Safety and Efficacy of Thymosin Beta 4 Ophthalmic Solution in Patients With Dry Eye

Study Overview
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Brief Summary
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Thymosin Beta 4 (Tβ4) is a synthetic copy of the naturally-occurring 43-amino acid peptide that is found in a variety of tissues. Tβ4 promotes/accelerates wound repair in dermal, ocular, and cardiac animal models. Two recent pre-clinical evaluations have demonstrated that Tβ4 promotes corneal ocular surface defects healing in animal models of dry eye. RGN-259 (formulation of Tβ4 ophthalmic solution) mechanism of action offers potential to be a product that meets a major unmet medical need in patients with dry eye.

Detailed Description
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Tβ4 promotes wound repair and regeneration in various tissues. In the eye, it promotes corneal epithelial cell migration, decreases inflammation and has anti-apoptotic activities. It up-regulates the gene expression of laminin-5, a major subepithelial adhesion protein, located in the basement membrane region of the cornea, conjunctiva, and important in wound healing. In compassionate-use cases, Tβ4 has demonstrated efficacy in repairing non-healing neurotrophic corneal ulcers and other corneal epithelial wounds. In twenty-four nonclinical toxicology and safety pharmacology studies, the safety of Tβ4 has been demonstrated for its current and planned uses in man. The results of the two recent dry eye murine mouse model studies show that Tβ4 reduced corneal staining more than positive controls and demonstrated statistically significant reduction in staining compared to vehicle control. The results of these studies, in addition to data from compassionate use studies in patients with non-healing corneal surface defects, suggests that Tβ4 has a significant potential to be an important new safe and effective therapeutic in the treatment of dry eye syndrome.

Official Title
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A Double-Masked, Randomized, Single-Center Study Evaluating the Safety and Efficacy of 0.1% Tβ4 Ophthalmic Solution Compared to Vehicle on the Signs and Symptoms of Dry Eye in the Controlled Adverse Environment (CAE) Model

Conditions
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Dry Eye Syndrome, Dry Eye

Intervention / Treatment
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* Drug: Thymosin beta 4
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have given a written, informed consent. Be able and willing to follow instructions, including participation in study assessments, and be present for the required study visits for the duration of the study. Have a best corrected visual acuity. Have a patient-reported history of dry eye in both eyes. Use and/or desire to use an artificial tear substitute for dry eye symptoms within the past 6 months. A negative urine pregnancy test if female of childbearing potential. Have a corneal fluorescein staining score of ≥ 2 in any corneal surface segment in at least one eye at Visit 1. - Exclusion Criteria: Have contraindications to the use of the study drug. Have known allergy or sensitivity to the study drug or components thereof. Have anterior blepharitis. Be diagnosed with an on-going ocular infection or active ocular inflammation. Use contact lenses within 1 week before Visit 1 or during the course of the study. Have previously had Laser-Assisted in Situ Keratomileusis (LASIK) surgery within 12 months prior to Visit 1. Be currently taking any topical ophthalmic prescription or over-the-counter (OTC) solutions, artificial tears, gels, or scrubs and cannot discontinue these medications for the duration of the trial. Have used topical ocular cyclosporine within 30 days prior to Visit 1. Have had a past or present evidence of malignancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Thymosin Beta 4<br>RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 | Drug: Thymosin beta 4<br>* A preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 for direct instillation into each eye, twice a day (BID) for 28 days.<br>* Other names: RGN-259 (eye drop formulation of Tβ4);|
| Placebo Comparator: Placebo<br>The placebo solution is composed of the same excipients as RGN-259 but does not contain Tβ4. The Placebo is identical to the RGN-259 eye drops in color, consistency, and odor. | Drug: Placebo<br>* A preservative-free, sterile eye drop solution containing 0.0% (w/w) Tβ4 for direct instillation into each eye, twice a day (BID) for 28 days.<br>* Other names: Vehicle Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal Staining (Inferior Region) in the Worst Eye in the Controlled Adverse Environment (CAE) Model, Which is a Regulated Environmental Setting Aimed at Exacerbating the Signs and Symptoms of Dry Eye | This is a test that uses orange dye (fluorescein) and a blue light to detect ocular surface defects associated with dry eye. If the test result is normal, the dye remains in the tear film on the surface of the eye and does not adhere to the eye itself. The test is carried out throughout the study till end of treatment Day 29. However, the primary outcome measure itself is determined on Day 29. The scale used to determine the difference in corneal fluorescein staining between RGN-259 and placebo is the ORA scale: 0= no staining (no detectable ocular defect)to 4= confluent staining( severe ocular defect). Worst eye: In the case that both eyes were eligible for analysis, the worst eye was chosen as the eye with the greater increase of inferior corneal staining from Visit 1 to Visit 2. If both eyes were equal, the eye with greater ocular discomfort at Visit 2 was chosen as the worst eye. If both eyes were equal at Visit 2, then the right eye was chosen as the worst eye. | Day 29 (end of treatment) | 
| Ocular Discomfort in the Worst Eye in the Controlled Adverse Environment(CAE) Model, Which is a Regulated Environmental Setting Aimed at Exacerbating the Signs and Symptoms of Dry Eye. | Dry eye causes ocular discomfort, which is measured using a validated 4-point ORA Scale from the start of the dosing till the end of treatment (Day 29). 0 = no discomfort to 4 = constant discomfort. If the measurement is lower, then improvement of ocular discomfort can be inferred. The test is carried out throughout the study till end of treatment Day 29. However, the primary outcome measure itself is determined on Day 29. Worst eye: In the case that both eyes were eligible for analysis, the worst eye was chosen as the eye with the greater increase of inferior corneal staining from Visit 1 to Visit 2. If both eyes were equal, the eye with greater ocular discomfort at Visit 2 was chosen as the worst eye. If both eyes had were equal at Visit 2, then the right eye was chosen as the worst eye. | Day 29 (end of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events as a Measure of Safety and Tolerability | The Adverse events, which will be followed, are: impairment of visual acuity, an increase in intraocular pressure (IOP), and an increase in corneal sensitivity in both eyes. | Throughout the study till Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thymosin beta 4, Dry eye syndrome, Dry eye