Neurotrophic Keratopathy
Conditions
Brief summary
The objective of this study is to evaluate the safety and effectiveness of OC-01 (varenicline) nasal spray as compared to placebo nasal spray for mean change from baseline in corneal fluorescein staining in subjects with Stage 1 (corneal epithelial hyperplasia/punctate keratopathy) neurotrophic keratopathy (NK) in one or both eyes.
Detailed description
Protocol OPP-102 is a Phase 2, multicenter, randomized, controlled, double- masked study designed to evaluate the safety and efficacy of OC-01 (varenicline) nasal spray in subjects with NK. Approximately 100 subjects at least 18 years of age with a physicians' diagnosis of Stage 1 NK as defined by the Mackie Criteria and meeting all other study eligibility criteria will be randomized 1:1 and will receive OC-01 (varenicline)/ nasal spray or placebo nasal spray for 8 weeks three times daily (TID) as follows: * OC-01 (varenicline) nasal spray, 1.2 mg/mL * Placebo (vehicle control) nasal spray All doses will be delivered as a 50 microliter (µL) nasal spray.
Interventions
DRUGOC-01 (varenicline) nasal spray 1.2 mg/ml
OC-01
Placebo (vehicle)
Sponsors
Oyster Point Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be at least 18 years of age at Visit 1. 2. Patients with Stage 1 (corneal epithelial hyperplasia/punctate keratopathy) NK in one or both eyes, as defined by the Mackie Criteria. 3. Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) in at least 1 corneal quadrant. 4. Schirmer's test without anesthesia ≥3 mm/ 5 minutes in the affected eye. 5. If a female is of childbearing potential, they must: use an acceptable means of birth control (acceptable methods of contraception include hormonal - oral, implantable, injectable, or transdermal contraceptives, mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom, IUD, or surgical sterilization of partner), and have a negative urine pregnancy test on Day 1.
Exclusion criteria
1. Have Stage 2 or Stage 3 NK affecting one or both eyes. 2. Have ocular graft versus host disease or Stevens-Johnson syndrome. 3. Have any active ocular infection (COVID-19 conjunctivitis, bacterial, viral, fungal, or protozoal) or active ocular inflammation not related to NK in the affected eye. 4. Be currently receiving autologous serum tears, amniotic membrane, cenegermin, fresh frozen plasma or cord blood derivative tears. 5. Have severe blepharitis and/or severe meibomian gland disease in the study eye.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Corneal Fluorescein Staining | 8 weeks | Corneal Fluorescein Staining was measured utilizing the Modified Oxford Grading scale. Scores range from a minimum of 0 (no staining) to a maximum of 5. A higher score indicates a worse outcome. The study eye is defined as the eye with the worst staining grade (if both eyes are eligible). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Visual Acuity at Week 8 | 8 weeks | Best Corrected Visual Acuity was assessed based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. ETDRS letters score range from 0 to 100 letters at each assessment. A higher score in ETDRS letters indicates a better outcome. A positive change from Baseline in ETDRS letter score indicates an improvement in visual acuity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OC-01 (Varenicline) Nasal Spray, 1.2 mg/mL OC-01 (varenicline) nasal spray, 1.2 mg/mL
OC-01 (varenicline) nasal spray 1.2 mg/ml: OC-01 | 53 |
| Placebo (Vehicle Control) Nasal Spray Placebo (vehicle control) nasal spray
Placebo (vehicle) nasal spray: Placebo (vehicle) | 60 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Placebo (Vehicle Control) Nasal Spray | OC-01 (Varenicline) Nasal Spray, 1.2 mg/mL | Total |
|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 16.33 | 65.3 years STANDARD_DEVIATION 14.48 | 63.3 years STANDARD_DEVIATION 15.54 |
| Best Correct Visual Acuity (Letters) | 75.9 Number of letters STANDARD_DEVIATION 18.54 | 75.4 Number of letters STANDARD_DEVIATION 14.42 | 75.7 Number of letters STANDARD_DEVIATION 16.61 |
| Corneal Fluorescein staining Score | 2.17 units on a scale STANDARD_DEVIATION 1.028 | 2.29 units on a scale STANDARD_DEVIATION 1.017 | 2.23 units on a scale STANDARD_DEVIATION 1.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 9 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 44 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 50 Participants | 47 Participants | 97 Participants |
| Sex: Female, Male Female | 47 Participants | 41 Participants | 88 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 58 |
| other Total, other adverse events | 39 / 54 | 34 / 58 |
| serious Total, serious adverse events | 5 / 54 | 3 / 58 |
Outcome results
Primary
Mean Change From Baseline in Corneal Fluorescein Staining
Corneal Fluorescein Staining was measured utilizing the Modified Oxford Grading scale. Scores range from a minimum of 0 (no staining) to a maximum of 5. A higher score indicates a worse outcome. The study eye is defined as the eye with the worst staining grade (if both eyes are eligible).
Time frame: 8 weeks
Population: Per Protocol Population included all subjects in the intent to treat (ITT) population that had a baseline corneal fluorescein staining score \>=2.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 (Varenicline) Nasal Spray, 1.2 mg/mL | Mean Change From Baseline in Corneal Fluorescein Staining | -0.6 score on a scale | Standard Error 0.17 |
| Placebo (Vehicle Control) Nasal Spray | Mean Change From Baseline in Corneal Fluorescein Staining | -0.9 score on a scale | Standard Error 0.15 |
Secondary
Mean Change From Baseline in Visual Acuity at Week 8
Best Corrected Visual Acuity was assessed based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. ETDRS letters score range from 0 to 100 letters at each assessment. A higher score in ETDRS letters indicates a better outcome. A positive change from Baseline in ETDRS letter score indicates an improvement in visual acuity.
Time frame: 8 weeks
Population: Per Protocol Population included all subjects in the intent to treat (ITT) population that had a baseline corneal fluorescein staining score \>=2.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 (Varenicline) Nasal Spray, 1.2 mg/mL | Mean Change From Baseline in Visual Acuity at Week 8 | 0.6 score on a scale | Standard Error 1.15 |
| Placebo (Vehicle Control) Nasal Spray | Mean Change From Baseline in Visual Acuity at Week 8 | 1.5 score on a scale | Standard Error 1.03 |