Neovascular Age-related Macular Degeneration
Conditions
Keywords
AMD, Wet-AMD, suprachoroidal, tyrosine kinase inhibitor, nAMD, SCS
Brief summary
This is an open-label, non-interventional extension study of up to 12 weeks in duration in subjects completing Cohorts 2, 3, and 4 of the Parent study, CLS1002-101.
Detailed description
This is an open-label, non-interventional extension study of up to 12 weeks in duration in subjects completing Cohorts 2. 3 and 4 of the Parent study, CLS1002-101. The Parent study is a 12-week, Phase 1/2a, multicenter study designed to assess the safety and tolerability of a single dose of CLS-AX administered suprachoroidally in subjects with neovascular age-related macular degeneration (nAMD) who show stable visual acuity following 3 or more injections with an intravitreal (IVT) anti-VEGF therapy in the preceding 5 months. Summary analyses will include 12-weeks data from the Parent study, CLS1002-101, and 12-weeks data from this extension study, CLS1002-102, for a total of 24 weeks follow-up, for all participants enrolled into the extension study.
Interventions
DRUGCLS-AX
injectable suspension of small molecule tyrosine kinase inhibitor (TKI) administered in the Parent study CLS1002-101
Sponsors
Clearside Biomedical, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Enrolled in and completed the Parent study, CLS1002-101, as part of Cohort 2 or Cohort 3 or Cohort 4.
Exclusion criteria
* Received prohibited medication in the Parent study, CLS1002-101. * Enrolled in the Parent study CLS1002-101 as part of Cohort 1. * Females of childbearing potential who are pregnant and or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 to Week 24 | The 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 (SAEs) | Day 1 to Week 24 | The 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 Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | Number of participants receiving additional intravitreal aflibercept injections during the course of the study for nAMD. |
| Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Weeks 4, 8, 12, 16, 20 and 24 | 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. |
| Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Weeks 4, 8, 12, 16, 20 and 24 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | 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 in Pre-Injection Intraocular Pressure (IOP) | Weeks 4, 8, 12, 16, 20 and 24 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 2 (Low-mid Dose) Extension Subjects who were administered by suprachoroidal injection 0.10 mg CLS-AX in cohort 2 of the parent study, CLS1002-101, will be followed for an additional 12 weeks following exit from the Parent study. No intervention will be administered in this extension study.
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI) administered in the Parent study CLS1002-101 | 3 |
| Cohort 3 (High-mid Dose) Extension Subjects who were administered by suprachoroidal injection 0.50 mg CLS-AX in cohort 3 of the parent study, CLS1002-101, will be followed for an additional 12 weeks following exit from the Parent study. No intervention will be administered in this extension study.
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI) administered in the Parent study CLS1002-101 | 7 |
| Cohort 4 (High Dose) Extension Subjects who were administered by suprachoroidal injection 1.0 mg CLS-AX in cohort 4 of the parent study, CLS1002-101, will be followed for an additional 12 weeks following exit from the Parent study. No intervention will be administered in this extension study.
CLS-AX: injectable suspension of small molecule tyrosine kinase inhibitor (TKI) administered in the Parent study CLS1002-101 | 5 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 2 (Low-mid Dose) Extension | Cohort 3 (High-mid Dose) Extension | Cohort 4 (High Dose) Extension | Total |
|---|---|---|---|---|
| Age, Continuous | 78.7 years STANDARD_DEVIATION 9.02 | 87.9 years STANDARD_DEVIATION 4.98 | 79.6 years STANDARD_DEVIATION 3.97 | 83.3 years STANDARD_DEVIATION 6.82 |
| Best Corrected Visual Acuity in the Study Eye at Baseline | 61.0 letters STANDARD_DEVIATION 8.19 | 59.0 letters STANDARD_DEVIATION 14.71 | 71.2 letters STANDARD_DEVIATION 2.17 | 63.5 letters STANDARD_DEVIATION 11.67 |
| Central Subfield Thickness in the Study Eye at Baseline | 214.0 microns STANDARD_DEVIATION 13.53 | 201.9 microns STANDARD_DEVIATION 24.38 | 214.8 microns STANDARD_DEVIATION 13.74 | 208.6 microns STANDARD_DEVIATION 19.43 |
| Duration of nAMD Diagnosis in the Study Eye | 56.63 months STANDARD_DEVIATION 23.759 | 67.29 months STANDARD_DEVIATION 44.329 | 36.42 months STANDARD_DEVIATION 38.955 | 54.87 months STANDARD_DEVIATION 39.442 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 7 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pre Injection Intraocular Pressure in the Study Eye at Baseline | 14.3 mmHg STANDARD_DEVIATION 1.53 | 13.9 mmHg STANDARD_DEVIATION 2.34 | 13.8 mmHg STANDARD_DEVIATION 3.56 | 13.9 mmHg STANDARD_DEVIATION 2.52 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 5 Participants | 15 Participants |
| Region of Enrollment United States | 3 participants | 7 participants | 5 participants | 15 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 0-2 Injections | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 13-18 Injections | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye >18 Injections | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 3-6 Injections | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Total Number of Prior nAMD Treatments in the Study Eye 7-12 Injections | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 3 / 3 | 2 / 7 | 1 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 7 | 0 / 5 |
Outcome results
Primary
Number of Participants With Serious Adverse Events (SAEs)
The number of participants with serious adverse events (SAEs) reported between the administration of CLS-AX and study exit.
Time frame: Day 1 to Week 24
Population: Defined as all enrolled participants who were administered CLS-AX in the Parent study, who have provided informed consent for participating in the Extension study, and from whom at least one safety measurement was obtained after the participant provided informed consent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2 (Low-mid Dose) Extension | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
The 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 24
Population: Defined as all enrolled participants who were administered CLS-AX in the Parent study, who have provided informed consent for participating in the Extension study, and from whom at least one safety measurement was obtained after the participant provided informed consent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2 (Low-mid Dose) Extension | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Mean Change From Baseline 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, 12, 16, 20 and 24
Population: Defined as all enrolled participants who were administered CLS-AX in the Parent study, who have provided informed consent for participating in the Extension study, and from whom at least one safety measurement was obtained after the participant provided informed consent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 4 | 0.7 letters | Standard Deviation 2.08 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 8 | -2.3 letters | Standard Deviation 2.08 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 12 | -5.0 letters | Standard Deviation 10.82 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 16 | -2.0 letters | Standard Deviation 0 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 20 | 0.0 letters | Standard Deviation 1.41 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 24 | -35.0 letters | Standard Deviation 46.67 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 24 | -1.9 letters | Standard Deviation 5.05 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 4 | 1.0 letters | Standard Deviation 2.19 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 16 | 1.9 letters | Standard Deviation 3.02 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 20 | 0.0 letters | Standard Deviation 2.65 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 8 | 2.5 letters | Standard Deviation 3.08 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 12 | -0.9 letters | Standard Deviation 2.85 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 8 | 1.8 letters | Standard Deviation 2.86 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 12 | 0.0 letters | Standard Deviation 3.16 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 24 | 0.4 letters | Standard Deviation 6.62 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 16 | 1.0 letters | Standard Deviation 4.85 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 4 | 0.8 letters | Standard Deviation 2.49 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | Week 20 | 1.0 letters | Standard Deviation 6.2 |
Secondary
Mean Change From Baseline 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, 12, 16, 20 and 24
Population: Defined as all enrolled participants who were administered CLS-AX in the Parent study, who have provided informed consent for participating in the Extension study, and from whom at least one safety measurement was obtained after the participant provided informed consent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 4 | 14.7 microns | Standard Deviation 14.47 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 8 | 5.7 microns | Standard Deviation 30.37 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 12 | 53.3 microns | Standard Deviation 83.34 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 16 | 18.0 microns | Standard Deviation 19.8 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 20 | 67.0 microns | — |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 24 | 6.0 microns | — |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 24 | 20.4 microns | Standard Deviation 33.1 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 4 | 23.5 microns | Standard Deviation 23.82 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 16 | 5.1 microns | Standard Deviation 28.26 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 20 | 20.0 microns | Standard Deviation 21.84 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 8 | 28.2 microns | Standard Deviation 21.48 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 12 | 36.6 microns | Standard Deviation 34.02 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 8 | 13.6 microns | Standard Deviation 18.08 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 12 | 19.4 microns | Standard Deviation 16.1 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 24 | 26.4 microns | Standard Deviation 65.26 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 16 | 13.4 microns | Standard Deviation 15.49 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 4 | 20.2 microns | Standard Deviation 26.64 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Central Subfield Thickness (CST) in the Study Eye | Week 20 | 26.2 microns | Standard Deviation 49.55 |
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.
Time frame: Day 1 to Week 24
Population: Defined as all enrolled participants who were administered CLS-AX in the Parent study, who have provided informed consent for participating in the Extension study, and from whom at least one safety measurement was obtained after the participant provided informed consent.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 24 | 0 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | 3 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 20 | 1 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 16 | 0 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 1 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 16 | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 20 | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 24 | 2 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | 2 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 0 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 16 | 0 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 20 | 2 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 0 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | 3 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections | Week 24 | 1 Participants |
Other Pre-specified
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, 12, 16, 20 and 24
Population: Defined as all enrolled participants who were administered CLS-AX in the Parent study, who have provided informed consent for participating in the Extension study, and from whom at least one safety measurement was obtained after the participant provided informed consent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 4 | -0.7 mmHg | Standard Deviation 4.16 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 8 | 0.3 mmHg | Standard Deviation 3.79 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 12 | 0.3 mmHg | Standard Deviation 2.31 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 16 | 0.5 mmHg | Standard Deviation 3.54 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 20 | 1.0 mmHg | Standard Deviation 0 |
| Cohort 2 (Low-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 24 | -1.0 mmHg | Standard Deviation 4.24 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 24 | 0.6 mmHg | Standard Deviation 1.99 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 4 | -0.5 mmHg | Standard Deviation 0.84 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 16 | 0.4 mmHg | Standard Deviation 1.72 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 20 | -0.6 mmHg | Standard Deviation 0.98 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 8 | 0.2 mmHg | Standard Deviation 1.72 |
| Cohort 3 (High-mid Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 12 | -0.1 mmHg | Standard Deviation 1.68 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 8 | 1.6 mmHg | Standard Deviation 3.78 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 12 | 0.2 mmHg | Standard Deviation 3.9 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 24 | 0.4 mmHg | Standard Deviation 3.91 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 16 | 1.2 mmHg | Standard Deviation 2.49 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 4 | 0.2 mmHg | Standard Deviation 5.45 |
| Cohort 4 (High Dose) Extension | Mean Change From Baseline in Pre-Injection Intraocular Pressure (IOP) | Week 20 | 0.0 mmHg | Standard Deviation 3.54 |
Other Pre-specified
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 24
Population: Defined as all enrolled participants who were administered CLS-AX in the Parent study, who have provided informed consent for participating in the Extension study, and from whom at least one safety measurement was obtained after the participant provided informed consent.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 1 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 20 | 1 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 16 | 0 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | 3 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 24 | 1 Participants |
| Cohort 2 (Low-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 16 | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 20 | 0 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 24 | 2 Participants |
| Cohort 3 (High-mid Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | 2 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 20 | 2 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 8 | 0 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Day 1 to Week 24 | 3 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 24 | 1 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 16 | 0 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 12 | 1 Participants |
| Cohort 4 (High Dose) Extension | Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections | Week 4 | 1 Participants |