Trial Outcomes & Findings for Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD (NCT NCT04626128)
NCT ID: NCT04626128
Last Updated: 2023-09-18
Results Overview
Number of participants with treatment-emergent adverse events (TEAEs) reported between the administration of CLS-AX and study exit.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Day 1 to Week 12
Results posted on
2023-09-18
Participant Flow
Participant milestones
| Measure |
Cohort 1 (Low Dose)
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
5
|
8
|
8
|
|
Overall Study
Safety Population
|
6
|
5
|
8
|
8
|
|
Overall Study
Pharmacokinetic Population
|
6
|
5
|
8
|
8
|
|
Overall Study
COMPLETED
|
6
|
4
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1 (Low Dose)
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD
Baseline characteristics by cohort
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
81.8 years
STANDARD_DEVIATION 11.55 • n=5 Participants
|
78.2 years
STANDARD_DEVIATION 10.92 • n=7 Participants
|
86.3 years
STANDARD_DEVIATION 6.48 • n=5 Participants
|
76.5 years
STANDARD_DEVIATION 5.78 • n=4 Participants
|
80.9 years
STANDARD_DEVIATION 8.98 • n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
8 participants
n=4 Participants
|
27 participants
n=21 Participants
|
|
Duration of nAMD Diagnosis in the Study Eye
|
50.13 months
STANDARD_DEVIATION 34.131 • n=5 Participants
|
49.78 months
STANDARD_DEVIATION 21.905 • n=7 Participants
|
66.64 months
STANDARD_DEVIATION 41.081 • n=5 Participants
|
48.21 months
STANDARD_DEVIATION 48.045 • n=4 Participants
|
54.39 months
STANDARD_DEVIATION 37.945 • n=21 Participants
|
|
Total Number of Prior nAMD Treatments in the Study Eye
0-2 injections
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Total Number of Prior nAMD Treatments in the Study Eye
3-6 injections
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Total Number of Prior nAMD Treatments in the Study Eye
7-12 injections
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Total Number of Prior nAMD Treatments in the Study Eye
13-18 injections
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Total Number of Prior nAMD Treatments in the Study Eye
>18 injections
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Pre injection Intraocular Pressure in the Study Eye at Baseline
|
15.3 mmHg
STANDARD_DEVIATION 3.08 • n=5 Participants
|
15.2 mmHg
STANDARD_DEVIATION 2.39 • n=7 Participants
|
13.3 mmHg
STANDARD_DEVIATION 2.76 • n=5 Participants
|
15.4 mmHg
STANDARD_DEVIATION 3.81 • n=4 Participants
|
14.7 mmHg
STANDARD_DEVIATION 3.10 • n=21 Participants
|
|
Best Corrected Visual Acuity in the Study Eye at Baseline
|
59.0 letters
STANDARD_DEVIATION 16.43 • n=5 Participants
|
65.6 letters
STANDARD_DEVIATION 8.73 • n=7 Participants
|
58.5 letters
STANDARD_DEVIATION 13.69 • n=5 Participants
|
65.8 letters
STANDARD_DEVIATION 8.31 • n=4 Participants
|
62.1 letters
STANDARD_DEVIATION 12.06 • n=21 Participants
|
|
Central Subfield Thickness in the Study Eye at Baseline
|
231.2 microns
STANDARD_DEVIATION 32.10 • n=5 Participants
|
209.4 microns
STANDARD_DEVIATION 17.39 • n=7 Participants
|
202.0 microns
STANDARD_DEVIATION 22.57 • n=5 Participants
|
218.8 microns
STANDARD_DEVIATION 40.01 • n=4 Participants
|
214.8 microns
STANDARD_DEVIATION 30.59 • n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Week 12Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
Number of participants with treatment-emergent adverse events (TEAEs) reported between the administration of CLS-AX and study exit.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
1 Participants
|
2 Participants
|
1 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Week 12Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
Number of participants with serious adverse events (SAEs) reported between the administration of CLS-AX and study exit.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Number of Participants With Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8 and 12.Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
Intraocular pressure (IOP) is a diagnostic measurement of the fluid pressure, measured in millimeters of mercury, inside the eye. IOP was measured using Goldmann applanation tonometry or by use of a Tonopen tonometer. Normal eye pressure is usually considered to be between 10 and 20 mmHg (AAO.org). Untreated elevated eye pressure is a risk factor for glaucoma.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP)
Week 8
|
-3.0 mmHg
Standard Deviation 3.16
|
0.6 mmHg
Standard Deviation 2.79
|
0.6 mmHg
Standard Deviation 1.90
|
1.6 mmHg
Standard Deviation 4.43
|
|
Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP)
Week 12
|
-3.0 mmHg
Standard Deviation 4.34
|
0.5 mmHg
Standard Deviation 1.91
|
0.9 mmHg
Standard Deviation 3.27
|
0.0 mmHg
Standard Deviation 3.38
|
|
Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP)
Week 4
|
-2.8 mmHg
Standard Deviation 4.67
|
-1.8 mmHg
Standard Deviation 4.15
|
-0.3 mmHg
Standard Deviation 0.95
|
0.0 mmHg
Standard Deviation 4.66
|
SECONDARY outcome
Timeframe: From Day 1 to Week 12Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
Number of participants receiving additional intravitreal aflibercept injections during the course of the study for nAMD. Participants qualified to receive additional IVT aflibercept injections based on protocol-defined criteria, including 1) loss of 10 or more letters in BCVA compared to the best prior study-assessed BCVA in the study eye that was attributed to intra- or sub-retinal fluid, 2) increase in central subfield thickness \>75 microns from Baseline in the study eye, or 3) presence of vision-threatening hemorrhage due to AMD in the study eye. Additionally, a participant could receive additional IVT aflibercept injections in the study eye for reasons beyond the protocol-defined criteria if it was in the participant's best interest per the Investigator's judgment following best medical practice.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections
Week 4
|
0 Participants
|
1 Participants
|
1 Participants
|
4 Participants
|
|
Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections
Week 8
|
4 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections
Week 12
|
1 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections
Day 1 to Week 12
|
4 Participants
|
4 Participants
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Week 12Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
Number of participants qualifying to receive additional intravitreal aflibercept injections during the course of the study. Criteria included 1) loss of 10 or more letters in BCVA compared to the best prior study-assessed BCVA in the study eye that was attributed to intra- or sub-retinal fluid, 2) increase in central subfield thickness \>75 microns from Baseline in the study eye, or 3) presence of vision-threatening hemorrhage due to AMD in the study eye.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections
Week 4
|
0 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections
Week 8
|
4 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections
Week 12
|
1 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections
Day 1 to Week 12
|
4 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8 and 12Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A central reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema. Only images that were gradable by the central reading center were included in the analysis.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye
Week 4
|
22.3 microns
Standard Deviation 23.46
|
22.0 microns
Standard Deviation 17.83
|
21.1 microns
Standard Deviation 22.62
|
26.6 microns
Standard Deviation 26.45
|
|
Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye
Week 8
|
62.8 microns
Standard Deviation 57.60
|
21.8 microns
Standard Deviation 32.58
|
21.9 microns
Standard Deviation 25.75
|
9.9 microns
Standard Deviation 17.87
|
|
Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye
Week 12
|
8.8 microns
Standard Deviation 14.50
|
45.8 microns
Standard Deviation 69.72
|
29.1 microns
Standard Deviation 37.89
|
18.6 microns
Standard Deviation 27.33
|
SECONDARY outcome
Timeframe: Weeks 4, 8 and 12Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
BCVA measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting test distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
Week 4
|
4.7 letters
Standard Deviation 3.78
|
0.2 letters
Standard Deviation 1.64
|
-0.6 letters
Standard Deviation 4.61
|
1.0 letters
Standard Deviation 2.20
|
|
Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
Week 8
|
-0.2 letters
Standard Deviation 7.41
|
-3.6 letters
Standard Deviation 2.30
|
0.6 letters
Standard Deviation 5.83
|
1.6 letters
Standard Deviation 2.94
|
|
Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
Week 12
|
2.2 letters
Standard Deviation 4.92
|
-6.3 letters
Standard Deviation 9.18
|
-2.1 letters
Standard Deviation 4.45
|
0.3 letters
Standard Deviation 3.28
|
SECONDARY outcome
Timeframe: Day 1 to Week 12Population: Defined as all participants that provide plasma samples for axitinib concentration analysis.
Maximum (or peak) plasma concentration of axitinib during the course of the study. Plasma samples were collected pre-dose at Baseline, 60 minutes post-dose at Baseline, and at Weeks 4 and 12. Peak quantifiable levels, based on a lower level of quantitation (LLOQ) of 0.01 ng/mL, were included in the analysis.
Outcome measures
| Measure |
Cohort 1 (Low Dose)
n=6 Participants
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 Participants
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 Participants
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 Participants
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Maximum Plasma Concentration [Cmax] of Axitinib
|
0.0101 ng/mL
Standard Deviation 0.00949
|
0.0264 ng/mL
Standard Deviation 0.0242
|
0.0749 ng/mL
Standard Deviation 0.111
|
0.0602 ng/mL
Standard Deviation 0.0251
|
Adverse Events
Cohort 1 (Low Dose)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 2 (Low-mid Dose)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 3 (High-mid Dose)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 4 (High Dose)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1 (Low Dose)
n=6 participants at risk
Subjects will receive a low dose of 0.03 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 2 (Low-mid Dose)
n=5 participants at risk
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 3 (High-mid Dose)
n=8 participants at risk
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
Cohort 4 (High Dose)
n=8 participants at risk
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Anti-VEGF: Standard of care therapy used to block vascular endothelial growth factor
|
|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
16.7%
1/6 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/5 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/5 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Eye disorders
Conjunctival haemorrhage
|
16.7%
1/6 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/5 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Eye disorders
Conjunctival oedema
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/5 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Eye disorders
Macular degeneration
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
40.0%
2/5 • Number of events 3 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Infections and infestations
Cystitis
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
20.0%
1/5 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/5 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/5 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
20.0%
1/5 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/5 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
0.00%
0/8 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over 12 weeks following CLS-AX administration.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All information concerning CLS1002-101 and the operations of Clearside Biomedical, Inc. are considered CONFIDENTIAL and shall remain the sole property of Clearside Biomedical Inc. The institutions and Investigators participating in this study shall have no right to publish or present the results of this study without the prior written consent of Clearside Biomedical, Inc.
- Publication restrictions are in place
Restriction type: OTHER