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

NCT ID: NCT06659445

Last Updated: 2025-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

324 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-28

Study Completion Date

2028-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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

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

Group Type ACTIVE_COMPARATOR

ONL1204 Opthalmic solution

Intervention Type DRUG

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

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

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

Group Type ACTIVE_COMPARATOR

ONL1204 Opthalmic solution

Intervention Type DRUG

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

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

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

Group Type EXPERIMENTAL

ONL1204 Opthalmic solution

Intervention Type DRUG

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

Sham Comparator (4 of 6 Treatment Groups)

Sham injection every 12 weeks

Group Type SHAM_COMPARATOR

Sham

Intervention Type OTHER

Sham injection

Sham Comparator (5 of 6 Treatment Groups)

Sham injection every 24 weeks

Group Type SHAM_COMPARATOR

Sham

Intervention Type OTHER

Sham injection

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

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

Group Type ACTIVE_COMPARATOR

Avacincaptad Pegol intravitreal solution

Intervention Type DRUG

Liquid formulation Avacincaptad Pegol administered by intravitreal (IVT) injection

Interventions

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ONL1204 Opthalmic solution

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

Intervention Type DRUG

Avacincaptad Pegol intravitreal solution

Liquid formulation Avacincaptad Pegol administered by intravitreal (IVT) injection

Intervention Type DRUG

Sham

Sham injection

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. 55 years of age or older at Screening.
2. Able and willing to give informed consent and attend study visits.
3. 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.
4. 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.
5. 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.

6. BCVA of 24 letters or more using ETDRS charts in the study eye at Screening.
7. Intraocular pressure (IOP) of 22 mmHg or lower in the study eye at Screening.

The GA lesion must meet all the following criteria:
8. Non-foveal GA associated with AMD without eMNV in the study eye per Investigator's evaluation and as confirmed by the central RC.
9. 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.
10. 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.
11. 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.
12. 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.
13. A pattern of hyper-autofluorescence in the junctional zone of GA in the study eye must be present as confirmed by the central RC.

Fellow Eye Inclusion Criterion:
14. BCVA of 19 letters or more using ETDRS charts in the fellow eye at Screening.

Exclusion Criteria

1. 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.
2. Previous ophthalmic disease gene therapy or planned participation in any gene therapy clinical study during the study period.
3. Current or planned use of systemic complement inhibitors during the study period.
4. 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.
5. 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.
6. Any previous treatment of pentosan polysulfate (Elmiron®) is exclusionary.
7. Known allergy to fluorescein, povidone iodine, or any ingredients of the study drug or avacincaptad pegol intravitreal solution.
8. Individuals who are currently pregnant, planning to become pregnant, or are nursing at Screening or during the study period.

9. Active ocular or periocular infection in the study eye.
10. Any contraindication to an IVT injection in the study eye.
11. Any media opacity in the study eye that limits visual acuity, clinical visualization of the retina, or retinal imaging as determined by the Investigator.
12. 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.
13. Any history of incisional retinal surgery in the study eye including but not limited to scleral buckle or vitrectomy. (Retinal laser for a tear or hole 3 months or more prior to Screening is not exclusionary).
14. History of incisional glaucoma surgery including trabeculectomy, tube shunt, or minimally invasive glaucoma surgery in the study eye. (Glaucoma laser procedures performed at least 6 months prior to Screening are not exclusionary).
15. Yttrium aluminum garnet capsulotomy in the study eye within 1 month prior to Screening.
16. Cataract surgery in the study eye planned or expected during the study period.
17. Aphakia with absence of the posterior capsule in the study eye. (Pseudophakia with an open posterior capsule is not exclusionary).
18. 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.
19. Any clinically significant retinal disease other than AMD except benign degenerative conditions (eg, Cobblestone degeneration) in the study eye.
21. Previous therapeutic radiation (including transpupillary thermotherapy, photodynamic therapy, or external-beam) in the region of the study eye.

Fellow Eye Exclusion Criterion:
22. Planned or expected IVT injection in the fellow eye for treatment of GA with agents other than FDA-approved complement inhibitors (pegcetacoplan or avacincaptad pegol IVT solution \[Izervay™\]) during the study period.

23. Active intraocular inflammation in either eye or a history of uveitis or endophthalmitis in either eye.
24. GA in either eye due to causes other than AMD.
25. Any ophthalmic condition in either eye that is likely to require surgery during the study period.
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ONL Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Associated Retina Consultants

Gilbert, Arizona, United States

Site Status RECRUITING

Associated Retina Consultants

Phoenix, Arizona, United States

Site Status RECRUITING

Doheny Image Reading Center

Pasadena, California, United States

Site Status RECRUITING

Bay Area Retina Associates

Walnut Creek, California, United States

Site Status RECRUITING

Retina Consultants of Southern Colorado

Colorado Springs, Colorado, United States

Site Status RECRUITING

Retina Group of New England

Waterford, Connecticut, United States

Site Status RECRUITING

Florida Retina Institute

Orlando, Florida, United States

Site Status RECRUITING

Retina Associates, Ltd.

Elmhurst, Illinois, United States

Site Status RECRUITING

Retina Partners Midwest, P.C.

Carmel, Indiana, United States

Site Status RECRUITING

Retina Research Institute at New England Retina Consultants

Springfield, Massachusetts, United States

Site Status RECRUITING

Associated Retinal Consultants, P.C.

Royal Oak, Michigan, United States

Site Status RECRUITING

The Retina Institute

St Louis, Missouri, United States

Site Status RECRUITING

Sierra Eye Associates

Reno, Nevada, United States

Site Status RECRUITING

Retina Associates of Western NY

Rochester, New York, United States

Site Status RECRUITING

Long Island Vitreoretinal Consultants

Westbury, New York, United States

Site Status RECRUITING

North Carolina Retina Associates, S.C.

Wake Forest, North Carolina, United States

Site Status RECRUITING

Erie Retina Research, LLC (Clinic)

Erie, Pennsylvania, United States

Site Status RECRUITING

Charleston Neuroscience Institute

Mt. Pleasant, South Carolina, United States

Site Status RECRUITING

Palmetto Retina Center

West Columbia, South Carolina, United States

Site Status RECRUITING

Retina Consultants of Texas

Beaumont, Texas, United States

Site Status RECRUITING

Retina Consultants of Texas

Bellaire, Texas, United States

Site Status RECRUITING

Retina Consultants of Texas

Katy, Texas, United States

Site Status RECRUITING

Retina Associates of South Texas, PA

San Antonio, Texas, United States

Site Status RECRUITING

Retina Consultants of Texas

San Antonio, Texas, United States

Site Status RECRUITING

Retina Consultants of Texas

The Woodlands, Texas, United States

Site Status RECRUITING

Pacific Northwest Retina

Bellevue, Washington, United States

Site Status RECRUITING

Pacific Northwest Retina, PLLC

Silverdale, Washington, United States

Site Status RECRUITING

Clinique d'ophtalmologie des Laurentides

Boisbriand, Quebec, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Study Coordinator

Role: CONTACT

734-412-8787

Facility Contacts

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Study Coordinator

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Other Identifiers

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ONL1204-GA-002

Identifier Type: -

Identifier Source: org_study_id

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