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

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

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.

Study Overview

• Status: Completed
• Conditions: Dry Eye; Sjogren's Syndrome; Graft vs. Host Disease
• Intervention / Treatment: Drug: Thymosin Beta 4 eye drops; Drug: Vehicle Control

Detailed Description

See above

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Southfield, Michigan, United States, 48034
      • Michigan Cornea Consultants, P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Thymosin Beta 4 eye drops; Patients will be randomized and will receive the same eye drops the Thymosin Beta 4.; Other Names: Tβ4
Placebo Comparator: 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.	Drug: Vehicle Control; Patients will be randomized and will receive the same eye drops without the Thymosin Beta 4.; Other Names: Vehicle

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Michigan Cornea Consultants, PC
• Collaborators: Kresge Eye Institute
• Investigators: Principal Investigator: Steven P Dunn, M.D., Michigan Cornea Consultants, P.C.

Publications and helpful links

General Publications

• Sosne G, Dunn SP, Kim C. Thymosin beta4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea. 2015 May;34(5):491-6. doi: 10.1097/ICO.0000000000000379.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 7, 2011
• First Submitted That Met QC Criteria: July 12, 2011
• First Posted (Estimate): July 13, 2011

Study Record Updates

• Last Update Posted (Estimate): December 23, 2015
• Last Update Submitted That Met QC Criteria: December 21, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; Systemic lupus erythematosus; Sjogren's Syndrome; Dry Eye; Scleroderma; Graft vs. Host Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Eye Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Sjogren's Syndrome; Graft vs Host Disease; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: 1003008179