Comparative Study of Thymosin Beta 4 Eye Drops vs. Vehicle in the Treatment of Severe Dry Eye

Study Overview
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Brief Summary
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Severe dry eye is a debilitating ocular disease resulting in loss of vision, reduced day-to-day function and significant discomfort. Tear substitutes are an important part of the treatment of all patients, however, even with aggressive us, the corneal(ocular)surface often remains very irregular due to poor surface healing. The agent being evaluated in this study, Thymosin Beta 4, promotes healing of the corneal surface and has been studied in patients with recalcitrant corneal ulcers and erosions with significant success (Arch Ophthalmol. 2010;128(5):636-638., Ann of the NY Acad of Sci, May, 2010). The study hypothesis is that Thymosin Beta 4, in its role as a modulator of corneal surface healing, may be able to promote healing of the corneal surface allowing for more conventional modalities to take over and maintain a smooth and regular ocular surface. The investigators hope to be able to demonstrate an improvement in visual acuity, surface healing and a reduction in dry-eye related symptoms.

Detailed Description
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See above

Official Title
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Comparative Study of Thymosin Beta 4 Eye Drops or Vehicle in the Treatment of Patients With Ocular Surface Defects Due to Severe Dry Eye

Conditions
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Dry Eye, Sjogren's Syndrome, Graft vs. Host Disease

Intervention / Treatment
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* Drug: Thymosin Beta 4 eye drops
* Drug: Vehicle Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Schirmers of < 5 mm at 5 minutes TFBUT: less than 10 seconds Corneal staining of >3 of 15: conjunctival staining of >3 of 18 Ocular Surface Disease Index of > 50 Presumed best corrected vision of 20/60 or better Exclusion Criteria: Acute or inflammatory corneal disease Pregnancy or lactation Monocular status Punctal occlusion within 30 days Ocular surgery within 3 months Corneal thinning of >50% Active corneal infection History of ocular malignancy Retinal neovascularization Current use of topical cyclosporin A

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thymosin Beta 4 eye drops<br>It is a preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into each eye, six times daily for 28 days | Drug: Thymosin Beta 4 eye drops<br>* Patients will be randomized and will receive the same eye drops the Thymosin Beta 4.<br>* Other names: Tβ4;|
| Placebo Comparator: Vehicle Control<br>It is composed of the same excipients as RGN-259 but does not contain Tβ4 for direct instillation into each eye, six times daily for 28 days. | Drug: Vehicle Control<br>* Patients will be randomized and will receive the same eye drops without the Thymosin Beta 4.<br>* Other names: Vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Sum of adverse events observed at Day 1, Day 14, Day 28 and Day 56. Measurable by Intra-ocular pressure (IOP) by applanation tonometry, Complete ophthalmologic evaluation including fundoscopy, An adverse event (baseline and all subsequent study visits). | Day 1, Day 14, Day 28 and Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal Fluorescein Staining | Ocular surface irregularity as measured by Slit Lamp Examination (SLE) with fluorescein dye staining of the cornea at days 56 (+28 day follow up). The scale used to determine the difference in corneal fluorescein staining is the Oxford scale. (The Oxford Scale measures corneal fluorescein staining) Corneal staining type was assessed by the investigator for each of 5 regions of the cornea, i.e., four quadrants plus central. The five regions were summed, for a maximum score of 25. A higher score represents greater disability. | Days 56 (+28 day follow up) | 
| Ocular Discomfort Index | Dry eye causes ocular discomfort, which is measured using a Ocular Surface Disease Index at 56 day (+28 day followup). (Symptomatic improvement using the validated Ocular Surface Disease Index (OSDI). The OSDI is a questionnaire that consists of 12 questions about ocular irritation and the effect of dry eye on vision. For every question, participants check a score between 0 and 4, where 0 equals none of the time and 4 equals all of the time. OSDI scores are calculated according to: OSDI = [(sum of scores for all questions answered)*100] / [(total number of questions answered)*4]. The OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. | Days 56 (+28 day follow up) | 
| Tear Film Break up Time | Tear film break up time (TFBUT) was measured to evaluating the quality of tear at 56 day (+28 day follow up). The tear film break-up time is defined as the interval between the last complete blink and the first appearance of a dry spot, or disruption in the tear film. Range : >10 seconds is thought to be normal, <5 seconds low (with high likelihood of dry eye symptoms). | Days 56 (+28 day follow up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry Eye, Sjogren's Syndrome, Graft vs. Host Disease, Rheumatoid arthritis, Systemic lupus erythematosus, Scleroderma