An Efficacy and Safety Study of Cenegermin Ophthalmic Solution Compared With Vehicle in the Treatment of PCED

Phase 3, Multicenter, Randomized, Double-Masked, Vehicle-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of Recombinant Human Nerve Growth Factor Eye Drop Solution in Participants With Persistent Corneal Epithelial Defect (PCED)

This is a phase 3, randomized, multicenter, double-masked, parallel group, vehicle-controlled prospective clinical trial to evaluate the safety and efficacy of cenegermin in inducing complete epithelial healing in participants with PCED. The primary objective is the evaluation of complete epithelial healing after 4 weeks of treatment. The study is comprised of 3 periods: an 8-week initial treatment period (Day 1 to Week 8), an 8-week extension treatment period (Week 9 to Week 16), and a 24-week follow-up period (Week 17 to Week 40).

Inclusion Criteria:

• Men or women aged 18 years or above (in South Korea, 19 years or above).

• Participants with PCED in the study eye with the following characteristics:

  1. PCED ≥ 1.0 mm in greatest diameter
  2. PCED of at least 14 days duration, refractory to 1 or more conventional nonsurgical treatments (ocular lubricants, discontinuation of preserved topical drops and medications, bandage contact lens) showing no clinical resolution.

• Use of most topical ophthalmic medications (including glaucoma medications) indicated for ocular conditions other than PCED is permitted in the study eye, if the participant has been on a stable dose for at least 30 days and does not expect to have change in dosing regimen throughout the entire duration of the study. Please see exclusion criteria list for exceptions.

• Use of prophylactic topical antibiotics up to 4 times per day in the study eye is permitted if the participant is already receiving them prior to enrollment.

Exclusion Criteria:

• Contralateral eye with vision of no light perception or anatomic absence of contralateral eye.

• Active ocular infection or inflammation in the study eye as follows:

  1. Bacterial, fungal, or protozoal infection at screening
  2. Active infectious stromal infiltrates or edema at screening
  3. Acute anterior uveitis of grade 2 or greater within 30 days of screening
  4. Acute intermediate uveitis or posterior uveitis within 30 days of screening
  5. Acute inflammation of the sclera or conjunctiva if it is not associated with the PCED

• Corneal epithelial defect associated with stromal thinning greater than 30% (estimated on clinical slit lamp exam) or if associated with stromal infiltrate (corneal haze is acceptable), in the study eye.

• Severe eyelid disease in the study eye, such as:

  1. Mechanical eyelid abnormalities that have direct contact with the PCED (e.g., trichiasis, severe entropion with lid margin keratinization, etc, if in direct contact with the PCED)
  2. Lagophthalmos greater than 2 mm as measured in the clinic
  3. Existing diagnosis of nocturnal lagophthalmos or Parkinson's disease
  4. Inability to fully close eyelids despite voluntary eyelid closure
  5. Severe ectropion with abnormal eyelid-globe congruity (e.g., the lower eyelid does not come into contact with the globe due to severe ectropion)

• Severe end-stage ocular surface disease in the study eye, including but not limited to:

  1. Severe limbal stem cell deficiency, defined as involvement of more than 270 cumulative degrees or more of limbal stem cell deficiency
  2. Keratinization of the bulbar conjunctiva or lid margin

• Use of the following medications and devices within the indicated time window prior to randomization:

  a. Local medications in study eye:

• Any prior use of cenegermin

• Blood-derived eye drops (autologous serum) or other ocular surface re-epithelizing agents, topical anesthetic use by the participant outside of the clinical exam setting, topical insulin, or topical steroids (unless associated with post-operative treatment regimen) within 7 days

• Botox (botulinum toxin) injections for pharmacologic tarsorrhaphy within 90 days b. Systemic medications:

• High-dose systemic corticosteroids (greater than 0.5 mg/kg/day) within 30 days

• Any changes in oral medication regimen intended for the treatment of the ocular surface (eg, oral doxycycline) within 30 days, or planned changes during the study period

• Systemic opioid use within 30 days

• Use of any systemic investigational product, ocular investigational product in the study eye, radiation of the head or neck, or systemic chemotherapy within 90 days, or planned to occur during the study period c. Devices:

• Use of contact lens (including therapeutic contact lens) within 7 days, or planned use of contact lens during the study period, in the study eye

• Anticipated need for punctal occlusion in the study eye during the study period. Participants with punctal occlusion or punctal plugs inserted prior to the study are eligible for enrolment provided that the punctual occlusion is maintained throughout the study.

• Presence of acute severe systemic disease as follows:

  1. Any acute or active severe systemic inflammatory disease (eg, acute systemic Stevens-Johnson Syndrome, acute systemic GVHD, severe systemic Sjogren's, mucous membrane pemphigoid)
  2. Presence of any systemic disease that may affect ability to participate in the clinical study according to the clinical judgment of the investigator

• Recent surgery or amniotic membrane therapy as follows:

  1. Recent major surgical procedure for the treatment of PCED (eg, conjunctival flap, complete tarsorrhaphy, superficial keratectomy for epithelial defect revision, etc) within 14 days of randomization
  2. Presence of amniotic membrane from AMT for ocular surface indication if not dissolved within area of PCED within 14 days of randomization. Examples include:

• Sutured AMT

• Self-retaining AMT

• Contact lens combined with AMT

• Other AMT treatment for the ocular surface c. Partial tarsorrhaphy (temporary or permanent) placed within 14 days of randomization. If a participant is enrolled with partial tarsorrhaphy placed more than 14 days prior to randomization, then the tarsorrhaphy must not be removed for the entire duration of the study.

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