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| ID | Type | Description | Link |
|---|---|---|---|
| 11-EI-0249 | Registry Identifier | National Institutes of Health Clinical Center |
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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:
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 μL (440 μg) 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sirolimus | Experimental | Participants initially received a 20 μL (440 μg) 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sirolimus | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Month 12 | |
| 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. | Baseline and Month 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. One eye (the study eye) was initially randomized to receive intravitreal sirolimus and the fellow eye was observed as the control. |
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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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Wai T Wong, MD, PhD | National Eye Institute (NEI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9022098 | Background | 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. | |
| 1630784 | 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. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sirolimus | Participants initially received a 20 μL (440 μg) 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sirolimus | Participants initially received a 20 μL (440 μg) 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2/month | Baseline and Month 12 | Eyes | Eyes |
|
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sirolimus | Participants initially received a 20 μL (440 μg) 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic cirrhosis | Hepatobiliary disorders | MedDRA (16.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Age-related macular degeneration | Eye disorders | MedDRA (15.1, 17.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wai T. Wong, MD, PhD | National Eye Institute | 301-496-7566 | wongw@nei.nih.gov |
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| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| D057092 | Geographic Atrophy |
| ID | Term |
|---|---|
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Baseline and Month 12 |
| Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Fellow Eye at 12 Months Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. One eye (the study eye) was initially randomized to receive intravitreal sirolimus and the fellow eye was observed as the control. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Baseline and Month 12 |
| 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. | The total area occupied by drusen was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm^2 on the retina. | Baseline and Month 12 |
| 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. | The total area occupied by drusen was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm^2 on the retina. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss.The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Baseline and Month 12 |
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Baseline and Month 12 |
| Development of Exudative Age-Related Macular Degeneration (AMD) as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline | Baseline and 12 Months |
| 15761121 | Background | Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005 Apr 15;308(5720):421-4. doi: 10.1126/science.1110189. Epub 2005 Mar 10. |
| 25525171 | Result | Petrou PA, Cunningham D, Shimel K, Harrington M, Hammel K, Cukras CA, Ferris FL, Chew EY, Wong WT. Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial. Invest Ophthalmol Vis Sci. 2014 Dec 18;56(1):330-8. doi: 10.1167/iovs.14-15877. |
| years |
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Counts |
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| Participants |
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| Eyes |
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| 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. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2/month | Baseline and Month 12 | Eyes | Eyes |
|
|
|
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. One eye (the study eye) was initially randomized to receive intravitreal sirolimus and the fellow eye was observed as the control. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | ETDRS letters | Baseline and Month 12 | Eyes | Eyes |
|
|
|
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Fellow Eye at 12 Months Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. One eye (the study eye) was initially randomized to receive intravitreal sirolimus and the fellow eye was observed as the control. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | ETDRS letters | Baseline and Month 12 | Eyes | Eyes |
|
|
|
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2 | Baseline and Month 12 | Eyes | Eyes |
|
|
|
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2 | Baseline and Month 12 | Eyes | Eyes |
|
|
|
| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | Ratio | Baseline and Month 12 |
|
|
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Posted | Mean | Standard Deviation | Ratio | Baseline and Month 12 |
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| 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. | The total area occupied by drusen was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm^2 on the retina. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 3 had drusen area graded at 12 months. | Posted | Mean | Standard Deviation | MPS DA | Baseline and Month 12 | Eyes | Eyes |
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| 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. | The total area occupied by drusen was determined using planimetry for color stereoscopic fundus images by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm^2 on the retina. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 3 had drusen area graded at 12 months. | Posted | Mean | Standard Deviation | MPS DA | Baseline and Month 12 | Eyes | Eyes |
|
|
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2 | Baseline and Month 12 | Eyes | Eyes |
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2 | Baseline and Month 12 | Eyes | Eyes |
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2 | Baseline and Month 12 | Eyes | Eyes |
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss.The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by subtracting the GA value for the study eye at baseline from the GA value for the study eye at Month 12. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | mm^2 | Baseline and Month 12 | Eyes | Eyes |
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | Posted | Mean | Standard Deviation | Ratio | Baseline and Month 12 | Eyes | Eyes |
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a SLO by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | Ratio | Baseline and Month 12 | Eyes | Eyes |
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | Ratio | Baseline and Month 12 | Eyes | Eyes |
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| 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. | Geographic atrophy (GA) is the death of photoreceptors and surrounding cells in the retina. The death of these photoreceptors results in lesions that cause vision loss. The area of GA was determined using planimetry for FAF images obtained with a mFC by masked graders at the Doheny Image Reading Center (University of Southern California, Los Angeles, CA). This outcome measure was calculated by dividing the absolute change in the total area of GA in the study eye at 12 months by the baseline value. | The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months. | Posted | Mean | Standard Deviation | Ratio | Baseline and Month 12 | Eyes | Eyes |
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| Secondary | Development of Exudative Age-Related Macular Degeneration (AMD) as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline | Zero participants were analyzed because no data were collected to analyze this outcome as no study or fellow eye developed neovascular changes during the study. | Posted | Baseline and 12 Months |
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| 2 |
| 6 |
| 6 |
| 6 |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
|
| Heart valve incompetence | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Basophil count decreased | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Blood alkaline phosphatase decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Blood calcium decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood glucose abnormal | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Bone density abnormal | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Full blood count abnormal | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Haemoglobin urine present | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
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| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
|
| Lipids decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
|
| Monocyte count abnormal | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Monocyte count decreased | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Portal hypertension | Hepatobiliary disorders | MedDRA (15.1) | Systematic Assessment |
|
| Red blood cell count increased | Investigations | MedDRA (15.1) | Systematic Assessment |
|
| Red blood cells urine | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
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| Skin lesion excision | Surgical and medical procedures | MedDRA (15.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
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| Visual acuity reduced | Eye disorders | MedDRA (15.0) | Systematic Assessment |
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| Lipids increased | Investigations | MedDRA (15.0) | Systematic Assessment |
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| Mild pain | General disorders | MedDRA (15.1) | Systematic Assessment | Verbatim adverse event description |
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Not provided
Not provided