Conjunctivitis, Allergic
Conditions
Keywords
reproxalap, ADX-102, allergic conjunctivitis
Brief summary
An Exploratory Clinical Trial Evaluating Reproxalap Ophthalmic Solutions (0.25% and 0.5%) in Subjects with Seasonal Allergic Conjunctivitis Using the Environmental Exposure Chamber (EEC)
Interventions
Reproxalap Ophthalmic Solution (0.25%) dosed twice.
Reproxalap Ophthalmic Solution (0.5%) dosed twice.
DRUGVehicle Ophthalmic Solution
Vehicle Ophthalmic Solution dosed twice.
Sponsors
Aldeyra Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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
* be at least 18 years of age of either gender and any race * have at least a two-year history of moderate-to-severe ragweed-induced allergic conjunctivitis based on principal investigator's judgement * have a positive skin prick test to ragweed pollen within the past year of screening
Exclusion criteria
* known contraindication or hypersensitivities to any components of the investigational product medication or components * history of uveitis, blepharitis, dry eye syndrome, herpes simplex keratitis, or herpes zoster keratitis; * presence of any ocular infection (bacterial, viral, or fungal) or active ocular inflammation (e.g., follicular conjunctivitis, allergic conjunctivitis) within 14 days prior to screening * presence of any chronic ocular degenerative condition or ocular inflammation that, in the opinion of the investigator, is likely to worsen over the course of the clinical trial; * presence of any chronic ocular degenerative condition or ocular inflammation that, in the opinion of the investigator, is likely to worsen over the course of the clinical trial * diagnosis of moderate-to-severe pinguecula or pterygium (particularly if it results in chronic erythema), Stevens-Johnson Syndrome, ocular cicatricial pemphigoid, mucous membrane pemphigoid, significant conjunctival scarring, chemical burn, herpetic or neurotrophic keratitis, Cryopyrin Associated Periodic Syndrome (CAPS), or keratoconus * woman of childbearing potential who is pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject-Reported Ocular Itching Score | Efficacy was assessed from 0 to 212 minutes in the allergen chamber. | Change from baseline comparison of reproxalap to vehicle for subject-reported ocular itching score from 0 to 212 minutes in the allergen chamber using a 0 -100 millimeter visual analogue scale (0 = none, 100 = severe) was assessed. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included itching score as a dependent variable, treatment, period, and interaction of treatment and period as fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject-Reported Ocular Tearing Score | Efficacy was assessed from 0 to 212 minutes in the allergen chamber. | Change from baseline comparison of reproxalap to vehicle for subject-reported ocular tearing score from 0 to 212 minutes in the allergen chamber using a 4-point scale (0 = none, 3 = severe) was assessed. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included itching score as a dependent variable, treatment, period, and interaction of treatment and period as fixed effects. |
| Investigator-Assessed Conjunctival Redness Score | Efficacy was assessed from 0 to 210 minutes in the allergen chamber. | Change from baseline comparison of reproxalap to vehicle for investigator-assessed conjunctival redness from 0 to 210 minutes in the allergen chamber using a 9-point scale with half unit increments (0 = normal, 4 = prominent) was assessed. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included itching score as a dependent variable, treatment, period, and interaction of treatment and period as fixed effects. |
Countries
Canada
Participant flow
Pre-assignment details
Seventy subjects were randomized in a three-way crossover design trial.
Participants by arm
| Arm | Count |
|---|---|
| Reproxalap (0.25%), Then Reproxalap (0.5%), Then Vehicle Reproxalap (0.25%) was administered once 5 minutes before and 90 minutes after allergen chamber entry, then there was a 14-day washout (Washout #1), then Reproxalap (0.5%) was administered once 5 minutes before and 90 minutes after allergen chamber entry, then there was a 14-day (Washout #2), then Vehicle was administered once 5 minutes before and 90 minutes after allergen chamber entry. | 22 |
| Reproxalap (0.5%), Then Vehicle, Then Reproxalap (0.25%) Reproxalap (0.5%) was administered once 5 minutes before and 90 minutes after allergen chamber entry, then there was a 14-day washout (Washout #1), then Vehicle) was administered once 5 minutes before and 90 minutes after allergen chamber entry, then there was a 14-day (Washout #2), then Reproxalap (0.25%) was administered once 5 minutes before and 90 minutes after allergen chamber entry. | 25 |
| Vehicle, Then Reproxalap (0.25%), Then Reproxalap (0.5%) Vehicle was administered once 5 minutes before and 90 minutes after allergen chamber entry, then there was a 14-day washout (Washout #1), then Reproxalap (0.25%) was administered once 5 minutes before and 90 minutes after allergen chamber entry, then there was a 14-day (Washout #2), then Reproxalap (0.5%) was administered once 5 minutes before and 90 minutes after allergen chamber entry. | 23 |
| Total | 70 |
Baseline characteristics
| Characteristic | Reproxalap (0.25%), Then Reproxalap (0.5%), Then Vehicle | Reproxalap (0.5%), Then Vehicle, Then Reproxalap (0.25%) | Vehicle, Then Reproxalap (0.25%), Then Reproxalap (0.5%) | Total |
|---|---|---|---|---|
| Age, Customized Mean | 45.50 years | 48.84 years | 46.17 years | 46.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 23 Participants | 18 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 5 Participants | 5 Participants | 14 Participants |
| Race/Ethnicity, Customized Native Hawaiian / Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other - Mixed | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 17 Participants | 13 Participants | 45 Participants |
| Region of Enrollment Canada | 22 participants | 25 participants | 23 participants | 70 participants |
| Sex: Female, Male Female | 12 Participants | 16 Participants | 14 Participants | 42 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 9 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 69 | 0 / 67 |
| other Total, other adverse events | 49 / 67 | 56 / 69 | 5 / 67 |
| serious Total, serious adverse events | 0 / 67 | 0 / 69 | 0 / 67 |
Outcome results
Primary
Subject-Reported Ocular Itching Score
Change from baseline comparison of reproxalap to vehicle for subject-reported ocular itching score from 0 to 212 minutes in the allergen chamber using a 0 -100 millimeter visual analogue scale (0 = none, 100 = severe) was assessed. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included itching score as a dependent variable, treatment, period, and interaction of treatment and period as fixed effects.
Time frame: Efficacy was assessed from 0 to 212 minutes in the allergen chamber.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap (0.25%) | Subject-Reported Ocular Itching Score | 16.410 units on a scale | Standard Error 1.6195 |
| Reproxalap (0.5%) | Subject-Reported Ocular Itching Score | 16.964 units on a scale | Standard Error 1.615 |
| Vehicle | Subject-Reported Ocular Itching Score | 22.310 units on a scale | Standard Error 1.6188 |
Secondary
Investigator-Assessed Conjunctival Redness Score
Change from baseline comparison of reproxalap to vehicle for investigator-assessed conjunctival redness from 0 to 210 minutes in the allergen chamber using a 9-point scale with half unit increments (0 = normal, 4 = prominent) was assessed. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included itching score as a dependent variable, treatment, period, and interaction of treatment and period as fixed effects.
Time frame: Efficacy was assessed from 0 to 210 minutes in the allergen chamber.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap (0.25%) | Investigator-Assessed Conjunctival Redness Score | 0.5004 units on a scale | Standard Error 0.0458 |
| Reproxalap (0.5%) | Investigator-Assessed Conjunctival Redness Score | 0.5462 units on a scale | Standard Error 0.0457 |
| Vehicle | Investigator-Assessed Conjunctival Redness Score | 0.6497 units on a scale | Standard Error 0.0458 |
Secondary
Subject-Reported Ocular Tearing Score
Change from baseline comparison of reproxalap to vehicle for subject-reported ocular tearing score from 0 to 212 minutes in the allergen chamber using a 4-point scale (0 = none, 3 = severe) was assessed. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline included itching score as a dependent variable, treatment, period, and interaction of treatment and period as fixed effects.
Time frame: Efficacy was assessed from 0 to 212 minutes in the allergen chamber.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap (0.25%) | Subject-Reported Ocular Tearing Score | 0.8777 units on a scale | Standard Error 0.0615 |
| Reproxalap (0.5%) | Subject-Reported Ocular Tearing Score | 0.8915 units on a scale | Standard Error 0.0613 |
| Vehicle | Subject-Reported Ocular Tearing Score | 1.0507 units on a scale | Standard Error 0.0614 |