Dry Eye
Conditions
Brief summary
The RENEW Trial is a Multi-Center, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Adaptive Phase 3 Clinical Trial to Assess the Safety and Efficacy of Reproxalap 0.25% Ophthalmic Solution Compared to Vehicle in Subjects with Dry Eye Disease
Interventions
DRUGReproxalap Ophthalmic Solution (0.25%) QID
Reproxalap Ophthalmic Solution (0.25%) administered QID for twelve weeks
DRUGVehicle Ophthalmic Solution QID
Vehicle Ophthalmic Solution administered QID for twelve weeks
DRUGReproxalap Ophthalmic Solution (0.25%) QID to BID
Reproxalap Ophthalmic Solution (0.25%) administered QID for four weeks, followed by BID administration for eight weeks
DRUGVehicle Ophthalmic Solution QID to BID
Vehicle Ophthalmic Solution administered QID for four weeks, followed by BID administration for eight weeks
Sponsors
Aldeyra Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be at least 18 years of age of either gender and any race; * Have a reported history of dry eye for at least 6 months prior to Visit 1; * Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1
Exclusion criteria
* Have any clinically significant slit-lamp findings at Visit 1, including active blepharitis; meibomian gland dysfunction (MGD); lid margin inflammation; or active ocular allergies that require therapeutic treatment, or, in the opinion of the investigator may interfere with the assessment of the safety or efficacy of reproxalap or vehicle; * Have or 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 12 months; * Have used ophthalmic cyclosporine or lifitegrast 5.0% ophthalmic solution within 90 days of Visit 1; * Have any planned ocular and/or lid surgeries over the study period or any ocular surgery within 6 months of Visit 1; * Have used temporary or permanent punctal plugs within 30 days prior to Visit 1 or anticipate their use during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | The efficacy assessment period (Day 1 through 85) was assessed at Weeks 1, 2, 4, 6, 8, 10, and 12; baseline was 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 higher 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 calculated using baseline score, treatment arm, visit, and the interaction of treatment arm and visit as fixed effects. |
| Fluorescein Nasal Region Score (0 = None - 4 = Severe) | The efficacy assessment period (Day 15 through 85) was assessed at Weeks 2, 4, 6, 8, 10, and 12; baseline was Day 1. | Change from baseline comparison of reproxalap to vehicle for fluorescein staining of the nasal region (0 = none - 4 = severe), where a higher 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 calculated using baseline fluorescein nasal score, treatment arm, visit, and the interaction of treatment arm and visit as fixed effects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reproxalap Ophthalmic Solution (0.25%) QID Reproxalap ophthalmic solution administered QID for twelve weeks | 105 |
| Vehicle Ophthalmic Solution QID Vehicle ophthalmic solution administered QID for twelve weeks | 106 |
| Reproxalap Ophthalmic Solution (0.25%) QID to BID Reproxalap ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks | 105 |
| Vehicle Ophthalmic Solution QID to BID Vehicle ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks | 106 |
| Total | 422 |
Baseline characteristics
| Characteristic | Reproxalap Ophthalmic Solution (0.25%) QID | Vehicle Ophthalmic Solution QID | Reproxalap Ophthalmic Solution (0.25%) QID to BID | Vehicle Ophthalmic Solution QID to BID | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 65 Participants | 56 Participants | 62 Participants | 57 Participants | 240 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 50 Participants | 43 Participants | 49 Participants | 182 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 8 Participants | 8 Participants | 8 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 98 Participants | 97 Participants | 98 Participants | 389 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Left Eye) Black | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Iris Color (Left Eye) Blue | 32 Participants | 38 Participants | 34 Participants | 26 Participants | 130 Participants |
| Iris Color (Left Eye) Brown | 41 Participants | 37 Participants | 44 Participants | 53 Participants | 175 Participants |
| Iris Color (Left Eye) Gray | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Iris Color (Left Eye) Green | 12 Participants | 10 Participants | 14 Participants | 12 Participants | 48 Participants |
| Iris Color (Left Eye) Hazel | 18 Participants | 20 Participants | 13 Participants | 12 Participants | 63 Participants |
| Iris Color (Left Eye) Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Iris Color (Right Eye) Black | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Iris Color (Right Eye) Blue | 32 Participants | 38 Participants | 34 Participants | 26 Participants | 130 Participants |
| Iris Color (Right Eye) Brown | 41 Participants | 37 Participants | 44 Participants | 53 Participants | 175 Participants |
| Iris Color (Right Eye) Gray | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Iris Color (Right Eye) Green | 12 Participants | 10 Participants | 14 Participants | 12 Participants | 48 Participants |
| Iris Color (Right Eye) Hazel | 18 Participants | 20 Participants | 13 Participants | 12 Participants | 63 Participants |
| Iris Color (Right Eye) Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 4 Participants | 8 Participants | 9 Participants | 25 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 7 Participants | 6 Participants | 7 Participants | 27 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 92 Participants | 91 Participants | 90 Participants | 90 Participants | 363 Participants |
| Region of Enrollment United States | 105 Participants | 106 Participants | 105 Participants | 106 Participants | 422 Participants |
| Sex: Female, Male Female | 78 Participants | 77 Participants | 75 Participants | 82 Participants | 312 Participants |
| Sex: Female, Male Male | 27 Participants | 29 Participants | 30 Participants | 24 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 106 | 0 / 105 | 0 / 106 |
| other Total, other adverse events | 88 / 105 | 7 / 106 | 94 / 105 | 1 / 106 |
| serious Total, serious adverse events | 3 / 105 | 3 / 106 | 1 / 105 | 2 / 106 |
Outcome results
Primary
Fluorescein Nasal Region Score (0 = None - 4 = Severe)
Change from baseline comparison of reproxalap to vehicle for fluorescein staining of the nasal region (0 = none - 4 = severe), where a higher 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 calculated using baseline fluorescein nasal score, treatment arm, visit, and the interaction of treatment arm and visit as fixed effects.
Time frame: The efficacy assessment period (Day 15 through 85) was assessed at Weeks 2, 4, 6, 8, 10, and 12; baseline was Day 1.
Population: Intent-to-Treat Fluorescein Nasal Score Population with observed data only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap Ophthalmic Solution (0.25%) QID | Fluorescein Nasal Region Score (0 = None - 4 = Severe) | -0.47 units on a scale | Standard Error 0.06 |
| Vehicle Ophthalmic Solution QID | Fluorescein Nasal Region Score (0 = None - 4 = Severe) | -0.46 units on a scale | Standard Error 0.058 |
| Reproxalap Ophthalmic Solution (0.25%) QID to BID | Fluorescein Nasal Region Score (0 = None - 4 = Severe) | -0.53 units on a scale | Standard Error 0.056 |
| Vehicle Ophthalmic Solution QID to BID | Fluorescein Nasal Region Score (0 = None - 4 = Severe) | -0.46 units on a scale | Standard Error 0.053 |
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 higher 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 calculated using baseline score, treatment arm, visit, and the interaction of treatment arm and visit as fixed effects.
Time frame: The efficacy assessment period (Day 1 through 85) was assessed at Weeks 1, 2, 4, 6, 8, 10, and 12; baseline was Day 1.
Population: Intent-to-treat Ocular Dryness Population with observed data only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap Ophthalmic Solution (0.25%) QID | Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | -11.5 score on a scale | Standard Error 2.44 |
| Vehicle Ophthalmic Solution QID | Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | -15.0 score on a scale | Standard Error 2.39 |
| Reproxalap Ophthalmic Solution (0.25%) QID to BID | Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | -17.8 score on a scale | Standard Error 2.2 |
| Vehicle Ophthalmic Solution QID to BID | Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS)) | -6.8 score on a scale | Standard Error 2.12 |