Aims To Investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Meniere’s disease (MD) Methodology The study was divided into two cohorts: an open-label trial with 10 adults, followed by a randomized trial with 11 adults (5 saline control; 6 SPT-2101). All participants had a diagnosis of unilateral definitive MD per Barany society criteria. The active treatment comprised a single injection of SPT-2101 performed in-office using micro-endoscopy to enable direct round-window niche visualization, with a saline placebo treatment arm. Outcome measures included overall safety, vertigo days (VDs) and definitive vertigo days (DVDs – days with vertigo episodes lasting 20 minutes or more), hearing thresholds, and Tinnitus and Dizziness Handicap Inventory (THI and DHI) scores collected at baseline and up to 3 months post-treatment. Participants randomised to the placebo group had to option to crossover if vertigo symptoms remained (n=4) Results There were no reported Serious Adverse Events or unexpected Adverse Events, and no impact on hearing thresholds. In Cohort 1, average VDs decreased from 15.07 to 2.95 in month 3. In Cohort 2, there was a significantly greater decrease in VDs for the treatment group (9.68 to 1.80) than the control group (9.48 to 9.84) (p<0.05). Average DVDs decreased from 2.82 to 0.67 for the treatment group, while the control group increased from 5.62 to 7.11 (p<0.05). There was no significant difference in DHI or THI scores from baseline to 3 months post-treatment. Two of the three participants who completed their crossover treatment showed resolution of their severe vertigo with treatment Conclusion Higher dexamethasone exposures resulted in better vertigo management, regardless of frequency and severity, during the treatment period, and treatment with SPT-2101 led to statistically superior vertigo management compared to control group