Neurotrophic Keratitis
Conditions
Brief summary
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.
Interventions
BIOLOGICALCSB-001 Ophthalmic Solution 0.1%
CSB-001: human recombinant dHGF (5-amino acid deleted hepatocyte growth factor)
BIOLOGICALVehicle Control
Matching vehicle control without the drug substance
Sponsors
Claris Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy as Assessed by Complete Corneal Healing | Week 8 through Week 10 | Percentage of subjects achieving complete corneal healing in study eye as assessed by the Central Reading Center (CRC). Complete corneal healing was defined as absence of corneal staining in the area of the defect/ulcer (i.e., 0 mm lesion) at Week 8 and the absence of corneal staining in the area of the defect/ulcer (i.e., 0 mm lesion) at Week 10. |
| Safety as Assessed by Adverse Event Reporting | Screening (Day 0) through Week 10 | Number of participants with ocular and systemic adverse events |
Countries
Canada, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.0 years |
| Age, Customized Age group, n (%) < 60 | 36 Participants |
| Age, Customized Age group, n (%) ≥ 60 | 93 Participants |
| Current Neurotrophic Keratitis (NK) Stage Stage 2 | 41 Participants |
| Current Neurotrophic Keratitis (NK) Stage Stage 3 | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 111 Participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 29 Participants |
| Time since Current NK stage Diagnosis | 2.45 months |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 69 | 1 / 62 | 0 / 25 |
| other Total, other adverse events | 18 / 69 | 35 / 62 | 5 / 25 |
| serious Total, serious adverse events | 8 / 69 | 7 / 62 | 1 / 25 |
Outcome results
None listed