This is a phase 3, randomized, multicenter, vehicle-controlled, double-masked study to evaluate the efficacy and safety of intranasal cenegermin compared with vehicle control in adult participants with NAION. Approximately 272 participants who meet all eligibility criteria will be randomly assigned in a 1:1 ratio to receive either cenegermin treatment (Group 1) or the vehicle control (Group 2).

Key Inclusion Criteria:

1. A clinical diagnosis of unilateral NAION in the study eye with symptom onset within 14 days prior to the planned date for first dose administration.
2. A BCVA score in the study eye of ≥ 15 letters and ≤ 65 letters measured using the ETDRS chart.
3. Sufficiently clear ocular media and adequate pupil dilation to enable assessment of the optic nerve and retina in both eyes.

Key Exclusion Criteria:

1. Bilateral NAION or sequential NAION with fellow eye involvement within 6 weeks of study eye involvement.
2. Clinical evidence of temporal arteritis (giant cell arteritis) signs or symptoms.
3. Abnormal laboratory findings suggestive of temporal arteritis (giant cell arteritis), in the absence of a known acute cause
4. Pain with eye movement
5. Intraocular pressure (IOP) greater than 25 mmHg in the study eye or history of glaucoma in the study eye.
6. Intermediate age-related macular degeneration (AMD) with subfoveal drusen, exudative AMD, or geographic atrophy in the study eye.

Note: Additional inclusion/exclusion criteria apply, as defined in the protocol.

The sponsor is also masked to the study treatment.