Sirolimus as Therapeutic Approach to Uveitis
Condition: Uveitis; Intermediate Uveitis; Posterior Uveitis; Panuveitis
MeSH terms: Uveitis; Panuveitis; Uveitis, Posterior; Uveitis, Intermediate; Pars Planitis
Intervention: Sirolimus (rapamycin); Sirolimus (rapamycin)
Intervention description: Will receive intravitreal injections of sirolimus (rapamycin) 352 µg in study eye on Days 0, 60, and 120.; Will receive subconjunctival injections of sirolimus 1320 µg in the study eye on Days 0, 60, and 120.
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-infectious; Uveitis; Panuveitis

Summary:

      The purpose of this study is to find out about the safety and effectiveness of the study
      drug, sirolimus, in patients with uveitis and to utilize the potential effectiveness of
      sirolimus, and yet to avoid the potential complications of systemic use of the drug. In this
      study, the investigators will administer sirolimus either around (subconjunctival injection)
      or inside the eye (intravitreal injection). Local administration of sirolimus to the eye is
      not expected to have effects on the rest of the body. Therefore, it may offer a safer way
      than the current methods used to control the inflammation caused by non-infectious uveitis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females greater than or equal to 18 years of age;

          2. Able to give informed consent and attend all study visits;

          3. Have diagnosis of uveitis determined by the Investigator to be non infectious;

               -  Have active uveitis, defined as having at least 1+ Vitreous Haze and/or at least
                  1+ Vitreous Cell Count (SUN scale), and:

                    -  are receiving no other treatment; or,

                    -  are receiving prednisone ≥10 mg/day (or equivalent dose of another
                       corticosteroid) and/or at least 1 other systemic immunosuppressant; or, b.
                       Have inactive disease, defined as having 0.5+ Vitreous Haze or less and a
                       grade of 0.5+ Vitreous Cell Count or less (SUN scale), and:

                    -  are receiving prednisone <10 mg/day (or equivalent dose of another
                       corticosteroid) and/or at least 1 other systemic immunosuppressant.

          4. Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior component
             is present, it must be less than the posterior component;

          5. Sufficient inflammation to require systemic treatment and, based on the Investigator's
             decision, warrants intravitreal or subconjunctival treatment;

          6. Best-corrected (ETDRS) visual acuity of 20/40 to 20/400 (approximately 70 to 20
             letters) in the study eye;

          7. Best- corrected ETDRS visual acuity of 20/400 or better in the fellow eye
             (approximately 20 letters).

        Exclusion Criteria:

          1. Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy
             (e.g., methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate
             mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids
             for the treatment of the uveitis, and the uveitis in the fellow eyes, in the opinion
             of the investigator, cannot be controlled with standard local therapies alone;

          2. Any significant ocular disease that could compromise vision in the study eye. These
             include, but are not limited to:

               -  Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or
                  non-proliferative diabetic retinopathy (NPDR) that compromise the vision.

               -  Age-related macular degeneration;

               -  Myopic degeneration with active subfoveal choroidal neovascularization.

          3. Any of the following treatments within 90 days prior to Day 0 or anticipated use of
             any of the following treatments to the study eye:

               -  Intravitreal injections (including but not limited to steroids or anti-vascular
                  endothelial growth factors);

               -  Posterior subtenon's steroids.

          4. Intraocular surgery within 90 days prior to Day 0 in the study eye;

          5. Capsulotomy within 30 days prior to Day 0 in the study eye;

          6. If the patient has had glaucoma surgery (trabeculectomy or aqueous shunt device),
             there must be adequate conjunctiva

          7. History of vitreoretinal surgery or scleral buckling

          8. Any ocular surgery (including cataract extraction or capsulotomy) of the study eye
             anticipated within the first 180 days following Day 0;

          9. Intraocular pressure ≥25 mmHg in the study eye (glaucoma patients maintained on no
             more than 2 topical medications with intraocular pressure (IOP) <25 mmHg are allowed
             to participate);

         10. Pupillary dilation inadequate for quality stereoscopic fundus photography in the study
             eye;

         11. Media opacity that would limit clinical visualization;

         12. Presence of any form of ocular malignancy in the study eye, including choroidal
             melanoma;

         13. History of herpetic infection in the study eye or adnexa;

         14. Presence of known active or inactive toxoplasmosis in either eye;

         15. Ocular or periocular infection in either eye;

         16. Participation in other investigational drug or device clinical trials within 30 days
             prior to Day 0, or planning to participate in other investigational drug or device
             clinical trials within 180 days following Day 0. This includes both ocular and
             non-ocular clinical trials.