) Minimal Pain 
☐ (3) Mild Pain 
☐ (4) Moderate Pain 
☐ (5) Severe Pain 


OXUCT-103 Clinical Trial Protocol V3.0 17-Feb-2023 
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Question 3: Rate your pain during the procedure on a scale of 1 – 5 
☐ (1) No Pain 
☐ (2) Minimal Pain 
☐ (3) Mild Pain 
☐ (4) Moderate Pain 
☐ (5) Severe Pain 
Question 4 Rate your pain after completion of the procedure on a scale of 1 – 5 
☐ (1) No Pain 
☐ (2) Minimal Pain 
☐ (3) Mild Pain 
☐ (4) Moderate Pain 
☐ (5) Severe Pain 
Question 5: Are you currently experiencing discomfort in the procedure eye?  
☐ Yes  
☐ No  
Question 6: Rate your current level of discomfort in your procedure eye on a scale of 1 – 5 
☐ (1) No Discomfort 
☐ (2) Minimal Discomfort 
☐ (3) Mild Discomfort 
☐ (4) Moderate Discomfort 
☐ (5) Severe Discomfort 
Question 7: Rate your discomfort during the procedure on a scale of 1 – 5  
☐ (1) No Discomfort 
☐ (2) Minimal Discomfort 
☐ (3) Mild Discomfort 
☐ (4) Moderate Discomfort 
☐ (5) Severe Discomfort 


OXUCT-103 Clinical Trial Protocol V3.0 17-Feb-2023 
Oxular Limited 
 
Confidential 
page 96 of 111 
Question 8: Rate your discomfort after completion of the procedure on a scale of 1 – 5  
☐ (1) No Discomfort 
☐ (2) Minimal Discomfort 
☐ (3) Mild Discomfort 
☐ (4) Moderate Discomfort 
☐ (5) Severe Discomfort 
 
Signature of site-
interviewer 
 
Date 
 
 
 


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page 97 of 111 
13.2 Subject’s Experience Assessment – Day 1, Visit 3 through Week 4, Visit 5 
Subject’s Experience Assessment: 
Current and Procedure Pain & Discomfort 
 
To be completed by the Site Interviewer 
 
Site Number 
 
Subject number 
 
Date 
 
Visit number (circle one) 
☐ Day 1 (Visit 3) 
☐ Day 7 (Visit 4) 
☐ Day 30 (Visit 5) 
Interviewer / completed by (print name) 
 
 
Instructions for site interviewer: Ask the study to subject the questions below. Questions can 
be asked at any time during the study visit and separated by at least five minutes from the 
completion of any post treatment measurement (e.g., OCT, IOP, etc.). Indicate the study 
subject’s response by checking one response for each question. 
Instructions for study subject (to be read to the subject by the interviewer): Please answer the 
following questions about your current level of pain and discomfort in the eye which received 
the study treatment.   
Question 1: Are you currently experiencing pain in the procedure eye?  
☐ Yes 
☐ No  
Question 2: Rate your current level of pain in your procedure eye on a scale of 1 – 5 
☐ (1) No Pain 
☐ (2) Minimal Pain 
☐ (3) Mild Pain 
☐ (4) Moderate Pain 
☐ (5) Severe Pain 
Question 3: Are you currently experiencing discomfort in the procedure eye?  
☐ Yes  
☐ No  


OXUCT-103 Clinical Trial Protocol V3.0 17-Feb-2023 
Oxular Limited 
 
Confidential 
page 98 of 111 
Question : Rate your current level of discomfort in your procedure eye on a scale of 1 – 5 
☐ (1) No Discomfort 
☐ (2) Minimal Discomfort 
☐ (3) Mild Discomfort 
☐ (4) Moderate Discomfort 
☐ (5) Severe Discomfort 
 
 
Signature of site-
interviewer 
 
Date 
 
 


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OXUCT-103 Clinical Trial Protocol V3.0 15 Feb 2023 
Oxular Limited 
 
Confidential 
page 110 of 111 
 
14 References 
Alcon Laboratories Inc. 2007. 'TRIESENCE™ (triamcinolone acetonide injectable 
suspension) 40 mg/mL - US Prescribing Information': 1-12. 
Bandoli, G., K. Palmsten, C. J. Forbess Smith, and C. D. Chambers. 2017. 'A Review of 
Systemic Corticosteroid Use in Pregnancy and the Risk of Select Pregnancy and Birth 
Outcomes', Rheum Dis Clin North Am, 43: 489-502. 
Barakat, M. R., C. C. Wykoff, V. Gonzalez, A. Hu, D. Marcus, E. Zavaleta, and T. A. Ciulla. 
2021. 'Suprachoroidal CLS-TA plus Intravitreal Aflibercept for Diabetic Macular 
Edema: A Randomized, Double-Masked, Parallel-Design, Controlled Study', 
Ophthalmol Retina, 5: 60-70. 
Boyer, D. S., Y. H. Yoon, R. Belfort, Jr., F. Bandello, R. K. Maturi, A. J. Augustin, X. Y. Li, 
H. Cui, Y. Hashad, S. M. Whitcup, and Mead Study Group Ozurdex. 2014. 'Three-
year, randomized, sham-controlled trial of dexamethasone intravitreal implant in 
patients with diabetic macular edema', Ophthalmology, 121: 1904-14. 
Campochiaro, P. A., C. C. Wykoff, D. M. Brown, D. S. Boyer, M. Barakat, D. Taraborelli, G. 
Noronha, and Group Tanzanite Study. 2018. 'Suprachoroidal Triamcinolone 
Acetonide for Retinal Vein Occlusion: Results of the Tanzanite Study', Ophthalmol 
Retina, 2: 320-28. 
Chang, T. S. 2009. 'Suprachoroidal Drug Delivery via Catheter: A Medico-Surgical Approach 
to Wet AMD', Retina Summit 2009 Abstract Book: 1-5. 
Clinical Trials Facilitation and Coordination Group. 2020. 'Recommendations related to 
contraception and pregnancy testing in clinical trials', Heads of Medicines Agencies 
Homepage: 1-10. 
Ehlers, J. P., S. Yeh, M. G. Maguire, J. R. Smith, P. Mruthyunjaya, N. Jain, L. A. Kim, C. Y. 
Weng, C. J. Flaxel, S. D. Schoenberger, and S. J. Kim. 2022. 'Intravitreal 
Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy 
of Ophthalmology', Ophthalmology, 129: 88-99. 
European Parliament/Council (EC). 2017. 'REGULATION (EU) 2017/745 OF THE 
EUROPEAN PARLIAMENT AND OF THE COUNCIL on medical devices', Official 
Journal of the European Union: 1-175. 
Medical Device Coordination Group (MDCG). 2020. 'Safety reporting in clinical 
investigations of medical devices under the Regulation (EU) 2017/745': 1-16. 
Olsen, T. W., X. Feng, K. Wabner, S. R. Conston, D. H. Sierra, D. V. Folden, M. E. Smith, 
and J. D. Cameron. 2006. 'Cannulation of the suprachoroidal space: a novel drug 
delivery methodology to the posterior segment', Am J Ophthalmol, 142: 777-87. 
Patel, S. R., D. E. Berezovsky, B. E. McCarey, V. Zarnitsyn, H. F. Edelhauser, and M. R. 
Prausnitz. 2012. 'Targeted administration into the suprachoroidal space using a 
microneedle for drug delivery to the posterior segment of the eye', Invest Ophthalmol 
Vis Sci, 53: 4433-41. 
Pearce, W., J. Hsu, and S. Yeh. 2015. 'Advances in drug delivery to the posterior segment', 
Curr Opin Ophthalmol, 26: 233-9. 
Price, K. W., T. A. Albini, and S. Yeh. 2020. 'Suprachoroidal Injection of Triamcinolone- 
Review of a Novel Treatment for Macular Edema Caused by Noninfectious Uveitis', 
US Ophthalmic Rev, 13: 76-79. 
Qamar, R. M., M. I. Saleem, and M. F. Saleem. 2013. 'Comparison of the efficacy between an 
intravitreal and a posterior subtenon injection of triamcinolone acetonide for the 
treatment of diffuse diabetic macular edema', Eurasian J Med, 45: 185-90. 
Qi, H. P., S. Bi, S. Q. Wei, H. Cui, and J. B. Zhao. 2012. 'Intravitreal versus subtenon 
triamcinolone acetonide injection for diabetic macular edema: a systematic review and 
meta-analysis', Curr Eye Res, 37: 1136-47. 


OXUCT-103 Clinical Trial Protocol V3.0 17-Feb-2023 
Oxular Limited 
 
Confidential 
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Rittiphairoj, T., T. A. Mir, T. Li, and G. Virgili. 2020. 'Intravitreal steroids for macular edema 
in diabetes', Cochrane Database Syst Rev, 11: CD005656. 
Rizzo, S., F. G. Ebert, E. D. Bartolo, F. Barca, F. Cresti, C. Augustin, and A. Augustin. 2012. 
'Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates', 
Retina, 32: 776-84. 
Shah, J., A. Vaze, T. Tang Lee Say, M. C. Gillies, and S. Fraser-Bell. 2020. 'Emerging 
corticosteroid delivery platforms for treatment of diabetic macular edema', Expert 
Opin Emerg Drugs, 25: 383-94. 
Tetz, M., S. Rizzo, and A. J. Augustin. 2012. 'Safety of submacular suprachoroidal drug 
administration via a microcatheter: retrospective analysis of European treatment 
results', Ophthalmologica, 227: 183-9. 
Udaondo, P., A. Adan, L. Arias-Barquet, F. J. Ascaso, F. Cabrera-Lopez, V. Castro-Navarro, 
J. Donate-Lopez, A. Garcia-Layana, F. J. Lavid, M. Rodriguez-Maqueda, and J. M. 
Ruiz-Moreno. 2021. 'Challenges in Diabetic Macular Edema Management: An Expert 
Consensus Report', Clin Ophthalmol, 15: 3183-95. 
US FDA. 2012. 'Safety Reporting Requirements for INDs and BA/BE Studies - Guidance for 
Industry and Investigators': 1-32. 
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and Devices  - (Draft) Guidance for Industry': 1-14. 
US FDA. 2021b. 'Sponsor Responsibilities - Safety Reporting Requirements and Safety 
Assessment for IND and Bioavailability/Bioequivalence Studies - Draft Guidance for 
Industry': 1-44. 
Wilkins, C. S., E. K. Sobol, G. M. Lema, J. G. Lee, R. B. Rosen, and A. Deobhakta. 2021. 
'Intravitreal dexamethasone insert in diabetic macular edema super-refractory to anti-
vascular endothelial growth factor therapy', Eur J Ophthalmol: 11206721211004391. 
Wykoff, C. C., R. N. Khurana, S. I. R. Lampen, G. Noronha, D. M. Brown, W. C. Ou, S. R. 
Sadda, and Hulk Study Group. 2018. 'Suprachoroidal Triamcinolone Acetonide for 
Diabetic Macular Edema: The HULK Trial', Ophthalmol Retina, 2: 874-77. 
Yeh, S., R. N. Khurana, M. Shah, C. R. Henry, R. C. Wang, J. M. Kissner, T. A. Ciulla, G. 
Noronha, and Peachtree Study Investigators. 2020. 'Efficacy and Safety of 
Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: 
Phase 3 Randomized Trial', Ophthalmology, 127: 948-55. 
Zur, D., M. Iglicki, and A. Loewenstein. 2019. 'The Role of Steroids in the Management of 
Diabetic Macular Edema', Ophthalmic Res, 62: 231-36. 
 

SAP_001.pdf: 
  Statistical Analysis Plan v1.0
 OXUCT-103 Clinical Trial 
Clinical Trial Identifier:  OXUCT-103 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
SAP Date: 22 Jan 2024 
Page 1 of 35 
OXUCT-103 “CAPE” 
Clinical Trial   
Statistical Analysis Plan v1.0 
Clinical Trial Protocol Title:
A Multi-Center, Randomized, Two-Arm, Parallel-Group, Single-masked, 24-week, Clinical 
Trial to Evaluate Safety and Tolerability of Two Dose Levels of Suprachoroidal Triamcinolone 
Acetonide Administered with the Oxulumis® Ophthalmic Administration Device in Subjects 
with Diabetic Macular Edema
Clinical Trial Reference Number: OXUCT-103
ClinicalTrials.gov Identifier: NCT05512962
Investigational Product Name:
Triamcinolone acetonide via suprachoroidal delivery with the Oxulumis® device in DME


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 2 of 35 
 
Table of Contents 
1. 
List of Abbreviations ........................................................................................................................ 6 
2. 
Administrative Trial Information ..................................................................................................... 8 
2.1. 
Clinical Trial ............................................................................................................................. 8 
2.1.1. 
Document Description ..................................................................................................... 8 
2.2. 
Clinical Trial Registration Information ..................................................................................... 8 
2.3. 
SAP Version.............................................................................................................................. 8 
2.3.1. 
SAP Revision History ........................................................................................................ 8 
2.4. 
Roles and Responsibilities ....................................................................................................... 9 
2.5. 
Document Approval ................................................................................................................ 9 
3. 
Introduction ................................................................................................................................... 10 
3.1. 
Study Background and Rationale .......................................................................................... 10 
3.2. 
Investigational Product.......................................................................................................... 10 
3.2.1. 
Risks / Benefits .............................................................................................................. 11 
3.3. 
Objectives .............................................................................................................................. 11 
3.3.1. 
Primary Objective and Endpoints .................................................................................. 11 
3.3.2. 
Exploratory Objectives and Endpoints .......................................................................... 11 
4. 
Study Methods .............................................................................................................................. 12 
4.1. 
Trial Design ............................................................................................................................ 12 
4.1.1. 
Trial Flow Chart.............................................................................................................. 13 
4.2. 
Methods to Minimize Bias ..................................................................................................... 13 
4.2.1. 
Randomization ............................................................................................................... 13 
4.2.2. 
Masking Procedures ...................................................................................................... 14 
4.2.3. 
Unmasking Procedures .................................................................................................. 14 
4.3. 
Sample Size ............................................................................................................................ 14 
4.4. 
Timing of Final Analysis ......................................................................................................... 14 
5. 
Trial Subjects ................................................................................................................................. 14 
5.1. 
Subject Disposition ................................................................................................................ 14 
5.2. 
Definition of Compliance and Assessment ............................................................................ 15 
5.3. 
Definition of Protocol Deviation ............................................................................................ 15 
5.3.1. 
Protocol Deviations ....................................................................................................... 15 
6. 
Analysis Populations ...................................................................................................................... 15 
6.1. 
Safety Analysis Population .................................................................................................... 16 
6.2. 
Exploratory Analysis Population ............................................................................................ 16 
6.3. 
Eligibility and Withdrawal Criteria ......................................................................................... 16 
6.3.1. 
Inclusion Criteria ............................................................................................................ 16 
6.3.2. 
Exclusion Criteria ........................................................................................................... 17 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 3 of 35 
6.3.3. 
Study Discontinuation ................................................................................................... 18 
6.3.4. 
Assessment for Follow-On Treatment and End of Study .............................................. 19 
7. 
Statistical Methods and Analysis ................................................................................................... 19 
7.1. 
Hypothesis ............................................................................................................................. 19 
7.2. 
Safety Analyses ...................................................................................................................... 20 
7.2.1. 
Primary Endpoint ........................................................................................................... 20 
7.3. 
Exploratory Analysis .............................................................................................................. 20 
7.3.1. 
Exploratory Efficacy (and/or Safety) Endpoints ............................................................ 20 
7.3.2. 
Analytical Procedures for the Exploratory Efficacy (and/or Safety) Endpoints ............. 21 
7.4. 
Confidence Intervals .............................................................................................................. 21 
7.5. 
Other Analyses and Statistical Considerations ...................................................................... 22 
7.5.1. 
Calculations or Transformations Used to Derive the Outcome .................................... 22 
7.5.2. 
Alternative Methods for Distributional Assumptions ................................................... 22 
7.5.3. 
Sensitivity Analysis Plan ................................................................................................. 22 
7.5.4. 
Interim Statistical Analysis ............................................................................................. 22 
7.6. 
Missing Data .......................................................................................................................... 22 
7.7. 
Adjustment for Multiplicity and Type 1 Error Control .......................................................... 22 
7.8. 
Non-Standard Statistical Methods ........................................................................................ 22 
7.9. 
Statistical Software ................................................................................................................ 22 
8. 
Presentation of Patient Data and Other Evaluations .................................................................... 22 
8.1. 
Screening Data ....................................................................................................................... 22 
8.2. 
Screening and Baseline Patient Characteristics .................................................................... 22 
8.3. 
Medical History...................................................................................................................... 23 
8.4. 
Concomitant Medication or Procedure ................................................................................. 23 
8.5. 
Physical Examination and Vital Signs..................................................................................... 23 
8.6. 
Laboratory Tests .................................................................................................................... 23 
8.6.1. 
Non-fasting Chemistry, Hematology and Thyroid Parameters ..................................... 23 
8.7. 
Reasons, Details and Timing of Withdrawal/Lost to Follow-Up Data ................................... 23 
9. 
Data Management and Other Procedures .................................................................................... 24 
9.1.1. 
Clinical Data Management Plan and Data Quality Assurance ....................................... 24 
9.1.2. 
Other Standard Operating Procedures and/or Documents .......................................... 24 
10. References ..................................................................................................................................... 24 
11. Appendix 1 – Study Schedule (Assessments and Procedures) ...................................................... 25 
12. Appendix 2 – General Conventions ............................................................................................... 27 
13. Appendix 3 – CONSORT Flow Diagram .......................................................................................... 28 
14. Appendix 4 – Tables, Figures and Graphs...................................................................................... 29 
14.1. Populations and Demographic Data ...................................................................................... 29 
14.1.1. 
Disposition of Subjects .................................................................................................. 29 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 4 of 35 
14.1.2. 
Study Populations .......................................................................................................... 29 
14.1.3. 
Demographics: Overall and by Treatment Dose for the SAF Population ...................... 29 
14.1.4. 
Vital Signs and Anthropometry by Treatment Dose for the SAF population ................ 29 
14.2. Medical History...................................................................................................................... 29 
14.2.1. 
Non-Ophthalmic Medical History by Treatment Dose for the SAF Population ............. 29 
14.2.2. 
Ophthalmic Medical History by Treatment Dose for the SAF Population ..................... 29 
14.3. Concomitant Medication and Concomitant Procedure by Treatment Dose for the SAF 
Population ......................................................................................................................................... 29 
14.3.1. 
Non-Ocular Concomitant Medications and Procedures by Treatment Dose ................ 29 
14.3.2. 
Ocular Concomitant Medications and Procedures by Treatment Dose and by Eye ..... 30 
14.4. Ocular Examination for the SAF Population .......................................................................... 30 
14.4.1. 
Lens Examination by Treatment Dose and by Visit ....................................................... 30 
14.4.2. 
IOP Measurement by Treatment Dose and by Visit ...................................................... 30 
14.5. Study Medication Administration by Treatment Dose.......................................................... 30 
14.5.1. 
For the SAF Population .................................................................................................. 30 
14.5.2. 
For the EEP Population .................................................................................................. 30 
14.5.3. 
For the PP Population .................................................................................................... 30 
14.6. Retinal Physician’s Documentation and Assessment of Administration – SAF Population .. 31 
14.6.1. 
Operative Assessment ................................................................................................... 31 
14.6.2. 
Type of Anesthesia Given .............................................................................................. 31 
14.6.3. 
Execution of Oxulumis® Procedure ............................................................................... 31 
14.6.4. 
Insertion Point ............................................................................................................... 31 
14.6.5. 
Deployment ................................................................................................................... 31 
14.6.6. 
Injection of Drug Via the Drug Line ............................................................................... 31 
14.6.7. 
Bleeding ......................................................................................................................... 31 
14.7. Retinal Physician’s Documentation and Assessment of Administration – EEP Population .. 31 
14.7.1. 
Operative Assessment ................................................................................................... 31 
14.7.2. 
Type of Anesthesia Given .............................................................................................. 32 
14.7.3. 
Execution of Oxulumis® Procedure ............................................................................... 32 
14.7.4. 
Insertion Point ............................................................................................................... 32 
14.7.5. 
Deployment ................................................................................................................... 32 
14.7.6. 
Injection of Drug Via the Drug Line ............................................................................... 32 
14.7.7. 
Bleeding ......................................................................................................................... 32 
14.8. Retinal Physician’s Documentation and Assessment of Administration – PP Population .... 32 
14.8.1. 
Operative Assessment ................................................................................................... 32 
14.8.2. 
Type of Anesthesia Given .............................................................................................. 32 
14.8.3. 
Execution of Oxulumis® Procedure ............................................................................... 33 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 5 of 35 
14.8.4. 
Insertion Point ............................................................................................................... 33 
14.8.5. 
Deployment ................................................................................................................... 33 
14.8.6. 
Injection of Drug Via the Drug Line ............................................................................... 33 
14.8.7. 
Bleeding ......................................................................................................................... 33 
14.9. Patient Experience Assessment by Treatment Dose and by Visit for the SAF Population .... 33 
14.10. Safety Data ............................................................................................................................ 33 
14.10.1. Non-ocular Adverse Events for the SAF Population ...................................................... 33 
14.10.2. Ocular Adverse Events by Treatment Dose and Device Lots for the SAF Population ... 34 
14.11. Exploratory Data by Treatment Dose and by Visit ................................................................ 34 
14.11.1. Exploratory Data for the EEP Population – Efficacy/Safety ........................................... 34 
14.11.2. Exploratory Data for the PP Population – Efficacy/Safety............................................. 35 
14.12. Follow-On by Treatment Dose by Visit for the SAF Population ............................................ 35 
 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 6 of 35 
1. 
List of Abbreviations 
Term 
Definition / Description 
ADE  
Adverse Device Effect 
AE  
Adverse Event 
AESI 
Adverse Event of Special Interest 
Anti-VEGF  
Anti-Vascular Growth Factor 
AMD  
Age-Related Macular Degeneration 
BCVA  
Best Corrected Visual Acuity 
BM 
Biomicroscopy 
CFP  
Color Fundus Photography 
CNV  
Choroidal Neovascularization 
CRF  
Case Report Form 
CRO  
Contract Research Organization 
CST  
Central Subfield Thickness 
CTP  
Clinical Trial Protocol 
DME  
Diabetic Macular Edema 
EDC  
Electronic Data Capture 
EMA  
European Medicines Agency 
EoS  
End of Study 
ETDRS  
Early Treatment Diabetic Retinopathy Study 
GCP  
Good Clinical Practice 
GLP  
Good Laboratory Practice 
HR  
High Resolution 
IB  
Investigator Brochure 
ICF  
Informed Consent Form 
ICH  
International Conference on Harmonization 
IFU  
Instruction for Use 
IOP  
Intraocular Pressure 
IRB  
Institutional/Independent Review Board 
ISO  
International Organization for Standards 
IVT 
Intravitreal 
MedDRA   
Medical Dictionary for Regulatory Activities 
ME  
Macular Edema 
OCT-A  
Optical Coherence Tomography Angiography 
OU  
Oculus Uterque – Both Eyes 
PDR  
Proliferative Diabetic Retinopathy 
PRP  
Panretinal Photocoagulation 
SAE  
Serious Adverse Event 
SADE  
Serious Adverse Device Effect 
SAP 
Statistical Analysis Plan 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 7 of 35 
SD-OCT  
Spectral Domain Optical Coherence Tomography 
SE  
Study Eye 
SUSAR  
Serious and Unexpected Suspected Adverse Reaction 
TA  
Triamcinolone Acetonide 
TEAE  
Treatment Emergent Non-Serious Adverse Effect 
UADE  
Unanticipated Adverse Device Effect 
US FDA  
United States Food and Drug Administration 
VEGF  
Vascular Endothelial Growth Factor 
 
 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 8 of 35 
2. 
Administrative Trial Information 
2.1. 
Clinical Trial 
The purpose of this twenty-four (24) week, randomized, two-arm, single-masked, clinical trial to 
evaluate safety, tolerability, and to explore the efficacy of two dose levels of suprachoroidal 
triamcinolone acetonide (TA) suspension (Triesence®, 2.4 mg, and 4.0mg) administered using the 
Oxulumis® ophthalmic administration device in subjects with pre-treated Diabetic Macular Edema. 
2.1.1. Document Description 
This document describes the Statistical Analysis Plan (SAP) for the OXUCT-103 “OXEYE” clinical trial “A 
Multi-Center, Randomized, Two-Arm, Parallel-Group, Single-masked, 24-week, Clinical Trial to 
Evaluate Safety and Tolerability of Two Dose Levels of Suprachoroidal Triamcinolone Acetonide 
Administered with the Oxulumis® Ophthalmic Administration Device in Subjects with Diabetic Macular 
Edema”. 
The purpose of this SAP is to provide a description of the statistical methods and procedures to be 
implemented for the analysis of data from the OXUCT-103 clinical trial. This document is based on the 
OXUCT-103 Clinical Trial Protocol v3.0 17 Feb 2023. 
2.2. 
Clinical Trial Registration Information 
Branded Name:   
 
CAPE 
Protocol Number: 
 
OXUCT-103 
Protocol Version:  
 
3.0 
Protocol Date:  
 
17 Feb 2023 
ClinicalTrials.gov Identifier: 
NCT05512962 
EudraCT No.: 
 
 
2022-001533-37 
Clinical Phase:  
 
II 
Sponsor:  
 
 
Oxular Ltd. 
2.3. 
SAP Version 
Version:  
 
 
1.0 
Date:   
 
 
22 Jan 2024 
2.3.1. SAP Revision History 
2.3.1.1. SAP Version  
This is the first version of the OXUCT-103 SAP and as such no revisions to this version of the SAP have 
been made. 
 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 9 of 35 
2.4. 
Roles and Responsibilities 
Lead SAP Writer: 
Urosh Vilimanovich, PhD 
Lead SAP Writer 
Wemedoo AG 
Lead Statistician: 
Ivan Soldatovic, MD, PhD 
Lead Statistician 
Wemedoo AG 
Sponsor’s Representative and 
Clinical Lead: 
PD Dr. med. Friedrich Asmus, MD  
Chief Medical Officer  
Oxular Ltd. 
 
2.5. 
Document Approval 
The Statistical Analysis Plan for the OXUCT-103 Clinical Trial has been approved by: 
 
Date:    
 
 
 
 
 
_____________________________________ 
Urosh Vilimanovich, PhD 
Lead SAP Writer 
Wemedoo AG 
Date:    
 
 
 
 
 
_____________________________________ 
Ivan Soldatovic, MD, PhD 
Lead Statistician 
Wemedoo AG 
 
 
 
 
 
 
Date:    
 
 
 
 
 
_____________________________________ 
PD Dr. med. Friedrich Asmus, MD 
Chief Medical Officer  
Oxular Ltd. 
 
 
 
 
1/23/2024
1/23/2024
1/23/2024


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 10 of 35 
3. 
Introduction 
The OXUCT-103 “CAPE” clinical trial is a multi-center, randomized, two-arm, parallel-group, 
single‑masked, 24-week, clinical trial to evaluate safety and tolerability of two dose levels of 
suprachoroidal triamcinolone acetonide (Triesence®) administered with the Oxulumis® ophthalmic 
administration device in subjects with previously treated diabetic macular edema. 
3.1. 
Study Background and Rationale 
There remains a high unmet need for a safe and efficacious treatment for DME in selected patients. 
Currently approved treatments including intravitreal (IVT) steroid implants or IVT anti-VEGF 
treatments in DME may not show satisfactory and/or sustained enough improvement of the macular 
edema and of vision (Wilkins et al., 2021; Ehlers et al. 2022). With existing ophthalmic steroid 
treatments, visual benefits may be compromised by meaningful side effects, which often trigger 
additional drug treatments or even ocular surgeries, e.g., intraocular lens replacement surgery (Boyer 
et al., 2014; Ehlers et al., 2022). Accordingly, there continue to be significant treatment challenges for 
the heterogenous population of patients with DME (Udaondo et al., 2021; Zur, Iglicki, and Loewenstein, 
2019). 
The current clinical trial evaluates a novel microcatheterization approach for steroid administration to 
the posterior suprachoroidal space. This approach has the potential to address challenges with respect 
to critical adverse events, efficacy, and durability of treatment compared to other currently applied 
treatment options, e.g., subtenon, or IVT administration of the same ophthalmic steroid suspension. 
Drug delivery is achieved via a low-volume (60µl, or 100µl) administration of triamcinolone acetonide 
suspension (Triesence®). The current trial evaluates two different dose levels to initially explore the 
safety of different administration volumes. The low dose is 2.4mg triamcinolone acetonide (60μl of the 
40mg/ml suspension). The mid-dose is 4.0mg TA (100μl of the 40mg/ml suspension). 
It is anticipated that posterior deployment of the drug in the suprachoroidal space, closer to the 
location of the disease activity compared to other treatment approaches, will show advantages in 
respect to safety, tolerability and therapeutic effects compared to IVT or subtenon administration. 
Local concentrations of TA in the retinal tissues are expected to be higher with posterior 
suprachoroidal administration compared to the same doses administered by IVT or subtenon injection. 
3.2. 
Investigational Product 
The Oxulumis® ophthalmic administration device is a sterile, semi-automatically operated, minimally 
invasive, single-use device. It is designed to deploy a therapeutic drug via a delivery-guiding illuminated 
ophthalmic microcatheter to ophthalmic compartments, e.g., to the suprachoroidal space. The 
illumination provides confirmation that the microcatheter is deployed correctly, prior to 
administration of the therapeutic drug. With a 27G insertion needle and an 7mm microcatheter, the 
Oxulumis® administration device is well suited to administer suspensions of drugs like Triesence® to 
the posterior retina. For the Oxulumis® administration procedure, subjects may receive topical 
anesthetics (e.g., anesthetic eye drops, gels, local subconjunctival, or subtenon anesthetic injections) 
to reduce potential pain and discomfort during the procedure. As for IVT injections, antiseptic 
conditions shall be applied following the standard procedures at the investigational site. Details about 
the Oxulumis® device and the ophthalmic administration are available in the Instruction for Use (IFU) 
manual.  
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 11 of 35 
3.2.1. Risks / Benefits 
To date, only a limited number of patients with ME have been treated with Triesence® administered 
with the Oxulumis®, limiting the ability to establish a robust benefit/risk profile. However, so far, no 
severe, serious adverse events or serious adverse device effects have been reported. 
The combination of the Oxulumis® plus triamcinolone acetonide suspension (Triesence®) used in the 
current trial is expected to address high unmet medical need to:  
1. Reduce the risk of steroid-induced complications and adverse events. 
2. Enhance the efficacy of triamcinolone acetonide suspension compared to IVT administration. 
3. Prolong the efficacy of triamcinolone acetonide suspension compared to IVT administration. 
Theoretical class risks associated with the suprachoroidal administration procedure include: 
endophthalmitis, choroidal hemorrhages, choroidal effusion, retinal penetration, and retinal 
detachment, amongst others. The atraumatic design, a tangential angle of approach for device 
insertion (not perpendicular to the sclera and not pointing to the vitreous cavity), and the 7mm length 
of the microcatheter, together with the rounded ball-like catheter tip, as well as control over the speed 
of the microcatheter deployment by adjustment of the Oxulumis® are design elements expected to 
prevent or substantially limit the risk of the adverse events summarized above. 
3.3. 
Objectives  
As per protocol, the OXUCT-103 “CAPE” clinical trial has defined a primary objective and a series of 
exploratory objectives. 
3.3.1. Primary Objective and Endpoints 
The primary objective of the OXUCT-103 “CAPE” clinical trial is to evaluate the safety and tolerability 
of two dose levels of triamcinolone acetonide administered with the Oxulumis® to the suprachoroidal 
space in subjects with DME. 
The primary outcome will be assessed by observing the frequency of ocular and systemic adverse 
events (treatment-emergent serious adverse events [SAEs] and treatment-emergent non-serious 
adverse events [TEAEs]), as well as the frequency of adverse device effects (ADEs, serious ADEs 
[SADEs]). 
3.3.2. Exploratory Objectives and Endpoints 
The exploratory objectives for the OXUCT-103 “CAPE” clinical trial include: 
• 
exploring the efficacy of two dose levels of triamcinolone acetonide with respect to changes 
in best-corrected visual acuity BCVA, edema control, and durability of the treatment effect of 
suprachoroidal triamcinolone acetonide suspension (Triesence®) In subjects with DME. 
• 
performing exploratory device evaluation in terms of device administration and IOP change 
safety issues. 
The exploratory objective will be assessed by the following endpoints: 
Efficacy: 
1. Mean Change in BCVA (ETDRS) at all study visits through Week 24 compared to baseline. 
2. Percentage of subjects with vision gain and vision loss of at least 5, at least 10, and at least 15 
letters at all study visits through Week 24 compared to baseline. 
3. Time to subjects requiring follow-on treatment. 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 12 of 35 
4. Mean Change in Central subfield thickness (CST) at all study visits through Week 24 compared 
to baseline. 
5. Mean Change in IOP at all study visits through Week 24 compared to baseline. 
Further SAP defined endpoints: 
6. Time to improvement of BCVA from baseline by at least 5, at least 10, and at least 15 letters. 
7. Duration of maintained improvement of BCVA of at least 5, at least 10, or at least 15 letters, 
where maintained improvement is defined as improvement over at least 4 weeks (= 2 
consecutive visits with a 4-week interval). 
8. Percentage of subjects with improvement from baseline CST by at least 10%, by at least 25µm, 
by at least 50µm, and by at least 75µm. 
9. Percentage of subjects with increase of intraocular pressure of at least 5mmHg, at least 
10mmHg, and at least 30 mmHg, at all study visits through Week 24 compared to baseline. 
10. Course of IOP through the first 60 minutes after administration of study drug and percentage 
of subjects with normal IOP at the end of the baseline visit. 
11. Percentage of subject with elevated IOP from baseline by at least 10mmHg at timepoints of 
more than 60min after completion of study treatment. 
12. Course of pain and discomfort scores after completion of study administration, as assessed in 
the Subject Experience Assessment questionnaires for Pain and Discomfort. 
13. Overview of the Physician Experience in Administration of Study Treatment based on the 
Retinal Physician’s Documentation and Assessment of Administration questionnaire. 
4. 
Study Methods 
4.1. 
Trial Design 
The OXUCT-103 trial is a phase II, twenty-four (24) week, randomized, two-arm, single-masked, clinical 
trial. The focus of this trial is to evaluate the feasibility, safety, and tolerability of the ophthalmic 
administration of a low and a mid-dose of suprachoroidal triamcinolone acetonide suspension 
(Triesence®) with the Oxulumis® in DME. In addition, for the two dose groups of the trial, efficacy data 
on visual and anatomic changes will be collected. The clinical trial was conducted by retinal specialists 
in clinics or academic hospitals in the United States at 6 investigational sites. 
With protocol amendment no. 2 (protocol version 3.0, dated 17 Feb 2023) a 2nd variant for the 
Oxulumis® procedure was introduced. The initial choice of the procedural variant is based on the 
expert assessment of the investigator at the screening visit, the procedure can either be performed:   
a) in an in-clinic setting first. In case the study treatment cannot be administered in this setting, the 
investigator can perform the procedural variant with a conjunctival/tenon incision. Activities for 
Visit 2 need to be completed within 14 days   
b) at the discretion of the investigator, the procedure can be performed directly in an 
operating/procedure room, if the procedural variant with the conjunctival/tenon incision is 
likely to be needed.  
An operating/procedure room will allow for the setting for a conjunctival/tenon incision, which is 
typically not performed in an in-office setting. 
After a screening period, approximately 20 eligible DME subjects will be randomized and treated 
(updated with protocol version 3.0) using a 1:1 ratio to receive a single administration of one of two 
dose levels of TA (low dose, 2.4mg. or mid-dose, 4.0mg, respectively). Only one (1) eye will be 
determined as the study eye and only the study eye will receive a single administration of study drug. 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 13 of 35 
Study eyes need to meet all inclusion criteria and none of the exclusion criteria. Treatment of the fellow 
eye is not considered part of the study treatment. The follow-up period after treatment administration 
will be up to twenty-four (24) weeks. Clinical visits will occur on Day 0, Day 1, Week 1, Week 4, and 
then every four (4) weeks thereafter for a total of twenty-four (24) weeks.  
From Week 4 on, subjects will be assessed for their need for follow-on treatment. 
If subjects show a need for the next treatment of DME according to pre-specified criteria, participation 
in this clinical investigation will end, and an (early termination) end of the study visit will be conducted 
at the respective visit date. In this case, the follow-up period will be shorter than 24 weeks. After 
completion of participation in this clinical trial, patients will continue treatment with therapeutic 
options determined by the treating retinal specialists in accordance with current medical practice for 
their DME. 
4.1.1. Trial Flow Chart 
The trial has been planned with up to 10 study visits, including the screening and baseline visit, over a 
period of 24 weeks (in addition to up to three weeks of screening). If administration of study treatment 
requires two treatment sessions, i.e. administration cannot be completed in the 1st session “in-clinic” 
and a 2nd treatment session for a conjincision procedure is scheduled, baseline visit activities need to 
be completed within 14 days. 
The screening visit (Visit 1) is planned to take place -21 to -2 days prior to the baseline visit (Visit 2), 
which is also when suprachoroidal triamcinolone is administered. Another eight follow-up visits are 
planned. The baseline visit is followed by Visit 3 the next day, and Visit 4 one week later, and then 
subsequently every four weeks until Visit 10 after 24 weeks.  
The flow chart of the OXUCT-103 clinical trial is shown in Figure 1, below. 
Figure 1. OXUCT-103 Clinical Trial Flow Chart (based on protocol version 3.0) 
Screening 
Baseline and 
Randomization 
Triamcinolone Acetonide 2.4mg (N=10) 
Triamcinolone Acetonide 4.0mg  (N=10) 
Visit 1 
Day -21 to -2 
Visit 2 
D0 
To be 
completed 
within 14 
days 
Visit 3 
D1 (+1) 
Visit 4 
W1 
(±3) 
Visit 5 
W4 
(±5) 
Visit 6 
W8 
(±5) 
Visit 7 
W12 
(±5) 
Visit 8 
W16 
(±5) 
Visit 9 
W20 
(±5) 
Visit 10 
W24 
(±5) 
4.2. 
Methods to Minimize Bias 
4.2.1. Randomization 
The OXUCT-103 clinical trial is designed as a two-arm, parallel-group, single-masked, randomized trial. 
Approximately 20 subjects will be treated using a 1:1 ratio to two treatment arms receiving either: 
1. Low Dose – 2.4mg dose of triamcinolone acetonide (low-dose arm) 
2. Mid Dose – 4.0mg dose of triamcinolone acetonide (mid-dose arm) 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 14 of 35 
as a single treatment with triamcinolone acetonide (Triesence®) administered with the Oxulumis® to 
the posterior suprachoroidal space of one eye, the study eye. This type of randomization method will 
provide a sufficiently balanced distribution of participants at the interim analysis time points, as well 
as for the final analysis arms.  If study treatments cannot be completed in up to two treatment sessions, 
further subjects will be randomized to meet the target subject number of approximately 20. 
4.2.2. Masking Procedures 
This is a single masked trial. The trial subjects will be masked for the treatment dose allocation. No 
masking of treatment assignment nor the dose is foreseen for the Investigator, the site staff nor the 
Sponsor team involved in the trial. Subjects will only be able to receive information about their 
treatment assignment after the end of the trial. 
4.2.3. Unmasking Procedures 
In case of any emergency, the treating site investigator can share the dose level upon request and 
needs to document all details regarding this procedure. 
4.3. 
Sample Size 
A total of approximately 20 subjects will receive a single treatment with Triesence® administered with 
the Oxulumis® to one eye, the study eye. Based on protocol version 3.0, dated 17 Feb. 2023, additional 
subjects will be enrolled, if the study treatment cannot be completed in randomized subjects, to target 
a total of approximately 20 treated subjects. 
The sample size is not based on power calculations. It is chosen based on clinical experience and 
considered to be adequate to fulfill the objectives of the clinical trial. A sample size of 20 subjects is 
estimated to detect common and very common adverse events, which is key to inform further trials in 
the Oxulumis® development program in respect to safety considerations. 
4.4. 
Timing of Final Analysis 
Once all subjects have completed the full course of the trial and their data has been entered into eCRF 
in the Oomnia EDC/CTMS, and source data verification has been performed as outlined in the trial 
protocol, all data queries have been reconciled and closed, and all instances of the eCRF have been 
locked, the trial database will be locked upon the written authorization of the sponsor’s 
representative. 
Upon database lock, the sponsor’s representative will give written authorization for database exported 
from the Oomnia EDC/CTMS system for forwarding to the Lead Statistician for analysis. 
5. 
Trial Subjects 
5.1. 
Subject Disposition 
A summary figure (CONSORT flow diagram, see Appendix 3, section 13) will be generated for the 
OXUCT-103 “CAPE” clinical trial at the subject level, including reasons for being excluded from the next 
analysis population (see section 6 for more details) for the populations listed below: 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 15 of 35 
• 
Screened subjects (SP) 
• 
Safety population (SAF) 
• 
Efficacy evaluable population (EEP) 
• 
Per protocol population (PP) 
The CONSORT flow diagram will give an overview of the subject disposition, while the additional tables 
and listings will provide more detailed information (e.g. primary reason for discontinuation and 
proportions). 
5.2. 
Definition of Compliance and Assessment 
5.3. 
Definition of Protocol Deviation 
For the purpose of the OXUCT-103 “CAPE” clinical trial, protocol deviations will be collected and 
reviewed during the trial. Important protocol deviations are deviations including those defined as 
violations in the protocol (Section 9.5), which are likely to have an impact on the efficacy and/or safety 
of trial treatments. In practice, in the protocol deviation documents the terms “major” are used for 
“important” (in the ICH classification) and the term “minor” for “non-important” (in the ICH 
classification) protocol deviations. 
5.3.1. Protocol Deviations 
Protocol deviations (both categorized as major and minor) and any action to be taken regarding the 
exclusion of subjects or affected data from specific analyses are defined in the following sections. 
5.3.1.1. Major Protocol Deviations 
Major (“important”) protocol deviations are defined as follows:  
• 
Not meeting the inclusion criteria or meeting the exclusion criteria, respectively 
• 
Missing trial visits or out of window study visits (depending on type of visit and on the time 
interval). A more detailed breakdown is available in the Protocol Deviation Specification 
document. 
• 
Intake of non-authorized concomitant treatment impacting subject safety and potentially 
efficacy outcomes, e.g. concomitant medication increaing the risk of AEs or additional non-
authorized treatments for study-specific disease or their compliacionts. 
• 
Missing important safety data points (IOP measurements, dilated fundus examinations, BCVA 
measurement, SD-OCT measurement, etc.)  
In specific situations, the sponsor can issue indivudal waivers on meeting certain eligibilty criteria, if 
the overall clinical assessment of the investigator in accordance with Oxular’s medical monitor 
suggests no altered risk/benefit for trial participation. 
Major (“important”) protocols deviations will be summarized in tables by treatment dose group. 
6. 
Analysis Populations 
Subjects suitable for study participation include individuals over 18 years of age, diagnosed with Type 1 
or Type 2 diabetes mellitus, with DME with short-lived, limited or no therapeutic response with prior 
therapy with ocular injections of steroids and/ or anti-VEGF agents.  


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 16 of 35 
For the purpose of the trial, outcomes will be assessed on two population groups:  
• 
Safety Analysis population 
• 
Exploratory Analysis population 
6.1. 
Safety Analysis Population 
The safety population (SAF) will include all subjects in whom the administration of study treatment 
was started, defined as at least one (1) time inserting the insertion needle of the device in the sclera, 
regardless of whether the treatment was completed. 
6.2. 
Exploratory Analysis Population 
The exploratory efficacy analysis will be performed on two populations: 
• 
Efficacy Evaluable Population (EEP): All subjects who received the study treatment and have 
at least one post baseline visit efficacy observation or measurement in the study eye. 
Efficacy assessments after a 1st treatment session or as part of a 2nd treatment session count 
as assessment of the baseline visit and not as post baseline efficacy observation. In addition, 
those subjects to whom the drug was partially administered to compartments that are not the 
suprachoroidal space will be considered EEP population.  
• 
Per Protocol (PP) Population: Efficacy Evaluable Population with exception of subjects with 
major (important) protocol deviations and with exception of those subjects to whom the drug 
was partially administered to compartments that are not the suprachoroidal space. 
6.3. 
Eligibility and Withdrawal Criteria 
6.3.1. Inclusion Criteria 
Patients must meet all of the following criteria in order to be eligible for this study:  
1.   Able to understand and sign an informed consent form. 
2.   At least 18 years of age. 
3.   Have been diagnosed with Type 1 or Type 2 diabetes mellitus. 
4.   Have DME involving the center of the fovea in the study eye with central subfield thickness 
(CST) on SD-OCT of: ≥ 320 for males or ≥ 305 for females on Spectralis (Heidelberg) or ≥ 305 
for males or ≥ 290 for females with Cirrus (Zeiss). 
5.   Have BCVA in the study eye of ≤73 ETDRS letters (approximate Snellen equivalent of 20/40 or 
worse) at the screening visit. The eligibility will be assessed based on the ETDRS BCVA letter 
score. 
6.   Short-lived, limited, or no response to prior ocular injection therapy (e.g., IVT or subtenon) of 
steroids and/or anti-VEGF agents based on the investigator’s assessment. Short-lived in this 
trial is defined as less than 4 weeks. 
7.   For women who are not postmenopausal (i.e., at least12 months of non-therapy induced 
amenorrhea or surgically sterile (absence of ovaries and/or uterus) agreement to remain 
abstinent or use combined contraceptive methods that result in a failure rate of less than 1% 
per year for the entire participation in this clinical trial. Examples of contraceptive methods 
with an expected failure rate of less than 1% per year include male sterilization, hormonal 
implants, proper use of combined oral or injected hormonal contraceptives, and certain 
intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom 
and a cervical cap) may be combined to achieve a failure rate of less than 1% per year, barrier 
methods must always be supplemented with the use of a spermicide. 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 17 of 35 
8.   Males must agree to use a barrier method of contraception starting from treatment 
administration through the end of participation in this clinical trial. 
9.   Subject must be willing not to participate in any other clinical trial including an investigational 
medicinal product (IMP) or an investigational device until the end of the participation in this 
trial. 
6.3.2. Exclusion Criteria 
Subjects will be eligible if they do not meet any of the following exclusion criteria:  
1. Presence of any significant ocular or non-ocular disease/disorder (or medication and/or 
laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence 
of the Oxular Medical Monitor, may either put the subject at risk because of participation in 
the trial, may influence the results of the trial, or the subject’s ability to participate in the trial. 
2. Macular edema considered due to a cause other than diabetes mellitus in the study eye. 
3. Condition, in the study eye, in which visual acuity is not expected to improve from the 
resolution of macular edema (e.g., foveal atrophy, clinically relevant loss of ellipsoid zone, 
pigment abnormalities, vitreomacular traction, or nonretinal causes). 
4. Conditions, in the study eye, that may render the suprachoroidal microcatheter insertion and 
deployment difficult or subject the patient to excessive risk of complications. Examples include 
but are not limited to ocular hypotony, scleral staphylomas, necrotizing scleritis, scleral 
melting, excessive choroidal scarring e.g., associated with pan-retinal photocoagulation, 
amongst others. 
5. Macular laser photocoagulation or panretinal laser photocoagulation (PRP) in the study eye 
performed within sixteen (16) weeks prior to screening. 
6. Active proliferative diabetic retinopathy (PDR) or sequelae of PDR (including iris 
neovascularization, vitreous hemorrhage, tractional retinal detachment, extensive scarring 
following PRP) at screening in the study eye. 
7. History of recurrent or active intraocular inflammation in either eye (e.g., uveitis) within 12 
weeks prior to screening. 
8. Infectious eye disease like infectious blepharitis, keratitis, or conjunctivitis in either eye within 
four (4) weeks of screening. 
9. IOP ≥ 22 mmHg, or glaucomatous disc changes (i.e., a cup disc ratio greater than 0.8) in the 
study eye at screening. 
10. History of glaucoma surgery, and or anti-glaucoma therapy with more than two active 
substances (in separate or a combination preparation) at the screening visit are exclusionary. 
11. History of closed-angle glaucoma. 
12. IOP <6mmHg (hypotony) in the study eye at screening. 
13. Spherical equivalent of the refractive error of −6 diopters of myopia or worse (prior to cataract 
or refractive surgery) at screening. 
14. Cataract or other media opacity that limits the ability to obtain the planned imaging 
assessments. 
15. History of retinal detachment. 
16. Subjects who were previously treated for DME in the study eye must not have received: 
a) an intravitreal anti-VEGF treatment within four (4) weeks before screening. The four-week 
interval before screening is used for IVT bevacizumab, ranibizumab, aflibercept, 
brolucizumab, or faricimab (i.e., a combined Anti-VEGF/anti-Ang2 agent), as also inclusion 
criterion No. 6 on therapeutic response must be met. 
b) Prior treatment with SUSVIMO® (Port Delivery System) implant at any time is 
exclusionary. 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 18 of 35 
c) Intra- or periocular/subtenon triamcinolone acetonide suspension within 12 weeks 
before screening. 
d) Intravitreal dexamethasone implant (Ozurdex®) within 24 weeks before screening. 
e) Prior treatment with longer duration implants (e.g., fluocinolone acetonide IVT implant, 
e.g., Iluvien®) at any time is exclusionary. 
f) Prior treatment with suprachoroidal steroids (commercial, investigational, or off label) at 
any time is exclusionary. 
17. Concurrent use of systemic glucocorticoid medications or systemic steroids within twelve (12) 
weeks before screening is exclusionary. Intranasal, inhaled, and extra-ocular topical 
corticosteroids are allowed. 
18. Treatment with ocriplasmin (Jetrea®) at any time. 
19. History of vitreoretinal surgery (including surgery for retinal detachment or scleral buckle) in 
the study eye. Vitrectomy is only exclusionary, if within 12 weeks prior to screening. 
20. Any other previous ophthalmic surgeries, uncomplicated cataract surgery, or uncomplicated 
trauma in the study eye within twelve (12) weeks prior to screening. Complicated cataract 
surgery or trauma that may impact access and/or drug delivery to the suprachoroidal space 
are exclusionary. 
21. Hypersensitivity to triamcinolone acetonide, or any of the excipients in the Triesence® 
formulation or Oxulumis® device components. 
22. Active malignancy or history of malignancy within the past five (5) years. 
23. Uncontrolled diabetes with a hemoglobin A1c (HbA1c) > 12% or any other uncontrolled 
systemic disease at screening. 
24. Uncontrolled hypertension, defined as blood pressure with a systolic value of ≥ 160mmHg or 
a diastolic value of ≥ 100 mmHg upon repeat assessment at screening. 
25. History of myocardial infarction, stroke, transient ischemic attack, acute congestive heart 
failure, or any acute coronary event within 90 days before screening. 
26. Subjects who are pregnant or breastfeeding at the screening visit, or who test positive for 
pregnancy at the screening visit or are unwilling to use adequate birth control methods to 
prevent pregnancy throughout the study. 
27. Subjects who were previously randomized in this trial, but in whom administration of study 
treatment could not be completed (added per OXUCT-103 “CAPE” protocol version 3.0). 
6.3.3. Study Discontinuation 
If any important safety concerns (e.g., SAEs, SADE, AESIs) arise, dosing of further subjects could be 
temporarily halted or stopped. If further dosing is stopped, study visits of enrolled subjects with e.g., 
follow-up visits including safety evaluations will still be performed as foreseen. If the Sponsor, Medical 
Monitor or designee, study center monitor, or appropriate regulatory officials discover conditions 
arising during the trial that indicate that the study should be halted, this action may be taken after 
appropriate consultation. 
In addition, both the Sponsor and the Investigator reserve the right to terminate the study according 
to the study contract. 
6.3.3.1. Discontinuation of Study Intervention  
Discontinuation of the study intervention on a subject level is not foreseen, as this is a one-time 
ophthalmic administration 2.4 mg or 4mg dose of Triesence® to the suprachoroidal space at the 
baseline visit.  


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 19 of 35 
6.3.3.2. Subject Discontinuation/Withdrawal from Study  
A subject’s participation in the trial may be discontinued at any time. Subjects will be asked to specify 
the reason for the termination but have the right not to answer. 
The investigator may decide to withdraw a subject from the study at any time with reasonable 
rationale, e.g., lack of improvement or clinically meaningful deterioration of DME after administration 
of Triesence® with the Oxulumis® device. 
Reasons for the subject’s withdrawal include, but are not limited to:  
• 
Subject refuses to continue participating in the trial 
• 
Subject’s non-compliance 
• 
Subject’s participation is terminated by the PI or investigator, although the subject consented 
since participation is no longer medically appropriate 
• 
Subject is ‘lost to follow up’  
If a subject withdraws from the clinical trial, the site will record the subject’s reasons for withdrawal 
on a Withdrawal Case Report Form (CRF). When subject withdrawal from the clinical trial is due to an 
adverse event the subject will be followed until resolution of that adverse event or determination that 
the subject’s condition is stable for a maximum duration of six (6) months. The status of the subject’s 
condition should be documented at the time of withdrawal. 
6.3.4. Assessment for Follow-On Treatment and End of Study 
From Week 4 on, each subject will be evaluated against prespecified criteria indicating the need for 
follow-on treatment (i.e., indicating the end of the current treatment interval and the end of study 
participation). 
Criteria are as follows: 
• 
At least 75 μm increase in CST on SD-OCT compared to the best-achieved CST value since the 
baseline visit [Visit 2, day 0]. 
• 
A decrease in BCVA of at least 10 ETDRS letters from the best achieved BCVA since the baseline 
visit [Visit 2, day 0], that in the opinion of the investigator, is due to worsening of DME. 
If one or both above criteria are met, the subject will be eligible for follow-on treatment and will be 
managed according to the local standard of care after ending participation in this clinical trial. If the 
investigator decides that the subject requires follow-on treatment during a study visit, the respective 
visit-day procedures will be extended to include the assessments foreseen for the EoS visit. 
7. 
Statistical Methods and Analysis 
7.1. 
Hypothesis 
No formal statistical hypothesis was developed for the OXUCT-103 “CAPE” trial. 
 
 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 20 of 35 
7.2. 
Safety Analyses 
7.2.1. Primary Endpoint 
The primary endpoints supporting the primary objective of evaluating the safety and tolerability of two 
dose levels of triamcinolone acetonide administered with the Oxulumis® are: 
1. Frequency of ocular and systemic adverse events (treatment-emergent serious adverse events 
[SAEs] and treatment-emergent non-serious adverse events [TEAEs]) 
2. Frequency of adverse device effects (ADEs, serious ADEs [SADEs]) 
7.2.1.1. Analytical Procedures for the Primary Endpoint 
The safety endpoint analysis will be performed on the SAF population. The primary endpoint analysis 
of ocular adverse events that occurred in the study eye will be split in two groups related to the two 
different device presentations used in the study: 
• 
First device lot (21120801), in use through end of  October 2022 
• 
Second device lots (22110812, 23011214), in use from January to August 2023. 
Data will be summarized separately for each treatment arm, as well as according to non-ocular and 
ocular AE occurrences. Adverse events will be summarized using frequencies and percentages per 
adverse event (as multi-response), as well as per subject.  
Treatment-emergent serious and non-serious adverse events (TEAEs) and serious and non-serious 
adverse device effects (ADEs) will be coded to system organ classes (SOCs) and preferred terms (PTs) 
using the Medical Dictionary for Regulatory Activities (MedDRA ) version 26.1. MedDRA -coded AEs 
will be presented as sheet tables while verbatim entries will be presented as data listings. 
7.3. 
Exploratory Analysis 
Exploratory analysis will include the following assessments: 
• 
Best-corrected visual acuity (BCVA) using the ETDRS methodology 
• 
IOP measurement 
• 
SD-OCT 
• 
Retinal Physician’s Documentation Assessment of Administration 
• 
Subject Experience Assessment 
These assessments will be evaluated through exploratory endpoints.  
7.3.1. Exploratory Efficacy (and/or Safety) Endpoints 
The exploratory efficacy (and/or safety) endpoints include the following: 
Mentioned in the study protocol: 
1. Mean Change in BCVA (ETDRS) at all study visits through Week 24 compared to baseline 
2. Percentage of subjects with vision gain and vision loss of at least 5, at least 10, and at least 15 
letters at all study visits through Week 24 compared to baseline 
3. Time to subjects requiring follow-on treatment 
4. Mean Change in Central subfield thickness (CST) at all study visits through Week 24 compared 
to baseline. 
5. Mean Change in IOP at all study visits through Week 24 compared to baseline pre-treatment 
IOP. 


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ůů ĞǆƉůŽƌĂƚŽƌǇ ĞĨĨŝĐĂĐǇ ĞŶĚƉŽŝŶƚ ǀĂƌŝĂďůĞƐ ǁŝůů ďĞ ƉƌĞƐĞŶƚĞĚ ƵƐŝŶŐ ĚĞƐĐƌŝƉƚŝǀĞƐƚĂƚŝƐƚŝĐĂů ŵĞƚŚŽĚƐ͘
EŽŵŝŶĂů ĞŶĚƉŽŝŶƚ ǀĂƌŝĂďůĞƐ ǁŝůů ďĞ ƉƌĞƐĞŶƚĞĚ ƵƐŝŶŐ ĨƌĞƋƵĞŶĐǇ ĐŽƵŶƚ ĂŶĚ ƉĞƌĐĞŶƚ ĨŽƌ ĞĂĐŚ Ăƌŵ
ƐĞƉĂƌĂƚĞůǇ͘EƵŵĞƌŝĐĂů;ĐŽŶƚŝŶƵŽƵƐͿĞŶĚƉŽŝŶƚǀĂƌŝĂďůĞƐǁŝůůďĞƉƌĞƐĞŶƚĞĚĂƐŵĞĂŶ͕ϵϱй/ĨŽƌŵĞĂŶ͕
ƐƚĂŶĚĂƌĚĚĞǀŝĂƚŝŽŶ͕ŵŝŶŝŵƵŵ͕ϮϱƚŚƉĞƌĐĞŶƚŝůĞ͕ŵĞĚŝĂŶ͕ϳϱƚŚƉĞƌĐĞŶƚŝůĞ͕ĂŶĚŵĂǆŝŵƵŵ͘
EŽŵŝŶĂůĞŶĚƉŽŝŶƚǀĂƌŝĂďůĞƐǁŝůůďĞƉƌĞƐĞŶƚĞĚƵƐŝŶŐĂďĂƌĐŚĂƌƚ ǁŝƚŚϵϱй/ ĞƌƌŽƌďĂƌƐǁŚŝůĞĐŽŶƚŝŶƵŽƵƐ
ǀĂƌŝĂďůĞƐǁŝůůďĞƉƌĞƐĞŶƚĞĚƵƐŝŶŐ ůŝŶĞŐƌĂƉŚƐǁŝƚŚϵϱй/ĂŶĚ ďŽǆƉůŽƚƐ͘
ϳ͘ϰ͘
ŽŶĨŝĚĞŶĐĞ/ŶƚĞƌǀĂůƐ
ůůƌĞƐƵůƚƐƌĞŐĂƌĚŝŶŐƚŚĞƉƌŝŵĂƌǇ ĂŶĚĞǆƉůŽƌĂƚŽƌǇĞŶĚƉŽŝŶƚƐǁŝůůďĞƉƌĞƐĞŶƚĞĚǁŝƚŚƉŽŝŶƚĞƐƚŝŵĂƚĞ
;ƉƌŽƉŽƌƚŝŽŶ͕ŵĞĂŶ͕ŵĞĚŝĂŶͿĂŶĚĂ ϵϱйĐŽŶĨŝĚĞŶĐĞŝŶƚĞƌǀĂů͕ĂƐĂƉƉůŝĐĂďůĞ͘


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 22 of 35 
7.5. 
Other Analyses and Statistical Considerations 
7.5.1. Calculations or Transformations Used to Derive the Outcome 
Appropriate transformation(s) (logarithmic, square root, reciprocity, etc.) will not be used to obtain 
normal distributions. Outcome variables, mean change in BCVA, central subfield thickness (CST), and 
IOP will be calculated as the difference between the value at Visit 3 through EoS and baseline. 
7.5.2. Alternative Methods for Distributional Assumptions 
Alternative methods for distributional assumptions will not be applied in this study. 
7.5.3. Sensitivity Analysis Plan 
No sensitivity analysis is planned for this study. 
7.5.4. Interim Statistical Analysis 
No interim analysis is to be performed for this study. 
7.6. 
Missing Data 
No imputation of missing data will be performed. In case the start date for an AE/ADE is missing or 
incomplete, so that it is not possible to evaluate if it has occurred pre- or post-treatment, this AE/ADE 
will be classified conservatively as treatment-emergent. 
7.7. 
Adjustment for Multiplicity and Type 1 Error Control 
The adjustment for multiplicity and type 1 error is not applicable for this study.  
7.8. 
Non-Standard Statistical Methods 
Non-standard statistical methods are not planned for statistical analyses for the OXUCT-103 clinical 
trial. 
7.9. 
Statistical Software 
SAS version 9.4 will be used for statistical analysis of the OXUCT-103 “CAPE” clinical trial. 
8. 
Presentation of Patient Data and Other Evaluations 
8.1. 
Screening Data 
Screening data will be presented for the SP population as subject data listings. 
8.2. 
Screening and Baseline Patient Characteristics 
The following patient characteristics will be obtained during the Screening Visit 1: 
• 
Demographic data  
• 
Medical history 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 23 of 35 
• 
Concomitant medication  
• 
Pre-treatment AEs collection 
• 
Height, weight, and vital signs (body temperature, blood pressure, and heart rate) 
• 
Lab assessment 
• 
Urine pregnancy test for females of childbearing potential 
Screening and baseline characteristics will be summarized for the SAF population in with respect to 
allocation to treatment. 
Numerical variables will be presented as mean ± SD or median (25-75th percentile), depending on data 
distribution. Categorical (nominal) data will be presented as count (percent).  
8.3. 
Medical History 
All medical history and concurrent medical conditions will be presented as entered by the investigator. 
in data listings.  Also, non-ophthalmic and ophthalmic medical history and concurrent medical 
conditions will be listed separately.  In case of missing dates/partial dates, no imputation of missing 
data will be performed. 
8.4. 
Concomitant Medication or Procedure 
Systemic and ocular concurrent medications or procedures will be presented separately as subject data 
listings. In case of missing dates/partial dates, no imputation of missing data will be performed. 
8.5. 
Physical Examination and Vital Signs 
Descriptive statistics will be presented for physical examination and vital signs data as mean ± SD or 
median (25-75th percentile), depending on data distribution. Categorical (nominal) data will be 
presented as count (percent).  
8.6. 
Laboratory Tests 
8.6.1. Non-fasting Chemistry, Hematology and Thyroid Parameters 
In this trial laboratory testing is only done for assessing factors impacting safety and eligibility for 
participating. Accordingly, any abnormal findings are recorded in medical history or if newly occurred 
as AEs. No separate statistical analysis of laboratory values is performed. 
8.7. 
Reasons, Details and Timing of Withdrawal/Lost to Follow-Up Data 
Early termination will be tabulated by analysis population (SAF, EEP, and PP) along with the reasons 
for discontinuation. The time point of withdrawal will also be presented (ie. date of discontinuation 
and last visit completed). In this protocol, termination/end-of-study related to meeting follow-on 
treatment criteria does not fall under the category of early termination. 
 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 24 of 35 
9. 
Data Management and Other Procedures 
9.1.1. Clinical Data Management Plan and Data Quality Assurance 
The CDMP will enforce appropriate handling of data at all steps of the project to assure a high-quality 
ready for analysis database at the end of the study. The Lead Data Manager and Project Lead 
(delegated by sponsor) is responsible for the oversight and knowledge of the data management 
process as well as review of the CDMP.  Together with them, a Data Manager from the Wemedoo AG 
team suggests and prepares the system for all needs as defined by the sponsor. The purpose of 
electronic Case Report Forms (eCRF) is to capture all clinical and workflow data as defined by the 
protocol. The data is necessary for statistical analysis and for GCP verification purposes. The type, 
number, and form of the data capture elements (DCEs) are defined by the protocol and statistical 
analysis plan. 
DCEs and data flow will be simulated within the Oomnia EDC/CTMS system prior to the initiation of 
the data capture process. The simulation will be presented to the Project Lead designated by the 
sponsor. If any discrepancies are detected, the Wemedoo AG data manager will correct and revise the 
data flow with the Project Lead. Upon addressing all issues detected during the simulation, the 
Wemedoo AG data manager will finalize and sign the document. 
The Trial Manager and Trial Statistician provide input to, and review of, updates and changes to the 
Data Management Plan, if needed, during the project. If required, the CDMP can be modified during a 
trial. The sponsor or his designee must request the CDMP in written form.  Any changes must also be 
verified by the Wemedoo AG data team and sponsor, or his designee. 
The Clinical Data Management Plan for the OXUCT-103 trial is described in the file, OXUCT-103 CDMP 
v2.0 19 May 2023.docx. 
9.1.2. Other Standard Operating Procedures and/or Documents 
For more details regarding the Oxuct-103 clinical trial, please refer to the finalized trial protocol, Oxuct-
103 Clinical Trial Protocol v2.0 24May2022 clean, dated 24 May 2022. 
10. References  
Boyer, D. S., Y. H. Yoon, R. Belfort, Jr., F. Bandello, R. K. Maturi, A. J. Augustin, X. Y. Li, H. Cui, Y. Hashad, 
S. M. Whitcup, and Mead Study Group Ozurdex. 2014. 'Three-year, randomized, sham-controlled trial 
of dexamethasone intravitreal implant in patients with diabetic macular edema', Ophthalmology, 121: 
1904-14. 
Ehlers, J. P., S. Yeh, M. G. Maguire, J. R. Smith, P. Mruthyunjaya, N. Jain, L. A. Kim, C. Y. Weng, C. J. 
Flaxel, S. D. Schoenberger, and S. J. Kim. 2022. 'Intravitreal Pharmacotherapies for Diabetic Macular 
Edema: A Report by the American Academy of Ophthalmology', Ophthalmology, 129: 88-99. 
Udaondo, P., A. Adan, L. Arias-Barquet, F. J. Ascaso, F. Cabrera-Lopez, V. Castro-Navarro, J. Donate-
Lopez, A. Garcia-Layana, F. J. Lavid, M. Rodriguez-Maqueda, and J. M. Ruiz-Moreno. 2021. 'Challenges 
in Diabetic Macular Edema Management: An Expert Consensus Report', Clin Ophthalmol, 15: 3183-95. 
Wilkins, C. S., E. K. Sobol, G. M. Lema, J. G. Lee, R. B. Rosen, and A. Deobhakta. 2021. 'Intravitreal 
dexamethasone insert in diabetic macular edema super-refractory to antivascular endothelial growth 
factor therapy', Eur J Ophthalmol: 11206721211004391. 
Zur, D., M. Iglicki, and A. Loewenstein. 2019. 'The Role of Steroids in the Management of Diabetic 
Macular Edema', Ophthalmic Res, 62: 231-36. 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 25 of 35 
11. Appendix 1 – Study Schedule (Assessments and Procedures) 
 
Screening  
Baseline 
Post-Baseline Follow-Up 
Days / weeks 
Day   
–21 to -2 
D0 
To be completed within 14 days 
D1 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
ET/EoS 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Visit Window 
 
in-clinicb 
variant with 
conj./tenon incisionj 
+1 
days 
±3 
days 
±5 
days 
±5 
days 
±5 
days 
±5 
days 
±5 
days 
±5 
days 
ICF 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility  
X 
X* 
X* 
 
 
 
 
 
 
 
 
Randomization  
 
X* 
Xk 
 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication  
X 
X* 
X* 
X 
X 
X 
X 
X 
X 
X 
X 
AEs and ADE  
X 
X** 
X** 
X 
X 
X 
X 
X 
X 
X 
X 
Height, Weight, Vital Signs  
X 
 
 
 
 
 
 
 
 
 
 
Lab Assessment  
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test b,d 
X 
X* 
X* 
 
X 
X 
X 
X 
X 
X 
X 
Slit-lamp BM  
OU 
OU* 
OUk 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
IOP  
OU 
OU*/SE***,i 
OU*,k/SE** 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
BCVAe,f 
OU 
OU* 
OU*,k 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
Dilated Ophthalmoscopy  
OU 
OU*/SE** 
OU*,k/SE** 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
Axial Length g 
OU 
 
 
 
 
 
 
 
 
 
 
SD-OCT  
OU 
SE*/SE** 
SE*,k 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
OCT-A  
OU 
 
 
 
 
 
 
OU 
 
 
OU 
Swept-Source or UWF  
OU 
SE*** 
 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
Color Fundus Photog.  
OU 
SE** 
SE*,k 
SE 
SE 
SE 
SE 
OU 
SE 
SE 
OU 
Overall Assessment of Expected Procedural 
Complexity 
X 
 
 
 
 
 
 
 
 
 
 
Study Medication Administration  
 
SE 
SE 
 
 
 
 
 
 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 26 of 35 
Procedure Documentation and Assessment 
 
X** 
X** 
 
 
 
 
 
 
 
 
Subject’s Experience Assessment  
 
X*** 
X*** 
X 
X 
X 
 
 
 
 
 
Assessment of need for follow-on treatment 
 
 
 
 
 
SE 
SE 
SE 
SE 
SE 
SE 
AEs = adverse events; ADEs = adverse device effects; BCVA = best corrected visual acuity; BM = biomicroscopy; CFP = color fundus photography, CMs = concomitant 
medications; EoS = end of study; ET = early termination; ETDRS = Early Treatment Diabetic Retinopathy Study; ICF = informed consent form; OCT-A (Ocular Coherence 
Tomography Angiography); OU = both eyes; SD-OCT = Spectral-Domain Ocular Coherence Tomography; SE = study eye; Tx = treatment. (*) Pre-treatment, (**)  
Attempt or Post-treatment, (***) Post Treatment. 
a. Visit dates and visit windows are calculated for the screening visit from the day of the first procedural attempt and for post baseline visits from the date of the completed study 
treatment administration. Between the maximum interval from start of activities for Visit 2 and the completion is 14 days including a 
potential 2nd treatment attempt in an operating/procedure room, see also footnote b. and c. 
b. Column shows the schedule of assessments for a study treatment carried out in a setting with access to devices for ophthalmic assessment or imaging. 
c. The treatment day can be primarily performed in an operating/procedure room or be split between a first in-clinic attempt followed by another attempt in an 
operating/procedure room in case of non-completion of administration of the study treatment in the clinic. If the operating/procedure room is not fully equipped with 
ophthalmic assessment and imaging devices, this assessment schedule is the minimum to be performed. 
d. Females of childbearing potential only. A urine pregnancy test will be performed at screening. A pregnancy test on D0 (urine) shall be negative for the subject to 
receive study treatment. Additional pregnancy tests will be performed at monthly intervals throughout study participation. 
e. BCVA assessments need to be performed in duplicates for the eyes that should be assessed at visits. 
f. BCVA eligibility will be assessed at the screening visit. 
g. Axial length measurement to assess the axial dimensions of the eye to support exploratory imaging of the location of the deployment of study drug in equipped sites only 
h. SS-OCT or UWF SD-OCT to visualize the site of deployment will be obtained at sites in which the equipment is available. 
i. On Day 0, subjects will be monitored for at least sixty (60) minutes immediately following study treatment with at least 2 IOP measurements. 
j. If the Oxulumis® procedure is attempted first in-clinic and then another procedural attempt in an operating/procedure room, the subject’s experience questionnaire will 
only be completed for the completed procedure, i.e., the procedure when study drug is administered. 
k. In case the study procedure is only performed in an operating/procedure room setting, the mandatory baseline assessments would have to be performed still at the 
investigational site, if not available in the operating/procedure room facility. This may be done prior to or on the same day of treatment administration. All baseline visit 
activities have to be completed within 14 days after their start.


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 27 of 35 
12.  Appendix 2 – General Conventions 
This section details general conventions to be followed while presenting the tables, listings, and 
figures. The following conventions will be applied to all data presentations and analyses. 
• 
All tables and listings will be displayed in Calibri or Segoe UI Light 10 pt font (where possible). 
• 
All tables, listings and figures will have header sections. 
• 
If needed, some of the tables, listings and figures could have footnote sections. 
• 
The outputs have to be created as per the templates that will be provided along with this 
analysis plan in case no changes are needed. 
• 
Summary tables and figures will contain a footnote that references any data listings or tables 
associated with the table (e.g., Source: Listing XX.X.XX). 
• 
The footnotes of tables and listings will be displayed in a separate line of the table, figures, or 
listing, respectively. 
• 
All arithmetic mean, median, standard deviation, minimum and maximum values will be 
formatted to one decimal place. More than one decimal place will be represented for results 
where one decimal place does not render useful information. 
• 
All p-values will be formatted to three decimal places. More than three decimal places will be 
used for results where three decimal places do not render useful information. 
• 
Confidence intervals will be formatted to one decimal place, where appropriate. 
• 
The number and percentage of responses will be presented in the form XX (XX.X%) where the 
percentage is in the parentheses. 
• 
All listings will be ordered by study period (day) and time points (if applicable). 
• 
Date variables will be formatted as DD/MMM/YYYY for presentation, if available. 
• 
Tables, figures, and listings will be presented both in landscape and portrait orientation 
depending on the data displayed. 
 
 
 
 
 
 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 28 of 35 
13. Appendix 3 – CONSORT Flow Diagram 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 29 of 35 
14. Appendix 4 – Tables, Figures and Graphs 
The numbering of the tables, figures, listings is prepared to meet the requirements of the ISO 
14155:2020 Clinical investigation of medical devices for human subjects — Good clinical practice. 
14.1. Populations and Demographic Data 
14.1.1. Disposition of Subjects 
14.1.1.1 
CONSORT Flow Diagram 
14.1.1.2 
Eligibility Criteria Violations (n, %) 
14.1.1.3 
Study Discontinuations and Reasons by Treatment Dose (n, %) 
14.1.1.4 
Follow-On Treatment Received (n, %) 
14.1.2. Study Populations 
14.1.2.1. 
SAF, EEP, and PP Populations Overall and by Study Eye Laterality (n, %) 
14.1.2.2. 
Major and Minor Protocol Deviations by Treatment Dose Group  and Study Eye Laterality  (n, %) 
14.1.3. Demographics: Overall and by Treatment Dose for the SAF Population 
14.1.3.1 
Subject Age, Gender, Racial Designation, and Ethnicity (descriptive; n, (%)) 
14.1.4. Vital Signs and Anthropometry by Treatment Dose for the SAF population 
14.1.4.1 
Body Temperature, SBP, DBP, and Heart Rate at Screening (descriptive) 
14.1.4.2 
Height, Weight, and BMI at Screening (descriptive) 
14.2. Medical History 
14.2.1. Non-Ophthalmic Medical History by Treatment Dose for the SAF Population 
14.2.1.1 
Relevant and Ongoing Non-Ophthalmic Medical Conditions per Patient (n, %) 
14.2.1.2 
Relevant Non-Ophthalmic Medical Conditions or Events by MedDRA SOC and PT (n, %; multi-
response) 
14.2.2. Ophthalmic Medical History by Treatment Dose for the SAF Population  
14.2.2.1 
Relevant and Ongoing Ophthalmic Medical Conditions per Patient (n, %) 
14.2.2.2 
Relevant Ophthalmic Medical Conditions or Events by MedDRA SOC and PT (n, %; multi-
response) 
14.3. Concomitant Medication and Concomitant Procedure by Treatment Dose for the 
SAF Population 
14.3.1. Non-Ocular Concomitant Medications and Procedures by Treatment Dose 
14.3.1.1 
Non-Ocular Concomitant Medications and Procedures (% n; multi-response) 
14.3.1.2 
Reason for Non-Ocular Concomitant Medication and Procedure (n, %) 
14.3.1.3 
Number of Non-Ocular Concomitant Medications and Procedures per Patient (n, %) 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 30 of 35 
14.3.2. Ocular Concomitant Medications and Procedures by Treatment Dose and by Eye 
14.3.2.1 
Ongoing and Non-Ongoing Ocular Concomitant Medications and Procedures (% n; multi-response) 
14.3.2.2 
Reason for Ocular Concomitant Medication and Procedure (n, %) 
14.3.2.3 
Number of Ocular Concomitant Medications and Procedures per Patient (n, %) 
14.4. Ocular Examination for the SAF Population 
14.4.1. Lens Examination by Treatment Dose and by Visit 
14.4.1.1 
Lens and Psudophakic Type/Status (n, %, multi-response) 
14.4.1.2 
Phakic Lens Nuclear Lens Opacity (NUC) Grade by Eye (n, %) 
14.4.1.3 
Phakic Lens Cortical (Cor) Grade by Eye (n, %) 
14.4.1.4 
Cortical Central 3mm Zone (CEN) Present by Eye (Y/N) (n, %) 
14.4.1.5 
Phakic Lens Posterior Subcapsular Cataract (PSC) Grade by Eye (n, %) 
14.4.2. IOP Measurement by Treatment Dose and by Visit 
14.4.2.1 
IOP by Eye (descriptive) 
14.5.2.2 
IOP – Study Eye (boxplot) 
14.4.2.3 
IOP – Study Eye (line chart) 
14.4.2.4 
IOP – Fellow Eye (boxplot) 
14.4.2.5 
IOP – Fellow Eye (line chart 
14.5.  Study Medication Administration by Treatment Dose  
14.5.1. For the SAF Population 
14.5.1.1 
Study Medication Administration Quadrant (n, %) 
14.5.1.2 
Location of Insertion Point (n, %, multi-response) 
14.5.1.3 
Trocar Insertion Distance from the Limbus (n, %)  
14.5.2. For the EEP Population 
14.5.2.1 
Study Medication Administration Quadrant (n, %) 
14.5.2.2 
Location of Insertion Point (n, %, multi-response) 
14.5.2.3 
Trocar Insertion Distance from the Limbus (n, %)  
14.5.3. For the PP Population 
14.5.3.1 
Study Medication Administration Quadrant (n, %) 
14.5.3.2 
Location of Insertion Point (n, %, multi-response) 
14.5.3.3 
Trocar Insertion Distance from the Limbus (n, %)  
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 31 of 35 
14.6. Retinal Physician’s Documentation and Assessment of Administration – SAF 
Population 
14.6.1. Operative Assessment  
14.6.1.1 
Antiseptic Applied for Disinfection (n, %) 
14.6.2. Type of Anesthesia Given 
14.6.2.1 
Forms of Anesthesia Administered (n, %, multi-response) 
14.6.2.2 
Quadrant of Application for Subconjunctival Lidocaine (n, %, multi-response) 
14.6.2.3 
Quadrant of Application for Subtenon Lidocaine (n, %, multi-response) 
14.6.3. Execution of Oxulumis® Procedure 
14.6.3.1 
First Attempt Success Rate (Y/N) (n, %) 
14.6.3.2 
Reason for First Attempt Failure (n, %, multi-response) 
14.6.3.3 
Study Medication Administration Failure with Reasons by Eye Laterality and Overall (n, %) 
14.6.3.4 
Number of Devices Used (n, %) 
14.6.4. Insertion Point 
14.6.4.1 
Angle of Trocar Insertion Relative to the Sclera Surface and Bevel Orientation (n, %) 
14.6.4.2 
Insertion Completed Through the Sclera (Y/N) (n, %)   
14.6.4.3 
Insertion Difficulty and Complications (n, %, multi-response)   
14.6.5. Deployment 
14.6.5.1 
Deployment Summary (Completion, Light Visibility, Speed and Kink Present) (Y/N) (n, %)   
14.6.6. Injection of Drug Via the Drug Line 
14.6.6.1 
Injection Completed as Expected by Eye Laterality (Y/N) (n, %)   
14.6.6.2 
Drug Injection Duration and Residence Time of the Catheter (n, %)   
14.6.6.3 
Pain Experienced During the Injection, Intervention Performed and Pain Start Time (n, %)   
14.6.6.4 
Duration of Experienced Pain (Descriptive) 
14.6.6.5 
Study Drug Injection Difficulty and Complications (n, %, multi-response)   
14.6.7. Bleeding 
14.6.7.1 
Intraocular Bleeding and Localization (n, %)   
14.6.7.2 
Scleral and Other Damage (n, %, multi-response)   
14.7. Retinal Physician’s Documentation and Assessment of Administration – EEP 
Population 
14.7.1. Operative Assessment  
14.7.1.1 
Antiseptic Applied for Disinfection (n, %) 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 32 of 35 
14.7.2. Type of Anesthesia Given 
14.7.2.1 
Forms of Anesthesia Administered (n, %, multi-response) 
14.7.2.2 
Quadrant of Application for Subconjunctival Lidocaine (n, %, multi-response) 
14.7.2.3 
Quadrant of Application for Subtenon Lidocaine (n, %, multi-response) 
14.7.3. Execution of Oxulumis® Procedure 
14.7.3.1 
First Attempt Success Rate (Y/N) (n, %) 
14.7.3.2 
Reason for First Attempt Failure (n, %, multi-response) 
14.7.3.3 
Number of Devices Used (n, %) 
14.7.4. Insertion Point 
14.7.4.1 
Angle of Trocar Insertion Relative to the Sclera Surface and Bevel Orientation (n, %) 
14.7.4.2 
Insertion Difficulty and Complications (n, %, multi-response)   
14.7.5. Deployment 
14.7.5.1 
Deployment Summary (Completion, Light Visibility, Speed and Kink Present) (Y/N) (n, %)   
14.7.6. Injection of Drug Via the Drug Line 
14.7.6.1 
Injection Completed as Expected by Eye Laterality (Y/N) (n, %)   
14.7.6.2 
Drug Injection Duration and Residence Time of the Catheter (n, %)   
14.7.6.3 
Pain Experienced During the Injection, Intervention Performed and Pain Start Time (n, %)   
14.7.6.4 
Duration of Experienced Pain (Descriptive) 
14.7.6.5 
Injection Location in Relation to Major Retinal Landmarks (n, %, multi-response) 
14.7.6.6 
Experienced Reflux and Severity (n, %)   
14.7.6.7 
Study Drug Injection Difficulty and Complications (n, %, multi-response)   
14.7.7. Bleeding 
14.7.7.1 
Intraocular Bleeding and Localization (n, %)   
14.7.7.2 
Scleral and Other Damage (n, %, multi-response)   
14.8. Retinal Physician’s Documentation and Assessment of Administration – PP 
Population 
14.8.1. Operative Assessment  
14.8.1.1 
Antiseptic Applied for Disinfection (n, %) 
14.8.2. Type of Anesthesia Given 
14.8.2.1 
Forms of Anesthesia Administered (n, %, multi-response) 
14.8.2.2 
Quadrant of Application for Subconjunctival Lidocaine (n, %, multi-response) 
14.8.2.3 
Quadrant of Application for Subtenon Lidocaine (n, %, multi-response) 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 33 of 35 
14.8.3. Execution of Oxulumis® Procedure 
14.8.3.1 
First Attempt Success Rate (Y/N) (n, %) 
14.8.3.2 
Reason for First Attempt Failure (n, %, multi-response) 
14.8.3.3 
Number of Devices Used (n, %) 
14.8.4. Insertion Point 
14.8.4.1 
Angle of Trocar Insertion Relative to the Sclera Surface and Bevel Orientation (n, %) 
14.8.4.2 
Insertion Difficulty and Complications (n, %, multi-response)   
14.8.5. Deployment 
14.8.5.1 
Deployment Summary (Completion, Light Visibility, Speed and Kink Present) (Y/N) (n, %)   
14.8.6. Injection of Drug Via the Drug Line 
14.8.6.1 
Drug Injection Duration and Residence Time of the Catheter (n, %)   
14.8.6.2 
Pain Experienced During the Injection, Intervention Performed and Pain Start Time (n, %)   
14.8.6.3 
Duration of Experienced Pain (Descriptive) 
14.8.6.4 
Injection Location in Relation to Major Retinal Landmarks (n, %, multi-response) 
14.8.6.5 
Experienced Reflux and Severity (n, %)   
14.8.6.6 
Study Drug Injection Difficulty and Complications (n, %, multi-response)   
14.8.7. Bleeding 
14.8.7.1 
Intraocular Bleeding and Localization (n, %)   
14.8.7.2 
Scleral and Other Damage (n, %, multi-response)   
14.9. Patient Experience Assessment by Treatment Dose and by Visit for the SAF 
Population 
14.9.1 
Current Level of Pain in the Study Eye (n, %) 
14.9.2 
Pain and Discomfort During the Procedure (n, %) 
14.9.3 
Current Level Of Discomfort in the Study Eye (n, %) 
14.10. Safety Data  
14.10.1. Non-ocular Adverse Events for the SAF Population 
14.10.1.1 
Non-ocular – AE Ongoing, Frequency, Outcome and Severity per Patient (n, %) 
14.10.1.2 
Non-ocular – AE Ongoing, Frequency, Outcome and Severity per Event (n, %, multi-response) 
14.10.1.3 
Non-ocular – AE Relatedness to Investigational Device, Investigational Product, and Investigational 
Procedure per Patient (n, %) 
 
 
14.10.1.4 
Non-ocular – Non-Treatment AEs by MedDRA SOC / PT per Patient (n, %) 
14.10.1.5 
Non-ocular – TEAEs by MedDRA SOC / PT per Patient (n, %) 
14.10.1.6 
Non-ocular – TEAEs by MedDRA SOC / PT per Event (n, %, multi-response) 
 
 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 34 of 35 
14.10.1.7 
Non-ocular – SAEs Frequency and Outcome per Patient (n, %) 
14.10.1.8 
Non-ocular – SAE Seriousness Criteria per Patient (n, %, multi-response) 
14.10.1.9 
Non-ocular – SAEs by MedDRA SOC / PT per Patient (n, %) 
14.10.1.10 
Non-ocular – SAEs by MedDRA SOC / PT per Event (n, %, multi-response) 
14.10.2. Ocular Adverse Events by Treatment Dose and Device Lots for the SAF Population  
14.10.2.1 
AE Frequency, Outcome and Severity per Patient (n, %) 
14.10.2.2 
AE Relatedness to Investigational Device, Investigational Product, and Investigational Procedure, and 
Intervention per Patient (n, %) 
 
 
14.10.2.3 
AEs of Special Interest per Patient – Study Eye (n, %) 
14.10.2.4 
AEs of Special Interest per Event – Study Eye (n, %) 
 
 
14.10.2.5 
TEAEs by MedDRA SOC / PT per Patient (n, %) 
14.10.2.6 
TEAEs by MedDRA SOC / PT per Event (n, %) 
14.10.2.7 
TEAEs by Severity and MedDRA SOC / PT (n, %) 
 
 
14.10.2.8 
Adverse Device Effects (ADEs) by MedDRA SOC / PT – Study Eye (n, %) 
14.10.2.9 
AE-Related Investigational Product and Device Intervention per Patient – Study Eye (n, %) 
14.10.2.10 
AE-Related Investigational Product and Device Intervention per Event – Study Eye (n, %, multi-response) 
14.10.2.11 
Other AE Related Action Taken per Event (n, %, multi-response) 
 
 
14.10.2.12 
SAE Seriousness Criteria per Patient (n, %, multi-response) 
14.10.2.13 
SAE Outcome per Patient (n, %) 
14.10.2.14 
Serious Treatment-Emergent AEs (TEAEs) – Study Eye (listing) 
14.10.2.15 
Serious ADEs (SADEs) by MedDRA SOC / PT per Patient – Study Eye (n, %) 
14.10.2.16 
Serious ADEs (SADEs) by MedDRA SOC / PT per Event – Study Eye (n, %) 
14.10.2.17 
SADE Seriousness Criteria per Patient – Study Eye (n, %, multi-response) 
14.11. Exploratory Data by Treatment Dose and by Visit 
14.11.1. Exploratory Data for the EEP Population – Efficacy/Safety 
14.11.1.1 
BCVA Values per Patient – Study Eye (line chart) 
14.11.1.2 
BCVA Values per Patient – Fellow Eye (line chart) 
14.11.1.3 
Overall Mean and Mean Change in BCVA from Baseline – Study Eye (descriptive) 
14.11.1.4 
Overall Mean and Mean Change in BCVA from Baseline – Fellow Eye (descriptive) 
14.11.1.5 
Overall Mean and Mean Change in BCVA from Baseline (boxplot) 
14.11.1.6 
Percentage of Subjects with Vision Gain and Vision Loss of at Least 5, 10, and 15 Letters from Baseline 
(n, %) 
14.11.1.7 
Percentage of Subjects with Vision Gain and Vision Loss (histogram) 
14.11.1.8 
Time to Subjects Meeting Criteria for Follow-on Treatment (days) (descriptive) 
14.11.1.9 
Central Subfield Thickness (CST) Values per Patient – Study Eye (line chart) 
14.11.1.10 
Central Subfield Thickness (CST) Values per Patient – Fellow Eye (line chart) 
14.11.1.11 
Overall Mean and Mean Change in CST from Baseline – Study Eye (descriptive) 
14.11.1.12 
Overall Mean and Mean Change in CST from Baseline – Fellow Eye (descriptive) 
14.11.1.13 
Overall Mean and Mean Change in CST from Baseline (boxplot) 


 
                                Statistical Analysis Plan v1.0 
 
                                                       OXUCT-103 Clinical Trial 
 
 
 
 
 
Clinical Trial Identifier:  OXUCT-103 
 
SAP Version:  1.0 
Sponsor:  Oxular Ltd. 
 
SAP Date: 22 Jan 2024 
Page 35 of 35 
14.11.1.14 
Mean Change in IOP from Baseline (descriptive) 
14.11.1.15 
Mean Change in IOP from Baseline (boxplot) 
14.11.1.16 
Time to Improvement of Baseline BCVA by at Least 5, 10, and 15 Letters (days) (descriptive) 
14.11.1.17 
Duration of Maintained Improvement of Baseline BCVA by at Least 5, 10, and 15 Letters (days) 
(descriptive) 
14.11.1.18 
Percentage of Subjects with Improvement from Baseline CST by at Least 10% (descriptive) 
14.11.1.19 
Percentage of Subjects with Improvement from Baseline CST by at Least 20, 50, and 75µm 
(descriptive) 
14.11.1.20 
Percentage of Subjects with Increase of IOP of at Least 5, 10, and 30 mmHg from Baseline (n, %) 
14.11.1.21 
Percentage of Subjects with Increase of IOP of at Least 5, 10, and 30 mmHg from Baseline (bar chart) 
14.11.1.22 
Course of IOP through the First 60 Minutes After Administration of Study Drug (descriptive) 
14.11.1.23 
Course of IOP through the First 60 Minutes After Administration of Study Drug (dot plot) 
14.11.1.24 
Percentage of Subjects with Elevated IOP by at Least 10mmHg at Over 60 Minutes After 
Administration (descriptive) 
14.11.2.  Exploratory Data for the PP Population – Efficacy/Safety 
14.11.2.1 
BCVA Values per Patient – Study Eye (line chart) 
14.11.2.2 
BCVA Values per Patient – Fellow Eye (line chart) 
14.11.2.3 
Overall Mean and Mean Change in BCVA from Baseline – Study Eye (descriptive) 
14.11.2.4 
Overall Mean and Mean Change in BCVA from Baseline – Fellow Eye (descriptive) 
14.11.2.5 
Overall Mean and Mean Change in BCVA from Baseline (boxplot) 
14.11.2.6 
Percentage of Subjects with Vision Gain and Vision Loss of at Least 5, 10, and 15 Letters from Baseline 
(n, %) 
14.11.2.7 
Percentage of Subjects with Vision Gain and Vision Loss (histogram) 
14.11.2.8 
Time to Subjects Meeting Criteria for Follow-on Treatment (days) (descriptive) 
14.11.2.9 
Central Subfield Thickness (CST) Values per Patient – Study Eye (line chart) 
14.11.2.10 
Central Subfield Thickness (CST) Values per Patient – Fellow Eye (line chart) 
14.11.2.11 
Overall Mean and Mean Change in CST from Baseline – Study Eye (descriptive) 
14.11.2.12 
Overall Mean and Mean Change in CST from Baseline – Fellow Eye (descriptive) 
14.11.2.13 
Overall Mean and Mean Change in CST from Baseline (boxplot) 
14.11.2.14 
Mean Change in IOP from Baseline (descriptive) 
14.11.2.15 
Mean Change in IOP from Baseline (boxplot) 
14.11.2.16 
Time to Improvement of Baseline BCVA by at Least 5, 10, and 15 Letters (days) (descriptive) 
14.11.2.17 
Duration of Maintained Improvement of Baseline BCVA by at Least 5, 10, and 15 Letters (days) 
(descriptive) 
14.11.2.18 
Percentage of Subjects with Improvement from Baseline CST by at Least 10% (descriptive) 
14.11.2.19 
Percentage of Subjects with Improvement from Baseline CST by at Least 20, 50, and 75µm 
(descriptive) 
14.11.2.20 
Percentage of Subjects with Increase of IOP of at Least 5, 10, and 30 mmHg from Baseline (n, %) 
14.11.2.21 
Percentage of Subjects with Increase of IOP of at Least 5, 10, and 30 mmHg from Baseline (bar chart) 
14.11.2.22 
Course of IOP through the First 60 Minutes After Administration of Study Drug (descriptive) 
14.11.2.23 
Course of IOP through the First 60 Minutes After Administration of Study Drug (dot plot) 
14.11.2.24 
Percentage of Subjects with Elevated IOP by at Least 10mmHg at Over 60 Minutes After 
Administration (descriptive) 
14.12. Follow-On by Treatment Dose by Visit for the SAF Population 
14.12.1 
Follow-On Treatment Eligibility Measurements (n, %)