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)
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.
• 55 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.
• Study Eye Inclusion Criteria:
• 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.
⁃ Fellow Eye Inclusion Criterion:
⁃ BCVA of 19 letters or more using ETDRS charts in the fellow eye at Screening.