Non-arterial anterior ischemic optic neuropathy (NAION)

Primary Objectives • To evaluate the efficacy of intranasal centermin compared to excipients in improving visual acuity in NAION patients. Key Secondary Objectives • To evaluate the efficacy of intranasal centermin compared to excipients over time in improving visual function and structural changes in the ganglion cell layer in NAION patients. Secondary Objectives • To evaluate the efficacy of intranasal centermin compared to excipients over time in improving visual acuity in NAION patients. • To evaluate the efficacy of intranasal centermin compared to excipients over time in improving visual field in NAION patients. • To evaluate the efficacy of intranasal centermin compared to excipients on structural changes in the optic nerve head and retina. • To evaluate the impact of intranasal centermin compared to excipients on vision-related quality of life (VR-QoL). Safety • To evaluate the safety and tolerability of intranasal centermin in NAION patients. • Evaluate the safety and tolerability of intranasal Cenegermin in NAION subjects based on specific parameters.

Cenegermin

Cenegermin-bkbj

Frozen Crystal Powder

µg

The improvement in best corrected visual acuity (BCVA) was defined as an improvement of ≥ 15 letters in visual acuity as measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart from the baseline period to week 24.

• Male and female participants aged 50 to 80 years

• Confirmed unilateral NAION in the test eye and symptom onset within the past 14 days

• Participants must be eligible for randomization and receive their first dose of the investigational drug within 14 days of symptom onset

• BCVA score of the test eye ≥ 15 letters and ≤ 65 letters, based on ETDRS measurements

• Relative afferent pupillary defect in the test eye (this requirement is not required if the non-test eye has a history of NAION or other optic nerve or retinal diseases not listed in the exclusion criteria).

• Bilateral or sequential NAION, with the non-test eye also affected within 6 weeks of the test eye's involvement.

• Clinical evidence of temporal (giant cell) arteritis, or C-reactive protein (CRP) > 2 times the upper limit of normal (ULN) for the test unit, or abnormal erythrocyte sedimentation rate (ESR) (> age/2 mm/hr for men, > [age + 10]/2 mm/hr for women), or thrombocytosis (platelet count > 450,000 uL) without a known acute cause (e.g., infection, anemia, trauma).

• Intraocular pressure (IOP) > 25 mmHg or a history of glaucoma in the test eye.

• Moderate age-related macular degeneration (AMD) in the test eye, with subfoveal crypts, geographic atrophy, or exudative AMD.

• Poorly controlled hyperglycemia (HbA1c ≥ 8.0%), any diabetic retinopathy, or a history of panretinal laser photocoagulation or macular laser photocoagulation.

• History or evidence of optic neuritis or intraocular inflammation (chronic or recurrent anterior uveitis, any mid-segment uveitis, or any posterior-segment uveitis) in either eye.

• History or evidence of infectious, nutritional, hereditary, radiation-induced, neoplastic (tumor-related), toxic, or mitochondrial neuropathy, or any active ocular infection in either eye.

• History of multiple sclerosis, collagen vascular disease, other systemic chronic inflammatory diseases, or chronic immunosuppressive diseases.

• Use or planned use of systemic corticosteroids within the past month, or cumulative use of intranasal medications for more than 7 days within the past month (excluding intranasal saline spray), or use of any medication within the past 6 months. The patient has a history of using any medications or supplements with a presumed neuroprotective effect (e.g., systemic Memantine, topical Brimonidine), receiving immunomodulatory therapy within the past 3 months, using Amiodarone within the past 12 months, receiving chemotherapy within the past 3 years, receiving head and neck radiation therapy within the past 20 years, or any medications or supplements known to carry a risk of other optic neuropathy or retinal toxicity (e.g., ethambutol, hydroxychloroquine).

• Planned use of phosphodiesterase-5 (PDE-5) inhibitors during the trial.