Trial Outcomes & Findings for The RENEW Trial: A Multi-Center, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Adaptive Phase 3 Clinical Trial to Assess the Safety and Efficacy of Subjects With Dry Eye Disease (NCT NCT03879863)

Last Updated: 2025-01-23

Results Overview

Change from baseline comparison of reproxalap to vehicle for subject-reported ocular dryness score VAS (0 = no discomfort - 100 = maximal discomfort), where a higher score means a worse outcome. The intervention was administered bilaterally. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline calculated using baseline score, treatment arm, visit, and the interaction of treatment arm and visit as fixed effects.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

422 participants

Primary outcome timeframe

The efficacy assessment period (Day 1 through 85) was assessed at Weeks 1, 2, 4, 6, 8, 10, and 12; baseline was Day 1.

Results posted on

2025-01-23

Participant Flow

Participant milestones

Participant milestones
Measure	Reproxalap Ophthalmic Solution (0.25%) QID Reproxalap ophthalmic solution administered QID (four times daily) for twelve weeks	Vehicle Ophthalmic Solution QID Vehicle ophthalmic solution administered QID (four times daily) for twelve weeks	Reproxalap Ophthalmic Solution (0.25%) QID to BID Reproxalap ophthalmic solution administered QID (four times daily) for four weeks, followed by BID (two times daily) administration for eight weeks	Vehicle Ophthalmic Solution QID to BID Vehicle ophthalmic solution administered QID (four times daily) for four weeks, followed by BID (two times daily) administration for eight weeks
Overall Study STARTED	105	106	105	106
Overall Study COMPLETED	98	102	94	104
Overall Study NOT COMPLETED	7	4	11	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The RENEW Trial: A Multi-Center, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Adaptive Phase 3 Clinical Trial to Assess the Safety and Efficacy of Subjects With Dry Eye Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Reproxalap Ophthalmic Solution (0.25%) QID n=105 Participants Reproxalap ophthalmic solution administered QID for twelve weeks	Vehicle Ophthalmic Solution QID n=106 Participants Vehicle ophthalmic solution administered QID for twelve weeks	Reproxalap Ophthalmic Solution (0.25%) QID to BID n=105 Participants Reproxalap ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks	Vehicle Ophthalmic Solution QID to BID n=106 Participants Vehicle ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks	Total n=422 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=99 Participants	50 Participants n=107 Participants	43 Participants n=206 Participants	49 Participants n=7 Participants	182 Participants n=31 Participants
Age, Categorical >=65 years	65 Participants n=99 Participants	56 Participants n=107 Participants	62 Participants n=206 Participants	57 Participants n=7 Participants	240 Participants n=31 Participants
Sex: Female, Male Female	78 Participants n=99 Participants	77 Participants n=107 Participants	75 Participants n=206 Participants	82 Participants n=7 Participants	312 Participants n=31 Participants
Sex: Female, Male Male	27 Participants n=99 Participants	29 Participants n=107 Participants	30 Participants n=206 Participants	24 Participants n=7 Participants	110 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=99 Participants	8 Participants n=107 Participants	8 Participants n=206 Participants	8 Participants n=7 Participants	33 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=99 Participants	98 Participants n=107 Participants	97 Participants n=206 Participants	98 Participants n=7 Participants	389 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=99 Participants	3 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	3 Participants n=31 Participants
Race/Ethnicity, Customized Asian	4 Participants n=99 Participants	4 Participants n=107 Participants	8 Participants n=206 Participants	9 Participants n=7 Participants	25 Participants n=31 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=99 Participants	7 Participants n=107 Participants	6 Participants n=206 Participants	7 Participants n=7 Participants	27 Participants n=31 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants
Race/Ethnicity, Customized White	92 Participants n=99 Participants	91 Participants n=107 Participants	90 Participants n=206 Participants	90 Participants n=7 Participants	363 Participants n=31 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants
Race/Ethnicity, Customized Other	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	2 Participants n=31 Participants
Region of Enrollment United States	105 Participants n=99 Participants	106 Participants n=107 Participants	105 Participants n=206 Participants	106 Participants n=7 Participants	422 Participants n=31 Participants
Iris Color (Right Eye) Black	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	3 Participants n=31 Participants
Iris Color (Right Eye) Blue	32 Participants n=99 Participants	38 Participants n=107 Participants	34 Participants n=206 Participants	26 Participants n=7 Participants	130 Participants n=31 Participants
Iris Color (Right Eye) Brown	41 Participants n=99 Participants	37 Participants n=107 Participants	44 Participants n=206 Participants	53 Participants n=7 Participants	175 Participants n=31 Participants
Iris Color (Right Eye) Hazel	18 Participants n=99 Participants	20 Participants n=107 Participants	13 Participants n=206 Participants	12 Participants n=7 Participants	63 Participants n=31 Participants
Iris Color (Right Eye) Gray	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants	3 Participants n=31 Participants
Iris Color (Right Eye) Green	12 Participants n=99 Participants	10 Participants n=107 Participants	14 Participants n=206 Participants	12 Participants n=7 Participants	48 Participants n=31 Participants
Iris Color (Right Eye) Other	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Iris Color (Left Eye) Black	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	3 Participants n=31 Participants
Iris Color (Left Eye) Blue	32 Participants n=99 Participants	38 Participants n=107 Participants	34 Participants n=206 Participants	26 Participants n=7 Participants	130 Participants n=31 Participants
Iris Color (Left Eye) Brown	41 Participants n=99 Participants	37 Participants n=107 Participants	44 Participants n=206 Participants	53 Participants n=7 Participants	175 Participants n=31 Participants
Iris Color (Left Eye) Hazel	18 Participants n=99 Participants	20 Participants n=107 Participants	13 Participants n=206 Participants	12 Participants n=7 Participants	63 Participants n=31 Participants
Iris Color (Left Eye) Gray	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants	3 Participants n=31 Participants
Iris Color (Left Eye) Green	12 Participants n=99 Participants	10 Participants n=107 Participants	14 Participants n=206 Participants	12 Participants n=7 Participants	48 Participants n=31 Participants
Iris Color (Left Eye) Other	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants

PRIMARY outcome

Timeframe: The efficacy assessment period (Day 1 through 85) was assessed at Weeks 1, 2, 4, 6, 8, 10, and 12; baseline was Day 1.

Population: Intent-to-treat Ocular Dryness Population with observed data only

Outcome measures

Outcome measures
Measure	Reproxalap Ophthalmic Solution (0.25%) QID n=85 Participants Reproxalap ophthalmic solution administered QID for twelve weeks	Vehicle Ophthalmic Solution QID n=86 Participants Vehicle ophthalmic solution administered QID for twelve weeks	Reproxalap Ophthalmic Solution (0.25%) QID to BID n=85 Participants Reproxalap ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks	Vehicle Ophthalmic Solution QID to BID n=85 Participants Vehicle ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks
Subject-reported Ocular Dryness Score (0 - 100 Visual Analogue Scale (VAS))	-11.5 score on a scale Standard Error 2.44	-15.0 score on a scale Standard Error 2.39	-17.8 score on a scale Standard Error 2.20	-6.8 score on a scale Standard Error 2.12

PRIMARY outcome

Timeframe: The efficacy assessment period (Day 15 through 85) was assessed at Weeks 2, 4, 6, 8, 10, and 12; baseline was Day 1.

Population: Intent-to-Treat Fluorescein Nasal Score Population with observed data only

Change from baseline comparison of reproxalap to vehicle for fluorescein staining of the nasal region (0 = none - 4 = severe), where a higher score means a worse outcome. The intervention was administered bilaterally. The least squares mean (standard error) was derived from mixed model repeated measures for change from baseline calculated using baseline fluorescein nasal score, treatment arm, visit, and the interaction of treatment arm and visit as fixed effects.

Outcome measures

Outcome measures
Measure	Reproxalap Ophthalmic Solution (0.25%) QID n=91 Participants Reproxalap ophthalmic solution administered QID for twelve weeks	Vehicle Ophthalmic Solution QID n=90 Participants Vehicle ophthalmic solution administered QID for twelve weeks	Reproxalap Ophthalmic Solution (0.25%) QID to BID n=89 Participants Reproxalap ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks	Vehicle Ophthalmic Solution QID to BID n=90 Participants Vehicle ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks
Fluorescein Nasal Region Score (0 = None - 4 = Severe)	-0.47 units on a scale Standard Error 0.060	-0.46 units on a scale Standard Error 0.058	-0.53 units on a scale Standard Error 0.056	-0.46 units on a scale Standard Error 0.053

Adverse Events

Reproxalap Ophthalmic Solution (0.25%) QID

Serious events: 3 serious events

Other events: 88 other events

Deaths: 0 deaths

Vehicle Ophthalmic Solution QID

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Reproxalap Ophthalmic Solution (0.25%) QID to BID

Serious events: 1 serious events

Other events: 94 other events

Deaths: 0 deaths

Vehicle Ophthalmic Solution QID to BID

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Reproxalap Ophthalmic Solution (0.25%) QID n=105 participants at risk Reproxalap ophthalmic solution administered QID for twelve weeks	Vehicle Ophthalmic Solution QID n=106 participants at risk Vehicle ophthalmic solution administered QID for twelve weeks	Reproxalap Ophthalmic Solution (0.25%) QID to BID n=105 participants at risk Reproxalap ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks	Vehicle Ophthalmic Solution QID to BID n=106 participants at risk Vehicle ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.94% 1/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Renal and urinary disorders Acute kidney injury	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.95% 1/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Infections and infestations Gastroenteritis salmonella	0.95% 1/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.94% 1/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Nervous system disorders Cerebrovascular accident	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.94% 1/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.95% 1/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.94% 1/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Infections and infestations Osteomyelitis	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.94% 1/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.
Infections and infestations Pneumonia	0.95% 1/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.00% 0/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.

Other adverse events

Other adverse events
Measure	Reproxalap Ophthalmic Solution (0.25%) QID n=105 participants at risk Reproxalap ophthalmic solution administered QID for twelve weeks	Vehicle Ophthalmic Solution QID n=106 participants at risk Vehicle ophthalmic solution administered QID for twelve weeks	Reproxalap Ophthalmic Solution (0.25%) QID to BID n=105 participants at risk Reproxalap ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks	Vehicle Ophthalmic Solution QID to BID n=106 participants at risk Vehicle ophthalmic solution administered QID for four weeks, followed by BID administration for eight weeks
General disorders General disorders and administration site conditions	83.8% 88/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	6.6% 7/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	89.5% 94/105 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.	0.94% 1/106 • The period of time over which adverse events were collected for each subject in the clinical trial was approximately three months.

Additional Information

Sr. Director, Clinical Operations

Aldeyra Therapeutics, Inc.

Phone: 781-257-3063

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place