Dry Eye DiseasePhase 3NCT04735393

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 study testing Reproxalap Ophthalmic Solution (0.25%) in people with Dry Eye Disease, run by Aldeyra Therapeutics, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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 Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Dry Eye Disease
What is being tested?: Reproxalap Ophthalmic Solution (0.25%)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 757 participants
Where: 1 siteUnited States
Study dates: 26 Jan 2021to 11 Oct 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Andover Eye Associates
Andover, Massachusetts, 01810

Other trials in United States

About this study

Official title: 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

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: Dry Eye Disease
Being tested: Reproxalap Ophthalmic Solution (0.25%), Placebo Comparator
Medical subject headings: Dry Eye Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Reproxalap Ophthalmic Solution (0.25%)Drug
Reproxalap Ophthalmic Solution (0.25%) administered for six weeks (QID for four weeks then BID for two weeks).
Placebo ComparatorDrug
Vehicle Ophthalmic Solution administered for six weeks (QID for four weeks then BID for two weeks).
Reproxalap Ophthalmic Solution (0.25%)Drug
Reproxalap Ophthalmic Solution (0.25%) administered for one year (QID for four weeks then BID for 11 months).
Placebo ComparatorDrug
Vehicle Ophthalmic Solution administered for one year (QID for four weeks then BID for 11 months).

Study groups in NCT04735393
Study group	Role	What they receive
Reproxalap (0.25%) for six weeks	Experimental	Reproxalap four times daily (QID) for four weeks followed by two times daily (BID) for two weeks Receives: Drug: Reproxalap Ophthalmic Solution (0.25%)
Vehicle for six weeks	Placebo comparator	Vehicle QID for four weeks followed by BID for two weeks Receives: Drug: Placebo Comparator
Reproxalap (0.25%) for 12 months	Experimental	Reproxalap (0.25%) QID for four weeks followed by BID for 11 months Receives: Drug: Reproxalap Ophthalmic Solution (0.25%)
Vehicle for 12 months	Placebo comparator	Vehicle QID for four weeks followed by BID for 11 months Receives: Drug: Placebo Comparator

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Safety assessment period (12-months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Jan 202111 Oct 2022

First posted3 Feb 2021
Study start26 Jan 2021
Primary completion11 Oct 2022
Study completion11 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Dry Eye DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 757 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04735393
Sponsor's protocol ID: ADX-102-DED-021
Status last verified: Jan 2025
First submitted: 25 Jan 2021
Last updated: 26 Nov 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Efficacy and Safety of BUFY01 Versus SVS20 in the Treatment of Dry Eye Disease
Dry Eye Disease
Not yet recruitingPhase 1
A Clinical Study to Evaluate the Safety and Effectiveness of MSCohi-O Lens in the Treatment of Immune-related Ocular Surface Diseases.
Keratitis, Autoimmunity
Recruiting
Treating Contact Lens Discomfort With Cyclosporine 0.1% Ophthalmic Solution
Dry Eye Disease (DED), Contact Lens Discomfort (CLD)
Not yet recruitingPhase 4
Evaporative Dry Eye
Dry Eye, Evaporative Dry Eye
Active, not recruitingPhase 2/3
A Clinical Study Evaluating Licaminlimab for Dry Eye Disease
Dry Eye Disease (DED)

All Dry Eye Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04735393
Acronym / sponsor ID: ADX-102-DED-021
Conditions: Dry Eye Disease
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 757 participants (actual)
Lead sponsor: Aldeyra Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 26 Jan 2021 (actual)
Primary completion: 11 Oct 2022 (actual)
Study completion: 11 Oct 2022 (actual)
First posted: 3 Feb 2021 (actual)
Results: Posted 26 Nov 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (8 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Reproxalap Ophthalmic Solution (0.25%)Reproxalap Ophthalmic Solution (0.25%) administered for six weeks (QID for four weeks then BID for two weeks).	Drug	Reproxalap (0.25%) for six weeks
Placebo ComparatorVehicle Ophthalmic Solution administered for six weeks (QID for four weeks then BID for two weeks).	Drug	Vehicle for six weeks
Reproxalap Ophthalmic Solution (0.25%)Reproxalap Ophthalmic Solution (0.25%) administered for one year (QID for four weeks then BID for 11 months).	Drug	Reproxalap (0.25%) for 12 months
Placebo ComparatorVehicle Ophthalmic Solution administered for one year (QID for four weeks then BID for 11 months).	Drug	Vehicle for 12 months

Primary outcome

Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
TE-SAEs of Increase in Intraocular Pressure
Time frame: Safety assessment period (12 months)
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.
TE-SAEs of the Cornea
Time frame: Safety assessment period (12 months)
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.
TE-SAEs of the Retina
Time frame: Safety assessment period (12-months)
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.

Results and safety

Results posted to the registry on 26 Nov 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Reproxalap	504	273
Vehicle	253	161

Primary outcome: Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease

Time frame: Safety assessment period (six weeks). Count of participants. Unit: Participants

Measure	Reproxalap n = 503	Vehicle n = 251
Value	0	0

Population analysed: 6-week safety population

Primary outcome: TE-SAEs of Increase in Intraocular Pressure

Time frame: Safety assessment period (six weeks). Count of participants. Unit: Participants

Measure	Reproxalap n = 503	Vehicle n = 251
Value	0	0

Population analysed: 6-week safety population

Primary outcome: TE-SAEs of the Cornea

Time frame: Safety assessment period (six weeks). Count of participants. Unit: Participants

Measure	Reproxalap n = 503	Vehicle n = 251
Value	0	0

Population analysed: 6-week safety population

Primary outcome: TE-SAEs of the Retina

Time frame: Safety assessment period (six weeks). Count of participants. Unit: Participants

Measure	Reproxalap n = 503	Vehicle n = 251
Value	0	0

Population analysed: 6-week safety population

Adverse events

Time frame: Safety assessment period (6 weeks or 12 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Reproxalap (6-week)	0 of 503 (0%)	205 of 503 (40.8%)	0 of 503
Vehicle (6-week)	0 of 251 (0%)	8 of 251 (3.2%)	0 of 251
Reproxalap (12-month)	3 of 299 (1%)	127 of 299 (42.5%)	0 of 299
Vehicle (12-month)	5 of 148 (3.4%)	3 of 148 (2%)	2 of 148

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41964731Radcliffe 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.
Individual participant dataSharing planned: No

Related trials for Dry Eye Disease

Recruiting
Efficacy and Safety of BUFY01 Versus SVS20 in the Treatment of Dry Eye Disease
Dry Eye Disease
Not yet recruitingPhase 1
A Clinical Study to Evaluate the Safety and Effectiveness of MSCohi-O Lens in the Treatment of Immune-related Ocular Surface Diseases.
Keratitis, Autoimmunity
Recruiting
Treating Contact Lens Discomfort With Cyclosporine 0.1% Ophthalmic Solution
Dry Eye Disease (DED), Contact Lens Discomfort (CLD)
Not yet recruitingPhase 4
Evaporative Dry Eye
Dry Eye, Evaporative Dry Eye
Active, not recruitingPhase 2/3
A Clinical Study Evaluating Licaminlimab for Dry Eye Disease
Dry Eye Disease (DED)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Reproxalap Ophthalmic Solution (0.25%) in people with Dry Eye Disease, run by Aldeyra Therapeutics, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease (time frame: Safety assessment period (six weeks)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04735393, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025; AzTrials last refreshed its copy on 30 Oct 2026.