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

Neovascular Age-related Macular Degeneration Clinical Trial

— OASIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04626128
• Other study ID #: CLS1002-101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 15, 2020
• Est. completion date: October 13, 2022

Study information

• Verified date: August 2023
• Source: Clearside Biomedical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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 information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: October 13, 2022
• Est. primary completion date: October 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• CLS-AX
injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
• Anti-VEGF
Standard of care therapy used to block vascular endothelial growth factor

Locations

Country	Name	City	State
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Retina Consultants of Texas	Bellaire	Texas
United States	Cumberland Valley Retina Consultants	Hagerstown	Maryland
United States	Northern California Retina Vitreous Associates Medical Group, LLC	Mountain View	California
United States	Retinal Consultants of Arizona	Phoenix	Arizona
United States	Retinal Consultants Medical Group	Sacramento	California
United States	Retina Consultants of Texas	San Antonio	Texas
United States	Retina Consultants of Texas	The Woodlands	Texas
United States	Center for Retina and Macular Disease	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Clearside Biomedical, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 to Week 12
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.	Day 1 to Week 12
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.	Weeks 4, 8 and 12.
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.	From Day 1 to Week 12
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.	Day 1 to Week 12
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.	Weeks 4, 8 and 12
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.	Weeks 4, 8 and 12
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.	Day 1 to Week 12