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

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

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)

Study Overview

• Status: Completed
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: Anti-VEGF; Drug: CLS-AX

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

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Consultants of Arizona
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates Medical Group, LLC
    • Sacramento, California, United States, 95825
      • Retinal Consultants Medical Group
  • Florida
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • San Antonio, Texas, United States, 78240
      • Retina Consultants of Texas
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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 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
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

Collaborators and Investigators

• Sponsor: Clearside Biomedical, Inc.
• Investigators: Study Director: Susan Coultas, PhD, Clearside Biomedical, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Actual): October 13, 2022
• Study Completion (Actual): October 13, 2022

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: tyrosine kinase inhibitor; AMD; SCS; Wet-AMD; suprachoroidal; Microinjector
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Axitinib; Aflibercept
• Other Study ID Numbers: CLS1002-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No