Vizol S DIGI EYE Efficacy and Safety Study in Patients With Dry Eye

• Vizol S DIGI EYE eye drops (Drug), also known as Test, (T): 1 drop 4 times a day
• 0,9% saline solution, eye drops (Drug), also known as Control, (C): 1 drop 4 times a day

Primary outcomes

• Mean change in the tear film break-up time (TFBUT) from Visit 1 (baseline) to Visit 2 (day 14) [baseline and week 2 follow up]: Tear film break-up time (TBUT) will be assessed following the instillation of fluorescein solution into the eye. Fluorescein will be instilled at the outer canthus to avoid ocular surface damage, with the excess saline on the strip shaken off, or a reduced area fluorescein strip used. Viewing will take place between 1 and 3 min after instillation. Two measurements per eye will be performed and the mean value documented and used for evaluation.

Secondary outcomes

• Mean change in the tear film break-up time (TFBUT) from Visit 1 (baseline) to Visit 3 (day 28) [baseline and week 4 follow up]: Tear film break-up time (TFBUT) will be assessed following the instillation of fluorescein solution into the eye. Fluorescein will be instilled at the outer canthus to avoid ocular surface damage, with the excess saline on the strip shaken off, or a reduced area fluorescein strip used. Viewing will take place between 1 and 3 min after instillation. Two measurements per eye will be performed and the mean value documented and used for evaluation
• percent (%) change in the tear film break-up time (TFBUT) from Visit 1 (baseline) to Visit 2 (day 14) and from Visit 1 (baseline) to Visit 3 (day 28) [baseline and week 2 follow-up; baseline and week 4 follow-up]: Tear film break-up time (TFBUT) will be assessed following the instillation of fluorescein solution into the eye. Fluorescein will be instilled at the outer canthus to avoid ocular surface damage, with the excess saline on the strip shaken off, or a reduced area fluorescein strip used. Viewing will take place between 1 and 3 min after instillation. Three measurements per eye will be performed and the mean value documented and used for evaluation
• change in the tear film break-up time (TFBUT) on Visit 1 (day 1) [baseline and 4 hour after 1st application]: Tear film break-up time (TBUT) will be assessed following the instillation of fluorescein solution into the eye. On Day 1 TBUT will be assessed at two time points (baseline and 4 hours post-dose). Fluorescein will be instilled at the outer canthus to avoid ocular surface damage, with the excess saline on the strip shaken off, or a reduced area fluorescein strip used. Viewing will take place between 1 and 3 min after instillation. Two measurements per eye will be performed and the mean value documented and used for evaluation.
• Mean change in ocular surface disease index (OSDI) score from Visit 1 (baseline) to Visit 2 (day 14) and Visit 3 (day 28) [baseline, week 2 follow-up and week 4 follow-up]: Symptoms of DED will be assessed using the Ocular Surface Disease Index (OSDI) questionnaire at each visit. The 12-item OSDI questionnaire scores range from 0 to 100, it contains 3 ocular symptom questions, 6 vision-related function questions, and 3 environmental trigger questions. Each question score ranges from 0 ("none of the time") to 4 ("all of the time"). The total score is calculated based on the following formula: Total score: OSDI = (\[sum of scores for all questions answered*100\]/\[total number of questions answered*4\]).
• Mean changes in ocular surface staining score (OSS) (total corneal and total conjunctival staining score) from Visit 1 (baseline) to Visit 2 (day 14) and Visit 1 to Visit 3 (day 28) [baseline, week 2 follow-up and week 4 follow-up]: Ocular surface staining of five corneal regions and six conjunctival regions will be observed at each visit by slit-lamp examination after instillation of fluorescein respectively. Surface staining will be scored as 0 (normal, no staining), 1 (mild, superficial stippling or macropunctate staining), 2 (moderate, macropunctate staining with some coalescent areas), or 3 (severe, numerous coalescent macropunctate areas or patches). Scores will be summed to yield total corneal and total conjunctival staining scores for each eye.
• Change in Dry Eye Symptom Score (DESS) on Visit 1 (day 1) [baseline and 0, 4 and 8±1 hour after 1st application]: Dry Eye Symptom Score will be assessed, using a 10-point Likert scale, where 0 indicates no symptoms and 10 indicates the most severe symptoms, based on the change from baseline in dry eye symptom scores on day 1 (baseline and 0, 4, and 8±1 hours after 1st dose application). Median values will be documented and used for evaluation.
• Change in Soothing Sensation Score (SSS) on Visit 1 (day 1) [baseline and 0, 4 and 8±1 hour after 1st application]: Soothing Sensation Score will be assessed, using a 10-point Likert scale, where 0 indicates no symptoms and 10 indicates the most severe symptoms, based on the change from baseline in soothing sensation scores on day 1 (baseline and 0, 4, and 8±1 hours after 1st dose application). Median values will be documented and used for evaluation.
• Change in Refreshing Effect Score (RES) on Visit 1 (day 1) [0, 0.25 and 1 hour after 1st application]: Refreshing Effect Score will be assessed, using a 10-point Likert scale on day 1 (0, 0.25 and 1 hour after 1st dose application), where 0 indicates no symptoms and 10 indicates the most severe symptoms. Median values will be documented and used for evaluation.

Other outcomes

• The presence of Adverse Event/ /Serious Adverse Event (AE/ /SAE) throughout the investigation period [baseline, week 2 follow-up and week 4 follow-up]: The patients will be asked to report any Pre-Treatment Sign and symptom/Adverse Events (PTSS/AEs) spontaneously.
• Best-corrected visual acuity (BCVA) [baseline, week 2 follow-up and week 4 follow-up]: Best corrected visual acuity (BCVA) will be assessed at each visit. BCVA assessment will be at 4 meters using an ETDRS chart (The Early Treatment Diabetic Retinopathy Study Group). Results will be calculated as logMAR scores. The logMAR scale (logarithm of the Minimum Angle of Resolution) ranges approximately from -0.3 to 1.0, where lower scores indicate better visual acuity and higher scores indicate worse visual acuity.
• Frequency of ocular signs [baseline, week 2 follow-up and week 4 follow-up]: Ocular signs will be assessed by slit-lamp examination at all study visits. The following signs will be assessed: • active inflammation or significant structural change or discharge (eyelids and conjunctiva); • active inflammation or active structural change, including focal scarring and fine deposition (cornea); • active inflammation (iris and anterior chamber); • level of lens opacity, pseudophakia, or aphakia (lens, with an emphasis on the visual axis)
• Change in tolerability assessment score (TAS) on Visit 1 (day 1) [Day 1]: Tolerability Assessment Score will be assessed on Day 1 following instillation. The symptoms (burning sensation, stinging sensation, blur, and foreign body sensation) will be evaluated using a a 10-point Likert scale, where 0 indicates no symptom and 10 indicates the most severe symptom. Tolerability Assessment Score will be listed and evaluated descriptively (number of patients (N), arithmetic mean, standard deviation (SD), median, minimum, and maximum). Results for 0-5 and 6-10 scores will be summarized using counts and percentages.

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* ≥18 years of age;
* Diagnosis of moderate to severe dry eye disease (DED) with a baseline
* Ocular Surface Disease Index (OSDI) score ≥23 (approximately 15% of the population should wear contact lenses);
* Tear Film Break-Up Time (TBUT) <10 s in one or both eyes at baseline;
* National Eye Institute (NEI) score for corneal fluorescein surface staining >5/15 and for conjunctival fluorescein surface staining >6/18 at baseline;
* Best corrected visual acuity (BCVA) of ≥20/80 (or ≥55 letters score or ≥0.6 Early Treatment Diabetic Retinopathy Study log of the minimum angle of resolution value) in both eyes at screening;
* Use of electronic devices (e.g., computers, laptops, smart phones, tablets, televisions (TVs), electronic book readers) with digital screens for more than 6 hours daily;
* Use of eyelid hygiene for at least 14 days prior to screening;
* Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the patients participating in the clinical trial.

Exclusion Criteria:

* History of hypersensitivity or intolerance to any component of investigational product (IP);
* History of hypersensitivity to fluorescein;
* Any active ocular disease or any anterior ocular surface findings (diseases and irregularities) other than dry eye disease;
* Ocular or refractive surgery (e.g., LASIK, photorefractive keratectomy (PRK) etc.) within the last 12 months from screening;
* Current punctual occlusion of any type;
* History of ocular trauma;
* History of herpes simplex or herpes zoster keratitis;
* History of any type of corneal ulcers;
* Any other acute or chronic disease which may interfere with the aims of the clinical trial or other relevant ocular pathology judged by the investigator that preclude safe administration of the IPs;
* Systemic diseases that alter the ocular surface;
* History of severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator;
* History of malignancy (other than localized basal cell carcinoma of the skin or in situ cervical cancer);
* Use any topical ophthalmic medication within the last 30 days (except for artificial tears or lubricants; patients will be required to discontinue any other artificial tear or lubricants within the last 14 days and during the trial);
* Use of systemic medications that may contribute to dry eye (unless on a stable regimen for ≥30 days before screening and throughout the study);
* History of or current drug or alcohol dependence;
* Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test;
* History of Coronavirus Disease 2019 (COVID-19) within the last 30 days (to be defined in line with national requirements);
* History of direct contact with insufficient protection to persons with COVID-19 within the last 14 days (to be defined in line with national requirements);
* Pregnancy or breastfeeding;
* Female patients with childbearing potential (any female after menarche unless postmenopausal for ≥12 months, or surgically sterilized) who are not willing to use a highly effective method of contraception during the study;
* Positive pregnancy test, for female patients with childbearing potential only;
* Patients suspected or known not to follow instructions;
* Patients who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial;
* Participation in another clinical trial within 3 months before screening or over a period of 5 half-lives, or double duration of the biological effect of the investigational product received, whichever is longer.

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• D. Veselinović, Prof. dr, Principal investigator, Specialized clinic for eye disease - klinika Veselinović