Phase 3, Multi-Center, Randomized, Double-Masked, Placebo-Controlled Study Assessing the Safety and Efficacy of Urcosimod Ophthalmic Solution in Participants With Neuropathic Corneal Pain (NCP).

This research study is to evaluate the safety of Urcosimod Ophthalmic Solution and its effect on the quality of life and vision in participants with Neuropathic Corneal Pain (NCP). The purpose of this research study will see if urcosimod can safely and effectively relieve the signs and symptoms of NCP, and whether it causes any side effects.

Inclusion criteria

• Aged 18 years of age or older.
• Able and willing to provide written informed consent prior to any study-related procedures.
• Presence of symptoms of neuropathic corneal pain for at least 3 months defined as the presence of ocular pain associated or not with ocular symptoms of burning, stinging, light sensitivity or discomfort.
• In at least one eye:

• Ocular pain score of 5 or more on 0-10 Visual Analogue Scale (VAS) AND in the same eye
• In Vivo Confocal Microscopy (IVCM) changes of the subbasal corneal nerve plexus assessed by an Investigator who has received study-specific training.
• Female participants must be one of the following: a) postmenopausal (defined as no menses for 1 year), b) surgically sterilized, c) practicing abstinence as a lifestyle choice (not as a form of contraception), or d) consistently and correctly using protocol-specified birth control for the duration of the study (e.g., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, or condom with spermicide; see Appendix 3).
• Female participants who are neither postmenopausal nor surgically sterile require a negative urine pregnancy test at the Screening and Day 1/Baseline visits.
• Best corrected distance visual acuity (BCDVA), in the study eye of at least Snellen >20/200.
• Participants that require topical ophthalmic medications during the study may be included if the medications are not topical ophthalmic blood-derived products, amniotic-membrane derived medications, cenegermin (Oxervate®), topical ophthalmic anti-allergic, anti-inflammatory, immunosuppressive and immunomodulators such as lifitegrast, and the dose has been stable for at least 3 months prior to Screening and is expected to remain stable throughout the study period.
• Ability and willingness to comply with study procedures.

Exclusion criteria

Participants who meet any of the following criteria at Visit 1/Screening or Visit 2/Baseline will be excluded from the study.

• Evidence of any active ocular infection (bacterial, viral, fungal or protozoal) in either eye.
• Evidence of any intraocular inflammation defined as anterior chamber flare > 0 and/or cells >0 by Standardization of Uveitis Nomenclature (SUN) grading, in either eye.
• Presence of any other ocular surface condition that may cause ocular pain including confluent punctuate staining, any corneal epithelial defect or ulcer, angle-closure glaucoma or uveitis, in either eye.
• Presence of eyelid abnormalities such as trichiasis and lagophthalmos that can be the primary cause of corneal epithelial damage and ocular pain.
• Evidence of any elevated corneal scars/corneal edema.
• Any other concomitant medical condition that, in the judgment of the Principal Investigator (PI), might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the participant's well-being.
• Use of topical ophthalmic calcineurin inhibitors such as Cyclosporin A, tacrolimus, pimecrolimus, or cenegermin (Oxervate®) in either eye in the 4 weeks prior to Visit 1/Screening visit.
• History of severe systemic allergic condition or severe ocular allergy.
• Inability to suspend use of intranasal tear secretagogues such as varenicline or device for dry eye at Visit 1/Screening and throughout the study period.
• Inability to suspend prohibited ocular topical medications at Visit 1/Screening.
• Inability to suspend use of blood-derived ocular treatments (e.g., autologous serum tears, platelet-rich plasma, etc.) or amniotic membrane-derived products at Visit 1/Screening visit.
• Inability to continue stable (for at least 3 months) oral medications for NCP without changes during the entire study period.
• No change or less than 50% improvement in ocular pain assessed by VAS score after topical anesthetic challenge.
• History of any ocular surgery within 3 months prior to Visit 1/Screening.
• Any anticipated ocular surgery during the entire study period.
• Inability to suspend use of refractive/therapeutic contact lenses (including scleral lenses), botulinum toxin or electro/magnetic stimulation devices on the eye, face or scalp, during the entire study period.
• Prior use of periocular or ocular botulinum toxin (Botox) within 3 months of Visit 1/Screening.
• Evidence of current drug or alcohol abuse or addiction.
• Participated in or used the investigational agent in another clinical study, within 30 days prior to Visit 1/Screening.
• Known hypersensitivity to any of the components of the study drug, preservative-free artificial tears or procedural medications (e.g., fluorescein, anesthetic drops, etc.).
• Previous participation in a clinical study or extended access program with urcosimod eye drops.