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

NCT00766649 | Completed Phase 1 Results DMC

• 2 other identifiers: 09000809-EI-0008
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Age-Related Macular Degeneration

Keywords

Age Related Macular Degeneration (AMD); Geographic Atrophy; Sirolimus; Age-Related Macular Degeneration; AMD

Outcome Measures

Primary Outcomes (2)

• Rate of Change in Area of Geographic Atrophy (GA) in the Study Eye at 24 Months as Compared to Baseline

  One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm\^2 on the retina.

  Baseline and Month 24

• Rate of Change in Area of Geographic Atrophy (GA) in the Fellow Eye at 24 Months as Compared to Baseline

  One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm\^2 on the retina.

  Baseline and Month 24

Secondary Outcomes (9)

• Number of Study Eyes With a 15 Letter Drop From Baseline at 24 Months

  Baseline and Month 24

• Absolute Change in Total Area of Geographic Atrophy (GA) in the Study Eye at 24 Months as Compared to Baseline

  Baseline and Month 24

• Absolute Change in Total Area of Geographic Atrophy (GA) in the Fellow Eye at 24 Months as Compared to Baseline

  Baseline and Month 24

• Relative Change in Total Area of Geographic Atrophy (GA) in the Study Eye at 24 Months as Compared to Baseline

  Baseline to Month 24

• Relative Change in Total Area of Geographic Atrophy (GA) in the Fellow Eye at 24 Months as Compared to Baseline

  Baseline and Month 24

Study Arms (1)

Sirolimus

EXPERIMENTAL

Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.

Also known as: Rapamune®, rapamycin

Sirolimus

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be older than 55 years of age.
• Participant must understand and sign the protocol's informed consent document.
• 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.
• Participant must have at least one large druse (more than or equal to 125 μm) in each eye.
• 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.
• Participant must have visual acuity between 20/20 and 20/400 in each eye.
• 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.

You may not qualify if:

• Participant is in another investigational study and actively receiving study therapy.
• Participant is unable to comply with study procedures or follow-up visits.
• 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).
• 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.
• Participant has had a vitrectomy.
• Participant is expected to need ocular surgery during the course of the trial.
• Participant has undergone lens removal in the last three months or yttrium aluminum garnet (YAG) laser capsulotomy within the last month.
• Participant is on chemotherapy.
• Participant is on immunosuppressive medication.
• Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve.
• Participant with a history of ocular herpes simplex virus (HSV).
• 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).
• History of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years.
• Laboratory values outside normal limits and considered clinically significant by the investigator.
• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997 Jan;104(1):7-21. doi: 10.1016/s0161-6420(97)30368-6.

  PMID: 9022098 BACKGROUND

• Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992 Jun;99(6):933-43. doi: 10.1016/s0161-6420(92)31871-8.

  PMID: 1630784 BACKGROUND

• Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. 1994 Nov 9;272(18):1413-20.

  PMID: 7933422 BACKGROUND

• Wong WT, Dresner S, Forooghian F, Glaser T, Doss L, Zhou M, Cunningham D, Shimel K, Harrington M, Hammel K, Cukras CA, Ferris FL, Chew EY. Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial. Invest Ophthalmol Vis Sci. 2013 Apr 26;54(4):2941-50. doi: 10.1167/iovs.13-11650.

  PMID: 23548622 RESULT

MeSH Terms

Conditions

Macular Degeneration; Geographic Atrophy

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Wai T. Wong
• Organization: National Eye Institute

wongw@nei.nih.gov

(301) 905-7301

Study Officials

• Wai T. Wong, MD, PhD

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2008
• First Posted: October 6, 2008
• Study Start: October 1, 2008
• Primary Completion: April 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 14, 2020
• Results First Posted: July 1, 2013

Record last verified: 2014-04

Locations

US (1)