Ocular Tolerability of Voclosporin Ophthalmic Solution Versus Restasis® in Subjects With Dry Eye Disease

Study Overview
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Brief Summary
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Evaluate the tolerability, efficacy and safety of VOS versus Restasis® in subjects with mild to moderate Dry Eye Disease (DED).

Detailed Description
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This is a Phase 2, multi-center, Investigator-masked, randomized, parallel-group study to evaluate the tolerability, efficacy and safety of VOS versus Restasis® over a 28-day treatment period in subjects with mild to moderate DED. Approximately 90 subjects will be randomized to either VOS or Restasis® at approximately 7 centers located in the US

Official Title
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An Investigator-Masked, Randomized, Parallel-Group Study of the Ocular Tolerability of Voclosporin Ophthalmic Solution Versus Restasis® in Subjects With Dry Eye Disease

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: Voclosporin Ophthalmic Solution
* Drug: Restasis®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a best corrected visual acuity (BCVA) in both eyes of +0.7 logarithm of the Minimum Angle of Resolution (logMAR) or better as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Have a documented history of DED in both eyes supported by a previous clinical diagnosis. Have ongoing DED, as defined by at least one eye (if one eye, the same eye) meeting all the following criteria: A symptom severity score of ≥30 for Eye Dryness on a Visual Analog Scale (VAS) (0-100) An unanesthetized Schirmer Tear Test (STT) score of ≥1 mm and ≤10 mm per 5 minutes (Note: STT Score obtained at Visit 1) Evidence of ocular surface staining (total fluorescein staining score of at least 3 [0-15 scale]). Have normal lid anatomy. Exclusion Criteria: Have any known hypersensitivity or contraindication to study treatments (including excipients), topical anesthetics or vital dyes. Be unable to demonstrate correct instillation of over-the-counter (OTC) ocular lubricant. Report discomfort in both eyes from instillation of OTC ocular lubricant during Visit 2 (based on score of ≥30 on the Drop Discomfort VAS). Have used Restasis® (cyclosporine ophthalmic emulsion) within 30 days prior to Visit 1. Have used Restasis® for more than 1 month (if prior use is reported). Have used Xiidra® (lifitegrast ophthalmic solution) within 14 days prior to Visit 1. Have had corneal graft surgery in either eye within 1 year. Have recent or current evidence of ocular infection or inflammation in either eye. Have current evidence of clinically significant blepharitis (defined as requiring lid hygiene therapy), conjunctivitis, or a history of herpes simplex or zoster keratitis in either eye.

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
Interventional Model Description: This is a Phase 2, multi-center, Investigator-masked, randomized, parallel-group study to evaluate the tolerability, efficacy and safety of VOS versus Restasis® over a 28-day treatment period in subjects with mild to moderate DED. Approximately 90 subjects will be randomized to either VOS or Restasis® at approximately 7 centers located in the US.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voclosporin ophthalmic solution (VOS)<br>0.2% VOS, Twice Daily (BID), both eyes for 28 days | Drug: Voclosporin Ophthalmic Solution<br>* Investigational Drug<br>* Other names: 0.2% VOS;|
| Active Comparator: Comparator<br>0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days | Drug: Restasis®<br>* Comparator<br>* Other names: RESTASIS® (cyclosporine ophthalmic emulsion) 0.05%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1 | Drop Discomfort was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment 1 minute post-instillation on Day 1. The VAS scale is 0 - 100, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort. | 1-minute Post Dose 1 installation (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Drop Discomfort Post Dose Instillation on Day 28 | Drop Discomfort was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment 1 minute post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort. | Day 28 | 
| Change From Baseline in Burning/Stinging Post Dose Instillation on Day 28 | Burning/Stinging was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no burning/stinging and 100 corresponds to worst burning/stinging. | Day 28 | 
| Change From Baseline in Foreign Body Sensation Post Dose Instillation on Day 28 | Foreign Body Sensation was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no foreign body sensation and 100 corresponds to worst foreign body sensation. | 28 days | 
| Change From Baseline in Photophobia Post Dose Instillation on Day 28 | Photophobia was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no photophobia and 100 corresponds to worst photophobia. | 28 days | 
| Change From Baseline in Eye Pain Post Dose Instillation on Day 28 | Eye pain was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no eye pain and 100 corresponds to worst eye pain. | 28 days | 
| Change From Baseline in Eye Dryness Post Dose Instillation on Day 28 | Eye dryness was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no eye dryness and 100 corresponds to worst eye dryness. | 28 days | 
| Change From Baseline in Itching Post Dose Instillation on Day 28 | Itching was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no itching and 100 corresponds to worst itching. | 28 days | 
| Change From Baseline in the Total of All Individual Symptom Severity Assessment Scores | The Individual Symptom Severity Assessment Visual Analog Scale (VAS) includes Burning/Stinging (scale 0 - 100; 0 = no Burning/Stinging, 100 = worst Burning/Stinging), Foreign Body Sensation (scale 0 - 100; 0 = no Foreign Body Sensation, 100 = worst Foreign Body Sensation), Photophobia (scale 0 - 100; 0 = no Photophobia, 100 = worst Photophobia), Eye Pain (scale 0 - 100; 0 = no Eye Pain, 100 = worst Eye Pain), Eye Dryness (scale 0 - 100; 0 = no Eye Dryness, 100 = worst Eye Dryness), and Itching (scale 0 - 100; 0 = no Itching, 100 = worst Itching). The total sum of all 6 symptoms (Burning/Stinging, Foreign Body Sensation, Photophobia, Eye Pain, Eye Dryness, Itching) were evaluated (scale 0 - 600; 0 = no visual symptoms, 600 = worst visual symptoms). | Day 28 | 
| Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) | The Symptom Assessment in Dry Eye (SANDE) is a subjective rating performed by the subjects for the frequency and severity of their dry eye symptoms. The total length of the line is 100mm. For Frequency of Symptoms 0mm = rarely and 100mm = all the time. For Severity of Symptoms 0mm = very mild and 100mm = very severe. Subjects were asked to subjectively rate the frequency and severity of their symptoms by placing an X on the relevant horizontal line. The length of the line between the rarely or very mild starting point and the first point where the subject's mark crosses each line was measured and recorded in millimeters. | Day 28 | 
| Change From Baseline in Unanesthetized Schirmer Test Score | The Schirmer Test Score recorded tear production on test strips. The Schirmer tear test was conducted 1 hour following administration of VOS/Comparator and 20 minutes following fluorescein corneal staining. Using a ruler and/or the millimeters recorded on the strips, a point halfway between the two lines was measured and this was recorded as the amount of wetting. Lower scores indicate less tear production and therefore a worse outcome. Normal tear production is ≥10mm of wetting on the test strip, and severe dry eye is <5mm of wetting on the test strip. | 28 days | 
| Change From Baseline in Fluorescein Corneal Staining (FCS) Score | The FCS score was summarized for each eye separately. Each of the 5 sections of cornea (superior, inferior, nasal, temporal, central) were graded using the National Eye Institute (NEI) scale; 0, 1 (mild), 2 (moderate), or 3 (severe). The total score was obtained by summing each of the 5 sections of the cornea from 0 - 15. Lower scores indicate less staining and therefore a better outcome. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry Eye, Calcineurin Inhibitors