Efficacy and Safety Evaluation of Dexamethasone (OCS-01) Eye Drops in Diabetic Macular Edema: A Phase 3 Randomized, Double-Masked, Multicenter Study

The primary objective of this Phase 3, double-masked, randomized, multicenter study is to evaluate the **efficacy** and **safety** of OCS-01 eye drops, containing **dexamethasone**, compared to a vehicle in subjects with **Diabetic Macular Edema (DME)** over a 52-week period. This objective is clinically relevant as DME is a common complication of diabetes that can lead to vision impairment, and effective treatment options are crucial for preserving vision and improving quality of life in affected individuals.

The clinical trial involves a total of **215 participants** diagnosed with **Diabetic Macular Edema (DME)**. The study population comprises both male and female adults aged between **18 to 85 years**. Participants were selected based on specific inclusion criteria, including a documented diagnosis of Type 1 or Type 2 diabetes mellitus, with an HbA1c level of ≤ 10.0% prior to screening. The trial includes individuals who are either treatment-naïve or have undergone previous treatments with anti-VEGF agents or corticosteroids, adhering to specified washout periods. Participants are required to have a **Best Corrected Visual Acuity (BCVA)** ETDRS letters score within a defined range in the study eye. The trial population includes vulnerable groups, and women of childbearing potential must have a negative pregnancy test and use adequate birth control throughout the study. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, double-masked, multicenter study to evaluate the efficacy and safety of OCS-01 eye drops in subjects with **Diabetic Macular Edema (DME)**. The trial will compare the investigational product, OCS-01, against a vehicle control over a period of 52 weeks. Participants will be randomly assigned to either the treatment or control group, ensuring that neither the participants nor the investigators know which treatment is being administered, thus maintaining the double-masked nature of the study.

The trial will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as age between 18 to 85 years, documented diagnosis of Type 1 or Type 2 diabetes mellitus, and specific visual acuity requirements. Participants must also be treatment-naïve or meet specific washout periods for previous treatments. Following successful screening, eligible participants will be enrolled and begin the treatment phase.

Throughout the trial, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. These visits will include assessments of **Best Corrected Visual Acuity (BCVA)** using the Early Treatment Diabetic Retinopathy Study (ETDRS) letters score, central subfield thickness (CST) measurements via SD-OCT, and safety evaluations such as adverse events, intraocular pressure, and other relevant clinical parameters. The primary endpoint is the mean change in BCVA ETDRS letters score at Week 52 compared with baseline.

The expected duration of participant involvement is approximately 52 weeks, with the possibility of early termination if specific conditions arise, such as significant adverse events or withdrawal of consent. The trial is anticipated to conclude by February 2026, with recruitment starting in May 2024. Participants will have an end-of-study visit to perform final assessments and ensure all study-related procedures are completed.

The clinical trial involves the evaluation of **OCS-01**, an investigational medication formulated as **eye drops, suspension**. The active substance in OCS-01 is **dexamethasone**, a chemical compound known for its anti-inflammatory properties. The pharmaceutical form is specifically designed for **ocular use**, ensuring targeted delivery to the eye. The maximum daily dose of OCS-01 is 2.7 mg, with a total maximum dose of 548.1 mg over the course of the study. The treatment period extends up to 52 weeks, with the medication administered as per the dosing schedule determined by the study protocol. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence and accurate assessment of the drug's efficacy and safety.

In addition to the experimental treatment, the study includes a **placebo** group for comparison. The placebo is also administered in the form of eye drops, suspension, and is used to evaluate the efficacy of OCS-01 by providing a baseline for comparison. The placebo is designed to be indistinguishable from the active treatment in appearance and administration, ensuring the study remains double-masked. The administration schedule for the placebo mirrors that of the experimental treatment, maintaining consistency across study groups.

The efficacy of OCS-01 eye drops in subjects with **Diabetic Macular Edema** (DME) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the mean change in Best Corrected Visual Acuity (BCVA) as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letters score at Visit 12 (Week 52) compared with baseline. Secondary endpoints include the proportion of subjects achieving a 3-line or greater gain in BCVA assessed with the ETDRS scale at Visit 12 (Week 52) compared with baseline, and the area under the curve (AUC) of BCVA ETDRS letter changes across postbaseline visits up to Visit 12 (Week 52).

Additional secondary efficacy measures involve the mean change in central subfield thickness (CST) as measured by spectral-domain optical coherence tomography (SD-OCT) at Visit 12 (Week 52) compared with baseline, as well as at each postbaseline visit. The mean change in BCVA ETDRS letters score at each postbaseline visit compared with baseline will also be evaluated, along with the proportion of subjects with a 3-line or greater gain in BCVA at each postbaseline visit. These assessments will be conducted using validated scales and instruments, ensuring the reliability and accuracy of the efficacy data collected throughout the trial.