Trial Outcomes & Findings for Sirolimus Versus Anti-Vascular Endothelial Growth Factor (antiVEGF) for Wet AMD (NCT NCT02357342)
NCT ID: NCT02357342
Last Updated: 2017-06-22
Results Overview
Change in edema from baseline to month 6 as measured by mean difference in microns of central subfield thickness on Heidelberg optical coherence topography in each treatment group
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
Baseline to 6 months
Results posted on
2017-06-22
Participant Flow
Participant milestones
| Measure |
Sirolimus
Intravitreal Sirolimus
Sirolimus: intravitreal injection at baseline, month 2 and month 4. Sham injections at months 1, 3 and 5
|
Standard of Care Intravitreal Anti-VEGF
Standard of Care intravitreal injections of either bevacizumab (1.25mg/0.05ml) or aflibercept (2mg/0.05ml). Bevacizumab injections were repeated at monthly intervals and aflibercept was given at baseline, month 2 and 4 and sham injections at months 1, 3 and 5. Subjects in this group continued the same drug they were on prior to joining the study.
|
|---|---|---|
|
First 6 Months
STARTED
|
20
|
20
|
|
First 6 Months
COMPLETED
|
18
|
20
|
|
First 6 Months
NOT COMPLETED
|
2
|
0
|
|
Extension Study
STARTED
|
4
|
9
|
|
Extension Study
COMPLETED
|
4
|
9
|
|
Extension Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sirolimus
Intravitreal Sirolimus
Sirolimus: intravitreal injection at baseline, month 2 and month 4. Sham injections at months 1, 3 and 5
|
Standard of Care Intravitreal Anti-VEGF
Standard of Care intravitreal injections of either bevacizumab (1.25mg/0.05ml) or aflibercept (2mg/0.05ml). Bevacizumab injections were repeated at monthly intervals and aflibercept was given at baseline, month 2 and 4 and sham injections at months 1, 3 and 5. Subjects in this group continued the same drug they were on prior to joining the study.
|
|---|---|---|
|
First 6 Months
Death
|
2
|
0
|
Baseline Characteristics
Sirolimus Versus Anti-Vascular Endothelial Growth Factor (antiVEGF) for Wet AMD
Baseline characteristics by cohort
| Measure |
Sirolimus
n=20 Participants
Intravitreal Sirolimus
Sirolimus: intravitreal injection
|
Standard of Care Intravitreal antiVEGF
n=20 Participants
antiVEGF intravitreal injections
Standard of Care intravitreal injections of antiVEGF: intravitreal injections of antiVEGF
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
20 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
40 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 monthsChange in edema from baseline to month 6 as measured by mean difference in microns of central subfield thickness on Heidelberg optical coherence topography in each treatment group
Outcome measures
| Measure |
Sirolimus
n=18 Participants
Intravitreal Sirolimus
Sirolimus: intravitreal injection at baseline, month 2 and month 4. Sham injections at months 1, 3 and 5
|
Standard of Care Intravitreal Anti-VEGF
n=20 Participants
Standard of Care intravitreal injections of either bevacizumab (1.25mg/0.05ml) or aflibercept (2mg/0.05ml). Bevacizumab injections were repeated at monthly intervals and aflibercept was given at baseline, month 2 and 4 and sham injections at months 1, 3 and 5. Subjects in this group continued the same drug they were on prior to joining the study.
|
|---|---|---|
|
Change in Edema From Baseline to Month 6 Central Subfield Thickness ) on Heidelberg Optical Coherence Topography
|
-30.0 microns
Interval -136.0 to 76.0
|
7.5 microns
Interval -113.0 to 128.0
|
PRIMARY outcome
Timeframe: Baseline to 6 monthsnumber of subjects with gain of 0-4 letters of visual acuity
Outcome measures
| Measure |
Sirolimus
n=18 Participants
Intravitreal Sirolimus
Sirolimus: intravitreal injection at baseline, month 2 and month 4. Sham injections at months 1, 3 and 5
|
Standard of Care Intravitreal Anti-VEGF
n=20 Participants
Standard of Care intravitreal injections of either bevacizumab (1.25mg/0.05ml) or aflibercept (2mg/0.05ml). Bevacizumab injections were repeated at monthly intervals and aflibercept was given at baseline, month 2 and 4 and sham injections at months 1, 3 and 5. Subjects in this group continued the same drug they were on prior to joining the study.
|
|---|---|---|
|
Visual Acuity
|
7 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: baseline to 6 monthsnumber of subjects with gain of 5 or more letters of visual acuity
Outcome measures
| Measure |
Sirolimus
n=18 Participants
Intravitreal Sirolimus
Sirolimus: intravitreal injection at baseline, month 2 and month 4. Sham injections at months 1, 3 and 5
|
Standard of Care Intravitreal Anti-VEGF
n=20 Participants
Standard of Care intravitreal injections of either bevacizumab (1.25mg/0.05ml) or aflibercept (2mg/0.05ml). Bevacizumab injections were repeated at monthly intervals and aflibercept was given at baseline, month 2 and 4 and sham injections at months 1, 3 and 5. Subjects in this group continued the same drug they were on prior to joining the study.
|
|---|---|---|
|
Visual Acuity (Best Corrected Visual Acuity)
|
9 participants
Interval 0.0 to 10.0
|
9 participants
Interval 0.0 to 10.0
|
Adverse Events
Sirolimus
Serious events: 1 serious events
Other events: 14 other events
Deaths: 2 deaths
Standard of Care Intravitreal Anti-VEGF
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sirolimus
n=20 participants at risk
Intravitreal Sirolimus
Sirolimus: intravitreal injection at baseline, month 2 and month 4. Sham injections at months 1, 3 and 5
|
Standard of Care Intravitreal Anti-VEGF
n=20 participants at risk
Standard of Care intravitreal injections of either bevacizumab (1.25mg/0.05ml) or aflibercept (2mg/0.05ml). Bevacizumab injections were repeated at monthly intervals and aflibercept was given at baseline, month 2 and 4 and sham injections at months 1, 3 and 5. Subjects in this group continued the same drug they were on prior to joining the study.
|
|---|---|---|
|
Vascular disorders
pulmonary embolism
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Cardiac disorders
myocardial infarction
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
subretinal hemorrhage
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
central retinal artery occlusion
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
anterior chamber inflammation
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
Other adverse events
| Measure |
Sirolimus
n=20 participants at risk
Intravitreal Sirolimus
Sirolimus: intravitreal injection at baseline, month 2 and month 4. Sham injections at months 1, 3 and 5
|
Standard of Care Intravitreal Anti-VEGF
n=20 participants at risk
Standard of Care intravitreal injections of either bevacizumab (1.25mg/0.05ml) or aflibercept (2mg/0.05ml). Bevacizumab injections were repeated at monthly intervals and aflibercept was given at baseline, month 2 and 4 and sham injections at months 1, 3 and 5. Subjects in this group continued the same drug they were on prior to joining the study.
|
|---|---|---|
|
Eye disorders
photopsia
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Endocrine disorders
underactive thyroid
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
unexplained vision Loss
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
intraretinal hemorrhage
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Endocrine disorders
hypothyroidism
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
decreased visual acuity
|
25.0%
5/20 • Number of events 5 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
angular blepharitis
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Skin and subcutaneous tissue disorders
pre-cancerous lesion
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 2 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Renal and urinary disorders
urinary tract infection
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Skin and subcutaneous tissue disorders
basal cell carcinoma
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
dot hemorrhage
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
corneal irritation
|
10.0%
2/20 • Number of events 2 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
10.0%
2/20 • Number of events 2 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Metabolism and nutrition disorders
hypokalemia
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
50.0%
1/2 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Cardiac disorders
Bradycardia
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Metabolism and nutrition disorders
vitamin B12 deficiency
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Blood and lymphatic system disorders
Right radial artery hematoma
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Reproductive system and breast disorders
Acute Hypotic Respiratory failure
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Nervous system disorders
shingles
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
increased intraocular pressure
|
10.0%
2/20 • Number of events 3 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
progressed posterior subcapsular cataract
|
5.0%
1/20 • Number of events 2 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
progressed nuclear sclerotic cataract
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
Serous Retinal Detachment
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
vitreous hemorrhage
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
Subretinal Hemorrhage
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
choroidal neovascular membrane
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
intraretinal and subretinal fluid
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Infections and infestations
Sinusitis
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Vascular disorders
Worsening hypertension
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Nervous system disorders
PRES syndrome
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Musculoskeletal and connective tissue disorders
arthritis, left sholder
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Metabolism and nutrition disorders
Anemia
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
General disorders
fatigue
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Respiratory, thoracic and mediastinal disorders
Acute Chronic Hypoxic Respitory Failure
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Cardiac disorders
Diastolic Dysfunction
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Renal and urinary disorders
Acute Kidney Inury
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Nervous system disorders
Acute Encephalopathy
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
uveitis
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
Posterior Synechiae
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
Endothelial Pigment
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
corneal edema
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Blood and lymphatic system disorders
worsening anemia
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
floaters
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
subconjunctival hemorrhage
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
recurrent subretinal hemorrhage
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
General disorders
headache (right side of head)
|
5.0%
1/20 • Number of events 2 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
eye pain following injection
|
5.0%
1/20 • Number of events 2 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Respiratory, thoracic and mediastinal disorders
bronchitis
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Nervous system disorders
parkinsons disease
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
pigment on lens surface
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
|
Eye disorders
hemorrhage on optic nerve
|
5.0%
1/20 • Number of events 1 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
0.00%
0/20 • On or after baseline visit (Day 0) to on or before month 12 visit.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place