Clinical trial NCT01387347: Safety and Efficacy of Thymosin Beta 4 Ophthalmic Solution in Patients With Dry Eye
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dry Eye Syndrome
Dry Eye
Keywords: Thymosin beta 4
Dry eye syndrome
Dry eye
Lead sponsor: ReGenTree, LLC
Sponsor class: INDUSTRY
Collaborators: name: ORA, Inc.
First posted: 2011-07-04
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Have given a written, informed consent.
2. 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.
3. Have a best corrected visual acuity.
4. Have a patient-reported history of dry eye in both eyes.
5. Use and/or desire to use an artificial tear substitute for dry eye symptoms within the past 6 months.
6. A negative urine pregnancy test if female of childbearing potential.
7. Have a corneal fluorescein staining score of ≥ 2 in any corneal surface segment in at least one eye at Visit 1.

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Exclusion Criteria:

1. Have contraindications to the use of the study drug.
2. Have known allergy or sensitivity to the study drug or components thereof.
3. Have anterior blepharitis.
4. Be diagnosed with an on-going ocular infection or active ocular inflammation.
5. Use contact lenses within 1 week before Visit 1 or during the course of the study.
6. Have previously had Laser-Assisted in Situ Keratomileusis (LASIK) surgery within 12 months prior to Visit 1.
7. 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.
8. Have used topical ocular cyclosporine within 30 days prior to Visit 1.
9. Have had a past or present evidence of malignancy.

Primary outcomes:
measure: 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
timeFrame: Day 29 (end of treatment)
measure: 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.
timeFrame: Day 29 (end of treatment)
Secondary outcomes:
measure: Number of Adverse Events as a Measure of Safety and Tolerability
timeFrame: Throughout the study till Day 29
Other outcomes:
Locations:
Study officials:
affiliation: Ora Clinical Research and Development
name: Gail Torkildsen, MD
role: PRINCIPAL_INVESTIGATOR
References: