Sirolimus Injections for Autoimmune Scleritis
- Autoimmune scleritis is an inflammatory disease that affects the white outer part of the eye. It is associated with immune system disorders like rheumatoid arthritis. It can cause blindness in severe cases. Most treatments for scleritis involve steroid or immune-suppressing drugs, but these can cause side effects in the whole body.
- Sirolimus is a drug used to help prevent transplant rejection. It helps prevent the immune system from attacking the body. Researchers want to try giving sirolimus injections into the eye to treat severe scleritis.
- To see if sirolimus is a safe and effective treatment for autoimmune scleritis.
- Individuals at least 18 years of age with autoimmune scleritis in at least one eye that has not responded to standard treatments.
- Participants will be screened with a medical history, physical exam, and eye exam. Blood and urine samples will also be collected.
- One eye will be selected as the study eye to receive injections.
- Participants will have six study visits over 4 months (initial visit and weeks 2, 4, 8, 12, and 16). The injection will be given at the first visit. If the study eye responds to the treatment, participants may have injections in the other eye at the second visit.
- If there is still inflammation after the first injection, or if the scleritis improves but then returns, participants may have a second injection at Week 4.
- Treatment will be monitored with blood tests and eye exams.
- Participants may have study visits and injections for up to 1 year if the treatment seems to be working.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study to Investigate Subconjunctival Sirolimus for the Treatment of Active Autoimmune Non-Necrotizing Anterior Scleritis|
- The number of participants who experience at least 2-step reduction or reduction to grade 0 of scleral infammation in the study eye according to the NEI photographic scleritis grading system within 8 weeks post-injection.
- Changes in vision, number of participants who experience a disease flare within 16 weeks, number tapered from immunosuppression after 16 weeks and, number of days to flare from baseline as well as number who require a second injection due to a f...
- Number and severity of systemic and ocular toxicities and adverse events, the number who experience vision loss of & iexcl, & Yacute; 15 Early Treatment Diabetic Retinopathy Study letters and number of participants who experience a rise ...
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||January 2015|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Scleritis is a chronic, painful and potentially blinding inflammatory disease characterized by edema of the episcleral and scleral tissues and is commonly associated with systemic autoimmune disorders. Sirolimus suppresses cytokine-driven T-cell proliferation and thus, inhibits the production, signaling and activity of many growth factors relevant to scleritis. Subconjunctival sirolimus administration could reduce or eliminate the need for topical and/or systemic immunosuppressive drugs often taken with immunosuppressive disorders that could result in reduced morbidity. The study objective is to investigate the safety, tolerability and potential efficacy of subconjunctival sirolimus as a possible treatment for active, autoimmune, non-necrotizing, anterior scleritis.
Five participants with active, autoimmune, non-necrotizing, anterior scleritis with scleral inflammatory grade of greater than or equal to 1 plus in at least one quadrant will be initially enrolled. Participants must have a history of past flares requiring oral NSAIDS, or oral or topical corticosteroids or immunosuppressive medication. Up to seven participants may be enrolled, as up to two participants may be accrued to account for participants who withdraw from the study prior to receiving any investigational product.
This is a phase I, single-center, open-label, non-randomized, prospective and uncontrolled pilot study to evaluate the safety and possible efficacy of subconjunctival sirolimus injections for active, autoimmune, non-necrotizing, anterior scleritis. If two eyes are active, the eye with worse inflammation will be injected first (study eye) at baseline followed two weeks later with injection of the second eye (fellow eye). If both eyes have equal inflammation, the study eye will be chosen at the physician's discretion after consultation with the participant. Participants that still demonstrate active inflammation or experience a flare-up after the initial study eye injection may be eligible for a re-injection at or after Week 4 (not to exceed a dose of 1,320 microgram per eye within an eight-week period).
The primary outcome is the number of participants who experience at least a 2-step reduction or reduction to grade 0 of scleral inflammation in the study eye according to a standardized photographic scleritis grading system developed at NEI by the Week 8 visit. Secondary outcomes include changes in visual acuity, step changes in scleral inflammation, the number of participants who experience a disease flare, the number of participants tapered from the standard immunosuppressive regimen after 16 weeks and, of the participants who experience a disease flare, the number of days to disease flare from baseline as well as the number of participants who require re-injection due to a flare. Safety outcomes include the number and severity of systemic and ocular toxicities and adverse events (AEs), the proportion of participants who experience vision loss greater than or equal to 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Hatice N Sen, M.D.||National Eye Institute (NEI)|