Dry Eye Disease
Conditions
Brief summary
The objective of this study is to evaluate the chronic safety and effectiveness of OC-01 Nasal Spray as compared to placebo on signs of dry eye disease (DED).
Detailed description
Study OPP-004 was a Phase 2, single-center, randomized, masked (including subjects, Investigators, and study site personnel), placebo-controlled study designed to evaluate the safety and efficacy of OC-01 (varenicline) nasal spray in adult subjects with DED. The study planned to randomize approximately 120 subjects at least 22 years of age with a physicians' diagnosis of Dry Eye Disease and meeting all other study eligibility criteria to receive an application of OC-01 or placebo BID for 12 weeks. Subjects who terminated early during the application period were asked to complete safety assessments (if the subjects agree) prior to study exit. Subjects who were terminated early from the study were not replaced.
Interventions
DRUGOC-01 0.1% 0.6 mg/ml
OC-01 (varenicline) nasal spray: 0.1 % (0.6 mg/ml)
DRUGOC-01 (varenicline) nasal spray: 0.2 % (1.2 mg/ml)
OC-01 (varenicline) nasal spray: 0.2 % (1.2 mg/ml)
OTHERplacebo comparator
vehicle control
Sponsors
Oyster Point Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have used and/or desired to us an artificial tear substitute for dry eye symptoms within 6 months prior to Visit 1
Exclusion criteria
* Have had any intraocular surgery (such as cataract surgery), extraocular surgery (such as blepharoplasty) in either eye within three months or refractive surgery (e.g. laser-assisted in-situ keratomileusis, laser epithelial keratomileusis, photorefractive keratectomy or corneal implant) within twelve months of Visit 1 * Have a history or presence of an ocular disorder or condition in either eye that would, in the opinion of the Investigator, likely interfere with the interpretation of the study results or participant safety such as significant corneal or conjunctival scarring; pterygium or nodular pinguecula; current ocular infection, conjunctivitis, or inflammation not associated with dry eye; anterior (epithelial) basement membrane corneal dystrophy or other clinically significant corneal dystrophy or degeneration; ocular herpetic infection; evidence of keratoconus; etc. Blepharitis not requiring treatment and mild meibomian gland disease that are typically associated with DED are allowed. * Have a systemic condition or disease not stabilized or judged by the Investigator to be incompatible with participation in the study or with the lengthier assessments required by the study (e.g., current systemic infection, uncontrolled autoimmune disease, uncontrolled immunodeficiency disease, history of myocardial infarction or heart disease, etc.) * Have a known hypersensitivity to any of the procedural agents or study drug components * Have any condition or history that, in the opinion of the investigator, may interfere with study compliance, outcome measures, safety parameters, and/or the general medical condition of the subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Schirmer's Test Score From Baseline to 84 Days | Visit 1 (baseline) and Visit 6 (84 days) | The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | Visit 1 (baseline) and Visit 4 (28 Days) | The Schirmer's test measures the amount of tears produced by placing a paper strip in the eye for 5 minutes and the distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome. |
| Mean Change in Schirmer's Test Score From Baseline to 84 Days (Visit 6) - Fellow Eye | Visit 1 (baseline) to Visit 6 (84 Days) | The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome. |
| Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 6 (Day 84) | Visit 1 (baseline) and Visit 6 (84 days) | The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome. |
| Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Fellow Eye | Visit 1 (baseline) to Visit 4 (28 Days) | The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome. |
| Mean Change in Total Corneal Fluorescein Staining | Visit 1 (baseline) and Visit 5 (56 days) | A standardized grading system of 0-3 is used for each of the five areas of the cornea (inferior, superior, nasal, temporal, central). Grade 0 will be specified when no staining is present. The total score ranges from 0-15. Lower scores indicate improvement. |
| Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Study Eye | Visit 1 (baseline) to Visit 4 (28 days)] | The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment of OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OC-01 0.1%, 0.6 mg/ml OC-01 (varenicline) nasal spray, 0.6 mg/mL
OC-01 0.1% 0.6 mg/ml: OC-01 (varenicline) nasal spray: 0.1 % (0.6 mg/ml) | 41 |
| OC-01 0.2%, 1.2 mg/ml OC-01 (varenicline) nasal spray, 1.2 mg/mL
OC-01 (varenicline) nasal spray: 0.2 % (1.2 mg/ml): OC-01 (varenicline) nasal spray: 0.2 % (1.2 mg/ml) | 41 |
| Placebo vehicle control
placebo comparator: vehicle control | 41 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 3 |
| Overall Study | Lost to Follow-up | 4 | 4 | 5 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | OC-01 0.1%, 0.6 mg/ml | OC-01 0.2%, 1.2 mg/ml | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 13.18 | 54.2 years STANDARD_DEVIATION 11.77 | 55.8 years STANDARD_DEVIATION 26.77 | 53.8 years STANDARD_DEVIATION 12.75 |
| Baseline Schirmer's Test Score | 5.5 mm STANDARD_DEVIATION 2.46 | 5.4 mm STANDARD_DEVIATION 2.47 | 5.3 mm STANDARD_DEVIATION 2.04 | 5.4 mm STANDARD_DEVIATION 2.33 |
| Race/Ethnicity, Customized Hispanic or Latino | 41 Participants | 41 Participants | 41 Participants | 123 Participants |
| Race/Ethnicity, Customized Race, Other | 41 Participants | 41 Participants | 41 Participants | 123 Participants |
| Sex: Female, Male Female | 32 Participants | 35 Participants | 33 Participants | 100 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 8 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 41 | 0 / 41 |
| other Total, other adverse events | 4 / 41 | 5 / 41 | 4 / 41 |
| serious Total, serious adverse events | 0 / 41 | 0 / 41 | 0 / 41 |
Outcome results
Primary
Mean Change in Schirmer's Test Score From Baseline to 84 Days
The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: Visit 1 (baseline) and Visit 6 (84 days)
Population: Subjects in the ITT Population-LOCF population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 0.1%, 0.6 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 84 Days | 10.8 mm | Standard Error 1.29 |
| OC-01 0.2%. 1.2 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 84 Days | 11.0 mm | Standard Error 1.29 |
| Placebo | Mean Change in Schirmer's Test Score From Baseline to 84 Days | 6.0 mm | Standard Error 1.29 |
Other Pre-specified
Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Fellow Eye
The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: Visit 1 (baseline) to Visit 4 (28 Days)
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 0.1%, 0.6 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Fellow Eye | 5.4 mm | Standard Error 1.36 |
| OC-01 0.2%. 1.2 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Fellow Eye | 9.2 mm | Standard Error 1.35 |
| Placebo | Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Fellow Eye | 6.7 mm | Standard Error 1.35 |
Other Pre-specified
Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Study Eye
The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment of OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: Visit 1 (baseline) to Visit 4 (28 days)]
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 0.1%, 0.6 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Study Eye | 10.2 mm | Standard Error 1.42 |
| OC-01 0.2%. 1.2 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Study Eye | 11.4 mm | Standard Error 1.42 |
| Placebo | Mean Change in Schirmer's Test Score From Baseline to 28 Days (Visit 4) - Study Eye | 6.9 mm | Standard Error 1.42 |
Other Pre-specified
Mean Change in Schirmer's Test Score From Baseline to 84 Days (Visit 6) - Fellow Eye
The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: Visit 1 (baseline) to Visit 6 (84 Days)
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 0.1%, 0.6 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 84 Days (Visit 6) - Fellow Eye | 7.9 mm | Standard Error 1.19 |
| OC-01 0.2%. 1.2 mg/ml | Mean Change in Schirmer's Test Score From Baseline to 84 Days (Visit 6) - Fellow Eye | 8.7 mm | Standard Error 1.18 |
| Placebo | Mean Change in Schirmer's Test Score From Baseline to 84 Days (Visit 6) - Fellow Eye | 4.8 mm | Standard Error 1.18 |
Other Pre-specified
Mean Change in Total Corneal Fluorescein Staining
A standardized grading system of 0-3 is used for each of the five areas of the cornea (inferior, superior, nasal, temporal, central). Grade 0 will be specified when no staining is present. The total score ranges from 0-15. Lower scores indicate improvement.
Time frame: Visit 1 (baseline) and Visit 5 (56 days)
Population: Subjects in the ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 0.1%, 0.6 mg/ml | Mean Change in Total Corneal Fluorescein Staining | -3.3 units on a scale | Standard Error 0.56 |
| OC-01 0.2%. 1.2 mg/ml | Mean Change in Total Corneal Fluorescein Staining | -3.7 units on a scale | Standard Error 0.6 |
| Placebo | Mean Change in Total Corneal Fluorescein Staining | -3.2 units on a scale | Standard Error 0.59 |
Other Pre-specified
Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28)
The Schirmer's test measures the amount of tears produced by placing a paper strip in the eye for 5 minutes and the distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: Visit 1 (baseline) and Visit 4 (28 Days)
Population: Subjects in the ITT-LOCF patient population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OC-01 0.1%, 0.6 mg/ml | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | 18 Participants |
| OC-01 0.2%. 1.2 mg/ml | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | 17 Participants |
| Placebo | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | 12 Participants |
Other Pre-specified
Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 6 (Day 84)
The Schirmer's test measures the amount of tears produced by numbing the eye and placing a paper strip in the eye for 5 minutes and distance of wetting was recorded following treatment with OC-01 or placebo. Schirmer's test scores range from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: Visit 1 (baseline) and Visit 6 (84 days)
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OC-01 0.1%, 0.6 mg/ml | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 6 (Day 84) | 15 Participants |
| OC-01 0.2%. 1.2 mg/ml | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 6 (Day 84) | 20 Participants |
| Placebo | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 6 (Day 84) | 10 Participants |