Study of ST-100 as Treatment for Dry Eye Disease

Study Overview
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Brief Summary
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The objective of this study is to compare the safety and efficacy of two different concentrations of ST-100 Ophthalmic Solution to placebo (vehicle) for the treatment of the signs and symptoms of dry eye.

Detailed Description
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This is a Phase 2, multi-center, double-masked, randomized, placebo-controlled clinical study. Subjects will be randomized to one of the following treatment arms at Visit 2 (Day 1): Low dose ST-100 Ophthalmic Solution: 1 drop twice daily (BID) in each eye High dose ST-100 Ophthalmic Solution: 1 drop BID in each eye Placebo Ophthalmic Solution (Vehicle): 1 drop BID in each eye Approximately 150 subjects will be randomly assigned to one of the three groups (1:1:1) to receive either ST-100 Ophthalmic Solution or placebo solution as topical ophthalmic drops administered bilaterally BID for 4 weeks. Subjects, Sponsor, Contract Research Organization (CRO), and site personnel will be masked to treatment assignment. The clinical hypotheses for this study is that low dose and high dose ST-100 Ophthalmic Solution twice daily (BID) is superior to its vehicle (BID) for the primary endpoints of signs and symptoms of dry eye.

Official Title
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A Phase 2 Multi-Center, Randomized, Double Masked, Placebo Controlled Study to Assess the Safety and Efficacy of ST-100 Ophthalmic Solution in Subjects Diagnosed With Dry Eye Disease

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: ST-100 Ophthalmic Solution
* Drug: Placebo Ophthalmic Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be at least 18 years of age; Provide written informed consent; Have a subject reported history of dry eye; Have a history of use of eye drops for dry eye symptoms; Ocular Discomfort & 4-symptom questionnaire; Schirmer's Test Score; Have conjunctival redness; Have corneal fluorescein staining; Have a sum corneal fluorescein staining score; Have a total lissamine green conjunctival score; Controlled Adverse Environment (CAE®); Exclusion Criteria: Have any clinically significant slit lamp findings at Visit 1; Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1; Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study; Have used any eye drops within 2 hours of Visit 1; Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months; Have used Restasis, Xiidra, or Cequa ophthalmic solutions within 45 days of Visit 1; Have any planned ocular and/or lid surgeries over the study period or any ocular surgery within the last 6 months; Have used, are using or anticipate using permanent or temporary punctal plugs during the study within 30 days of Visit 1; Be currently taking any topical ophthalmic prescription; Be currently taking or have taken Omega-3 supplements within the last 3 months; Be unable to read an eye chart; Be a woman who is pregnant, nursing, or planning a pregnancy; Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 5 (or early termination visit) if of childbearing potential; Be a woman of childbearing potential who is not using an acceptable means of birth control; Have a known allergy and/or sensitivity to the test article or its components; Have a condition or be in a situation that the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study; Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days of Visit 1; Be currently using any medication known to cause ocular drying that is not used on a stable dosing regimen for at least 30 days prior to Visit 1; Have a known history of meibomian gland procedures (e.g., LipiFlow, LPI, probing, etc.) within 6 months of study enrollment; Be unable or unwilling to follow instructions, including participation in all study assessments and visits.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low Dose ST-100 Ophthalmic Solution<br>Low Dose ST100-001 Ophthalmic solution, 20mg/ml | Drug: ST-100 Ophthalmic Solution<br>* One drop in each eye twice a day<br>* Other names: ST-100;|
| Active Comparator: High Dose ST-100 Ophthalmic Solution<br>High Dose ST100-001 Ophthalmic Solution, 50mg/ml | Drug: ST-100 Ophthalmic Solution<br>* One drop in each eye twice a day<br>* Other names: ST-100;|
| Placebo Comparator: Placebo Ophthalmic Solution<br>Placebo Ophthalmic Solution (vehicle) | Drug: Placebo Ophthalmic Solution<br>* One drop in each eye twice a day<br>* Other names: Vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ora Calibra® Corneal Fluorescein Staining Scale | Mean change on 5 corneal regions using 0-4 Ora Calibra® Fluorescein Staining Scale where 4 is the worst. | Visit 2 (Day 1) to Visit 7 (Day 29) | 
| Ora Calibra® Ocular Discomfort Scale | Mean change using the 0-4 Ora Calibra® Ocular Discomfort Scale where 4 is the worst. | Visit 2 (Day 1) to Visit 7 (Day 29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescein Staining | Fluorescein staining (Ora Calibra® scale) at pre-CAE®, post-CAE®, and pre- to post-CAE® regions: central, superior, inferior, temporal, nasal, corneal sum, conjunctival sum, and total eye score | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Lissamine Green Staining | Lissamine green staining (Ora Calibra® scale) at pre-CAE®, post-CAE®, and pre- to post-CAE® regions: central, superior, inferior, temporal, nasal, corneal sum, conjunctival sum, and total eye score | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Tear Film Break-up | Tear film break-up time at pre-CAE®, post- CAE®, and pre- to post-CAE® | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Ora Calibra® Conjunctival Redness Scale | Ora Calibra® Conjunctival Redness 0-4 Scale where 4 is the worst at pre-CAE®, post- CAE®, and pre- to post-CAE® | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Ora Calibra® Drop Comfort Scale | Ora Calibra® Drop Comfort 0-10 Scale where 10 is the worst | Visit 2 (Day 1) | 
| Ocular Surface Disease Index | Ocular Surface Disease Index (OSDI) 0-4 Scale where 4 is the worst at pre-CAE® | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Four Symptom Questionnaire | Four symptom questionnaire rated on 0-5 scale where 5 is the worst at pre-CAE®, post-CAE®, and pre- to post-CAE® | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Ora Calibra® Ocular Discomfort Scale | Ora Calibra® Ocular Discomfort 0-4 Scale where 4 is the worst during CAE® exposure. | Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Daily Diary | Ora Calibra® Ocular Discomfort Scale & 4-Symptom Questionnaire is rating multiple symptoms (overall Ocular Discomfort plus Burning, Dryness, Grittiness, and Stinging) each on a 0-5 scale where 0 = none and 5 = worst. | Visit 2 (Day 1) to Visit 7 (Day 29) | 
| Visual Analog Scale | Visual Analog Scale (VAS) rating Burning/Stinging, Itching, Foreign Body Sensation, Blurred Vision, Eye Dryness, Photophobia, Pain on 0-100% scale where 100% is the worst at pre-CAE® | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) | 
| Schirmer's Test | Unanesthetized Schirmer's Test at pre-CAE® | Visit 7 (Day 29) | 
| Ora Calibra® Ocular Discomfort Scale | Ora Calibra® Ocular Discomfort 0-4 Scale where 4 is the worst outside of the CAE® at pre-CAE®, post-CAE®, and pre- to post-CAE® | Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8), Visit 6 (Day 15), and Visit 7 (Day 29) |