CompletedNCT04735393Updated Nov 26, 2025Results posted

A Multi-Center, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Clinical Trial Evaluating the Safety of Reproxalap Ophthalmic Solution in Subjects With Dry Eye Disease

A Phase 3 interventional study of Reproxalap Ophthalmic Solution (0.25%) and Placebo Comparator in Dry Eye Disease, sponsored by Aldeyra Therapeutics, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-26.

Sponsored by Aldeyra Therapeutics, Inc. · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 757
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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

Conditions studied

Dry Eye Disease

Browse trials for

Dry Eye Syndromes 1,286

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts 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

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.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 757 participants (actual)

Study arms

Experimental
Reproxalap (0.25%) for six weeks
Reproxalap four times daily (QID) for four weeks followed by two times daily (BID) for two weeks
Drug: Reproxalap Ophthalmic Solution (0.25%)
Placebo comparator
Vehicle for six weeks
Vehicle QID for four weeks followed by BID for two weeks
Drug: Placebo Comparator
Experimental
Reproxalap (0.25%) for 12 months
Reproxalap (0.25%) QID for four weeks followed by BID for 11 months
Drug: Reproxalap Ophthalmic Solution (0.25%)
Placebo comparator
Vehicle for 12 months
Vehicle QID for four weeks followed by BID for 11 months
Drug: Placebo Comparator

Interventions

DrugReproxalap Ophthalmic Solution (0.25%)
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).
DrugReproxalap Ophthalmic Solution (0.25%)
Reproxalap Ophthalmic Solution (0.25%) administered for one year (QID for four weeks then BID for 11 months).
DrugPlacebo Comparator
Vehicle Ophthalmic Solution administered for one year (QID for four weeks then BID for 11 months).

What researchers measure

Primary outcomes

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)
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)
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)
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)
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)
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)
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)
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)

Results

Posted Nov 26, 2025

Participant flow

Participant flow — Overall Study
Milestone	Reproxalap	Vehicle
Started	504	253
As treated	501	250
Completed	273	161
Not completed	231	92
Withdrew: Lost to follow-up	46	24
Withdrew: Physician decision	2	1
Withdrew: Not detailed	1	2
Withdrew: Withdrawal by subject	71	28
Withdrew: Adverse event	56	7
Withdrew: Protocol violation	6	1
Withdrew: Trial terminated by sponsor	49	29

Outcome measures

PrimaryTreatment-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)
Reported as:: Count of participants · Participants

Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease
Participants	Reproxalap	Vehicle
Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease	0	0

PrimaryTE-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)
Reported as:: Count of participants · Participants

TE-SAEs of Increase in Intraocular Pressure
Participants	Reproxalap	Vehicle
TE-SAEs of Increase in Intraocular Pressure	0	0

PrimaryTE-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)
Reported as:: Count of participants · Participants

TE-SAEs of the Cornea
Participants	Reproxalap	Vehicle
TE-SAEs of the Cornea	0	0

PrimaryTE-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)
Reported as:: Count of participants · Participants

TE-SAEs of the Retina
Participants	Reproxalap	Vehicle
TE-SAEs of the Retina	0	0

Post-hocChange 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)
Reported as:: Least squares mean · LogMAR

Change From Baseline in Visual Acuity
LogMAR	Reproxalap	Vehicle
Change From Baseline in Visual Acuity	-0.030 ± 0.0035	-0.016 ± 0.0046

PrimaryTE-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)
Reported as:: Count of participants · Participants

TE-SAEs of Visual Acuity Decrease
Participants	Reproxalap	Vehicle
TE-SAEs of Visual Acuity Decrease	0	0

PrimaryTE-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)
Reported as:: Count of participants · Participants

TE-SAEs of Increase in Intraocular Pressure
Participants	Reproxalap	Vehicle
TE-SAEs of Increase in Intraocular Pressure	0	0

PrimaryTE-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)
Reported as:: Count of participants · Participants

TE-SAEs of the Cornea
Participants	Reproxalap	Vehicle
TE-SAEs of the Cornea	0	0

PrimaryTE-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)
Reported as:: Count of participants · Participants

TE-SAEs of the Retina
Participants	Reproxalap	Vehicle
TE-SAEs of the Retina	0	0

Adverse events

Collected over Safety assessment period (6 weeks or 12 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Reproxalap (6-week)	0/503 (0%)	0/503 (0%)	205/503 (40.8%)
Vehicle (6-week)	0/251 (0%)	0/251 (0%)	8/251 (3.2%)
Reproxalap (12-month)	0/299 (0%)	3/299 (1%)	127/299 (42.5%)
Vehicle (12-month)	2/148 (1.4%)	5/148 (3.4%)	3/148 (2%)

Most frequent serious events

Most frequent serious events
Event	Reproxalap (6-week)	Vehicle (6-week)	Reproxalap (12-month)	Vehicle (12-month)
AppendicitisInfections and infestations	0/503	0/251	0/299	1/148
COVID-19 InfectionInfections and infestations	0/503	0/251	0/299	1/148
Unknown cause of deathGeneral disorders	0/503	0/251	0/299	1/148
Premature ventricular contractionsCardiac disorders	0/503	0/251	0/299	1/148
Unstable AnginaCardiac disorders	0/503	0/251	0/299	1/148
Worsening coronary artery diseaseCardiac disorders	0/503	0/251	0/299	1/148
Right tonsil squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/503	0/251	0/299	1/148
Worsening of chronic back painMusculoskeletal and connective tissue disorders	0/503	0/251	1/299	0/148
Kidney infectionInfections and infestations	0/503	0/251	1/299	0/148
Supraventricular TachycardiaCardiac disorders	0/503	0/251	1/299	0/148

Most frequent other events

Most frequent other events
Event	Reproxalap (6-week)	Vehicle (6-week)	Reproxalap (12-month)	Vehicle (12-month)
General disorders and administration site conditionsGeneral disorders	205/503	8/251	127/299	3/148

Baseline characteristics

6-week safety population

Age, Categorical
Age, Categorical(Participants)	Reproxalap (6-week)	Vehicle (6-week)	Total
<=18 years	0	0	0
Between 18 and 65 years	336	165	501
>=65 years	167	86	253

Age, Continuous
Age, Continuous(years)	Reproxalap (6-week)	Vehicle (6-week)	Total
Mean	55.7 ± 15.8	56.9 ± 15.8	56.0 ± 15.75

Sex: Female, Male
Sex: Female, Male(Participants)	Reproxalap (6-week)	Vehicle (6-week)	Total
Female	356	176	532
Male	147	75	222

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Reproxalap (6-week)	Vehicle (6-week)	Total
Hispanic or Latino	154	75	229
Not Hispanic or Latino	349	176	525
Unknown or Not Reported	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Reproxalap (6-week)	Vehicle (6-week)	Total
American Indian or Alaska Native	28	15	43
Asian	68	42	110
Black or African American	54	26	80
Native Hawaiian or Other Pacific Islander	1	0	1
White	343	162	505
Other	1	2	3
Multiple	8	4	12

Study locations

1 site

Andover Eye Associates
Andover, Massachusetts 01810, United States

References and documents

Publications

Radcliffe NM, Sheppard J, Simmons B, Owen D, Nguyen A, Cavanagh B, Brady TC. Phase 3 Randomized Clinical Trial Evaluating the Safety of Reproxalap in Patients With Dry Eye Disease. Ophthalmol Ther. 2026 May;15(5):1807-1821. doi: 10.1007/s40123-026-01379-0. Epub 2026 Apr 11. PubMed 41964731 ↗

Study documents

Protocol and statistical analysis plan · Aug 16, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT04735393
Lead sponsor: Aldeyra Therapeutics, Inc.
Responsible party: Sponsor
First posted: Feb 3, 2021
Start date: Jan 26, 2021
Primary completion: Oct 11, 2022
Completion: Oct 11, 2022
Results posted: Nov 26, 2025
Last update: Nov 26, 2025

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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