Clinical trial NCT01517074
Conditions: Scleritis
Keywords: Sirolimus Scleritis Autoimmune Scleritis
Sponsor: National Eye Institute (NEI)
Start date: 2012-01-01; Completion date: 2014-04-01
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

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.

Objectives:

To see if sirolimus is a safe and effective treatment for autoimmune scleritis.

Eligibility:

Individuals at least 18 years of age with autoimmune scleritis in at least one eye that has not responded to standard treatments.

Design:

* 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.
* Injections will be monitored with blood tests and eye exams.
* Participants may have study visits and injections for up to 1 year if the injections seem to be working.

Detailed description:
OBJECTIVE:

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.

STUDY POPULATION:

Five participants with active, autoimmune, non-necrotizing, anterior scleritis with scleral inflammatory grade ≥ 1+ in at least one quadrant will be initially enrolled. Participants must have a history of past flares requiring oral non-steroidal anti-inflammatory drugs (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.

DESIGN:

This is a phase I/II, 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 μg per eye within an eight-week period).

OUTCOME MEASURES:

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 the National Eye Institute (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 ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).

Arms: arm 1: Participants will receive a15 μL (660 μg) subconjunctival injection of sirolimus in the study eye at baseline if a single quadrant or two adjacent quadrants are involved. If greater than two quadrants are involved (i.e., 3 or 4 quadrant involvement) or two non-adjacent quadrants are involved, two 15 μL (660 μg) injections will be given in two quadrants 180 degrees apart (total dose of 30 μL or 1,320 μg). Participants that still demonstrate active inflammation (incomplete or no response to initial injection) or experience a flare-up (as defined by a ≥1-step increase in scleral inflammation) after the initial injection will be eligible for a re-injection in the study eye at or after Week 4 (not to exceed a dose of 1,320 μg per eye within an eight-week period).
Interventions: intervention 1: Sirolimus
Intervention descriptions: intervention 1: Subconjunctival injection

Protocol documents: