Dry Eye, Dry Eye Syndromes
Conditions
Keywords
reproxalap, ADX-102, Tranquility
Brief summary
The TRANQUILITY Trial: Multi-Center Randomized, Double-Masked, Parallel Design, Vehicle-Controlled Phase 2/3 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 over two consecutive days (Day one pre-dry eye chamber and Day two dry eye chamber assessment).
Vehicle Ophthalmic Solution administered over two consecutive days (Day one pre-dry eye chamber and Day two dry eye chamber assessment).
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 |
|---|---|---|
| Conjunctival Redness Assessed Over 90 Minutes in the Dry Eye Chamber | The efficacy assessment period was assessed during the 90-minute dry eye chamber at Day 2; baseline was Pre-Dose #1 at Day 1. | Change from baseline comparison of reproxalap to vehicle for conjunctival redness on a 0 to 4 scale ( 0 = normal, 4 = prominent), where a high score means a worse outcome. The intervention was administered bilaterally. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included baseline, site, treatment group, and nominal time point as fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Schirmer Test Change From Baseline After the First Dose on Day 1 | The efficacy assessment period was before and after the final dose on Day 1; baseline was Pre-Dose #1 at Day 1. | Change from baseline comparison of reproxalap to vehicle for Schirmer test on a millimeter line (0 = none, 35 = maximum), where a shorter length indicates a worse outcome. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included baseline and treatment group as fixed effects. |
Countries
United States
Participant flow
Pre-assignment details
There were 331 randomized subjects, of which 329 were unique (23 in the initial exploratory cohort and 306 in the main cohort). Two subjects in the main cohort were randomized twice by accident and two subjects were randomized but not dosed, making the safety population 327 subjects. The Safety population is presented in the Participant Flow, Baseline Characteristics, and Adverse Events. Efficacy analysis was conducted on subjects in the main cohort (306 subjects, intent-to-treat population).
Participants by arm
| Arm | Count |
|---|---|
| Reproxalap Ophthalmic Solution (0.25%) Reproxalap ophthalmic solution administered seven times over two consecutive days | 164 |
| Vehicle Vehicle ophthalmic solution administered seven times over two consecutive days | 163 |
| Total | 327 |
Baseline characteristics
| Characteristic | Reproxalap Ophthalmic Solution (0.25%) | Vehicle | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 77 Participants | 81 Participants | 158 Participants |
| Age, Categorical Between 18 and 65 years | 87 Participants | 82 Participants | 169 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 12 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 154 Participants | 151 Participants | 305 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Left Eye) Black | 1 Participants | 4 Participants | 5 Participants |
| Iris Color (Left Eye) Blue | 48 Participants | 44 Participants | 92 Participants |
| Iris Color (Left Eye) Brown | 75 Participants | 73 Participants | 148 Participants |
| Iris Color (Left Eye) Gray | 2 Participants | 1 Participants | 3 Participants |
| Iris Color (Left Eye) Green | 14 Participants | 23 Participants | 37 Participants |
| Iris Color (Left Eye) Hazel | 24 Participants | 18 Participants | 42 Participants |
| Iris Color (Left Eye) Other | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Right Eye) Black | 1 Participants | 4 Participants | 5 Participants |
| Iris Color (Right Eye) Blue | 48 Participants | 44 Participants | 92 Participants |
| Iris Color (Right Eye) Brown | 75 Participants | 73 Participants | 148 Participants |
| Iris Color (Right Eye) Gray | 2 Participants | 1 Participants | 3 Participants |
| Iris Color (Right Eye) Green | 14 Participants | 23 Participants | 37 Participants |
| Iris Color (Right Eye) Hazel | 24 Participants | 18 Participants | 42 Participants |
| Iris Color (Right Eye) Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Black or African American | 18 Participants | 22 Participants | 40 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 132 Participants | 127 Participants | 259 Participants |
| Region of Enrollment United States | 164 participants | 163 participants | 327 participants |
| Sex: Female, Male Female | 118 Participants | 120 Participants | 238 Participants |
| Sex: Female, Male Male | 46 Participants | 43 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 164 | 0 / 163 |
| other Total, other adverse events | 118 / 164 | 2 / 163 |
| serious Total, serious adverse events | 0 / 164 | 0 / 163 |
Outcome results
Primary
Conjunctival Redness Assessed Over 90 Minutes in the Dry Eye Chamber
Change from baseline comparison of reproxalap to vehicle for conjunctival redness on a 0 to 4 scale ( 0 = normal, 4 = prominent), where a high score means a worse outcome. The intervention was administered bilaterally. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included baseline, site, treatment group, and nominal time point as fixed effects.
Time frame: The efficacy assessment period was assessed during the 90-minute dry eye chamber at Day 2; baseline was Pre-Dose #1 at Day 1.
Population: Intent-to-treat population with observed data only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap Ophthalmic Solution (0.25%) | Conjunctival Redness Assessed Over 90 Minutes in the Dry Eye Chamber | 0.185 units on a scale | Standard Error 0.0233 |
| Vehicle | Conjunctival Redness Assessed Over 90 Minutes in the Dry Eye Chamber | 0.156 units on a scale | Standard Error 0.0229 |
Secondary
Schirmer Test Change From Baseline After the First Dose on Day 1
Change from baseline comparison of reproxalap to vehicle for Schirmer test on a millimeter line (0 = none, 35 = maximum), where a shorter length indicates a worse outcome. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included baseline and treatment group as fixed effects.
Time frame: The efficacy assessment period was before and after the final dose on Day 1; baseline was Pre-Dose #1 at Day 1.
Population: Intent-to-treat population with observed data only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap Ophthalmic Solution (0.25%) | Schirmer Test Change From Baseline After the First Dose on Day 1 | 5.9 millimeters | Standard Error 0.53 |
| Vehicle | Schirmer Test Change From Baseline After the First Dose on Day 1 | 3.5 millimeters | Standard Error 0.53 |
Post Hoc
Conjunctival Redness Assessed Over 90 Minutes in the Dry Eye Chamber Using Computer Automated Grading
Change from baseline comparison of reproxalap to vehicle for conjunctival redness on a 0 to 255 scale ( 0 = none, 255 = maximum), where a high score means a worse outcome. The intervention was administered bilaterally. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included baseline, site, treatment group, and nominal time point as fixed effects.
Time frame: The efficacy assessment period was assessed during the 90-minute dry eye chamber at Day 2; baseline was Pre-Dose #1 at Day 1.
Population: Intent-to-treat population with observed data only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap Ophthalmic Solution (0.25%) | Conjunctival Redness Assessed Over 90 Minutes in the Dry Eye Chamber Using Computer Automated Grading | 0.309 units on a scale | Standard Error 0.216 |
| Vehicle | Conjunctival Redness Assessed Over 90 Minutes in the Dry Eye Chamber Using Computer Automated Grading | 0.962 units on a scale | Standard Error 0.2121 |
Post Hoc
Number of Subject Eyes That Are Schirmer Test Responders (Eyes 10 Millimeters or More Increase From Baseline)
The number of subject eyes that are schirmer test responders (eyes with 10 millimeters or more increase from baseline) using a millimeter line (0 = none, 35 = maximum), where a shorter length indicates a worse outcome.
Time frame: Efficacy was assessed after a single dose on Day 1; baseline was assessed approximately two weeks before dosing.
Population: Intent-to-treat population with observed data only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reproxalap Ophthalmic Solution (0.25%) | Number of Subject Eyes That Are Schirmer Test Responders (Eyes 10 Millimeters or More Increase From Baseline) | 125 eyes |
| Vehicle | Number of Subject Eyes That Are Schirmer Test Responders (Eyes 10 Millimeters or More Increase From Baseline) | 64 eyes |
95% CI: [1.67, 4.14]