Evaluation of the Efficacy and Safety of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease

Study Overview
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Brief Summary
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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
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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

Official Title
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Multicenter, Randomized, Controlled, Double-Masked, Clinical Trial to Evaluate the Efficacy and Safety of OC-01 (Varenicline) Nasal Spray on Signs and Symptoms of Dry Eye Disease (The ONSET-2 Study)

Conditions
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Dry Eye Disease (DED)

Intervention / Treatment
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* Drug: OC-01 (varenicline) nasal spray
* Drug: Placebo (vehicle) nasal spray


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OC-01 Low Dose, 0.6 mg/mL<br>OC-01 (varenicline) nasal spray, 0.6 mg/ML | Drug: OC-01 (varenicline) nasal spray<br>* OC-01 (varenicline) nasal spray<br>|
| Active Comparator: OC-01 High Dose, 1.2 mg/mL<br>OC-01 (varenicline) nasal spray, 1.2 mg/ML | Drug: OC-01 (varenicline) nasal spray<br>* OC-01 (varenicline) nasal spray<br>|
| Placebo Comparator: Placebo (vehicle) nasal spray<br>Placebo (vehicle) nasal spray | Drug: Placebo (vehicle) nasal spray<br>* Placebo (vehicle) nasal spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 28 Days [Visit 1 (baseline) and Visit 4b (28 days)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 28 Days [Visit 1 (baseline) and Visit 4a (28 days)] | 
| 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. | 28 Days [Visit 1 (baseline) and Visit 4b (28 days)] | 
| 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. | 28 Days [Visit 1 (baseline) and Visit 4b (28 days)] | 
| 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. | 14 Days [Visit 1 (baseline) and Visit 3 (14 days)] | 
| 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. | 7 Days [Visit 1 (baseline) and Visit 2 (7 days)] |