Sirolimus for Advanced Age-Related Macular Degeneration (SIRGA2)

• ClinicalTrials.gov Identifier: NCT01445548
• Recruitment Status: Completed
• First Posted: October 3, 2011
• Results First Posted: May 9, 2014
• Last Update Posted: July 7, 2021
• Sponsor: National Eye Institute (NEI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Age-Related Macular Degeneration; Geographic Atrophy
• Intervention: Drug: Sirolimus
• Enrollment: 6

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Period Title: Overall Study
Started	6
Completed	5
Not Completed	1
Reason Not Completed
Adverse Event	1

Baseline Characteristics

Arm/Group Title		Sirolimus
Arm/Group Description		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.
Overall Number of Baseline Participants		6
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6 participants
		74.33 (8.45)
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 16.7%
	>=65 years	5 83.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	Female	2 33.3%
	Male	4 66.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	6 participants
		6

Outcome Measures

1. Primary Outcome

Title	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.
Description	[Not Specified]
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2/month
	0.19 (0.08)

2. Primary Outcome

Title	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.
Description	[Not Specified]
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2/month
	0.13 (0.06)

3. Secondary Outcome

Title	Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: ETDRS letters
	-15.6 (7.23)

4. Secondary Outcome

Title	Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Fellow Eye at 12 Months Compared to Baseline
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: ETDRS letters
	0 (13.47)

5. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2
	2.26 (0.94)

6. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2
	1.53 (0.75)

7. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Mean (Standard Deviation); Unit of Measure: Ratio
	0.18 (0.09)

8. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Mean (Standard Deviation); Unit of Measure: Ratio
	0.14 (0.09)

9. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 3 had drusen area graded at 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	3
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	3
Mean (Standard Deviation); Unit of Measure: MPS DA
	0.02 (0.19)

10. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 3 had drusen area graded at 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	3
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	3
Mean (Standard Deviation); Unit of Measure: MPS DA
	0.29 (0.78)

11. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2
	2.75 (1.83)

12. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2
	1.44 (1.17)

13. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2
	2.4 (0.82)

14. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: mm^2
	1.6 (0.76)

15. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: Ratio
	0.21 (0.14)

16. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: Ratio
	0.15 (0.10)

17. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: Ratio
	0.21 (0.12)

18. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

The analysis was intention-to-treat (ITT). Although 6 participants were enrolled, only 5 were followed for 12 months.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	5
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	5
Mean (Standard Deviation); Unit of Measure: Ratio
	0.13 (0.10)

19. Secondary Outcome

Title	Development of Exudative Age-Related Macular Degeneration (AMD) as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline
Description	[Not Specified]
Time Frame	Baseline and 12 Months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Sirolimus
Arm/Group Description:	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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Sirolimus
Arm/Group Description	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.
All-Cause Mortality
	Sirolimus
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Sirolimus
	Affected / at Risk (%)	# Events
Total	2/6 (33.33%)
Cardiac disorders
Heart valve incompetence † 1	1/6 (16.67%)	1
Hepatobiliary disorders
Hepatic cirrhosis † 1	1/6 (16.67%)	1
Injury, poisoning and procedural complications
Hip fracture † 2	1/6 (16.67%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (16.0); 2 Term from vocabulary, MedDRA (15.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sirolimus
	Affected / at Risk (%)	# Events
Total	6/6 (100.00%)
Blood and lymphatic system disorders
Leukopenia † 3	1/6 (16.67%)	1
Eye disorders
Age-related macular degeneration † 1	2/6 (33.33%)	2
Ocular discomfort † 2	1/6 (16.67%)	1
Visual acuity reduced † 2	1/6 (16.67%)	1
General disorders
Mild pain † 3 [1]	1/6 (16.67%)	1
Hepatobiliary disorders
Portal hypertension † 3	1/6 (16.67%)	1
Infections and infestations
Urinary tract infection † 2	3/6 (50.00%)	3
Investigations
Alanine aminotransferase increased † 2	2/6 (33.33%)	2
Aspartate aminotransferase increased † 3	1/6 (16.67%)	1
Basophil count decreased † 3	1/6 (16.67%)	1
Blood alkaline phosphatase decreased † 2	1/6 (16.67%)	1
Blood bilirubin increased † 3	1/6 (16.67%)	1
Blood calcium decreased † 2	1/6 (16.67%)	1
Blood glucose abnormal † 2	3/6 (50.00%)	3
Blood urea increased † 2	2/6 (33.33%)	2
Bone density abnormal † 2	1/6 (16.67%)	1
Full blood count abnormal † 3	1/6 (16.67%)	1
Haematocrit decreased † 3	1/6 (16.67%)	1
Haemoglobin urine present † 3	1/6 (16.67%)	1
Lipids decreased † 2	1/6 (16.67%)	1
Liver function test abnormal † 3	1/6 (16.67%)	1
Monocyte count abnormal † 3	1/6 (16.67%)	1
Monocyte count decreased † 3	1/6 (16.67%)	1
Neutrophil count decreased † 4	1/6 (16.67%)	1
Platelet count decreased † 2	1/6 (16.67%)	1
Red blood cell count increased † 3	1/6 (16.67%)	1
Red blood cells urine † 2	2/6 (33.33%)	2
Lipids increased † 2	1/6 (16.67%)	1
Metabolism and nutrition disorders
Hyperlipidaemia † 2	1/6 (16.67%)	1
Hypertriglyceridaemia † 2	1/6 (16.67%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 2	1/6 (16.67%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer † 2	1/6 (16.67%)	1
Nervous system disorders
Memory impairment † 3	1/6 (16.67%)	1
Renal and urinary disorders
Nephrolithiasis † 2	1/6 (16.67%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory disorder † 2	1/6 (16.67%)	1
Surgical and medical procedures
Skin lesion excision † 2	1/6 (16.67%)	1
Vascular disorders
Hypertension † 2	2/6 (33.33%)	2
Hypotension † 2	1/6 (16.67%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (15.1, 17.0); 2 Term from vocabulary, MedDRA (15.0); 3 Term from vocabulary, MedDRA (15.1); 4 Term from vocabulary, MedDRA (16.0); [1] Verbatim adverse event description

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Wai T. Wong, MD, PhD
• Organization: National Eye Institute
• Phone: 301-496-7566
• EMail: wongw@nei.nih.gov

Publications of Results:

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.

Other Publications:

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.

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.

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.

• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
• ClinicalTrials.gov Identifier: NCT01445548
• Other Study ID Numbers: 110249; 11-EI-0249 ( Registry Identifier: National Institutes of Health Clinical Center )
• First Submitted: September 30, 2011
• First Posted: October 3, 2011
• Results First Submitted: April 7, 2014
• Results First Posted: May 9, 2014
• Last Update Posted: July 7, 2021