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Study to Evaluate Suprachoroidally Administered CLS-AX in the Treatment of Neovascular Age-Related Macular Degeneration

Phase 2
Completed
Conditions
Neovascular Age-related Macular Degeneration
Interventions
Registration Number
NCT05891548
Lead Sponsor
Clearside Biomedical, Inc.
Brief Summary

Phase 2b, randomized, double-masked, parallel-group, active-controlled, multicenter, 36-week study designed to assess the safety and efficacy of suprachoroidally administered CLS-AX 1.0 mg with a flexible dosing regimen in participants with neovascular age-related macular degeneration previously treated with intravitreal anti-vascular endothelial growth factor (VEGF) standard of care therapy. Only one eye will be chosen as the study eye.

Detailed Description

Phase 2b, randomized, double-masked, parallel-group, active-controlled, multicenter, 36-week study designed to assess the safety and efficacy of suprachoroidally administered CLS-AX 1.0 mg with a flexible dosing regimen in participants with neovascular age-related macular degeneration previously treated with intravitreal anti-VEGF standard of care therapy. Active-control will be 2 mg intravitreal injections of aflibercept dosed per the EYLEA Prescribing Information. Only one eye will be chosen as the study eye.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Diagnosis of neovascular age-related macular degeneration (nAMD) in the study eye within 36 months of Visit 1.
  • Subfoveal choroidal neovascularization (CNV) secondary to nAMD of any lesion type in the study eye that shows total lesion area ≤30 mm2, CNV component area of ≥50% of the total lesion area, and and CNV must not be associated with subfoveal hemorrhage, subfoveal fibrosis, or subfoveal atrophy.
  • Previous treatment in the study eye with between 2 and 4 anti-VEGF intravitreal injections for nAMD (faricimab, ranibizumab, bevacizumab, brolucizumab, or aflibercept) per standard of care within 6 months of Visit 1.
  • History of response to prior intravitreal anti-VEGF treatment in the study eye.
  • ETDRS BCVA of between 20 and 80 letters (inclusive) in the study eye.

Key

Exclusion Criteria
  • ETDRS BCVA <20 letters in the study eye.
  • Central subfield thickness > 400 μm or retinal pigment epithelium detachment thickness >400 μm on SD-OCT in the study eye.
  • Subretinal hemorrhage, fibrosis or atrophy of >50% of the total lesion area and/or that involves the fovea on fundus fluorescein angiography and/or color fundus photography in the study eye.
  • CNV due to causes other than AMD, such are ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis, in the study eye.
  • Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1.0 mg CLS-AXCLS-AXSuprachoroidal injection of 10 mg/mL (1.0 mg in 0.1 mL) of CLS-AX
AfliberceptAfliberceptIntravitreal injection of aflibercept (2 mg in 0.05 mL)
Primary Outcome Measures
NameTimeMethod
Evaluations of Outcomes Related to ETDRS BCVA in the Study Eye Over TimeBaseline, Weeks 4, 12, 16, 20, 24, 28, 32 and 36

Best Corrected Visual Acuity (BCVA) letter score 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). An increase in BCVA letter score from baseline indicates an improvement in visual acuity.

Secondary Outcome Measures
NameTimeMethod
Evaluations of Outcomes Related to Fluid Detected on Optical Coherence Tomography in the Study Eye Over TimeBaseline, Weeks 4, 12, 16, 20, 24, 28, 32 and 36

Spectral-domain optical coherence tomography (SD-OCT) is a non-invasive diagnostic technique that provides high-resolution, cross-sectional tissue imaging and analysis of structural changes in the eye during disease progression. A central reading center will provide measurements and standardized gradings of outcomes related to retinal thickness and fluid in the eye, respectively.

Central subfield retinal thickness (CST) is defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) in millimeters in the circular region centered on the anatomic fovea with a radius of 500 microns.

The presence and location of intraretinal and subretinal fluid in the central subfield (center 1 mm) is graded as Absent (the best grade attainable); Definite, outside center subfield; Definite, center subfield involved; and Definite, both center subfield and outer subfields involved.

Evaluations of Outcomes Related to Lesion Size on Fundus Fluorescein Angiography in the Study Eye Over TimeBaseline, Week 36

Fundus fluorescein angiography (FFA) is an invasive diagnostic procedure used to assess the anatomy, physiology, and pathology of retinal and choroidal circulation. It involves injecting fluorescein dye into a vein in the arm/hand and taking pictures as it circulates through the eye. A central reading center will provide measurements of outcomes related to the size of lesions/leakage in the eye.

Total area of Choroidal Neovascularization (CNV) includes classic and occult components and ranges from 0-42 mm2, with 0 mm2 being the best measurement attainable.

Total lesion area includes the total CNV and associated lesion components and ranges from 0-42 mm2, with 0 mm2 being the best measurement attainable.

Total area of leakage includes the total area leakage from neovascularization and ranges from 0-42 mm2, with 0 mm2 being the best measurement attainable.

Evaluation of the Number of Study Drug Injections and Supplemental Therapy Injections in the Study Eye Over TimeFrom Baseline Through Week 36

Number of masked study drug injections and supplemental therapy injections administered in the study eye.

Evaluation of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs)From first dose of masked study drug through the end of the study (up to 36 weeks)

The analysis of serious adverse events (SAEs) includes both ocular and non-ocular (systemic) adverse events (AEs) meeting SAE criteria as defined in International Conference on Harmonisation (ICH) E6 Good Clinical Practice Consolidated Guidance. TEAEs are defined as adverse events that emerge during or after treatment with masked treatment having been absent pre-treatment or worsens relative to the pre-treatment state.

Investigators will seek information on AEs at each contact with the participant. All AEs are recorded and the Investigator will independently assess seriousness, severity, and causality of each AE.

Trial Locations

Locations (32)

Retina Group of Florida

🇺🇸

Fort Lauderdale, Florida, United States

Southeast Retina Center

🇺🇸

Augusta, Georgia, United States

Western Carolina Retinal Associates P.A.

🇺🇸

Asheville, North Carolina, United States

Cumberland Valley Retina Consultants

🇺🇸

Hagerstown, Maryland, United States

Florida Retina Consultants

🇺🇸

Lakeland, Florida, United States

California Retina Consultants

🇺🇸

Bakersfield, California, United States

Retina Consultants of Orange County

🇺🇸

Fullerton, California, United States

Retina Specialty Institute

🇺🇸

Pensacola, Florida, United States

Texas Retina Associates - Dallas

🇺🇸

Dallas, Texas, United States

Retina Consultants of Texas - Katy

🇺🇸

Katy, Texas, United States

Northern California Retina Vitreous Associates Medical Group, Inc

🇺🇸

Mountain View, California, United States

Retina Consultants San Diego

🇺🇸

Poway, California, United States

Retinal Consultants of Southern California

🇺🇸

Redlands, California, United States

Georgia Retina, PC

🇺🇸

Marietta, Georgia, United States

Wolfe Eye Clinic

🇺🇸

Des Moines, Iowa, United States

Sierra Eye Associates

🇺🇸

Reno, Nevada, United States

Vitreo-Retinal Associates, PC

🇺🇸

Worcester, Massachusetts, United States

Envision Ocular LLC

🇺🇸

Bloomfield, New Jersey, United States

Retina Research Institute of Texas

🇺🇸

Abilene, Texas, United States

Texas Retina Associates - Arlington

🇺🇸

Arlington, Texas, United States

Texas Retina Associates-Plano

🇺🇸

Plano, Texas, United States

Retina Consultants of Texas-San Antonio

🇺🇸

San Antonio, Texas, United States

Retina Group of Washington

🇺🇸

Fairfax, Virginia, United States

Spokane Eye Clinical Research

🇺🇸

Spokane, Washington, United States

Austin Retina

🇺🇸

Austin, Texas, United States

Retina Consultants of Texas-Bellairre

🇺🇸

Bellaire, Texas, United States

Associated Retina Consultants

🇺🇸

Phoenix, Arizona, United States

Retinal Research Institute, LLC

🇺🇸

Phoenix, Arizona, United States

Retinal Consultants Medical Group, Inc.

🇺🇸

Sacramento, California, United States

Retina Associates of Florida

🇺🇸

Tampa, Florida, United States

Tennessee Retina PC

🇺🇸

Nashville, Tennessee, United States

Illinois Retina Associates

🇺🇸

Oak Park, Illinois, United States

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