Neovascular Age-related Macular Degeneration
Conditions
Keywords
AMD, Wet-AMD, suprachoroidal, tyrosine kinase inhibitor, Microinjector, SCS
Brief summary
To evaluate the safety and tolerability of suprachoroidally administered CLS-AX following intravitreal anti-VEGF therapy in subjects with neovascular age-related macular degeneration (AMD)
Detailed description
Multi-center, open-label, dose-escalation, phase 1/2a, safety and tolerability study to evaluate four dose groups of suprachoroidally administered CLS-AX following intravitreal anti-VEGF therapy in up to a maximum of 25 subjects with neovascular age-related macular degeneration
Interventions
Sponsors
Clearside Biomedical, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Four groups of approximately 5 participants are assigned to receive interventions in sequential dose escalation fashion based on prior milestones being reached.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of neovascular age-related macular degeneration in the study eye. * Active subfoveal choroidal neovascularization (CNV) secondary to AMD * Two or more prior anti-VEGF intravitreal injections * EDTRS BCVA score ≤ 75 and ≥ 20 letters
Exclusion criteria
* Any active ocular disease, ocular disorders or conditions, prior ocular surgery or infection in the study eye other than nAMD * Other than IVT anti-VEGF treatments, no topical ocular or intraocular or periocular corticosteroid, or other treatments for CNV * IOP ≥ 25mmHg or cup-to-disc ratio \>0.8 * Uncontrolled systemic disease (high risk or evidence of arterial and venous thromboembolism, CVA or stroke, unstable cardiovascular disease, uncontrolled hyperthyroidism, poor glycemic control, gastrointestinal bleed and/or high risk of GI perforation or fistula formation) or any other condition or therapy that would make the participant unsuitable for the study * Currently enrolled in an investigational drug or device study or has used an investigational drug or device within 30 days or the Screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 to Week 12 | Number of participants with treatment-emergent adverse events (TEAEs) reported between the administration of CLS-AX and study exit. |
| Number of Participants With Serious Adverse Events | Day 1 to Week 12 | Number of participants with serious adverse events (SAEs) reported between the administration of CLS-AX and study exit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 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. |
| Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Weeks 4, 8 and 12 | 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. |
| Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Weeks 4, 8 and 12. | 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. |
| Maximum Plasma Concentration [Cmax] of Axitinib | Day 1 to Week 12 | 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. |
| Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Weeks 4, 8 and 12 | 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. |
| Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | From Day 1 to Week 12 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 6 |
| 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 | 5 |
| 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 | 8 |
| 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 | 8 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 (Low Dose) | Cohort 2 (Low-mid Dose) | Cohort 3 (High-mid Dose) | Cohort 4 (High Dose) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 81.8 years STANDARD_DEVIATION 11.55 | 78.2 years STANDARD_DEVIATION 10.92 | 86.3 years STANDARD_DEVIATION 6.48 | 76.5 years STANDARD_DEVIATION 5.78 | 80.9 years STANDARD_DEVIATION 8.98 |
| Best Corrected Visual Acuity in the Study Eye at Baseline | 59.0 letters STANDARD_DEVIATION 16.43 | 65.6 letters STANDARD_DEVIATION 8.73 | 58.5 letters STANDARD_DEVIATION 13.69 | 65.8 letters STANDARD_DEVIATION 8.31 | 62.1 letters STANDARD_DEVIATION 12.06 |
| Central Subfield Thickness in the Study Eye at Baseline | 231.2 microns STANDARD_DEVIATION 32.1 | 209.4 microns STANDARD_DEVIATION 17.39 | 202.0 microns STANDARD_DEVIATION 22.57 | 218.8 microns STANDARD_DEVIATION 40.01 | 214.8 microns STANDARD_DEVIATION 30.59 |
| Duration of nAMD Diagnosis in the Study Eye | 50.13 months STANDARD_DEVIATION 34.131 | 49.78 months STANDARD_DEVIATION 21.905 | 66.64 months STANDARD_DEVIATION 41.081 | 48.21 months STANDARD_DEVIATION 48.045 | 54.39 months STANDARD_DEVIATION 37.945 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 8 Participants | 8 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pre injection Intraocular Pressure in the Study Eye at Baseline | 15.3 mmHg STANDARD_DEVIATION 3.08 | 15.2 mmHg STANDARD_DEVIATION 2.39 | 13.3 mmHg STANDARD_DEVIATION 2.76 | 15.4 mmHg STANDARD_DEVIATION 3.81 | 14.7 mmHg STANDARD_DEVIATION 3.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 8 Participants | 8 Participants | 27 Participants |
| Region of Enrollment United States | 6 participants | 5 participants | 8 participants | 8 participants | 27 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 12 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 0-2 injections | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 13-18 injections | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye >18 injections | 4 Participants | 2 Participants | 5 Participants | 5 Participants | 16 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 3-6 injections | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 7-12 injections | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 6 | 2 / 5 | 1 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With Serious Adverse Events
Number of participants with serious adverse events (SAEs) reported between the administration of CLS-AX and study exit.
Time frame: Day 1 to Week 12
Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Low Dose) | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort 4 (High Dose) | Number of Participants With Serious Adverse Events | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Number of participants with treatment-emergent adverse events (TEAEs) reported between the administration of CLS-AX and study exit.
Time frame: Day 1 to Week 12
Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Low Dose) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Cohort 4 (High Dose) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
Secondary
Maximum Plasma Concentration [Cmax] of Axitinib
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.
Time frame: Day 1 to Week 12
Population: Defined as all participants that provide plasma samples for axitinib concentration analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Low Dose) | Maximum Plasma Concentration [Cmax] of Axitinib | 0.0101 ng/mL | Standard Deviation 0.00949 |
| Cohort 2 (Low-mid Dose) | Maximum Plasma Concentration [Cmax] of Axitinib | 0.0264 ng/mL | Standard Deviation 0.0242 |
| Cohort 3 (High-mid Dose) | Maximum Plasma Concentration [Cmax] of Axitinib | 0.0749 ng/mL | Standard Deviation 0.111 |
| Cohort 4 (High Dose) | Maximum Plasma Concentration [Cmax] of Axitinib | 0.0602 ng/mL | Standard Deviation 0.0251 |
Secondary
Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Low Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 4 | -2.8 mmHg | Standard Deviation 4.67 |
| Cohort 1 (Low Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 12 | -3.0 mmHg | Standard Deviation 4.34 |
| Cohort 1 (Low Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 8 | -3.0 mmHg | Standard Deviation 3.16 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 4 | -1.8 mmHg | Standard Deviation 4.15 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 12 | 0.5 mmHg | Standard Deviation 1.91 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 8 | 0.6 mmHg | Standard Deviation 2.79 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 8 | 0.6 mmHg | Standard Deviation 1.9 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 4 | -0.3 mmHg | Standard Deviation 0.95 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 12 | 0.9 mmHg | Standard Deviation 3.27 |
| Cohort 4 (High Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 4 | 0.0 mmHg | Standard Deviation 4.66 |
| Cohort 4 (High Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 12 | 0.0 mmHg | Standard Deviation 3.38 |
| Cohort 4 (High Dose) | Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP) | Week 8 | 1.6 mmHg | Standard Deviation 4.43 |
Secondary
Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Low Dose) | 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 |
| Cohort 1 (Low Dose) | 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 |
| Cohort 1 (Low Dose) | 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 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 4 | 0.2 letters | Standard Deviation 1.64 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 12 | -6.3 letters | Standard Deviation 9.18 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 8 | -3.6 letters | Standard Deviation 2.3 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 8 | 0.6 letters | Standard Deviation 5.83 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 4 | -0.6 letters | Standard Deviation 4.61 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 12 | -2.1 letters | Standard Deviation 4.45 |
| Cohort 4 (High Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 4 | 1.0 letters | Standard Deviation 2.2 |
| Cohort 4 (High Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 12 | 0.3 letters | Standard Deviation 3.28 |
| Cohort 4 (High Dose) | Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 8 | 1.6 letters | Standard Deviation 2.94 |
Secondary
Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Low Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 4 | 22.3 microns | Standard Deviation 23.46 |
| Cohort 1 (Low Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 12 | 8.8 microns | Standard Deviation 14.5 |
| Cohort 1 (Low Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 8 | 62.8 microns | Standard Deviation 57.6 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 4 | 22.0 microns | Standard Deviation 17.83 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 12 | 45.8 microns | Standard Deviation 69.72 |
| Cohort 2 (Low-mid Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 8 | 21.8 microns | Standard Deviation 32.58 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 8 | 21.9 microns | Standard Deviation 25.75 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 4 | 21.1 microns | Standard Deviation 22.62 |
| Cohort 3 (High-mid Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 12 | 29.1 microns | Standard Deviation 37.89 |
| Cohort 4 (High Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 4 | 26.6 microns | Standard Deviation 26.45 |
| Cohort 4 (High Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 12 | 18.6 microns | Standard Deviation 27.33 |
| Cohort 4 (High Dose) | Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye | Week 8 | 9.9 microns | Standard Deviation 17.87 |
Secondary
Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections
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.
Time frame: Day 1 to Week 12
Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (Low Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 0 Participants |
| Cohort 1 (Low Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 4 Participants |
| Cohort 1 (Low Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 1 (Low Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 4 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 2 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 2 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 4 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 2 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 1 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 2 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |
| Cohort 4 (High Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 3 Participants |
| Cohort 4 (High Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 0 Participants |
| Cohort 4 (High Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 3 Participants |
| Cohort 4 (High Dose) | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 2 Participants |
Secondary
Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections
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.
Time frame: From Day 1 to Week 12
Population: Defined as all enrolled participants who were administered CLS-AX, and from whom at least one post-Baseline safety measurement was obtained.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (Low Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 0 Participants |
| Cohort 1 (Low Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 4 Participants |
| Cohort 1 (Low Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 1 (Low Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 4 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 2 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 2 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 4 Participants |
| Cohort 2 (Low-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 1 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 2 Participants |
| Cohort 3 (High-mid Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |
| Cohort 4 (High Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 12 | 4 Participants |
| Cohort 4 (High Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 1 Participants |
| Cohort 4 (High Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 4 Participants |
| Cohort 4 (High Dose) | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |