Dry Eye, Keratoconjunctivitis Sicca
Conditions
Brief summary
The purpose of this study is to assess the safety and efficacy of 5% tavilermide and 1% tavilermide ophthalmic solutions compared with placebo ophthalmic solution in treating the signs and symptoms of dry eye.
Interventions
DRUGTavilermide ophthalmic solution
BID topical dosing
OTHERPlacebo
BID topical dosing
Sponsors
Mimetogen Pharmaceuticals USA, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Subject-reported history of dry eye disease in both eyes for at least 6 months; * History of use of artificial tear eye drops for dry eye symptoms; * Total score of ≥40 on SANDE; * TFBUT; * Corneal fluorescein staining; * Lissamine green conjunctival staining; * Schirmer's test score.
Exclusion criteria
* Have participated in a previous tavilermide (MIM-D3) study; * Have clinically significant slit lamp findings at Visit 1; * Have a history of lacrimal duct obstruction within 12 months of Visit 1; * Have an uncontrolled systemic disease; * Be a woman who is pregnant, nursing or planning a pregnancy; * Be a woman of childbearing potential who is not using an acceptable means of birth control; * 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; * Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 45 days prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eye Dryness Score as Measured by the VAS | Baseline to Day 85 in 5% Tavilermide versus Placebo | The Visual Analog Scale (VAS) where subjects were asked to rate their eye dryness (OU) by placing a vertical mark on the horizontal line to indicate their current level of discomfort. 0 mm corresponds to No Discomfort, and 100 mm corresponds to Maximal Discomfort. The length of the assessment line is 100 mm. |
| Change From Baseline in Total Corneal Fluorescein Staining as Measured by the NEI Scale | Baseline to Day 85 in 5% Tavilermide versus Placebo | The National Eye Institute (NEI) scale is a standardized grading system of 0-3 was used for each of the 5 areas on each cornea (central, superior, temporal, nasal, and inferior) . Grade 0 was specified when no staining is present. The maximum score was 15. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tavilermide 5% Tavilermide ophthalmic solution: BID topical dosing | 257 |
| Tavilermide 1% Tavilermide ophthalmic solution: BID topical dosing | 97 |
| Vehicle Placebo: BID topical dosing | 253 |
| Total | 607 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative Reasons | 3 | 1 | 2 |
| Overall Study | Adverse Event | 4 | 0 | 3 |
| Overall Study | Protocol Violation | 1 | 2 | 2 |
| Overall Study | Randomized in error or Disqualified | 8 | 1 | 7 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 4 |
Baseline characteristics
| Characteristic | Tavilermide 5% | Tavilermide 1% | Vehicle | Total |
|---|---|---|---|---|
| Age, Continuous | 61.1 Years STANDARD_DEVIATION 13.47 | 59.7 Years STANDARD_DEVIATION 14.63 | 60.5 Years STANDARD_DEVIATION 14 | 60.6 Years STANDARD_DEVIATION 13.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 9 Participants | 29 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 232 Participants | 88 Participants | 224 Participants | 544 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Eye Dryness Score | 63.3 units on a scale STANDARD_DEVIATION 20.38 | 65.8 units on a scale STANDARD_DEVIATION 19.06 | 65.0 units on a scale STANDARD_DEVIATION 20.22 | 64.4 units on a scale STANDARD_DEVIATION 20.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 5 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 8 Participants | 27 Participants | 56 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 219 Participants | 81 Participants | 213 Participants | 513 Participants |
| Sex: Female, Male Female | 201 Participants | 80 Participants | 184 Participants | 465 Participants |
| Sex: Female, Male Male | 56 Participants | 17 Participants | 69 Participants | 142 Participants |
| Total Corneal Fluorescein Staining | 7.4 units on a scale STANDARD_DEVIATION 1.92 | 7.4 units on a scale STANDARD_DEVIATION 1.77 | 7.6 units on a scale STANDARD_DEVIATION 2.06 | 7.5 units on a scale STANDARD_DEVIATION 1.96 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 261 | 0 / 99 | 0 / 255 |
| other Total, other adverse events | 16 / 261 | 1 / 99 | 8 / 255 |
| serious Total, serious adverse events | 2 / 261 | 0 / 99 | 3 / 255 |
Outcome results
Primary
Change From Baseline in Eye Dryness Score as Measured by the VAS
The Visual Analog Scale (VAS) where subjects were asked to rate their eye dryness (OU) by placing a vertical mark on the horizontal line to indicate their current level of discomfort. 0 mm corresponds to No Discomfort, and 100 mm corresponds to Maximal Discomfort. The length of the assessment line is 100 mm.
Time frame: Baseline to Day 85 in 5% Tavilermide versus Placebo
Population: ITT Population with Markov Chain Monte Carlo (MCMC) on all randomized subjects
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tavilermide 5% | Change From Baseline in Eye Dryness Score as Measured by the VAS | -15.1 score on a scale | Standard Error 1.64 |
| Tavilermide 1% | Change From Baseline in Eye Dryness Score as Measured by the VAS | -20.6 score on a scale | Standard Error 2.66 |
| Placebo | Change From Baseline in Eye Dryness Score as Measured by the VAS | -16.5 score on a scale | Standard Error 1.67 |
p-value: 0.553395% CI: [-3.2, 6]ANCOVA
Primary
Change From Baseline in Total Corneal Fluorescein Staining as Measured by the NEI Scale
The National Eye Institute (NEI) scale is a standardized grading system of 0-3 was used for each of the 5 areas on each cornea (central, superior, temporal, nasal, and inferior) . Grade 0 was specified when no staining is present. The maximum score was 15. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.
Time frame: Baseline to Day 85 in 5% Tavilermide versus Placebo
Population: ITT Population with MCMC on all randomized subjects
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tavilermide 5% | Change From Baseline in Total Corneal Fluorescein Staining as Measured by the NEI Scale | -2.6 units on a scale | Standard Error 0.17 |
| Tavilermide 1% | Change From Baseline in Total Corneal Fluorescein Staining as Measured by the NEI Scale | -2.3 units on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline in Total Corneal Fluorescein Staining as Measured by the NEI Scale | -2.1 units on a scale | Standard Error 0.17 |
p-value: 0.019295% CI: [-1.1, -0.1]ANCOVA