Trial Outcomes & Findings for Safety and Efficacy of Thymosin Beta 4 Ophthalmic Solution in Patients With Dry Eye (NCT NCT01387347)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

Day 29 (end of treatment)

Results posted on

2015-07-10

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	36	36
Overall Study COMPLETED	34	35
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Lost to Follow-up	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=36 Participants 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.	Thymosin Beta 4 n=36 Participants 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.	Total n=72 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Age, Continuous	55.3 years STANDARD_DEVIATION 12.76 • n=5 Participants	57.1 years STANDARD_DEVIATION 12.07 • n=7 Participants	56.02 years STANDARD_DEVIATION 12.37 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	29 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants	36 participants n=7 Participants	72 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 29 (end of treatment)

Population: Intent to Treat population

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.

Outcome measures

Outcome measures
Measure	Thymosin Beta 4 n=36 Participants 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.	Placebo n=36 Participants 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.
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	2.08 units on a scale Standard Deviation 0.71	1.9 units on a scale Standard Deviation 0.63

PRIMARY outcome

Timeframe: Day 29 (end of treatment)

Population: Intent to Treat (ITT)

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.

Outcome measures

Outcome measures
Measure	Thymosin Beta 4 n=36 Participants 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.	Placebo n=36 Participants 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.
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.	1.3 Units on a Scale Standard Deviation 1.1	1.6 Units on a Scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Throughout the study till Day 29

Population: Intention to treat (ITT)

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.

Outcome measures

Outcome measures
Measure	Thymosin Beta 4 n=36 Participants 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.	Placebo n=36 Participants 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.
Number of Adverse Events as a Measure of Safety and Tolerability	2 Events	0 Events

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Thymosin Beta 4

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=36 participants at risk 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.	Thymosin Beta 4 n=36 participants at risk 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.
Eye disorders General disorder ocular and administration site conditions AND Instillation site pain,	5.6% 2/36 • Number of events 4	0.00% 0/36

Additional Information

Won S. Yang, President & CEO

ReGenTree, LLC

Phone: 609-734-4328

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60