Dry Eye Disease (DED)
Conditions
Brief summary
The objective of this study is to evaluate the safety and effectiveness of OC-01 Nasal Spray as compared to placebo on signs and symptoms of dry eye disease.
Detailed description
This was a Phase 3, multicenter, randomized, controlled, double-masked (including subjects, Investigators, study site personnel, and Sponsor personnel) study designed to evaluate the safety and efficacy of OC-01 (varenicline) nasal spray 0.6 mg/mL and 1.2 mg/mL in adult participants with DED. The study randomized 758 subjects at least 22 years of age with a physicians' diagnosis of DED and meeting all other study eligibility criteria to receive OC-01 (varenicline) nasal spray or placebo twice daily (BID) for 28 days with three additional long-term follow-up visits at 6 weeks, 6 months, and 12 months. Participants who terminated from the study during the treatment period were asked to complete safety assessments (if the participants agree) prior to study exit. Participants who were terminated early from the study were not replaced
Interventions
OC-01 (varenicline) nasal spray
Placebo (vehicle) nasal spray
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 use 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) or extraocular surgery 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 any 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 dry eye disease 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 |
|---|---|---|
| Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | 28 Days [Visit 1 (baseline) and Visit 4b (28 days)] | The primary endpoint was the percentage of subjects who achieve ≥10 mm improvement in Schirmer's Test Score from baseline to 28 days in the study eye following treatment with OC-01. Schirmer's test scores from 0-35 mm where a higher score is indicative of a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Eye Dryness Score in CAE at Week 4 at 5 Minutes | 28 Days [Visit 1 (baseline) and Visit 4a (28 days)] | Change in Eye Dryness Score Eye from baseline in CAE at 4 Weeks at 5 minutes post treatment. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome. |
| Mean Change From Baseline in Eye Dryness Score From Baseline to Day 28 | 28 Days [Visit 1 (baseline) and Visit 4b (28 days)] | Change in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome. |
| Mean Change Form Baseline in Schirmer's Test Score From Baseline to Day 28 | 28 Days [Visit 1 (baseline) and Visit 4b (28 days)] | Change in Schirmer test score from baseline to Day 28. Schirmer's test scores from 0-35 mm where a higher score is indicative of a better outcome. |
| Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 2 | 14 Days [Visit 1 (baseline) and Visit 3 (14 days)] | Chang in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better otucome. |
| Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 1 | 7 Days [Visit 1 (baseline) and Visit 2 (7 days)] | Change in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OC-01 Low Dose 0.6 mg/mL BID for 28 Days OC-01 (varenicline) nasal spray, 0.6 mg/ML BID for 28 days
OC-01 (varenicline) nasal spray: OC-01 (varenicline) nasal spray | 260 |
| OC-01 High Dose 1.2 mg/mL BID for 28 Days OC-01 (varenicline) nasal spray, 1.2 mg/ML BID for 28 days
OC-01 (varenicline) nasal spray: OC-01 (varenicline) nasal spray | 246 |
| Placebo (Vehicle) Nasal Spray BID for 28 Days Placebo (vehicle) nasal spray BID for 28 days
Placebo (vehicle) nasal spray: Placebo (vehicle) nasal spray | 252 |
| Total | 758 |
Baseline characteristics
| Characteristic | OC-01 Low Dose 0.6 mg/mL BID for 28 Days | OC-01 High Dose 1.2 mg/mL BID for 28 Days | Placebo (Vehicle) Nasal Spray BID for 28 Days | Total |
|---|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 12.76 | 58.4 years STANDARD_DEVIATION 13.03 | 58.4 years STANDARD_DEVIATION 13.29 | 58.8 years STANDARD_DEVIATION 13.02 |
| Baseline Schirmer's Test Score (mm) | 5.1 mm STANDARD_DEVIATION 2.95 | 5.4 mm STANDARD_DEVIATION 2.93 | 4.9 mm STANDARD_DEVIATION 2.89 | 5.1 mm STANDARD_DEVIATION 2.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 37 Participants | 36 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 233 Participants | 209 Participants | 216 Participants | 658 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 2 Participants | 6 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Asian | 11 Participants | 7 Participants | 5 Participants | 23 Participants |
| Race/Ethnicity, Customized Race Black or African American | 27 Participants | 35 Participants | 29 Participants | 91 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 219 Participants | 200 Participants | 211 Participants | 630 Participants |
| Region of Enrollment United States | 260 participants | 246 participants | 252 participants | 758 participants |
| Sex: Female, Male Female | 194 Participants | 181 Participants | 201 Participants | 576 Participants |
| Sex: Female, Male Male | 66 Participants | 65 Participants | 51 Participants | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 260 | 2 / 245 | 1 / 251 |
| other Total, other adverse events | 253 / 260 | 243 / 245 | 158 / 251 |
| serious Total, serious adverse events | 5 / 260 | 12 / 245 | 9 / 251 |
Outcome results
Primary
Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28)
The primary endpoint was the percentage of subjects who achieve ≥10 mm improvement in Schirmer's Test Score from baseline to 28 days in the study eye following treatment with OC-01. Schirmer's test scores from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: 28 Days [Visit 1 (baseline) and Visit 4b (28 days)]
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OC-01 Low Dose, 0.6 mg/mL | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | 123 Participants |
| OC-01 High Dose, 1.2 mg/mL | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | 121 Participants |
| Placebo (Vehicle) Nasal Spray | Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28) | 70 Participants |
Secondary
Mean Change Form Baseline in Schirmer's Test Score From Baseline to Day 28
Change in Schirmer test score from baseline to Day 28. Schirmer's test scores from 0-35 mm where a higher score is indicative of a better outcome.
Time frame: 28 Days [Visit 1 (baseline) and Visit 4b (28 days)]
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 Low Dose, 0.6 mg/mL | Mean Change Form Baseline in Schirmer's Test Score From Baseline to Day 28 | 11.3 mm | Standard Error 0.61 |
| OC-01 High Dose, 1.2 mg/mL | Mean Change Form Baseline in Schirmer's Test Score From Baseline to Day 28 | 11.5 mm | Standard Error 0.64 |
| Placebo (Vehicle) Nasal Spray | Mean Change Form Baseline in Schirmer's Test Score From Baseline to Day 28 | 6.3 mm | Standard Error 0.61 |
Secondary
Mean Change From Baseline in Eye Dryness Score From Baseline to Day 28
Change in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome.
Time frame: 28 Days [Visit 1 (baseline) and Visit 4b (28 days)]
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 Low Dose, 0.6 mg/mL | Mean Change From Baseline in Eye Dryness Score From Baseline to Day 28 | -19.8 mm | Standard Error 1.54 |
| OC-01 High Dose, 1.2 mg/mL | Mean Change From Baseline in Eye Dryness Score From Baseline to Day 28 | -22.2 mm | Standard Error 1.61 |
| Placebo (Vehicle) Nasal Spray | Mean Change From Baseline in Eye Dryness Score From Baseline to Day 28 | -15.4 mm | Standard Error 1.57 |
Secondary
Mean Change From Baseline in Eye Dryness Score in CAE at Week 4 at 5 Minutes
Change in Eye Dryness Score Eye from baseline in CAE at 4 Weeks at 5 minutes post treatment. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome.
Time frame: 28 Days [Visit 1 (baseline) and Visit 4a (28 days)]
Population: Subjects in the mITT-2 population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 Low Dose, 0.6 mg/mL | Mean Change From Baseline in Eye Dryness Score in CAE at Week 4 at 5 Minutes | -10.3 mm | Standard Error 1.62 |
| OC-01 High Dose, 1.2 mg/mL | Mean Change From Baseline in Eye Dryness Score in CAE at Week 4 at 5 Minutes | -9.0 mm | Standard Error 1.75 |
| Placebo (Vehicle) Nasal Spray | Mean Change From Baseline in Eye Dryness Score in CAE at Week 4 at 5 Minutes | -7.4 mm | Standard Error 1.74 |
Secondary
Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 1
Change in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome.
Time frame: 7 Days [Visit 1 (baseline) and Visit 2 (7 days)]
Population: Subjects in the ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 Low Dose, 0.6 mg/mL | Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 1 | -15.7 mm | Standard Error 1.33 |
| OC-01 High Dose, 1.2 mg/mL | Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 1 | -15.4 mm | Standard Error 1.4 |
| Placebo (Vehicle) Nasal Spray | Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 1 | -13.3 mm | Standard Error 1.35 |
Secondary
Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 2
Chang in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better otucome.
Time frame: 14 Days [Visit 1 (baseline) and Visit 3 (14 days)]
Population: Subjects in the ITT-LOCF population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OC-01 Low Dose, 0.6 mg/mL | Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 2 | -16.5 mm | Standard Error 1.38 |
| OC-01 High Dose, 1.2 mg/mL | Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 2 | -17.9 mm | Standard Error 1.45 |
| Placebo (Vehicle) Nasal Spray | Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 2 | -12.7 mm | Standard Error 1.41 |