Dry Eye Disease
Conditions
Brief summary
A Multi-Center, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Clinical Trial Evaluating the Safety of 0.25% Reproxalap Ophthalmic Solution in Subjects with Dry Eye Disease
Interventions
Reproxalap Ophthalmic Solution (0.25%) administered for six weeks (QID for four weeks then BID for two weeks).
DRUGPlacebo Comparator
Vehicle Ophthalmic Solution administered for six weeks (QID for four weeks then BID for two weeks).
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; * 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 within 90 days of Visit 1; * 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 |
|---|---|---|
| Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease | Safety assessment period (six weeks) | The proportion of 6-week safety population subjects that experience at least one visual acuity TE-SAE decrease (defined as an increase of 0.22 or greater in logMAR score) categorized as probably or definitely related to test article. |
| TE-SAEs of Increase in Intraocular Pressure | Safety assessment period (six weeks) | The proportion of 6-week safety population subjects that experience at least one intraocular pressure TE-SAE (increase from baseline of greater than or equal to 10 mmHg and intraocular pressure of greater than 25 mmHg) categorized as probably or definitely related to test article. |
| TE-SAEs of the Cornea | Safety assessment period (six weeks) | The proportion of 6-week safety population subjects that experience at least one cornea-related TE-SAE (detected via slit-lamp examination) categorized as probably or definitely related to test article. |
| TE-SAEs of the Retina | Safety assessment period (six weeks) | The proportion 6-week safety population subjects that experience at least one retinal TE-SAE (detected via fundoscopy) categorized as probably or definitely related to test article. |
| TE-SAEs of Visual Acuity Decrease | Safety assessment period (12 months) | The proportion of 12-month safety population subjects that experience at least one visual acuity TE-SAE (defined as an increase of 0.22 or greater in logMAR score) categorized as probably or definitely related to test article. |
Countries
United States
Participant flow
Pre-assignment details
The 6-week safety population are subjects randomized and treated in either the 6-week or 12-month cohort. The 12-month safety population are subjects randomized and treated in the 12-month cohort. There was a total of 757 randomized subjects in the trial. There were 6 subjects randomized and not dosed.
Participants by arm
| Arm | Count |
|---|---|
| Reproxalap (6-week) Reproxalap was administered four times daily for four weeks followed by two times daily for two weeks. | 503 |
| Vehicle (6-week) Vehicle was administered four times daily for four weeks followed by two times daily for two weeks. | 251 |
| Total | 754 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 56 | 7 |
| Overall Study | Lost to Follow-up | 46 | 24 |
| Overall Study | Not Detailed | 1 | 2 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Protocol Violation | 6 | 1 |
| Overall Study | Trial terminated by Sponsor | 49 | 29 |
| Overall Study | Withdrawal by Subject | 71 | 28 |
Baseline characteristics
| Characteristic | Reproxalap (6-week) | Vehicle (6-week) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 167 Participants | 86 Participants | 253 Participants |
| Age, Categorical Between 18 and 65 years | 336 Participants | 165 Participants | 501 Participants |
| Age, Continuous | 55.7 years STANDARD_DEVIATION 15.8 | 56.9 years STANDARD_DEVIATION 15.8 | 56.0 years STANDARD_DEVIATION 15.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 154 Participants | 75 Participants | 229 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 349 Participants | 176 Participants | 525 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 28 Participants | 15 Participants | 43 Participants |
| Race/Ethnicity, Customized Asian | 68 Participants | 42 Participants | 110 Participants |
| Race/Ethnicity, Customized Black or African American | 54 Participants | 26 Participants | 80 Participants |
| Race/Ethnicity, Customized Multiple | 8 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 343 Participants | 162 Participants | 505 Participants |
| Sex: Female, Male Female | 356 Participants | 176 Participants | 532 Participants |
| Sex: Female, Male Male | 147 Participants | 75 Participants | 222 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 / 503 | 0 / 251 | 0 / 299 | 2 / 148 |
| other Total, other adverse events | 205 / 503 | 8 / 251 | 127 / 299 | 3 / 148 |
| serious Total, serious adverse events | 0 / 503 | 0 / 251 | 3 / 299 | 5 / 148 |
Outcome results
Primary
TE-SAEs of Increase in Intraocular Pressure
The proportion of 6-week safety population subjects that experience at least one intraocular pressure TE-SAE (increase from baseline of greater than or equal to 10 mmHg and intraocular pressure of greater than 25 mmHg) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (six weeks)
Population: 6-week safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | TE-SAEs of Increase in Intraocular Pressure | 0 Participants |
| Vehicle | TE-SAEs of Increase in Intraocular Pressure | 0 Participants |
Primary
TE-SAEs of Increase in Intraocular Pressure
The proportion of 12-month safety population subjects that experience at least one intraocular pressure TE-SAE (increase from baseline of greater than or equal to 10 mmHg and intraocular pressure of greater than 25 mmHg) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (12 months)
Population: 12-month safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | TE-SAEs of Increase in Intraocular Pressure | 0 Participants |
| Vehicle | TE-SAEs of Increase in Intraocular Pressure | 0 Participants |
Primary
TE-SAEs of the Cornea
The proportion of 6-week safety population subjects that experience at least one cornea-related TE-SAE (detected via slit-lamp examination) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (six weeks)
Population: 6-week safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | TE-SAEs of the Cornea | 0 Participants |
| Vehicle | TE-SAEs of the Cornea | 0 Participants |
Primary
TE-SAEs of the Cornea
The proportion of 12-month safety population subjects that experience at least one cornea-related TE-SAE (detected via slit-lamp examination) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (12 months)
Population: 12-month safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | TE-SAEs of the Cornea | 0 Participants |
| Vehicle | TE-SAEs of the Cornea | 0 Participants |
Primary
TE-SAEs of the Retina
The proportion 6-week safety population subjects that experience at least one retinal TE-SAE (detected via fundoscopy) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (six weeks)
Population: 6-week safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | TE-SAEs of the Retina | 0 Participants |
| Vehicle | TE-SAEs of the Retina | 0 Participants |
Primary
TE-SAEs of the Retina
The proportion 12-month safety population subjects that experience at least one retinal TE-SAE(detected via fundoscopy) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (12-months)
Population: 12-month safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | TE-SAEs of the Retina | 0 Participants |
| Vehicle | TE-SAEs of the Retina | 0 Participants |
Primary
TE-SAEs of Visual Acuity Decrease
The proportion of 12-month safety population subjects that experience at least one visual acuity TE-SAE (defined as an increase of 0.22 or greater in logMAR score) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (12 months)
Population: 12-month safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | TE-SAEs of Visual Acuity Decrease | 0 Participants |
| Vehicle | TE-SAEs of Visual Acuity Decrease | 0 Participants |
Primary
Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease
The proportion of 6-week safety population subjects that experience at least one visual acuity TE-SAE decrease (defined as an increase of 0.22 or greater in logMAR score) categorized as probably or definitely related to test article.
Time frame: Safety assessment period (six weeks)
Population: 6-week safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reproxalap | Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease | 0 Participants |
| Vehicle | Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease | 0 Participants |
Post Hoc
Change From Baseline in Visual Acuity
Overall change from baseline in visual acuity logMAR score. Visual acuity values were averaged across both eyes for each participant.
Time frame: Efficacy assessment period (12 months)
Population: 12-month primary safety analysis population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Reproxalap | Change From Baseline in Visual Acuity | -0.030 LogMAR | Standard Error 0.0035 |
| Vehicle | Change From Baseline in Visual Acuity | -0.016 LogMAR | Standard Error 0.0046 |