Phase 1 Iontophoretic Delivery of Dexamethasone for Tx of Anterior Scleritis

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ABSTRACT Non-infectious scleritis is an inflammatory disease of the eye wall (sclera). Its estimated US prevalence is 50,000. Scleritis typically is managed with oral non-steroidal inflammatory drugs, systemic corticosteroids, and/or systemic immunosuppressive drugs. In tertiary settings, most patients require long-term therapy, including systemic corticosteroids and/or immunosuppression. Even in the context of systemic disease, scleritis often drives the treatment regimen. For this high impact orphan disease, an effective locally administered treatment regimen that avoided systemic side effects would be very desirable. This proposal requests funding for an initial evaluation of iontophoretic delivery of dexamethasone for non-infectious, non-necrotizing scleritis, conducted under IND. Eyegate Pharma is developing an iontophor-etic delivery system to deliver dexamethasone phosphate ophthalmic solution (40 mg/mL) to the eye, targeting the indications of uveitis and dry eyes. Dexamethasone is a well-known corticosteroid, available in other formulations for ocular and systemic delivery for decades. We consider iontophoretic corticosteroid delivery as likely to be effective for treatment of scleritis, because it provides a means of delivering drug past the subconjunctival vascular plexus, which rapidly clears eyedrops. Available evidence suggesting that iontophoretically delivered dexamethasone may be effective for scleritis includes: effectiveness of systemic corticosteroids and depot corticosteroids placed adjacent to the sclera for scleritis, and partial effectiveness of corticosteroid eyedrops. No development-limiting adverse events have been encountered in 42 uveitis patients and 105 dry eye patients enrolled in studies evaluating iontophoretic delivery of dexamethasone. The proposed study-phase 1, but not first-in-human-will aim to assess the safety and tolerability of iontophoretic delivery of dexamethasone for anterior scleritis in a dose-varying study. Sets of four patients will be enrolled and treated. The dose for the next set will be increased or else the study terminated based on the incidence of dose- limiting toxicity at each dose. The primary objective of this study is to identify a range of doses that appear safe and tolerable. The secondary objective is to provide a preliminary assessment of efficacy based on observed responses to treatment and the proportion requiring rescue therapy. If results are favorable, further development of the approach in phase 2 studies is planned.