Safety and efficacy of topical OCS-01 ophthalmic suspension for the treatment of diabetic macular oedema: stage 1 of a multicentre, double-blind, randomised, vehicle-controlled phase 2/3 trial.

Background: Topical ocular treatments for diabetic macular oedema (DMO) have not previously been considered effective. We aimed to assess the efficacy and safety of topical OCS-01 (dexamethasone 1.5% ophthalmic suspension) in the treatment of DMO. Methods: This is a multicentre, double-blind, randomised, vehicle-controlled phase 2/3 trial. The objective of Stage 1 (reported herein, Stage 2 is ongoing) was to evaluate the efficacy and safety of a dosing regimen of OCS-01 to use in Stage 2, specifically to estimate the magnitude of the treatment effect on BCVA. Stage 1 was conducted at 27 ophthalmology clinics in the USA and four in Hungary. Patients aged 18-85 years with DMO involving the central macula (central subfield thickness (CST) ≥310 μm by SD-OCT), and ETDRS letter score 24-65 in the study eye were included in the study. Key exclusion criteria were macular oedema with causes other than DMO, decreased BCVA due to causes other than DMO, significant macular ischemia which would have prevented gain in BCVA, or other ocular disease that may have caused substantial reduction in BCVA. Patients were randomised, using an automated interactive response system to generate randomisation codes, stratified for baseline BCVA (<60 versus ≥60) and lens status (phakic or nonphakic), in blocks of 6 in a 2:1 ratio to receive topical ocular OCS-01 or matching vehicle. Treatment was given six times/day for 6 weeks (loading phase), followed by three times/day for 6 weeks (maintenance phase). Patients, investigators and the study team were masked to treatment assignment. Masking of treatment was maintained by using a vehicle that was identical to OCS-01 but did not contain dexamethasone, and OCS-01 and vehicle were supplied in identical packaging. The primary endpoint was change from baseline to Week 6 in ETDRS letter score in the Intent-to-Treat Set (all randomised patients). Safety analyses were based on the Safety Set (all patients who received ≥1 dose of study drug). The trial is registered with ClinicalTrials.gov, NCT05066997. Findings: Between Oct 5, 2021 and March 16, 2023, 100 patients (53 male, 47 female) received OCS-01 and 48 (26 male, 22 female) received vehicle; 85 and 39 patients, respectively, completed the study. LS mean (SE) change from baseline to Week 6 in BCVA ETDRS letter score was significantly greater with OCS-01 than Vehicle: 7.2 (0.85) letters versus 3.1 (1.26) letters (LS mean difference 4.1 (1.52) letters, 95% CI 1.1,7.0, p = 0.0070). Ocular adverse events (AEs) in the study eye occurred in 47/100 (47%) patients in the OCS-01 group and 22/48 (46%) Vehicle patients. Interpretation: Whilst acknowledging that no formal hypothesis was tested in Stage 1, topical OCS-01 was well tolerated, with no unexpected safety findings, and improved visual acuity in patients with DMO over the 12-week duration of Stage 1 of this study. Further data are required. The dosing regimen was found to be appropriate for use in Stage 2, which will provide longer-term data. Funding: Oculis Sàrl, Lausanne, Switzerland.