Efficacy and Safety of Hydrocortisone Sodium Phosphate in Dry Eye Disease with Moderate Meibomian Gland Dysfunction: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of topical hydrocortisone treatment in patients with **Dry Eye** and moderate **Meibomian Gland Dysfunction** (MGD). The study aims to compare the change in MGD-DE symptom score from baseline (D0) to Day 14 (D14) in patients treated with lid hygiene, artificial tears, and a medical device (BlephaEyeBag®) with or without hydrocortisone. This is clinically relevant as it seeks to determine the effectiveness of hydrocortisone in alleviating symptoms associated with these conditions, potentially improving patient outcomes.

The secondary objectives include assessing the efficacy of the treatment by evaluating ocular symptoms and signs of Dry Eye and MGD. This involves measuring changes in the Ocular Surface Disease Index (OSDI) score and Visual Analogue Scale (VAS) score for symptoms such as itching, dry eye sensation, burning, foreign body sensation, ocular redness, ocular fatigue, and blurry vision. Additionally, ocular signs such as conjunctival hyperemia, tear film stability, ocular surface damage, and tear volume will be assessed. The study also aims to evaluate the grading of MGD, lid abnormalities, and eyelid telangiectasia. Safety assessments include monitoring the safety of the medication and changes in visual acuity over time, as well as the incidence of increased intraocular pressure (IOP) between D0, D14, D28, and D84. These secondary objectives are crucial for understanding the broader impact of the treatment on ocular health and safety.

The clinical trial involves participants diagnosed with **Dry Eye** and **Meibomian Gland Dysfunction**. The study population includes both male and female subjects aged 18 years and older, with a documented diagnosis of dry eye disease characterized by a tear break-up time (TBUT) of 5 seconds or less, and moderate symptoms indicated by an OSDI score greater than 23. Participants must have normal ophthalmic findings except for the conditions under study. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants. Participants are required to understand the study instructions and adhere to the prescribed medications. They must also provide informed consent before participating in the study. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the **efficacy** and safety of topical **hydrocortisone sodium phosphate** treatment in patients with dry eye disease associated with moderate meibomian gland dysfunction. This is a randomized, double-blind, controlled trial with an estimated duration from October 2021 to April 2025. Participants will be randomly assigned to receive either the investigational treatment or a control, with both groups undergoing lid hygiene, artificial tears, and the use of a medical device, BlephaEyeBag®. The primary objective is to assess the change in MGD-DE symptom score from baseline to Day 14, with secondary endpoints including changes in ocular symptoms and signs, as well as safety assessments such as intraocular pressure and adverse events.

The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age ≥ 18 years, documented diagnosis of dry eye with a TBUT value ≤ 5 seconds, and an OSDI score > 23. Participants will then attend follow-up visits on Days 14, 28, and 84 to monitor changes in symptoms, inflammatory cytokine levels in tears, and safety parameters. The end-of-study visit will occur on Day 84, marking the conclusion of the participant's involvement. The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including non-compliance with study procedures or the occurrence of serious adverse events.

The clinical trial involves the use of **Softacort 3.35 mg/ml**, an experimental medication formulated as **eye drops, solution**. The active substance in this medication is **hydrocortisone sodium phosphate**, a chemical compound. The medication is administered via **ocular use**. The dosage regimen includes a maximum daily dose of 4 drops, with a total maximum dose of 42 drops over the treatment period. The maximum treatment period is 12 weeks. The eye drops are provided in single-dose containers, ensuring sterility and ease of use. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

In addition to the experimental medication, the study includes non-experimental treatments as part of the standard-of-care therapy for participants. These treatments consist of lid hygiene, the use of artificial tears, and a medical device known as **BlephaEyeBag**. The BlephaEyeBag is a silk and cotton device that can be reheated in a microwave, designed to provide therapeutic warmth to the eyelids. This device is used to manage symptoms associated with moderate meibomian gland dysfunction, a condition linked to dry eye disease. The combination of these treatments aims to evaluate the efficacy and safety of the experimental medication in comparison to standard care.

The efficacy of the clinical trial will be assessed by evaluating changes in the **Meibomian Gland Dysfunction-Dry Eye (MGD-DE)** symptom score from baseline (Day 0) to Day 14. This primary endpoint will determine the effectiveness of the treatment regimen, which includes lid hygiene, artificial tears, and the use of a medical device (BlephaEyeBag®), with or without the addition of hydrocortisone. Additionally, exploratory efficacy will be assessed by measuring changes in the levels of inflammatory cytokines in tears, including IL-6, TNF alpha, IL-1b, IL-10, IFNγ, IL-17A, IL-2, and IL-4, from baseline to Day 14.

Secondary efficacy endpoints include changes in the Ocular Surface Disease Index (OSDI) score and MGD-DE symptom score at various timepoints (Day 14, Day 28, and Day 84). Other secondary endpoints involve changes in visual analog scale (VAS) scores for symptoms such as itching, dry eye sensation, burning, foreign body sensation, ocular redness, ocular fatigue, and blurry vision. Ocular signs of dry eye disease (DED) will be evaluated through changes in hyperemia score, tear break-up time (TBUT), and corneal and conjunctival staining using the Oxford grading scale and Van Bijsterveld scale. The Schirmer I test will also be conducted to assess tear production. Ocular signs of MGD will be graded on a scale from 0 to 4, and lid abnormalities will be scored from 0 to 2, with assessments conducted up to Day 84.