Pilot Study of the Evaluation of Subconjunctival Sirolimus in the Treatment of Bilateral GA Associated With AMD

• Status: Completed
• Trial end date: 2012-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Eye Institute (NEI)
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria

1. Participant must be older than 55 years of age.

2. Participant must understand and sign the protocol's informed consent document.

3. Participant must have at least ½ disc area (approximately 1 mm^2) of GA compatible with AMD present in each eye. GA is defined as one or more well-defined, usually more or less circular patches of partial or complete de-pigmentation of the RPE, typically with exposure of underlying choroidal blood vessels. Even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a round patch of RPE partial de-pigmentation may still be classified as early GA. The GA in each eye must be able to be photographed in their entirety.

4. Participant must have at least one large druse (more than or equal to 125 μm) in each eye.

5. Participant must have a steady fixation in both eyes in the foveal or parafoveal area and media clear enough for good quality photographs. This will permit randomization.

6. Participant must have visual acuity between 20/20 and 20/400 in each eye.

7. Female participants must be considered post-menopausal and must not be breast-feeding. Female participants over age 55 who have not had a period for one year will be considered post-menopausal.

Exclusion Criteria

1. Participant is in another investigational study and actively receiving study therapy.

2. Participant is unable to comply with study procedures or follow-up visits.

3. Participant has evidence of ocular disease other than AMD in either eye that may confound the outcome of the study (e.g., diabetic retinopathy with 10 or more hemorrhages or microaneurysms, uveitis, pseudovitelliform macular degeneration moderate/severe myopia).

4. Participant has any of the following: a) a history of macular laser, b) a history of photodynamic therapy (PDT), c) received an intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent for wet/exudative AMD at any point, d) received an intravitreal injection of any other agent (not an anti-VEGF agent) within four months prior to study enrollment or e) received topical treatment of any agent for advanced AMD within one month prior to enrollment. Participants currently taking or who have previously taken AREDS vitamin supplementation are not excluded.

5. Participant has had a vitrectomy.

6. Participant is expected to need ocular surgery during the course of the trial.

7. Participant has undergone lens removal in the last three months or yttrium aluminum garnet (YAG) laser capsulotomy within the last month.

8. Participant is on chemotherapy.

9. Participant is on immunosuppressive medication.

10. Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve.

11. Participant with a history of ocular herpes simplex virus (HSV).

12. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).

13. History of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years.

14. Laboratory values outside normal limits and considered clinically significant by the investigator.

15. Participant is currently taking one of the following drugs: amprenavir, atazanavir, clarithromycin, darunavir, delavirdine, erythromycin, fluconazole (at doses of 200 mg or greater), fluvoxamine, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, quinupristin, ritonavir, saquinavir, telithromycin, troleandomycin, verapamil or voriconazole.