Study to Evaluate the Safety and Efficacy of CSB-001 Ophthalmic Solution 0.1% in Neurotrophic Keratitis Subjects

Study Overview
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Brief Summary
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This study will enroll subjects with stage 2 or 3 neurotrophic keratitis. Subjects will be randomized in a 1:1 ratio to the CSB-001 investigational treatment arm or vehicle control arm. All subjects will dose with the randomized treatment four times daily for 8 weeks (controlled treatment phase). During the controlled treatment phase, subjects will return to the clinic weekly from Day 0 to Week 8, and again at Week 10. Subjects randomized to the vehicle arm who are not healed will have the opportunity to participate in an open-label uncontrolled treatment phase.

Official Title
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A Multi-Center, Randomized, Double-Masked, Vehicle-Controlled, Parallel-Group, Study to Evaluate the Safety and Efficacy of CSB-001 Ophthalmic Solution 0.1% in Stage 2 and 3 Neurotrophic Keratitis Subjects

Conditions
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Neurotrophic Keratitis

Intervention / Treatment
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* Biological: CSB-001 Ophthalmic Solution 0.1%
* Biological: Vehicle Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with stage 2 (PED) or stage 3 (corneal ulcer) neurotrophic keratitis (NK). Subjects with bilateral NK may enroll in the study but only one eye will be selected as the study eye (worse eye) and be treated with test article. Subjects with no clinical evidence of improvement in the PED or corneal ulcer within the 2 weeks prior to study enrollment despite the use of conventional non-surgical treatments for neurotrophic keratitis (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops and medications that can decrease corneal sensitivity; therapeutic contact lenses [either silicone hydrogel or rigid gas permeable]) as determined by the investigator or referring physician's medical record. Subjects with clinical evidence of decreased corneal sensitivity within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant in the study eye in the opinion of the investigator assessed with a cotton wisp. Pinhole distance visual acuity score ≤ 75 ETDRS letters measured with a LogMAR chart (≥ 0.2 LogMAR, ≤ 20/32 Snellen or worse Snellen or ≤ 0.625 decimal fraction) in the study eye. Subjects must have the ability and willingness to comply with study procedures. Exclusion Criteria: Any active ocular infection (bacterial, viral, fungal, or protozoal) or active ocular inflammation not related to NK in either eye in the opinion of the investigator. Infectious epithelial keratitis including herpetic keratitis (i.e., dendritic lesions or geographic ulcers) in either eye is excluded. Subjects on oral antibiotic at the time of screening are eligible but should continue the medication for the duration of the study. Previous use of Oxervate in the study eye with last administration within the past 2 months. Any other ocular disease, except glaucoma, that will require topical ocular treatment in the study eye over the course of the study. Use of any other topical treatments other than the study medication provided by the Sponsor and allowed by the study protocol can be administered to the study eye over the course of the study. The following are exceptions: a) Allowance for use of preservative-free antibiotic eye drops if prescribed by the investigator and b) Allowance for use of a non-preserved IOP-lowering prostaglandin topical ocular drop administered once-daily (QD) in glaucomatous eyes over the course of the study. Note: Other inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSB-001 Investigational Treatment Arm<br>One drop CSB-001 four times daily for 8 weeks in the study eye | Biological: CSB-001 Ophthalmic Solution 0.1%<br>* CSB-001: human recombinant dHGF (5-amino acid deleted hepatocyte growth factor)<br>|
| Placebo Comparator: Vehicle Control Arm<br>One drop matching vehicle four times daily for 8 weeks in the study eye | Biological: Vehicle Control<br>* Matching vehicle control without the drug substance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as Assessed by Complete Corneal Healing | Proportion of subjects achieving complete corneal healing as assessed by the Central Reading Center | Week 8 through Week 10 | 
| Safety as Assessed by Adverse Event Reporting | Incidence of ocular and systemic adverse events | Screening through Week 10 | 
| Safety as Assessed by Slit-lamp Biomicroscopy | Change from baseline in staining using NEI scale (0 = absent to 3 = severe for 5 areas of the cornea) with Grade 0 (no staining) to maximum of Grade 15 | Screening through Week 10 | 
| Safety as Assessed by Intraocular Pressure | Change in baseline in intraocular pressure using the Goldmann tonometry | Screening through Week 10 | 
| Safety as Assessed by Dilated Fundus Examination | Change from baseline in observed anomalies of the peripheral retina, macula, choroid, optic nerve and vitreous (cup/disc ratio) | Screening through Week 10 | 
| Safety as Assessed by Best-Corrected Distance Visual Acuity | Change from baseline using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart | Screening through Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as Assessed by Corneal Healing | Time to corneal healing based on assessments by the Central Reading Center | Week 1 through Week 10 | 
| Efficacy as Assessed by Corneal Healing at Week 4 | Proportion of subjects achieving corneal healing at Week 4 assessed by the Central Reading Center | Week 1 through Week 4 | 
| Efficacy as Assessed by Corneal Healing at Week 4 and Week 8 Sustained for Two Weeks | Proportion of subjects achieving corneal healing at Week 4 and Week sustained for 2 weeks as assessed by the investigator | Weeks 4 and 8 through Week 10 | 
| Efficacy as Assessed by Decrease in Lesion Size | Time to ≥20% decrease in lesion size (maximum diameter) from baseline assessed by the Central Reading Center | Week 1 through Week 10 | 
| Efficacy as Assessed by Time to Corneal Healing | Time to corneal healing based on assessments by the investigator | Week 1 through Week 10 | 
| Efficacy as Assessed by Best Corrected Distance Visual Acuity | Proportion of subjects achieving a ≥15-letter gain in the study eye from baseline in Best Corrected Distance Visual Acuity | Week 1 through Weeks 4 and 8 |