Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD

Study Overview
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Brief Summary
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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
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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

Official Title
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OASIS: Open-label, Dose-escalation, Phase 1/2a Study of the Safety and Tolerability of Suprachoroidally Administered CLS-AX Following Intravitreal Anti-VEGF Therapy in Subjects With Neovascular Age-related Macular Degeneration

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: CLS-AX
* Drug: Anti-VEGF


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Four groups of approximately 5 participants are assigned to receive interventions in sequential dose escalation fashion based on prior milestones being reached.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Low Dose)<br>Subjects will receive a low dose of 0.03 mg CLS-AX | Drug: CLS-AX<br>* injectable suspension of small molecule tyrosine kinase inhibitor (TKI)<br>* Other names: axitinib injectable suspension;Drug: Anti-VEGF<br>* Standard of care therapy used to block vascular endothelial growth factor<br>* Other names: aflibercept (2mg);|
| Experimental: Cohort 2 (Low-mid Dose)<br>Subjects will receive a low-mid dose of 0.10 mg CLS-AX | Drug: CLS-AX<br>* injectable suspension of small molecule tyrosine kinase inhibitor (TKI)<br>* Other names: axitinib injectable suspension;Drug: Anti-VEGF<br>* Standard of care therapy used to block vascular endothelial growth factor<br>* Other names: aflibercept (2mg);|
| Experimental: Cohort 3 (High-mid Dose)<br>Subjects will receive a high-mid dose of 0.50 mg CLS-AX | Drug: CLS-AX<br>* injectable suspension of small molecule tyrosine kinase inhibitor (TKI)<br>* Other names: axitinib injectable suspension;Drug: Anti-VEGF<br>* Standard of care therapy used to block vascular endothelial growth factor<br>* Other names: aflibercept (2mg);|
| Experimental: Cohort 4 (High Dose)<br>Subjects will receive a high-mid dose of 1.0 mg CLS-AX | Drug: CLS-AX<br>* injectable suspension of small molecule tyrosine kinase inhibitor (TKI)<br>* Other names: axitinib injectable suspension;Drug: Anti-VEGF<br>* Standard of care therapy used to block vascular endothelial growth factor<br>* Other names: aflibercept (2mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 to Week 12 | 
| 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. | Day 1 to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Weeks 4, 8 and 12. | 
| 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. | From Day 1 to Week 12 | 
| 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. | Day 1 to Week 12 | 
| 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. | Weeks 4, 8 and 12 | 
| 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. | Weeks 4, 8 and 12 | 
| 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. | Day 1 to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, suprachoroidal, tyrosine kinase inhibitor, Microinjector, SCS, Wet-AMD