Dry Eye, Dry Eye Syndromes
Conditions
Keywords
Dry Eye, Dry Eye Syndrome, DES
Brief summary
The objective of this study is to compare the safety and efficacy of RGN-259 Ophthalmic Solution to placebo for the treatment of the signs and symptoms of dry eye.
Interventions
DRUGRGN-259
A preservative-free, sterile eye drop solution containing Thymosin beta 4 for direct instillation into each eye, four times a day (QID) for 14 days
DRUGPlacebo
It is composed of the same excipients as RGN-259 but does not contain Thymosin beta 4
Sponsors
ReGenTree, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All subjects, investigators, and study personnel involved with the conduct of the study will be masked with regard to treatment assignments.
Intervention model description
Subjects will be randomized in a 1:1 ratio RGN-259 to placebo ophthalmic solution.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be at least 18 years of age; * Provide written informed consent; * Have a subject reported history of dry eye prior to Visit 1; * Have a history of use or desire to use eye drops for dry eye symptoms
Exclusion criteria
* Have any clinically significant slit-lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters; * Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1; * Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study; * Have used any eye drops within 2 hours of Visit 1; * Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 6 months; * Have used Restasis®, Xiidra® Cequa®, or TrueTear® within 45 days of Visit 1 or Lipiflow® within 6 months of Visit 1; * Have an intraocular pressure (IOP) \> 25 mmHg at Visit 1; * Have any planned ocular and/or lid surgeries over the study period; * Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1; * Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study); * Have corrected visual acuity greater than or equal to logarithm of the minimum angle of resolution (logMAR) +0.7 as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in both eyes at Visit 1; * Have an uncontrolled systemic disease; * Be a woman who is pregnant, nursing or planning a pregnancy; * Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 4 (or early termination visit) if of childbearing potential. Non-childbearing potential is defined as a woman who is permanently sterilized (e.g., has had a hysterectomy or bilateral tubal ligation or bilateral oophorectomy), or is post-menopausal (without menses for 12 consecutive months); * Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom; intrauterine device (IUD); or surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, she must agree to use adequate birth control as defined above for the remainder of the study; * Have a known allergy and/or sensitivity to the study drug or its components; * Have a condition or be in a situation which the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study; * Have used an investigational drug or device within 30 days of Visit 1; * Be currently using any medication known to cause ocular drying (e.g., antihistamines, anti-depressants) or increased lacrimation (e.g., cholinergics) that is not used on a stable dosing regimen for at least 30 days prior to Visit 1; * Be receiving systemic corticosteroid therapy (not including inhaled corticosteroids), ophthalmic topical steroids, topical nonsteroidal antiinflammatory drugs (NSAIDs), topical antibiotics, immunotherapy, or cytotoxic therapy within 14 days of Visit 1 or anticipate such therapy throughout the study period. * Be unable or unwilling to follow instructions, including participation in all study assessments and visits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Inferior Corneal Staining Change From Pre-CAE®(Controlled Adverse Environment) to Post-CAE® at Day 15 (Visit 4) Using the Ora Calibra® Scale | Day 15 | Inferior corneal staining was assessed using the Ora Calibra® Corneal and Conjunctival Staining Scale, which is a 0 to 4 scale and where higher numbers indicating more severe staining. |
| Change From Baseline in Ocular Discomfort at Day 15 (Visit 4) Pre-CAE® Using the Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire | Day 15 | The severity of ocular discomfort was measured using the Ora Calibra® Ocular Discomfort \& 4-Symptom Questionnaire which is a 0 to 5 scale and where higher numbers indicating more severe discomfort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Discomfort During CAE® at Visit 4 | Day 15 | Subjects' perceived severity of ocular discomfort during CAE® exposure was measured using the Ocular Discomfort Scale which is a 0 to 4 scale and where higher numbers indicating more severe discomfort. |
| Fluorescein Staining (Ora Calibra® Scale) at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre and Post-CAE®) | Day 8, Day 15 | Corneal and conjunctival staining were assessed using the Ora Calibra® Corneal and Conjunctival Staining Scale, which is a 0 to 20 scale and where higher numbers indicating more severe staining. |
| Lissamine Green Staining (Ora Calibra® Scale) at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre- and Post-CAE®) | Day 8, Day 15 | Lissamine green staining were assessed using the Ora Calibra® Corneal and Conjunctival Staining Scale, which is a 0 to 20 scale and where higher numbers indicating more severe staining. |
| Tear Film Break-Up Time (TFBUT©) at Visits 3 and 4 (Pre- and Post-CAE®) | Day 8, Day 15 | TFBUT© measures tear film stability and was assessed by measuring, in seconds, the time from eye opening to the formation of micelles in the tear film. Measurements were obtained using a stopwatch. Longer TFBUT values indicate greater tear film stability and less severe dry eye. |
| Unanesthetized Schirmer's Test at Visit 3, Visit 4 (Pre-CAE®) | Day 8, Day 15 | The Unanesthetized Schirmer's Test measures tear production. A sterile Schirmer test strip was placed in the lower temporal lid margin of each eye, and after 5 minutes, the length of the moistened area on the strip was recorded in millimeters (mm). Higher values indicate greater tear production and a better outcome. |
| Drop Comfort Assessment After Randomization at Visit 2 | Day 1 | Drop comfort for each eye was assessed using subject-reported drop comfort scale, which is a 0 to 10 scale and where higher numbers indicating more uncomfortable. |
| Ocular Discomfort & 4-Symptom Questionnaire at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre- and Post-CAE®), Excluding the Hierarchical Efficacy Measure | Day 8, Day 15 | The severity of 5 symptoms was measured using the Ora Calibra® Ocular Discomfort \& 4-Symptom Questionnaire which is a 0 to 5 scale and where higher numbers indicating more severe discomfort. |
| Ocular Surface Disease Index (OSDI)© at Visits 3 and 4 (Pre-CAE®) | Day 8, Day 15 | The severity of dry eye disease and its impact on vision-related function were measured using the Ocular Surface Disease Index. Scores range from 0 to 100, with higher scores indicating greater disability. |
| Ocular Discomfort Outside CAE® at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre- and Post-CAE®) | Day 8, Day 15 | Subjects' perceived severity of ocular discomfort was measured using the Ocular Discomfort Scale which is a 0 to 4 scale and where higher numbers indicating more severe discomfort. |
Countries
United States
Participant flow
Recruitment details
Subjects were screened during a 14-day study run-in period prior to randomization. And after run-in period and confirmation of inclusion and exclusion criteria, all eligible subjects were randomized in a 1:1 ratio to receive 0.1% RGN-259 or placebo ophthalmic solution bilaterally, four times per day (QID) for 14 days. The study comprised of 4 visits over the course of approximately 4 weeks
Pre-assignment details
One participant was enrolled and completed the study twice and received placebo in both periods. This subject was counted once in the ITT population but twice in the safety population. Another participant randomized to the 0.1% RGN-259 arm did not receive treatment and was included only in the ITT population. Consequently, the ITT population included 351 participants in the 0.1% RGN-259 arm and 348 in the placebo arm; the safety population included 350 and 349 participants, respectively.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 12.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 325 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 19 Participants |
| Race (NIH/OMB) Black or African American | 44 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 570 Participants |
| Sex: Female, Male Female | 267 Participants |
| Sex: Female, Male Male | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 350 | 0 / 349 |
| other Total, other adverse events | 47 / 350 | 31 / 349 |
| serious Total, serious adverse events | 0 / 350 | 0 / 349 |
Outcome results
None listed