Trial Outcomes & Findings for Pilot Study of the Evaluation of Subconjunctival Sirolimus in the Treatment of Bilateral GA Associated With AMD (NCT NCT00766649)

NCT ID: NCT00766649

Last Updated: 2020-07-14

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Baseline and Month 24

Results posted on

2020-07-14

Participant Flow

Participant milestones

Participant milestones
Measure
Sirolimus
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Overall Study
STARTED
11
Overall Study
COMPLETED
1
Overall Study
NOT COMPLETED
10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sirolimus
n=11 Participants
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
Age, Categorical
>=65 years
11 Participants
n=5 Participants
Age, Continuous
78.4 years
STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
Region of Enrollment
United States
11 participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Month 24

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

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Participants
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Rate of Change in Area of Geographic Atrophy (GA) in the Study Eye at 24 Months as Compared to Baseline
0.102 MPS DA/month
Standard Deviation 0.049

PRIMARY outcome

Timeframe: Baseline and Month 24

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

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Participants
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Rate of Change in Area of Geographic Atrophy (GA) in the Fellow Eye at 24 Months as Compared to Baseline
0.087 MPS DA/month
Standard Deviation 0.034

SECONDARY outcome

Timeframe: Baseline and Month 24

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.

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Participants
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Number of Study Eyes With a 15 Letter Drop From Baseline at 24 Months
4 eyes

SECONDARY outcome

Timeframe: Baseline and Month 24

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

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Eyes
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Absolute Change in Total Area of Geographic Atrophy (GA) in the Study Eye at 24 Months as Compared to Baseline
2.46 MPS DA
Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline and Month 24

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 fellow eye at baseline from the GA value for the study eye at Month 24. One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm\^2 on the retina.

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Eyes
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Absolute Change in Total Area of Geographic Atrophy (GA) in the Fellow Eye at 24 Months as Compared to Baseline
2.08 MPS DA
Standard Deviation 0.83

SECONDARY outcome

Timeframe: Baseline to Month 24

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 24 months by the baseline value. One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm\^2 on the retina. As the unit of measure for both the absolute change in the total area of GA and the baseline value for the total area of GA is MPS DA, the unit of measure for the relative change in the total area of GA is "ratio."

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Eyes
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Relative Change in Total Area of Geographic Atrophy (GA) in the Study Eye at 24 Months as Compared to Baseline
0.55 Ratio
Standard Deviation 0.62

SECONDARY outcome

Timeframe: Baseline and Month 24

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 fellow eye at 24 months by the baseline value. One Macular Photocoagulation Study Disc Area (MPS DA) is equivalent to 1.77 mm\^2 on the retina. As the unit of measure for both the absolute change in the total area of GA and the baseline value for the total area of GA is MPS DA, the unit of measure for the relative change in the total area of GA is "ratio."

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Eyes
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Relative Change in Total Area of Geographic Atrophy (GA) in the Fellow Eye at 24 Months as Compared to Baseline
0.40 Ratio
Standard Deviation 0.25

SECONDARY outcome

Timeframe: Baseline and Month 24

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.

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Eyes
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Change in Total Area of Drusen in the Study Eye at 24 Months as Compared to Baseline
0.04 MPS DA
Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline and Month 24

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.

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Eyes
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Change in Total Area of Drusen in the Fellow Eye at 24 Months as Compared to Baseline
0.08 MPS DA
Standard Deviation 0.36

SECONDARY outcome

Timeframe: Baseline and Month 24

Outcome measures

Outcome measures
Measure
Sirolimus
n=8 Participants
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Change in Drusen Volume as Measured by Optical Coherence Tomography (OCT) at 24 Months as Compared to Baseline
0.04 mm^3
Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The PROS thickness analysis was not performed. As a result, data were not collected for this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Sirolimus

Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Sirolimus
n=11 participants at risk
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Gastrointestinal disorders
Intestinal perforation
9.1%
1/11 • Number of events 1 • 42 months

Other adverse events

Other adverse events
Measure
Sirolimus
n=11 participants at risk
Participants receive a 20 μL (440 μg) subconjunctival injection of sirolimus in the study eye at baseline and every three months thereafter.
Eye disorders
Eye discharge
9.1%
1/11 • Number of events 1 • 42 months
Eye disorders
Eye haemorrhage
9.1%
1/11 • Number of events 1 • 42 months
Eye disorders
Eye irritation
9.1%
1/11 • Number of events 1 • 42 months
Eye disorders
Foreign body sensation in eyes
9.1%
1/11 • Number of events 1 • 42 months
General disorders
Oedema peripheral
9.1%
1/11 • Number of events 1 • 42 months
Infections and infestations
Influenza
9.1%
1/11 • Number of events 1 • 42 months
Infections and infestations
Nasopharyngitis
9.1%
1/11 • Number of events 1 • 42 months
Infections and infestations
Otitis externa
9.1%
1/11 • Number of events 1 • 42 months
Injury, poisoning and procedural complications
Back injury
9.1%
1/11 • Number of events 1 • 42 months
Injury, poisoning and procedural complications
Periorbital haematoma
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Alanine aminotransferase increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Blood chloride increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Blood creatine phosphokinase decreased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Blood creatinine increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Blood glucose increased
27.3%
3/11 • Number of events 3 • 42 months
Investigations
Blood lactate dehydrogenase increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Blood magnesium increased
36.4%
4/11 • Number of events 4 • 42 months
Investigations
Blood phosphorus decreased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Blood potassium increased
18.2%
2/11 • Number of events 2 • 42 months
Investigations
Blood uric acid increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Blood urine
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Carbon dioxide increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Haemoglobin decreased
18.2%
2/11 • Number of events 2 • 42 months
Investigations
Haemoglobin increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Intraocular pressure increased
9.1%
1/11 • Number of events 2 • 42 months
Investigations
Lymphocyte count decreased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Mean cell volume increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Monocyte count increased
18.2%
2/11 • Number of events 2 • 42 months
Investigations
Platelet count decreased
18.2%
2/11 • Number of events 2 • 42 months
Investigations
Protein total decreased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Red blood cell count decreased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Red blood cells urine positive
18.2%
2/11 • Number of events 2 • 42 months
Investigations
Red cell distribution width increased
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Urine ketone body present
9.1%
1/11 • Number of events 1 • 42 months
Investigations
Urine leukocyte esterase
9.1%
1/11 • Number of events 1 • 42 months
Investigations
White blood cell count increased
18.2%
2/11 • Number of events 2 • 42 months
Investigations
White blood cells urine
9.1%
1/11 • Number of events 1 • 42 months
Metabolism and nutrition disorders
Hypercholesterolaemia
9.1%
1/11 • Number of events 1 • 42 months
Musculoskeletal and connective tissue disorders
Arthralgia
9.1%
1/11 • Number of events 1 • 42 months
Musculoskeletal and connective tissue disorders
Back pain
18.2%
2/11 • Number of events 2 • 42 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
18.2%
2/11 • Number of events 4 • 42 months
Nervous system disorders
Headache
9.1%
1/11 • Number of events 1 • 42 months
Skin and subcutaneous tissue disorders
Rash
9.1%
1/11 • Number of events 1 • 42 months
Surgical and medical procedures
Cataract operation
9.1%
1/11 • Number of events 2 • 42 months
Vascular disorders
Varicose vein
9.1%
1/11 • Number of events 1 • 42 months

Additional Information

Wai T. Wong

National Eye Institute

Phone: (301) 905-7301

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place