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

Phase 2

Completed

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

Interventions: Drug: Vehicle Control
Drug: Thymosin Beta 4 eye drops

Registration Number: NCT01393132

Lead Sponsor: Michigan Cornea Consultants, PC

Brief Summary: 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: See above

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vehicle Control	Vehicle Control	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.
Thymosin Beta 4 eye drops	Thymosin Beta 4 eye drops	It is a preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into each eye, six times daily for 28 days

Primary Outcome Measures

Name	Time	Method
Safety	Day 1, Day 14, Day 28 and Day 56	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).

Secondary Outcome Measures

Name	Time	Method
Corneal Fluorescein Staining	Days 56 (+28 day follow up)	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.
Tear Film Break up Time	Days 56 (+28 day follow up)	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).
Ocular Discomfort Index	Days 56 (+28 day follow up)	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.