Dry Eye
Conditions
Brief summary
A Multi-Center Randomized, Double-Masked, Parallel Design, Vehicle-Controlled Phase 2 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
1. 18 years of age (either gender and any race); 2. Reported history of dry eye for at least 6 months prior to Visit 1; 3. Reported history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1.
Exclusion criteria
1. 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; 2. Diagnosis of an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1; 3. Contact lens use within 7 days of Visit 1 or anticipate using contact lenses during the trial; 4. Eye drop use within 2 hours of Visit 1; 5. Previous laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months; 6. Cyclosporine 0.05% or 0.09% or lifitegrast 5.0% ophthalmic solution use within 90 days of Visit 1; 7. Be receiving systemic corticosteroid therapy (not including inhaled corticosteroids) within 14 days of Visit 1 or anticipate such therapy throughout the study period; 8. Planned ocular and/or lid surgeries over the study period or any ocular surgery within 6 months of Visit 1; 9. 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 Via Digital Photography 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 measure for change from baseline included baseline, treatment group, and nominal time point as fixed effects. |
| Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | 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 subject-reported ocular dryness score VAS (0 = no discomfort, 100 = maximal discomfort), 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 measure for change from baseline included baseline, treatment group, and nominal time point as fixed effects. |
| 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 intervention was administered bilaterally. The least squares mean (standard error) was derived from mixed model repeated measure for change from baseline included baseline and treatment group as fixed effects. |
Countries
United States
Participant flow
Pre-assignment details
One hundred fifty-eight subjects were randomized in the trial.
Participants by arm
| Arm | Count |
|---|---|
| Reproxalap (0.25%) Reproxalap ophthalmic solution administered 7 times over two consecutive days | 80 |
| Vehicle Vehicle ophthalmic solution administered 7 times over two consecutive days | 78 |
| Total | 158 |
Baseline characteristics
| Characteristic | Reproxalap (0.25%) | Vehicle | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 37 Participants | 30 Participants | 67 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 48 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 11 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 67 Participants | 142 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Left Eye) Black | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Left Eye) Blue | 18 Participants | 18 Participants | 36 Participants |
| Iris Color (Left Eye) Brown | 44 Participants | 31 Participants | 75 Participants |
| Iris Color (Left Eye) Gray | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Left Eye) Green | 11 Participants | 12 Participants | 23 Participants |
| Iris Color (Left Eye) Hazel | 7 Participants | 17 Participants | 24 Participants |
| Iris Color (Left Eye) Other | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Right Eye) Black | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Right Eye) Blue | 18 Participants | 18 Participants | 36 Participants |
| Iris Color (Right Eye) Brown | 44 Participants | 31 Participants | 75 Participants |
| Iris Color (Right Eye) Gray | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Right Eye) Green | 11 Participants | 12 Participants | 23 Participants |
| Iris Color (Right Eye) Hazel | 7 Participants | 17 Participants | 24 Participants |
| Iris Color (Right Eye) Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 67 Participants | 68 Participants | 135 Participants |
| Region of Enrollment United States | 80 participants | 78 participants | 158 participants |
| Sex: Female, Male Female | 59 Participants | 55 Participants | 114 Participants |
| Sex: Female, Male Male | 21 Participants | 23 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 77 |
| other Total, other adverse events | 52 / 79 | 3 / 77 |
| serious Total, serious adverse events | 0 / 79 | 0 / 77 |
Outcome results
Primary
Conjunctival Redness Assessed Via Digital Photography 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 measure for change from baseline included baseline, 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 (0.25%) | Conjunctival Redness Assessed Via Digital Photography Over 90 Minutes in the Dry Eye Chamber | 0.066 units on a scale | Standard Error 0.0346 |
| Vehicle | Conjunctival Redness Assessed Via Digital Photography Over 90 Minutes in the Dry Eye Chamber | 0.183 units on a scale | Standard Error 0.0353 |
Primary
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 intervention was administered bilaterally. The least squares mean (standard error) was derived from mixed model repeated measure 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 (0.25%) | Schirmer Test Change From Baseline After the First Dose on Day 1 | 4.2 length in millimeters | Standard Error 0.83 |
| Vehicle | Schirmer Test Change From Baseline After the First Dose on Day 1 | 2.1 length in millimeters | Standard Error 0.84 |
Primary
Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS))
Change from baseline comparison of reproxalap to vehicle for subject-reported ocular dryness score VAS (0 = no discomfort, 100 = maximal discomfort), 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 measure for change from baseline included baseline, 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 (0.25%) | Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | -5.7 units on a scale | Standard Error 2.44 |
| Vehicle | Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | -3.8 units on a scale | Standard Error 2.51 |