Trial Outcomes & Findings for 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 (NCT NCT04735393)
NCT ID: NCT04735393
Last Updated: 2025-11-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
757 participants
Primary outcome timeframe
Safety assessment period (six weeks)
Results posted on
2025-11-26
Participant Flow
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.
Participant milestones
| Measure |
Reproxalap
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
Overall Study
STARTED
|
504
|
253
|
|
Overall Study
As Treated
|
501
|
250
|
|
Overall Study
COMPLETED
|
273
|
161
|
|
Overall Study
NOT COMPLETED
|
231
|
92
|
Reasons for withdrawal
| Measure |
Reproxalap
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
46
|
24
|
|
Overall Study
Physician Decision
|
2
|
1
|
|
Overall Study
Not Detailed
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
71
|
28
|
|
Overall Study
Adverse Event
|
56
|
7
|
|
Overall Study
Protocol Violation
|
6
|
1
|
|
Overall Study
Trial terminated by Sponsor
|
49
|
29
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Reproxalap (6-week)
n=503 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for two weeks.
|
Vehicle (6-week)
n=251 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for two weeks.
|
Total
n=754 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=492 Participants
|
0 Participants
n=492 Participants
|
0 Participants
n=984 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
336 Participants
n=492 Participants
|
165 Participants
n=492 Participants
|
501 Participants
n=984 Participants
|
|
Age, Categorical
>=65 years
|
167 Participants
n=492 Participants
|
86 Participants
n=492 Participants
|
253 Participants
n=984 Participants
|
|
Age, Continuous
|
55.7 years
STANDARD_DEVIATION 15.8 • n=492 Participants
|
56.9 years
STANDARD_DEVIATION 15.8 • n=492 Participants
|
56.0 years
STANDARD_DEVIATION 15.75 • n=984 Participants
|
|
Sex: Female, Male
Female
|
356 Participants
n=492 Participants
|
176 Participants
n=492 Participants
|
532 Participants
n=984 Participants
|
|
Sex: Female, Male
Male
|
147 Participants
n=492 Participants
|
75 Participants
n=492 Participants
|
222 Participants
n=984 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
154 Participants
n=492 Participants
|
75 Participants
n=492 Participants
|
229 Participants
n=984 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
349 Participants
n=492 Participants
|
176 Participants
n=492 Participants
|
525 Participants
n=984 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=492 Participants
|
0 Participants
n=492 Participants
|
0 Participants
n=984 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
28 Participants
n=492 Participants
|
15 Participants
n=492 Participants
|
43 Participants
n=984 Participants
|
|
Race/Ethnicity, Customized
Asian
|
68 Participants
n=492 Participants
|
42 Participants
n=492 Participants
|
110 Participants
n=984 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
54 Participants
n=492 Participants
|
26 Participants
n=492 Participants
|
80 Participants
n=984 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=492 Participants
|
0 Participants
n=492 Participants
|
1 Participants
n=984 Participants
|
|
Race/Ethnicity, Customized
White
|
343 Participants
n=492 Participants
|
162 Participants
n=492 Participants
|
505 Participants
n=984 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=492 Participants
|
2 Participants
n=492 Participants
|
3 Participants
n=984 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
8 Participants
n=492 Participants
|
4 Participants
n=492 Participants
|
12 Participants
n=984 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (six weeks)Population: 6-week safety population
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.
Outcome measures
| Measure |
Reproxalap
n=503 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=251 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
Treatment-Emergent Serious Adverse Events (TE-SAEs) of Visual Acuity Decrease
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (six weeks)Population: 6-week safety population
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.
Outcome measures
| Measure |
Reproxalap
n=503 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=251 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
TE-SAEs of Increase in Intraocular Pressure
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (six weeks)Population: 6-week safety population
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.
Outcome measures
| Measure |
Reproxalap
n=503 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=251 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
TE-SAEs of the Cornea
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (six weeks)Population: 6-week safety population
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.
Outcome measures
| Measure |
Reproxalap
n=503 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=251 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
TE-SAEs of the Retina
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (12 months)Population: 12-month safety population
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.
Outcome measures
| Measure |
Reproxalap
n=299 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=148 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
TE-SAEs of Visual Acuity Decrease
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (12 months)Population: 12-month safety population
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.
Outcome measures
| Measure |
Reproxalap
n=299 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=148 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
TE-SAEs of Increase in Intraocular Pressure
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (12 months)Population: 12-month safety population
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.
Outcome measures
| Measure |
Reproxalap
n=299 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=148 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
TE-SAEs of the Cornea
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Safety assessment period (12-months)Population: 12-month safety population
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.
Outcome measures
| Measure |
Reproxalap
n=299 Participants
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=148 Participants
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
TE-SAEs of the Retina
|
0 Participants
|
0 Participants
|
POST_HOC outcome
Timeframe: Efficacy assessment period (12 months)Population: 12-month primary safety analysis population
Overall change from baseline in visual acuity logMAR score. Visual acuity values were averaged across both eyes for each participant.
Outcome measures
| Measure |
Reproxalap
n=592 eyes
Reproxalap was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
Vehicle
n=290 eyes
Vehicle was administered four times daily for four weeks followed by two times daily for either two weeks or 11 months.
|
|---|---|---|
|
Change From Baseline in Visual Acuity
|
-0.030 LogMAR
Standard Error 0.0035
|
-0.016 LogMAR
Standard Error 0.0046
|
Adverse Events
Reproxalap (6-week)
Serious events: 0 serious events
Other events: 205 other events
Deaths: 0 deaths
Vehicle (6-week)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Reproxalap (12-month)
Serious events: 3 serious events
Other events: 127 other events
Deaths: 0 deaths
Vehicle (12-month)
Serious events: 5 serious events
Other events: 3 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Reproxalap (6-week)
n=503 participants at risk
Reproxalap was administered four times daily for four weeks followed by two times daily for two weeks.
|
Vehicle (6-week)
n=251 participants at risk
Vehicle was administered four times daily for four weeks followed by two times daily for two weeks.
|
Reproxalap (12-month)
n=299 participants at risk
Reproxalap was administered four times daily for four weeks followed by two times daily for 11 months.
|
Vehicle (12-month)
n=148 participants at risk
Vehicle was administered four times daily for four weeks followed by two times daily for 11 months.
|
|---|---|---|---|---|
|
Infections and infestations
Appendicitis
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/299 • Safety assessment period (6 weeks or 12 months)
|
0.68%
1/148 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
|
Infections and infestations
COVID-19 Infection
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/299 • Safety assessment period (6 weeks or 12 months)
|
0.68%
1/148 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
|
General disorders
Unknown cause of death
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/299 • Safety assessment period (6 weeks or 12 months)
|
0.68%
1/148 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
|
Cardiac disorders
Premature ventricular contractions
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/299 • Safety assessment period (6 weeks or 12 months)
|
0.68%
1/148 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
|
Cardiac disorders
Unstable Angina
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/299 • Safety assessment period (6 weeks or 12 months)
|
0.68%
1/148 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
|
Cardiac disorders
Worsening coronary artery disease
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/299 • Safety assessment period (6 weeks or 12 months)
|
0.68%
1/148 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Right tonsil squamous cell carcinoma
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/299 • Safety assessment period (6 weeks or 12 months)
|
0.68%
1/148 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
|
Musculoskeletal and connective tissue disorders
Worsening of chronic back pain
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.33%
1/299 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/148 • Safety assessment period (6 weeks or 12 months)
|
|
Infections and infestations
Kidney infection
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.33%
1/299 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/148 • Safety assessment period (6 weeks or 12 months)
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/503 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/251 • Safety assessment period (6 weeks or 12 months)
|
0.33%
1/299 • Number of events 1 • Safety assessment period (6 weeks or 12 months)
|
0.00%
0/148 • Safety assessment period (6 weeks or 12 months)
|
Other adverse events
| Measure |
Reproxalap (6-week)
n=503 participants at risk
Reproxalap was administered four times daily for four weeks followed by two times daily for two weeks.
|
Vehicle (6-week)
n=251 participants at risk
Vehicle was administered four times daily for four weeks followed by two times daily for two weeks.
|
Reproxalap (12-month)
n=299 participants at risk
Reproxalap was administered four times daily for four weeks followed by two times daily for 11 months.
|
Vehicle (12-month)
n=148 participants at risk
Vehicle was administered four times daily for four weeks followed by two times daily for 11 months.
|
|---|---|---|---|---|
|
General disorders
General disorders and administration site conditions
|
40.8%
205/503 • Number of events 205 • Safety assessment period (6 weeks or 12 months)
|
3.2%
8/251 • Number of events 8 • Safety assessment period (6 weeks or 12 months)
|
42.5%
127/299 • Number of events 127 • Safety assessment period (6 weeks or 12 months)
|
2.0%
3/148 • Number of events 3 • Safety assessment period (6 weeks or 12 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place