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| Name | Class |
|---|---|
| ORA, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Thymosin Beta 4 | Active Comparator | RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thymosin beta 4 | Drug | 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. |
|
| 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) |
| 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 |
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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.
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gail Torkildsen, MD | Ora Clinical Research and Development | Principal Investigator |
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Subjects who initially qualified for study entry, had adequate baseline staining and redness and positive controlled adverse environment response, were instructed to discontinue all ophthalmic medications and instill a commercially-available sterile irrigating (balanced salt) solution (i.e., the run-in solution) twice a day until Visit 2, Day 0.
The study took place at Ora Clinical Research and Development (a medical clinic)by Dr. Gail Torkildsen.The first subject was screened on 13 August 2011 and the last subject last visit to the clinic was on 20 September 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | 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. Placebo : 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. |
| FG001 | Thymosin Beta 4 | RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4. Thymosin beta 4 : 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | 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. Placebo : 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intent to Treat population | Posted | Mean | Standard Deviation | units on a scale | Day 29 (end of treatment) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 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. Placebo : 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| General disorder ocular and administration site conditions AND Instillation site pain, | Eye disorders | MedDRA 13.1 | Non-systematic Assessment | stinging post administration study gtts (eye drops) |
There were no limitations to trial RGN-DE-202 entitled:"Safety and Efficacy of Thymosin beta 4 Ophthalmic Solution in Patients with Dry Eye". All subjects were enrolled.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Won S. Yang, President & CEO | ReGenTree, LLC | 609-734-4328 | wonsyang@regentreellc.com |
| ID | Term |
|---|---|
| D015352 | Dry Eye Syndromes |
| ID | Term |
|---|---|
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| C033402 | thymosin beta(4) |
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|
| Placebo | Drug | 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. |
|
|
| BG001 |
| Thymosin Beta 4 |
RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 Thymosin beta 4 : 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Thymosin Beta 4 | RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 Thymosin beta 4 : 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. |
| OG001 | Placebo | Placebo is a preservative-free, sterile eye drop solution containing 0% Tβ4 Thymosin beta 4 : A preservative-free, sterile eye drop solution containing 0% Tβ4 for direct instillation into each eye, twice a day (BID) for 28 days. |
|
|
|
| Primary | 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. | Intent to Treat (ITT) | Posted | Mean | Standard Deviation | Units on a Scale | Day 29 (end of treatment) |
|
|
|
|
| Secondary | 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. | Intention to treat (ITT) | Posted | Number | Events | Throughout the study till Day 29 |
|
|
|
| 0 |
| 36 |
| 2 |
| 36 |
| EG001 | Thymosin Beta 4 | RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 Thymosin beta 4 : 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. | 0 | 36 | 0 | 36 |
|
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| t-test, 2 sided |
| 0.0244 |
| 2-Sided |
| No |
| Superiority or Other |