Sirolimus Versus Anti-Vascular Endothelial Growth Factor (antiVEGF) for Wet AMD

Phase 2 clinical trial, single site, randomized, subject-masked study to determine safety and efficacy of intravitreal injections of Sirolimus in subjects with wet Age-Related Macular Degeneration (wet AMD) with persistent intraretinal or subretinal edema due to neovascular AMD despite previous AntiVEGF treatment.

Forty subjects will be randomized to receive intravitreal Sirolimus or standard of care treatment in a 1:1 ratio. Over the course of the six month trial plus a 6 month optional extension, subjects will be evaluated monthly. Treatment with Sirolimus will be given at baseline, month 2 and month 4 with sham injections given at months 1, 3 and 5. For subjects in the extension Sirolimus will also be given at months 6, 8 and 10 with sham at month 7, 9, and 11. Subjects in the standard of care group will receive anti-VEGF injections or sham monthly. Retreatment criteria will be based upon continued subretinal edema, intraretinal edema or active chorioretinal neovascularization (CNV)

Change in Edema From Baseline to Month 6 Central Subfield Thickness ) on Heidelberg Optical Coherence Topography

Change in edema from baseline to month 6 as measured by mean difference in microns of central subfield thickness on Heidelberg optical coherence topography in each treatment group

Inclusion Criteria: best corrected visual acuity of 5-65, inclusive, in study eye presence of choroid neovascularization secondary to AMD persistent edema despite at least 3 previous intravitreal anti-VEGF injections in the past 5 months Exclusion Criteria: greater than 100 micron decrease in central subfield thickness on Optical Coherence Topography (OCT) since last standard of care visit history of major ophthalmic surgery in the study eye in the past 3 months history of significant ocular disease or condition other than exudative AMD that may confound results

Minturn RJ, Bracha P, Klein MJ, Chhablani J, Harless AM, Maturi RK. Intravitreal sirolimus for persistent, exudative age-related macular degeneration: a Pilot Study. Int J Retina Vitreous. 2021 Feb 16;7(1):11. doi: 10.1186/s40942-021-00281-0.