A Multicenter, Randomized, Vehicle-Controlled, Double-Masked to Open-Label Study to Evaluate the Safety and Efficacy of Lacripep in Subjects With Neurotrophic Keratitis

A Multicenter, Randomized, Vehicle-Controlled, Double-Masked to Open-Label Study to Evaluate the Safety and Efficacy of Lacripep 4 μM Ophthalmic Solution in Subjects With Neurotrophic Keratitis

Objective: To evaluate the safety of Lacripep 4 μM Ophthalmic Solution and its effect on the ocular surface, visual function, corneal sensitivity, and quality of life of subjects with Stage 1 NK.

The study will compare Lacripep 4 μM Ophthalmic Solution to vehicle ophthalmic solution for the treatment of Stage 1 neurotrophic keratitis (NK). Approximately 54 subjects will be enrolled and will enter a 2-week run-in period with open-label vehicle ophthalmic solution. At Visit 2 (Day 1; Baseline/Randomization), eligible subjects will be randomized to either Lacripep 4 μM Ophthalmic Solution or vehicle ophthalmic solution. Subjects will dose three times a day (TID) in both eyes (OU) for 8 weeks, with clinic visits at Week 2, Week 4, and Week 8.

A central reading center will assess study images to ensure objective, standardized, and unbiased grading.

At the Week 8 visit, subjects will be assigned to open-label treatment with Lacripep 4 μM Ophthalmic Solution for 4 weeks, through Week 12. The initiation of 4 weeks of open-label active treatment is designed to explore the potential effects of both a shorter and a longer treatment period: i.e., 4 weeks of active treatment for subjects originally randomized to vehicle ophthalmic solution, and 12 total weeks of active treatment for subjects originally randomized to Lacripep 4 μM Ophthalmic Solution. Subjects will continue to dose TID in both eyes.

All Week 1-8 treatment assignments will remain masked through database lock.

Inclusion Criteria:

Subjects who meet all the following inclusion criteria at Visit 1 (Screening) will be eligible to participate in the study.

1. Are ≥18 years of age.

2. Provide informed consent before any study-related procedures are performed.

3. Are willing and able to comply with study procedures and the study schedule.

4. Female subjects must either be incapable of pregnancy or must use an effective method of birth control for the duration of the study. Female subjects of childbearing potential must have a negative pregnancy test and not be nursing.

5. Have all of the following in at least one eye:

   1. Stage 1 NK as defined by:

      • Grade 3 cCFS using the National Eye Institute (NEI) scale (0-3 in one-point increments).
      • Corneal sensitivity ≤4 cm in the central zone, as measured by Cochet-Bonnet aesthesiometer.

   2. BCDVA +0.2 to +1.0 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent 20/32 to 20/200).

   3. IOP ≤21 mmHg.

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria at Visit 1 (Screening) will not be eligible to participate in the study. Ocular criteria apply to each eye independently, unless otherwise noted.

1. Have received prior treatment with Lacripep Ophthalmic Solution or Oxervate® (cenegermin-bkbj) Ophthalmic Solution within 6 months prior to Visit 1 (Screening) and failed to demonstrate a clinically meaningful response, as determined by the Investigator.
2. Have participated in a NK study within 90 days prior to Visit 1 (Screening).
3. Have participated in any other clinical study or used an investigational agent within 30 days prior to Screening or plans to participate in another clinical study at any time during the conduct of this study.
4. Have a glycated hemoglobin (HbA1c) score >9% within 90 days prior to Visit 1 (Screening).
5. Have a history of or current conditions that may confound the study data; such conditions include but are not limited to ocular cicatricial pemphigoid, graft versus host disease, neuromyelitis optica, Stevens-Johnson syndrome, and Salzmann's nodular degeneration.
6. Have an unstable history of severe systemic allergy or severe ocular allergy (including seasonal conjunctivitis expected during the study period) or chronic conjunctivitis and/or keratitis other than dry eye disease.
7. Have been diagnosed with glaucoma or are a glaucoma suspect who requires or may require treatment during the study.
8. Have, in the opinion of the Investigator, evidence of an active ocular infection (bacterial, viral, protozoal) in either eye.
9. Have any intraocular inflammation (Tyndall score >0).
10. Have, in the opinion of the Investigator, severe vision loss due to retinal disease, with no potential for visual improvement.
11. Have an eyelid abnormality that may alter eyelid function; such abnormalities include but are not limited to blepharospasm, cerebrovascular accident, entropion, ectropion, and floppy lid syndrome.
12. Have punctal occlusion or punctal plugs that will not be maintained during the study period.
13. Have had any corneal surface procedure within 90 days prior to Visit 1 (Screening). This includes laser-assisted in situ keratomileusis (LASIK), phototherapeutic or photorefractive keratectomy (PTK or PRK), radial keratotomy (RK), small-incision lenticule extraction (SMILE), penetrating keratoplasty (PK), automated lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping endothelial keratoplasty (DSEK), superior limbic keratoconjunctivitis (SLK) surgery, and placement of any amniotic membrane.
14. Have, in the opinion of the Investigator, NK that was induced by a neurosurgical procedure.
15. Have undergone any other ocular surgery (including peripheral iridotomy (PI), laser iridotomy (LI) eyelid surgery and any surgical refractive procedures) within 90 days prior to Visit 1 (Screening) or expect to undergo ocular surgery during the study period.
16. Have, in the opinion of the Investigator, history of viral corneal disease that resulted in significant corneal scarring.
17. Have viral corneal disease without scarring that is considered unstable prior to Visit 1 (Screening), defined as discontinuation of topical ocular antiviral therapy or topical ocular steroid therapy within 2 weeks prior to Screening, or evidence of viral reactivation during the run-in period.
18. Have received Botox (botulinum toxin) ocular injections to induce pharmacologic blepharoptosis within 45 days prior to Visit 1 (Screening).
19. Have used any non-study issued eye drops or neurostimulators within 14 days prior to Visit 2 (Day 1; Baseline/Randomization).
20. Anticipate a need to use therapeutic contact lenses or unwilling to discontinue wearing contact lenses for refractive correction during the study period.
21. Have, in the opinion of the Investigator, an unstable medical condition that may confound the study data; such conditions include but are not limited to diabetes, thyroid disease, autoimmune disease, Parkinson's disease, and multiple sclerosis.
22. Evidence of current drug or alcohol abuse or addiction, in the opinion of the Investigator.
23. Are pregnant, nursing, or planning a pregnancy during the study period.
24. Are an employee of a site directly involved in the management, administration, or support of the study or an immediate family member of the same.