Phase 2 N=6 Treatment

Sirolimus for Advanced Age-Related Macular Degeneration

Age-Related Macular Degeneration · Geographic Atrophy

Bottom Line

View on ClinicalTrials.gov: NCT01445548 ↗

Enrolled (actual)

Serious AEs

33.3%

Results posted

May 2014

Primary outcome: Primary: Rate of Change in Area of Geographic Atrophy (GA), Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline. — 0.19 mm^2/month

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Sirolimus (Drug)
Age: Adult, Older Adult · 56+ yrs
Sex: All
Sponsor: National Eye Institute (NEI)
Primary completion: Apr 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Rate of Change in Area of Geographic Atrophy (GA), Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline.	0.19	—
PRIMARY Rate of Change in Area of Geographic Atrophy (GA), Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Fellow Eye at 12 Months Compared to Baseline.	0.13	—
SECONDARY Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline	-15.6	—
SECONDARY Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Fellow Eye at 12 Months Compared to Baseline	—	—
SECONDARY Absolute Change in Total Area of Macular GA, Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline.	2.26	—
SECONDARY Absolute Change in Total Area of Macular GA, Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Fellow Eye at 12 Months Compared to Baseline.	1.53	—
SECONDARY Relative Change in Total Area of Macular GA, Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline.	0.18	—
SECONDARY Relative Change in Total Area of Macular GA, Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Fellow Eye at 12 Months Compared to Baseline.	0.14	—
SECONDARY Absolute Change in Drusen Area Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline.	0.02	—
SECONDARY Absolute Change in Drusen Area Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Fellow Eye at 12 Months Compared to Baseline.	0.29	—
SECONDARY Absolute Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Modified Fundus Camera (mFC), in the Study Eye at 12 Months Compared to Baseline.	2.75	—
SECONDARY Absolute Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Modified Fundus Camera (mFC), in the Fellow Eye at 12 Months Compared to Baseline.	1.44	—
SECONDARY Absolute Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Confocal Scanning Laser Ophthalmoscope (SLO), in the Study Eye at 12 Months Compared to Baseline.	2.4	—
SECONDARY Absolute Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Confocal Scanning Laser Ophthalmoscope (SLO), in the Fellow Eye at 12 Months Compared to Baseline.	1.6	—
SECONDARY Relative Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Confocal Scanning Laser Ophthalmoscope (SLO), in the Study Eye at 12 Months Compared to Baseline.	0.21	—
SECONDARY Relative Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Confocal Scanning Laser Ophthalmoscope (SLO), in the Fellow Eye at 12 Months Compared to Baseline.	0.15	—
SECONDARY Relative Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Modified Fundus Camera (mFC), in the Study Eye at 12 Months Compared to Baseline.	0.21	—
SECONDARY Relative Change in Area of GA, as Measured by Fundus Autofluorescence (FAF) Imaging Using a Modified Fundus Camera (mFC), in the Fellow Eye at 12 Months Compared to Baseline.	0.13	—
SECONDARY Development of Exudative Age-Related Macular Degeneration (AMD) as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline	—	—

Summary

This study will determine whether 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 at the back of the eye needed for sharp, clear vision. There are two types of AMD, wet and dry. In dry AMD, cells in the macula die. GA may be partially caused by inflammation. Sirolimus helps prevent inflammation and therefore may help people with GA. Researchers want to see whether sirolimus can help prevent vision loss in people with GA. People at least 56 years of age who have GA related to AMD in both eyes may be eligible for this study. This study requires at least 8 visits to the National Eye Institute over 1 year. Study visits will be every 2 months for 1 year. Participants will undergo the following procedures: * 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 sirolimus injections. * Participants will have a sirolimus injection into the study eye at the first visit and every 2 months thereafter unless contraindicated. There will be a follow-up eye exam 1 month after the first injection.

Eligibility Criteria

Inclusion Criteria

56 or older
Must understand and sign the protocol's informed consent document
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 and often circular patches of partial or complete depigmentation 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 depigmentation may be classified as early GA. The GA in each eye must be able to be photographed in their entirety, and it must not be contiguous with any areas of peripapillary atrophy, which can complicate area measurements

Must have at least one large druse (greater than or equal to 125 μm) in each eye
Must not have any evidence or history of exudative disease related to AMD in either eye as determined by a recent fluorescein angiogram performed within 4 months of study enrollment
Must have a steady fixation in both eyes in the foveal or parafoveal area and media clear enough for good quality photographs
Must have visual acuity of 20/400 or better in each eye
Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse, or agree to practice two acceptable methods of contraception throughout the course of the study and four months after their last study injection. Acceptable methods of contraception include:
hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
intrauterine device,
barrier methods (diaphragm, condom) with spermicide, or
surgical sterilization (hysterectomy or tubal ligation).

Exclusion Criteria

Actively receiving study therapy in another investigational study
Unable to comply with study procedures or follow-up visits
Evidence of an 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)
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, or d) received an intravitreal injection of any other agent (not an anti-VEGF agent) within four months prior to study enrollment

Participants currently taking or who have previously taken AREDS vitamin supplementation are not excluded.

Has had a vitrectomy
Expected to need ocular surgery during the course of the trial
Has undergone lens removal in the last three months or yttrium aluminum- garnet (YAG) laser capsulotomy within the last month
On chemotherapy
On immunosuppressive medication
On ocular or systemic medications known to be toxic to the lens, retina or optic nerve
History of ocular herpes simplex virus (HSV)
Has 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)
Has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years
Has laboratory values outside normal limits and considered clinically significant by the investigator
Is currently taking one of the following drugs: amprenavir, atazanavir, clarithromycin, darunavir, delavirdine, erythromycin, fluconazole (at doses of 200mg or greater), fluvoxamine, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, quinupristin, ritonavir, saquinavir, telithromycin, troleandomycin, verapamil or voriconazole
Female participant is pregnant or breast-feeding.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01445548). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.