Dry Eye
Conditions
Brief summary
The TRANQUILITY 2 Trial: Multi-Center Randomized, Double-Masked, Parallel Design, Vehicle-Controlled Phase 3 Clinical Trial to Assess the Efficacy and Safety of 0.25% Reproxalap Ophthalmic Solution Compared to Vehicle in Subjects with Dry Eye Disease
Interventions
Reproxalap Ophthalmic Solution (0.25%) administered 7 times over two consecutive days
DRUGVehicle Ophthalmic Solution
Vehicle Ophthalmic Solution administered 7 times over two consecutive days
Sponsors
Aldeyra Therapeutics, 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 No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age (either gender and any race); * Reported history of dry eye for at least 6 months prior to Visit 1; * Reported history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1
Exclusion criteria
* 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; * Diagnosis of an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1; * Contact lens use within 7 days of Visit 1 or anticipate using contact lenses during the trial; * Eye drop use within 2 hours of Visit 1; * Previous laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months; * Cyclosporine 0.05% or 0.09% or lifitegrast 5.0% ophthalmic solution use within 90 days of Visit 1; * Be receiving systemic corticosteroid therapy (not including inhaled corticosteroids) within 14 days of Visit 1 or anticipate such therapy throughout the study period; * Planned ocular and/or lid surgeries over the study period or any ocular surgery within 6 months of Visit 1; * Temporary punctal plugs during the study that have not been stable within 30 days of Visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Schirmer Test Mean Change From Baseline | The efficacy assessment period was before and after the final dose on Day 1 (Dose 4). Baseline was approximately two weeks before dosing at Screening. | Change from baseline comparison of reproxalap to vehicle for Schirmer test (0 to 35 mm). Higher scores represent greater tear production. The least squares mean (standard error) was derived from a mixed model repeated measures analysis of change from baseline, with baseline as a covariate, and time point and treatment group as factors. |
| Number of Subject Eyes That Are Schirmer Test Responders | The efficacy assessment period was before and after the final dose on Day 1 (Dose 4). Baseline was approximately two weeks before dosing at Screening. | Comparison of reproxalap to vehicle for number of subject eyes that are Schirmer test responders (10 millimeters or more increase from baseline). A generalized estimating equation analysis was performed with baseline as a covariate, and time point and treatment group as factors. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reproxalap Reproxalap ophthalmic solution (0.25%) was administered 7 times over two consecutive days. | 181 |
| Vehicle Vehicle ophthalmic solution was administered 7 times over two consecutive days. | 180 |
| Total | 361 |
Baseline characteristics
| Characteristic | Total | Reproxalap | Vehicle |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 180 Participants | 98 Participants | 82 Participants |
| Age, Categorical Between 18 and 65 years | 181 Participants | 83 Participants | 98 Participants |
| Age, Continuous | 63.1 years STANDARD_DEVIATION 12.6 | 64.2 years STANDARD_DEVIATION 12.2 | 61.9 years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 10 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 348 Participants | 171 Participants | 177 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 9 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 61 Participants | 25 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 279 Participants | 147 Participants | 132 Participants |
| Sex: Female, Male Female | 249 Participants | 123 Participants | 126 Participants |
| Sex: Female, Male Male | 112 Participants | 58 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 181 | 0 / 180 |
| other Total, other adverse events | 145 / 181 | 6 / 180 |
| serious Total, serious adverse events | 0 / 181 | 0 / 180 |
Outcome results
Primary
Number of Subject Eyes That Are Schirmer Test Responders
Comparison of reproxalap to vehicle for number of subject eyes that are Schirmer test responders (10 millimeters or more increase from baseline). A generalized estimating equation analysis was performed with baseline as a covariate, and time point and treatment group as factors.
Time frame: The efficacy assessment period was before and after the final dose on Day 1 (Dose 4). Baseline was approximately two weeks before dosing at Screening.
Population: Intent-to-treat population with observed data only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reproxalap | Number of Subject Eyes That Are Schirmer Test Responders | 116 eyes |
| Vehicle | Number of Subject Eyes That Are Schirmer Test Responders | 54 eyes |
p-value: <0.000195% CI: [1.67, 4.13]Generalized estimating equation
Primary
Schirmer Test Mean Change From Baseline
Change from baseline comparison of reproxalap to vehicle for Schirmer test (0 to 35 mm). Higher scores represent greater tear production. The least squares mean (standard error) was derived from a mixed model repeated measures analysis of change from baseline, with baseline as a covariate, and time point and treatment group as factors.
Time frame: The efficacy assessment period was before and after the final dose on Day 1 (Dose 4). Baseline was approximately two weeks before dosing at Screening.
Population: Intent-to-treat population with observed data only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap | Schirmer Test Mean Change From Baseline | 1.8 length in millimeters | Standard Error 0.4 |
| Vehicle | Schirmer Test Mean Change From Baseline | -0.5 length in millimeters | Standard Error 0.4 |