The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is intended as: * complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the central reading center using corneal fluorescein staining, * assessing the duration of complete healing, * improvement in visual acuity and improvement in corneal sensitivity.
An 8-week phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with a 24 or 32 week follow-up period to evaluate the efficacy of a formulation containing anti-oxidant of recombinant human nerve growth factor (rhNGF) in 20 μg/ml, eye drops solution versus vehicle containing anti-oxidant in patients with Stage 2 and 3 Neurotrophic Keratitis. The primary objective was to evaluate the efficacy of 20 μg/ml 6 times a day of recombinant human nerve growth factor (rhNGF) containing anti-oxidant, eye drops solution compared to vehicle (formulation containing anti-oxidant) given 6 times a day in inducing a complete healing of stage 2 (PED) and 3 (corneal ulcer) NK as measured by the central reading center, evaluating the clinical pictures of corneal fluorescein staining. Secondary objectives were to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity, and percentage of patients achieving complete corneal clearing defined as complete absence of staining on the modified Oxford Scale.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
48
Formulation containing antioxidant
Loma Linda University Ophthalmology
Loma Linda, California, United States
Jules Stein Eye Institute
Los Angeles, California, United States
Shiley Eye Center University of California
San Diego, California, United States
Bascom Palmer Eye Institute University of Miami
Miami, Florida, United States
Tufts Medical Center
Boston, Massachusetts, United States
Massachusetts Eye & Ear Infirmary
Boston, Massachusetts, United States
Massachusetts Eye Research and Surgery Institution
Cambridge, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
New York Eye and Ear Infirmary
New York, New York, United States
Penn Eye Care Scheie Eye Institute
Philadelphia, Pennsylvania, United States
...and 2 more locations
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer
Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as defined by the central reading center on clinical pictures.
Time frame: Week 8
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by the Investigator
Percentage of patients experiencing complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as measured by the investigator.
Time frame: Week 8
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reading Center and Investigator.
Percentage of patients experiencing complete healing of the PED or corneal ulcer at 4, and 6 weeks as measured by the central reading center evaluating the clinical pictures and investigator.
Time frame: At weeks 4 and 6
Percentage of Patients With Complete Corneal Clearing
Percentage of patients with complete corneal clearing at weeks 4, 6, and 8 defined as grade 0 on the modified Oxford scale. Grade 0 indicates the absence of conjunctival staining; grade V indicates severe conjunctival staining.
Time frame: at weeks 4, 6, and 8
Mean Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)
Change in Best Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8. Best Corrected Distance Visual Acuity consists of letters read at 4m only.
Time frame: Baseline, Week 8
Percentage of Patients That Achieve a 15 Letter Gain in BCDVA
Percentage of patients that achieve a 15 letter gain in Best Corrected Distance Visual Acuity (BCDVA) at 4 weeks, 6 weeks, 8 weeks
Time frame: Weeks 4, week 6 and week 8
Improvement in Corneal Sensitivity
Improvement in corneal sensitivity was measured by the Cochet-Bonnet aesthesiometer at 4, 6 and 8 weeks. Corneal sensitivity is measured continuously in each patient in cm: * Area of the Persistent Epithelial Defect (PED) or corneal ulcer * All quadrants, but outside the PED or corneal ulcer area: Superior nasal, inferior nasal, superior temporal, inferior temporal. Improvement is defined as an increase of at least 0.5 cm in the location of concern.
Time frame: At 4, 6 and 8 weeks after start of the treatment
Patients Experiencing Deterioration
Number of patients experiencing deterioration (increase in lesion size ≥ 1mm and/or decrease in BCDVA by \>5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and/or progression in lesion depth to corneal melting or perforation and/or onset of infection) in stage 2 or 3 NK from baseline to Week 8.
Time frame: from baseline to Week 8.
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