Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveitis
Objective: Uveitis refers to intraocular inflammatory diseases that are an important cause
of visual loss. Standard systemic immunosuppressive medications for uveitis can cause
significant adverse effects and many patients continue to experience disease flare-ups.
Sirolimus suppresses cytokine-driven T-cell proliferation and thus, inhibits the production,
signaling and activity of many growth factors relevant to uveitis. Subconjunctival sirolimus
administration could reduce or eliminate the need for topical and/or systemic
immunosuppressive drugs that could result in reduced morbidity. This protocol will
investigate subconjunctival sirolimus as a possible treatment for active anterior uveitis.
Study Population: Five participants with active anterior uveitis will be initially accrued
in this study. Participants must require treatment for their uveitis with systemic and/or
topical anti-inflammatory medications at high frequency intervals [greater than or equal to
three times daily (T.I.D.)] or local steroid treatment (periocular steroid injections) is
contraindicated because of significant intraocular pressure (IOP) elevation with local
steroid treatments in the past (i.e., steroid responder), have at least a grade of 1+ for
anterior chamber cells and have visual acuity of at least 20/400 in the study eye. Up to
seven participants may be enrolled, as up to two participants may be accrued to replace
enrolled participants who withdraw from the study prior to receiving any study medication.
Design: This is a Phase I, non-randomized, prospective, uncontrolled single-center study to
evaluate subconjunctival sirolimus as a treatment for active anterior uveitis. All
participants will receive a single 30-microL (1,320 microg) subconjunctival sirolimus
injection in the study eye at baseline and will be followed for 16 weeks post-injection.
Outcome Measures: The primary outcome is the number of participants who experience at least
a 2-step reduction in anterior chamber inflammation within four weeks post-injection.
Secondary outcomes include changes in visual acuity and anterior chamber inflammation
grading, the number of participants who experience a disease flare within the 16-week study
duration and, of the participants who experience a disease flare, the number of days to
disease flare from baseline. Secondary outcomes also include the presence or extent of
cystoid macular edema.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary outcome is the number of participants who experience at least a 2-step reduction in inflammation within four weeks post-injection.
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|