Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD
- Conditions
- Neovascular Age-related Macular Degeneration
- Interventions
- Drug: Anti-VEGF
- Registration Number
- NCT04626128
- Lead Sponsor
- Clearside Biomedical, Inc.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 (Low Dose) Anti-VEGF Subjects will receive a low dose of 0.03 mg CLS-AX Cohort 1 (Low Dose) CLS-AX Subjects will receive a low dose of 0.03 mg CLS-AX Cohort 3 (High-mid Dose) Anti-VEGF Subjects will receive a high-mid dose of 0.50 mg CLS-AX Cohort 2 (Low-mid Dose) CLS-AX Subjects will receive a low-mid dose of 0.10 mg CLS-AX Cohort 4 (High Dose) Anti-VEGF Subjects will receive a high-mid dose of 1.0 mg CLS-AX Cohort 2 (Low-mid Dose) Anti-VEGF Subjects will receive a low-mid dose of 0.10 mg CLS-AX Cohort 3 (High-mid Dose) CLS-AX Subjects will receive a high-mid dose of 0.50 mg CLS-AX Cohort 4 (High Dose) CLS-AX Subjects will receive a high-mid dose of 1.0 mg CLS-AX
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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.
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 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.
Trial Locations
- Locations (9)
Northern California Retina Vitreous Associates Medical Group, LLC
🇺🇸Mountain View, California, United States
Retinal Consultants Medical Group
🇺🇸Sacramento, California, United States
Retinal Consultants of Arizona
🇺🇸Phoenix, Arizona, United States
California Retina Consultants
🇺🇸Bakersfield, California, United States
Cumberland Valley Retina Consultants
🇺🇸Hagerstown, Maryland, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Retina Consultants of Texas
🇺🇸The Woodlands, Texas, United States
Center for Retina and Macular Disease
🇺🇸Winter Haven, Florida, United States