Eye Injections of Triamcinolone Acetonide for Retinal Blood Vessel Disorders

The use of intravitreal injections of corticosteroid (triamcinolone acetonide) appears to be a promising treatment for a variety of ocular diseases associated with inflammation. To date, the only drug available, 'Kenalog-40 Injection' produced by Bristol Myers Squibb, has not been formulated for intraocular use. This formulation when used intraocularly has been associated with cases of non-bacterial endophthalmitis, which is thought to be due to the presence of benzyl alcohol and/or polysorbate 80. Both are suspected irritants.

The purpose of this study is to evaluate the safety of a novel preservative-free formulation of triamcinolone acetonide (TAC-PF) at four dosage levels.

The study will be an open-label, single-masked, randomized Phase I study that will investigate the safety and potential efficacy of the new formulation of TAC-PF. Sixteen participants with retinal vascular disease will be randomly assigned to receive via intravitreal injection at one of 4 dose levels (1 mg, 4 mg, 8 mg, or 16 mg) of TAC-PF. Depending on a participant's response, injections may be repeated at up to 3 month intervals. Participants will be followed for 3 years.

The primary outcome will be an assessment of post-injection intraocular toxicity related events including increased inflammation, increased intraocular pressure, significant decreases in BCVA, cataract formation, retinal detachment, and intraocular hemorrhage. The secondary outcomes will be an improvement of 15 letters in best-corrected visual acuity (BCVA, ETDRS) from baseline to year 3, and decreases in retinal thickening and area of leakage.

• INCLUSION CRITERIA - GENERAL:

All participants must:

• Understand and sign the informed consent.
• Must have visual acuity in the fellow eye the same or better than the study eye.
• Have BCVA worse than 20/80 in the study eye.
• Have sufficiently clear ocular media to permit good quality retinal photographs and angiography to allow assessment of the macular area according to standard clinical practice.
• Be willing to use reliable forms of birth control during the study period.
• Be able to comply with the study requirements.

Inclusion criteria

- DISEASE-SPECIFIC:

Participants with neovascular AMD:

• Have a diagnosis of AMD defined by the presence of drusen larger than 63 micrometers, in at least one eye.
• Must be at least 50 years of age.
• Have the presence of choroidal neovascularization under the fovea determined by the investigator and defined as any one of the following fluorescein angiographic (FA) features:

• Early stippled hyperfluorescence of flat retinal pigment epithelium with ill-defined boundary and little or mild leakage in the late frames of the fluorescein.
• Irregular elevation of the retinal pigment epithelium that does not exhibit discrete or bright hyperfluorescence in the early transit phase of the angiogram. Stippled hyperfluorescence may be present. Late frames may show persistent fluorescein staining or leakage within a sensory retinal detachment overlying this area.
• Late phase leakage of undetermined source with leakage at the level of the retinal pigment epithelium in the late frames of the angiogram in which the source of the late leakage cannot be determined from earlier-phase frames of the angiogram.
• A well-demarcated area of bright hyperfluorscence in the early phase of the angiogram with leakage through the mid- and late- phase frames which obscures the boundaries of the area.

Participants with central retinal vein occlusion:

• Have macular edema in the study eye secondary to CRVO.
• Must be at least 18 years of age.

Participants with diabetic macular edema:

• Have clinically significant macular edema in the study eye secondary to diabetic retinpathy.
• Must be at least 18 years of age.
• Must have documented hemoglobin A1C of 12% or less within one month of baseline.

Exclusion criteria

- GENERAL:

All participants must not:

• Have intraocular pressure greater than 25 or history suggesting glaucoma (e.g., history of the diagnosis of glaucoma, past or present use of medications to control intraocular pressure, or disc/nerve fiber layer defects suggestive of glaucoma) or glaucomatous visual field defects as documented by Goldmann or Humphrey perimetry taken within 6 months to qualification.
• Be allergic to iodine or iodine-containing dyes.
• Be allergic to fluorescein dyes.
• Have medical conditions that make consistent follow-up over the treatment period unlikely (e.g., stroke, severe MI, or terminal carcinoma).
• Be currently using or be likely to need systemic or ocular medications known to be toxic to the lens, retina, or optic nerve, such as:

• Deferoxamine
• Chloroquine/Hydroxychloroquine (Plaquenil)
• Tamoxifen
• Phenothiazines
• Ethambutol
• Have a positive urine pregnancy test (for women of childbearing potential).
• Have concurrent administration of other experimental therapies for the present disease.
• Have any contraindication to performing the necessary diagnostic procedures.
• Have a history of or current acute ocular or periocular infection (including any history of ocular herpes zoster or simplex).
• Have had any major intraocular surgical procedure within one month of enrollment.
• Have used ocular or systemic steroids or used steroid-containing inhalers or nasal sprays for more than 6 days a month, on average, or any regular use of pills containing steroids.
• Have a known history of untoward complications from corticosteroid therapy, including elevated intraocular pressure in response to topical or periocular corticosteroids.
• Have a history of other antiangiogenic treatment of concomitant administration of other therapies for the present disease.

Exclusion criteria

- DISEASE SPECIFIC:

Participants with Neovascular AMD must not:

• Have any feeder vessels as seen on the high-speed ICG.
• Have choroidal neovascularization (CNV) in the study eye, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis, or posterior uveitis.
• Have geographic atrophy under the fovea in the study eye.
• Have decreased vision, in the study eye, due to retinal disease not attributable to CNV, such as nonexudative forms of ARM, geographic atrophy, inherited retinal dystrophy, uveitis, or epiretinal membrane.
• Have fibrosis, hemorrhage, pigment epithelial detachments, or other hypofluorescent lesions obscuring greater than 50% of the CNV lesion.

Participants with Central Retinal Vein Occlusion must not:

• Have choroidal neovascularization.
• Have had pan retinal laser photocoagulation within three months of randomization.

Participants with Diabetic Macular Edema must not:

• Have had cataract surgery within six months of randomization.
• Have had laser photocoagulation, either focal or scatter treatment, within three months of randomization.