Gevokizumab Treatment for Active Scleritis By IL-1 Inhibition (GATSBY)

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Scleritis is a chronic, painful and potentially blinding inflammatory disease characterized by edema of the episcleral and sclera tissues and is commonly associated with systemic autoimmune disorders. Gevokizumab is an interleukin-1β (IL-1β) inhibitor, thus possibly preventing the IL-1β that may be responsible for scleral breakdown in patients with anterior scleritis. The study objective is to evaluate the safety and potential efficacy of gevokizumab as a possible treatment of non-infectious, active, anterior scleritis. Study Population: Ten participants with non-infectious, active, anterior scleritis with a scleral inflammatory grade of ≥ +1 in at least one eye will be initially enrolled. However, up to an additional two participants may be enrolled to account for participants who withdraw from the study prior to Week 16. Participants may be on ≤ 20 mg/day of prednisone or the equivalent at the time of enrollment but all other immunosuppressive drugs will be stopped with the initiation of study drug. This is a Phase 1/2, open label, non-randomized, prospective, single-arm, pilot trial to evaluate the safety and potential efficacy of gevokizumab in non-infectious, active, anterior scleritis. The study consists of an initial phase followed by an extension phase. For the initial phase, all participants will receive one subcutaneous injection of 60 mg gevokizumab at Baseline and Weeks 4, 8 and 12. At Week 16, participants will be assessed for eligibility in the extension phase of the study. Participants who do not continue in the extension phase of the study will discontinue the study drug and may receive salvage therapy using standard-of-care treatment at the investigators discretion. Participants who do not continue in the extension phase will return for a final safety visit at Week 28. Participants who are determined eligible for the extension phase may continue in the extension phase and receive one gevokizumab injection (60 mg) every four weeks until the Week 36 visit. Participants in the extension phase will have safety visits at Weeks 40 and 52. The primary outcome is the number of participants with at least a 2-step reduction or reduction to grade 0 in scleral inflammation in the study eye (or eyes, if both eyes meet study eye criteria), according to a standardized photographic scleritis grading system developed at NEI (see Appendix 3), on or before the Week 16 visit as compared to Baseline. Secondary outcomes include changes in visual acuity, changes in intraocular pressure and changes in scleral grading. Safety outcomes include the number and severity of systemic and ocular toxicities and adverse events (AEs), and the proportion of participants with loss of ≥ 15 ETDRS letters at any follow-up visit.