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

ODYSSEY: A Phase 2b Study of Suprachoroidally Administered CLS-AX in Participants With Neovascular Age-Related Macular Degeneration

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: CLS-AX; Drug: Aflibercept

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Donna Bezner, M.S.; Phone Number: 404.850.3421; Email: donna.bezner@clearsidebio.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute, LLC
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates Medical Group, Inc
    • Poway, California, United States, 92064
      • Retina Consultants San Diego
    • Redlands, California, United States, 92374
      • Retinal Consultants of Southern California
    • Sacramento, California, United States, 95825
      • Retinal Consultants Medical Group, Inc.
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Retina Group of Florida
    • Lakeland, Florida, United States, 33805
      • Florida Retina Consultants
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Georgia Retina, PC
  • Illinois
    • Oak Park, Illinois, United States, 60304
      • Illinois Retina Associates
  • Iowa
    • Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Vitreo-Retinal Associates, PC
  • Nevada
    • Reno, Nevada, United States, 89431
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Envision Ocular LLC
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associates P.A.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates - Arlington
    • Austin, Texas, United States, 78705
      • Austin Retina
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas-Bellairre
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates - Dallas
    • Katy, Texas, United States, 77494
      • Retina Consultants of Texas - Katy
    • Plano, Texas, United States, 75075
      • Texas Retina Associates-Plano
    • San Antonio, Texas, United States, 78240
      • Retina Consultants of Texas-San Antonio
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Retina Group of Washington
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.0 mg CLS-AX; Suprachoroidal injection of 10 mg/mL (1.0 mg in 0.1 mL) of CLS-AX	Drug: CLS-AX; CLS-AX will be administered by suprachoroidal injection into the study eye on Day 1 and then every 12 to 24 weeks as determined by protocol-defined disease activity criteria.; Other Names: axitinib injectable suspension
Active Comparator: Aflibercept; Intravitreal injection of aflibercept (2 mg in 0.05 mL)	Drug: Aflibercept; Aflibercept will be administered by intravitreal injection into the study eye once every 8 weeks (Q8W).; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluations of Outcomes Related to ETDRS BCVA in the Study Eye Over Time	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.	Baseline, Weeks 4, 12, 16, 20, 24, 28, 32 and 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluations of Outcomes Related to Fluid Detected on Optical Coherence Tomography in the Study Eye Over Time	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.	Baseline, Weeks 4, 12, 16, 20, 24, 28, 32 and 36
Evaluations of Outcomes Related to Lesion Size on Fundus Fluorescein Angiography in the Study Eye Over Time	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.	Baseline, Week 36
Evaluation of the Number of Study Drug Injections and Supplemental Therapy Injections in the Study Eye Over Time	Number of masked study drug injections and supplemental therapy injections administered in the study eye.	From Baseline Through Week 36
Evaluation of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs)	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.	From first dose of masked study drug through the end of the study (up to 36 weeks)

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): May 31, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: June 4, 2023
• First Posted (Actual): June 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: AMD; Wet AMD; Tyrosine kinase inhibitor; Suprachoroidal; Microinjector; Suprachoroidal Space (SCS)
• 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: CLS1002-202

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