Clinical trial NCT00766649
Conditions: Age-Related Macular Degeneration
Keywords: Age Related Macular Degeneration (AMD) Geographic Atrophy Sirolimus Age-Related Macular Degeneration AMD
Sponsor: National Eye Institute (NEI)
Start date: 2008-10-01; Completion date: 2012-07-01
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study will determine if a drug called sirolimus is safe to give to people with geographic atrophy GA and if it can help preserve vision in patients. GA is an advanced form of dry age-related macular degeneration (AMD). AMD affects the macula, the central part of the retina needed for sharp, clear vision. There are two types of AMD, wet and dry. In dry AMD, cells in the macula die.GA may at least partly be caused by inflammation. Sirolimus helps prevent inflammation and therefore may help treat GA.

People with GA in both eyes with visual acuity between 20/20 and 20/400 in each eye may be eligible for this study. Participants undergo the following tests and procedures:

* Sirolimus injections in the study eye at each 3-month clinic visit. The drug is injected under the outer layer of the eye after the patient receives antiseptic and numbing drops. Antibiotic drops are continued for 2 days after the injection.
* Eye examinations before the first injection, 1 month after the first injection, during each clinic visit (11 to 15 visits over 2 to 3 years) and 3 months after the final injection. The examination includes testing visual acuity, measuring eye pressure and checking eye movements. To examine the inside of the eye, the pupil is dilated with eye drops. Regular photographs of the inside of the eye and optical coherence tomography photographs, which allow measurement of the thickness of the retina, may be taken during the eye examination.
* Autofluorescence imaging. The patient sits in a chair with his or her head placed in a chin rest in front of a camera. A light in the camera is used to scan the eye.
* Blood tests. Blood is drawn at the first visit and at up to seven study visits to check blood chemistries, such as liver and kidney function.
* Urine pregnancy test for women who are able to become pregnant.

Detailed description:
Objective: Age-related macular degeneration (AMD), the leading cause of blindness in people over age 55 in the United States, is a heterogeneous clinical entity in which retinal degeneration occurs predominantly in the macula in the context of aging and leads to impairment of central visual acuity. AMD occurs in two general forms, one of which involves choroidal neovascularization (CNV) with subsequent formation of a disciform scar. This is often referred to as the neovascular or "wet" form. A second form, the subject of this study, is termed "dry" or atrophic macular degeneration and involves a constellation of clinical features that can include drusen, pigment clumping and/or retinal pigment epithelium (RPE) dropout and geographic atrophy (GA). GA can begin as a thinning of the RPE with involvement of the underlying choriocapillaris and lead subsequently to an atrophic change in the macula. Inflammation may play a role in the pathogenesis of GA. Sirolimus inhibits the production, signaling and activity of many inflammatory factors relevant to the development of GA. Therefore, the objective of this study is to investigate the safety and possible efficacy of multiple sirolimus subconjunctival injections in participants with bilateral GA.

Study Population: Ten participants with bilateral GA associated with AMD, with the potential to replace up to five participants if some fail to reach one year of follow-up.

Design: In this controlled, unmasked, Phase I/II study, one eye of eligible participants will be randomized to treatment while the fellow eye will be observed. Participants will receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter. The study will be completed once all participants have received two years of study medication and follow-up.

Outcome Measures: The primary outcome is the rate of change in area of GA, based on masked grading by an external Reading Center, of fundus photography in the study eye and fellow eye at two years compared with baseline. Secondary outcomes will include worsening of best-corrected visual acuity (BCVA) of three or more lines (15 or more letters), changes in area of GA as measured on autofluorescence, changes in drusen volume as measured by optical coherence tomography, changes in photoreceptor outer segment (PROS) thickness as measured by optical coherence tomography, as well as changes in drusen area based on masked digital grading of fundus photographs. Safety outcomes will include the number and severity of systemic and ocular toxicities, adverse events and infections.

Arms: arm 1: Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Interventions: intervention 1: Sirolimus
Intervention descriptions: intervention 1: Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.

Protocol documents: