Sirolimus for Advanced Age-Related Macular Degeneration
- Age-related macular degeneration (AMD) is a leading cause of blindness in older people. It affects the macula, the part of the retina needed for clear vision. An advanced form of AMD, called geographic atrophy (GA), may be partly caused by inflammation. Sirolimus is a drug that can help prevent inflammation. Researchers want to see if sirolimus can help prevent vision loss in people with GA.
- To determine if sirolimus can help prevent vision loss in people with geographic atrophy.
- People at least 56 years of age who have geographic atrophy related to AMD in both eyes.
- Participants should not have had specific injection- or laser-based AMD therapies, or need eye surgery within the next 2 years.
- This study requires at least 15 visits to the National Eye Institute over 2 years. Study visits will be every 2 months for 2 years.
- Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and eye exams. One eye will be selected as the study eye to receive the study drug.
- Participants will have a sirolimus injection into the study eye. There will be a followup exam 1 month later, with an eye exam but no injection.
- Participants will have regular visits with eye exams and injections for 2 years.
- Two months after the final injection, participants will have a final clinic visit with an eye exam.
Age-Related Macular Degeneration
Bilateral Geographic Atrophy
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of the Evaluation of Intravitreal Sirolimus in the Treatment of Bilateral Geographic Atrophy Associated With Age-Related Macular Degeneration|
- Rate of change in area of GA based on masked grading by an external Reading Center of fundus photographs in the study eye and fellow eye at two years compared to baseline. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Changes in best-corrected visual acuity, changes in drusen area, absolute and relative changes in area of GA, and development of exudative AMD. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||July 2014|
|Estimated Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
Objective: Age-related macular degeneration (AMD), the leading cause of blindness in people over age 65 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 subsequently lead 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 serial sirolimus intravitreal injections in participants with bilateral GA.
Study Population: Six participants with bilateral GA associated with AMD will be enrolled Initially, 10 participants with bilateral GA associated with AMD were to be enrolled. However, only six will be enrolled, as sirolimus intravitreal injections will no longer be administered to participants.
Design: In this single-center, prospective, controlled, unmasked, Phase I/II study, one eye of eligible participants was initially randomized to investigational product (intravitreal sirolimus) while the fellow eye was observed. Participants initially received a 20 (micro)L (440 (microg) intravitreal injection sirolimus in the study eye at baseline and every two months thereafter unless contraindicated. As of September 2012, sirolimus intravitreal injections were no longer administered to participants. Both the study and fellow eyes will be observed every two months until the study terminates. The study will not terminate until all participants have been followed through Month 12.
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 photographs in the study eye and fellow eye at Month 12 compared to baseline. Secondary outcomes will include changes in best-corrected visual acuity (BCVA), changes in drusen area based on masked digital grading of fundus photography, absolute and relative changes in area of GA measured using fundus photography and autofluorescence imaging, and development of exudative AMD measured using optical coherence tomography (OCT). Safety outcomes will include the number and severity of adverse events (AEs). Ocular safety outcomes will be indicated by changes in visual acuity, ocular surface changes, intraocular inflammation and any other ocular changes not consistent with the natural progression of GA.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Wai T Wong, M.D.||National Eye Institute (NEI)|