Study to Evaluate Efficacy and Safety of ONL1204 in Patients With GA Associated With AMD

NCT06659445 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ONL1204-GA-002
• Study Type: interventional
• Target: 324
• Locations: 2 countries
• Sites: 28

Brief Summary

The purpose of this study is to collect efficacy and safety information of intravitreal injection for 3 experimental arms, including 2 dose levels of ONL1204 and 2 treatment frequencies in patients with GA associated with AMD. GA associated with AMD is one of the world's leading causes of visual disability and legal blindness globally. Associated with aging, cigarette smoking, obesity, diets low in certain nutrients, a lifestyle related to cardiac risk, and a growing list of genetic factors, AMD is becoming an increasingly prevalent public health concern, especially as the global population ages. ONL1204 is a first-in-class inhibitor of fragment apoptosis stimulator receptor-mediated cell death that has demonstrated protection of multiple retinal cell types in numerous preclinical models of retinal disease, including models of dry AMD.

Conditions

Geographic Atrophy (GA); Age - Related Macular Degeneration (AMD)

Keywords

Phase 2; ONL1204; Geographic Atrophy (GA); Age-related Macular Degeneration (AMD)

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint

  GA lesion area

  From enrollment to the end of treatment at 48 weeks.

Secondary Outcomes (2)

• Secondary Endpoints (Safety)

  From enrollment to the end of treatment at 48 weeks.

• Secondary Endpoints (Safety)

  From enrollment to the end of treatment at 48 weeks.

Study Arms (6)

ONL1204 Opthalmic solution (1 of 6 Treatment Groups) administered by intravitreal injection

ACTIVE COMPARATOR

ONL1204 100 µg administered by intravitreal (IVT) injection every 12 weeks

Drug: ONL1204 Opthalmic solution

ONL1204 Opthalmic solution (2 of 6 Treatment Groups) administered by intravitreal injection

ACTIVE COMPARATOR

ONL1204 200 µg administered by intravitreal (IVT) injection every 12 weeks

Drug: ONL1204 Opthalmic solution

ONL1204 Opthalmic solution (3 of 6 Treatment Groups) administered by intravitreal injection

EXPERIMENTAL

ONL1204 200 µg administered by intravitreal (IVT) injection every 24 weeks

Drug: ONL1204 Opthalmic solution

Sham Comparator (4 of 6 Treatment Groups)

SHAM COMPARATOR

Sham injection every 12 weeks

Other: Sham

Sham Comparator (5 of 6 Treatment Groups)

SHAM COMPARATOR

Sham injection every 24 weeks

Other: Sham

Avacincaptad pegol intravitreal solution (6 of 6 Treatment Groups - US ONLY)

ACTIVE COMPARATOR

Avacincaptad pegol administered by intravitreal (IVT) injection - (2 mg (0.1 mL of 20 mg/mL solution) once monthly

Drug: Avacincaptad Pegol intravitreal solution

Interventions

ONL1204 Opthalmic solution DRUG

Liquid formulation ONL1204 Ophthalmic Solution administered by intravitreal (IVT) injection

ONL1204 Opthalmic solution (1 of 6 Treatment Groups) administered by intravitreal injection; ONL1204 Opthalmic solution (2 of 6 Treatment Groups) administered by intravitreal injection; ONL1204 Opthalmic solution (3 of 6 Treatment Groups) administered by intravitreal injection

Avacincaptad Pegol intravitreal solution DRUG

Liquid formulation Avacincaptad Pegol administered by intravitreal (IVT) injection

Avacincaptad pegol intravitreal solution (6 of 6 Treatment Groups - US ONLY)

Sham OTHER

Sham injection

Sham Comparator (4 of 6 Treatment Groups); Sham Comparator (5 of 6 Treatment Groups)

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older at Screening.
• Able and willing to give informed consent and attend study visits.
• Women or intersex individuals must be willing to use 2 forms of effective contraception during the study and for at least 90 days following the last dose of study drug, be postmenopausal for at least 12 months prior to study entry, or surgically sterile. If of childbearing potential, a negative urine pregnancy test is required at Screening and prior to the administration of study drug at each visit.
• Men or intersex individuals with partners of childbearing potential must be willing to use permissible methods of contraception and refrain from sperm donation during the study and for at least 90 days following the last dose of study drug.
• If currently using Age-related Eye Disease Study 2 (AREDS, AREDS2, or similar nutraceutical therapy at Screening, patient must be willing to continue use for the duration of the study. If not currently using AREDS2 or similar, patient must be willing to continue not to use therapy for the duration of the study. Patient must agree to choose either approach.
• BCVA of 24 letters or more using ETDRS charts in the study eye at Screening.
• Intraocular pressure (IOP) of 22 mmHg or lower in the study eye at Screening.
• The GA lesion must meet all the following criteria:
• Non-foveal GA associated with AMD without eMNV in the study eye per Investigator's evaluation and as confirmed by the central RC.
• GA ≥0.85 disc area (DA) (2.125 mm2) and ≤8.05 DA (20.125 mm2) in the study eye as confirmed by the central RC.
• If GA in the study eye is multifocal, at least 1 focal lesion must be ≥0.425 DA (1.063 mm2) as confirmed by the central RC.
• Non-foveal GA (GA lesion up to the fovea, but not subfoveal) with the lesion's closest border 1725 microns or less from the foveal center in the study eye, as confirmed by the central RC.
• The entire GA lesion in the study eye must be completely visualized on the macula-centered FAF image, must be able to be imaged in its entirety, and must not be contiguous with any areas of peripapillary atrophy per the Investigator's evaluation and as confirmed by the central RC.
• A pattern of hyper-autofluorescence in the junctional zone of GA in the study eye must be present as confirmed by the central RC.
• BCVA of 19 letters or more using ETDRS charts in the fellow eye at Screening.

You may not qualify if:

• Current or planned participation in another investigational clinical study or use of any other investigational drugs or devices at least 6 months prior to enrollment or during the study period without prior written Sponsor approval.
• Previous ophthalmic disease gene therapy or planned participation in any gene therapy clinical study during the study period.
• Current or planned use of systemic complement inhibitors during the study period.
• Any ocular or systemic condition that, in the opinion of the Investigator, makes the patient unsuitable for treatment with an investigational drug or that would compromise the safety or efficacy assessments of the study.
• Treatment with any ocular or systemic medication that is known to be toxic to the lens, retina, or optic nerve (including, but not limited to, aminoglycosides, vancomycin, hydroxychloroquine, interferon, tacrolimus, cisplatin, bis-chloroethyl nitrosourea, carmustine, ethambutol, and tamoxifen) within 90 days prior to Screening or anticipated during the study period.
• Known allergy to fluorescein, povidone iodine, or any ingredients of the study drug or avacincaptad pegol intravitreal solution.
• Individuals who are currently pregnant, planning to become pregnant, or are nursing at Screening or during the study period.
• Active ocular or periocular infection in the study eye.
• Any contraindication to an IVT injection in the study eye.
• Any media opacity in the study eye that limits visual acuity, clinical visualization of the retina, or retinal imaging as determined by the Investigator.
• Previous IVT pharmaceutical treatment in the study eye with any agent except Food and Drug Administration (FDA)-approved complement inhibitors and treatment with FDA-approved complement inhibitors within 12 weeks prior to Screening.
• Yttrium aluminum garnet capsulotomy in the study eye within 1 month prior to Screening.
• Cataract surgery in the study eye planned or expected during the study period.
• Any current evidence or history in the study eye of exudative ("wet") AMD, including any RPE rips or evidence of actively leaking neovascularization anywhere in the retina based on the FA or SD-OCT as assessed per the Investigator's evaluation and confirmed by the central RC.
• Any clinically significant retinal disease other than AMD except benign degenerative conditions (eg, Cobblestone degeneration) in the study eye.

Sponsors & Collaborators

• ONL Therapeutics: lead

Study Sites (28)

Associated Retina Consultants

Gilbert, Arizona, 85297, United States

RECRUITING

Associated Retina Consultants

Phoenix, Arizona, 85020, United States

RECRUITING

Doheny Image Reading Center

Pasadena, California, 91103, United States

RECRUITING

Bay Area Retina Associates

Walnut Creek, California, 94598, United States

RECRUITING

Retina Consultants of Southern Colorado

Colorado Springs, Colorado, 80909-1183, United States

RECRUITING

Retina Group of New England

Waterford, Connecticut, 06385, United States

RECRUITING

Florida Retina Institute

Orlando, Florida, 32806, United States

RECRUITING

Retina Associates, Ltd.

Elmhurst, Illinois, 60126, United States

RECRUITING

Retina Partners Midwest, P.C.

Carmel, Indiana, 46032, United States

RECRUITING

Retina Research Institute at New England Retina Consultants

Springfield, Massachusetts, 01107, United States

RECRUITING

Associated Retinal Consultants, P.C.

Royal Oak, Michigan, 48073, United States

RECRUITING

The Retina Institute

St Louis, Missouri, 63128, United States

RECRUITING

Sierra Eye Associates

Reno, Nevada, 89502, United States

RECRUITING

Retina Associates of Western NY

Rochester, New York, 14620, United States

RECRUITING

Long Island Vitreoretinal Consultants

Westbury, New York, 11590, United States

RECRUITING

North Carolina Retina Associates, S.C.

Wake Forest, North Carolina, 27587, United States

RECRUITING

Erie Retina Research, LLC (Clinic)

Erie, Pennsylvania, 16505, United States

RECRUITING

Charleston Neuroscience Institute

Mt. Pleasant, South Carolina, 29464, United States

RECRUITING

Palmetto Retina Center

West Columbia, South Carolina, 29169, United States

RECRUITING

Retina Consultants of Texas

Beaumont, Texas, 77707, United States

RECRUITING

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

RECRUITING

Retina Consultants of Texas

Katy, Texas, 77494, United States

RECRUITING

Retina Associates of South Texas, PA

San Antonio, Texas, 78240, United States

RECRUITING

Retina Consultants of Texas

San Antonio, Texas, 78240, United States

RECRUITING

Retina Consultants of Texas

The Woodlands, Texas, 77384, United States

RECRUITING

Pacific Northwest Retina

Bellevue, Washington, 98004, United States

RECRUITING

Pacific Northwest Retina, PLLC

Silverdale, Washington, 98383, United States

RECRUITING

Clinique d'ophtalmologie des Laurentides

Boisbriand, Quebec, J7H0E8, Canada

RECRUITING

MeSH Terms

Conditions

Geographic Atrophy; Macular Degeneration

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Central Study Contacts

Study Coordinator

CONTACT

734-412-8787; info@onltherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: October 26, 2024
• Study Start: October 28, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (27); CA (1)