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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
01

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

02

Conditions studied

  • Dry Eye Disease

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03

In context

Dry Eye Syndromes

1,366 studies on the registry are indexed under Dry Eye Syndromes; 207 are open to participants now.

This study's enrollment of 757 is above the median of 60 across 1,129 interventional studies indexed under Dry Eye Syndromes.

Browse Dry Eye Syndromes studies →

Lead sponsor

Aldeyra Therapeutics, Inc. is the lead sponsor of 35 studies on the registry; 1 is open to participants now.

Of its 29 completed or terminated interventional studies of FDA-regulated products, 25 (86%) have results posted.

Browse Aldeyra Therapeutics, Inc. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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:

  • 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.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

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).

06

What researchers measure

Primary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

07

Results

Posted Nov 26, 2025

Participant flow

Participant flow — Overall Study
MilestoneReproxalapVehicle
Started504253
As treated501250
Completed273161
Not completed23192
Withdrew: Lost to follow-up4624
Withdrew: Physician decision21
Withdrew: Not detailed12
Withdrew: Withdrawal by subject7128
Withdrew: Adverse event567
Withdrew: Protocol violation61
Withdrew: Trial terminated by sponsor4929

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
ParticipantsReproxalapVehicle
Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease00
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
ParticipantsReproxalapVehicle
TE-SAEs of Increase in Intraocular Pressure00
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
ParticipantsReproxalapVehicle
TE-SAEs of the Cornea00
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
ParticipantsReproxalapVehicle
TE-SAEs of the Retina00
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
LogMARReproxalapVehicle
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
ParticipantsReproxalapVehicle
TE-SAEs of Visual Acuity Decrease00
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
ParticipantsReproxalapVehicle
TE-SAEs of Increase in Intraocular Pressure00
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
ParticipantsReproxalapVehicle
TE-SAEs of the Cornea00
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
ParticipantsReproxalapVehicle
TE-SAEs of the Retina00

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
GroupDeathsSeriousOther
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
EventReproxalap (6-week)Vehicle (6-week)Reproxalap (12-month)Vehicle (12-month)
AppendicitisInfections and infestations0/5030/2510/2991/148
COVID-19 InfectionInfections and infestations0/5030/2510/2991/148
Unknown cause of deathGeneral disorders0/5030/2510/2991/148
Premature ventricular contractionsCardiac disorders0/5030/2510/2991/148
Unstable AnginaCardiac disorders0/5030/2510/2991/148
Worsening coronary artery diseaseCardiac disorders0/5030/2510/2991/148
Right tonsil squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/5030/2510/2991/148
Worsening of chronic back painMusculoskeletal and connective tissue disorders0/5030/2511/2990/148
Kidney infectionInfections and infestations0/5030/2511/2990/148
Supraventricular TachycardiaCardiac disorders0/5030/2511/2990/148
Most frequent other events
Most frequent other events
EventReproxalap (6-week)Vehicle (6-week)Reproxalap (12-month)Vehicle (12-month)
General disorders and administration site conditionsGeneral disorders205/5038/251127/2993/148

Baseline characteristics

6-week safety population

Age, Categorical
Age, Categorical(Participants)Reproxalap (6-week)Vehicle (6-week)Total
<=18 years000
Between 18 and 65 years336165501
>=65 years16786253
Age, Continuous
Age, Continuous(years)Reproxalap (6-week)Vehicle (6-week)Total
Mean55.7 ± 15.856.9 ± 15.856.0 ± 15.75
Sex: Female, Male
Sex: Female, Male(Participants)Reproxalap (6-week)Vehicle (6-week)Total
Female356176532
Male14775222
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Reproxalap (6-week)Vehicle (6-week)Total
Hispanic or Latino15475229
Not Hispanic or Latino349176525
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Reproxalap (6-week)Vehicle (6-week)Total
American Indian or Alaska Native281543
Asian6842110
Black or African American542680
Native Hawaiian or Other Pacific Islander101
White343162505
Other123
Multiple8412
08

Study locations

1 site
  • Andover Eye Associates
    Andover, Massachusetts 01810, United States
09

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

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jan 2021 to primary completion in Oct 2022, 20 months.

Results were first posted in Nov 2025, 3 years 1 month after primary completion. A results delay was requested in May 2023.

Of 81 industry-sponsored phase 3 interventional studies under Dry Eye Syndromes, half reached primary completion within 9 months of starting (the median), counting those still running; a quarter within 6 and three quarters within 15. This study's 20 months is above that.

Counting every sponsor, half of 96 studies reached it within 10 months; a quarter within 7 and three quarters within 15.

How these figures are worked out, and which studies are left out of them.

Registered
Jan 25, 2021
First posted
Feb 3, 2021
StartActual
Jan 26, 2021
Primary completionActual
Oct 11, 2022
CompletionActual
Oct 11, 2022
Results delay requested
May 31, 2023
Results first posted
Nov 26, 2025
Last update
Nov 26, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 26, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

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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