Clinical trial NCT06659445: Study to Evaluate Efficacy and Safety of ONL1204 in Patients With GA Associated With AMD
Official title: A Phase 2 Multicenter, Randomized, Double-masked, Sham-controlled, Reference-arm Study to Evaluate Efficacy and Safety of ONL1204 in Patients With Geographic Atrophy (GA) Associated With Age-related Macular Degeneration (AMD)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Geographic Atrophy (GA)
Age - Related Macular Degeneration (AMD)
Keywords: Phase 2
ONL1204
Geographic Atrophy (GA)
Age-related Macular Degeneration (AMD)
Lead sponsor: ONL Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-10-26
Enrollment: 324
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

   Study Eye Inclusion Criteria:
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.

   Study Eye Exclusion Criteria:
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.
20. Intraocular surgery in the study eye (including lens replacement surgery) within 3 months prior to Screening. See Exclusion Criteria 12 and 13 pertaining to retinal and glaucoma surgery, respectively.
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.

    Either Eye Exclusion Criteria:
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.

Primary outcomes:
measure: Primary Endpoint
timeFrame: From enrollment to the end of treatment at 48 weeks.
Secondary outcomes:
measure: Secondary Endpoints (Safety)
timeFrame: From enrollment to the end of treatment at 48 weeks.
measure: Secondary Endpoints (Safety)
timeFrame: From enrollment to the end of treatment at 48 weeks.
Other outcomes:
Locations:
Study officials:
References: