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

Study Overview
=================
Brief Summary
-----------------
The RENEW Trial is a Multi-Center, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Adaptive Phase 3 Clinical Trial to Assess the Safety and Efficacy of Reproxalap 0.25% Ophthalmic Solution Compared to Vehicle in Subjects with Dry Eye Disease

Official Title
-----------------
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 Reproxalap 0.25% Ophthalmic Solution Compared to Vehicle in Subjects With Dry Eye Disease

Conditions
-----------------
Dry Eye

Intervention / Treatment
-----------------
* Drug: Reproxalap Ophthalmic Solution (0.25%) QID
* Drug: Vehicle Ophthalmic Solution QID
* Drug: Reproxalap Ophthalmic Solution (0.25%) QID to BID
* Drug: Vehicle Ophthalmic Solution QID to BID


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be at least 18 years of age of either gender and any race; Have a reported history of dry eye for at least 6 months prior to Visit 1; Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1 Exclusion Criteria: Have any clinically significant slit-lamp findings at Visit 1, including active blepharitis; meibomian gland dysfunction (MGD); lid margin inflammation; or active ocular allergies that require therapeutic treatment, or, in the opinion of the investigator may interfere with the assessment of the safety or efficacy of reproxalap or vehicle; Have or be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal) or active ocular inflammation at Visit 1; Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study; Have used any eye drops within 2 hours of Visit 1; Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months; Have used ophthalmic cyclosporine or lifitigrast 5.0% ophthalmic solution within 90 days of Visit 1; Have any planned ocular and/or lid surgeries over the study period or any ocular surgery within 6 months of Visit 1; Have used temporary or permanent punctal plugs within 30 days prior to Visit 1 or anticipate their use during the study period

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reproxalap Ophthalmic Solution (0.25%) QID<br> | Drug: Reproxalap Ophthalmic Solution (0.25%) QID<br>* Reproxalap Ophthalmic Solution (0.25%) administered QID for twelve weeks<br>|
| Placebo Comparator: Vehicle Ophthalmic Solution QID<br> | Drug: Vehicle Ophthalmic Solution QID<br>* Vehicle Ophthalmic Solution administered QID for twelve weeks<br>|
| Experimental: Reproxalap Ophthalmic Solution (0.25%) QID to BID<br> | Drug: Reproxalap Ophthalmic Solution (0.25%) QID to BID<br>* Reproxalap Ophthalmic Solution (0.25%) administered QID for four weeks, followed by BID administration for eight weeks<br>|
| Placebo Comparator: Vehicle Ophthalmic Solution QID to BID<br> | Drug: Vehicle Ophthalmic Solution QID to BID<br>* Vehicle Ophthalmic Solution administered QID for four weeks, followed by BID administration for eight weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject-reported ocular dryness score (0 - 100 VAS) | The method of assessment is subject-reported ocular dryness score (0 - 100 VAS) | Efficacy assessment period (Week 2 through Week 12) | 
| Fluorescein nasal region score (Ora Calibra® scale) | The method of assessment is Fluorescein nasal region score (Ora Calibra® scale) | Efficacy assessment period (Week 2 through Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescein staining | The method of assessment for this outcome is the Fluorescein staining Ora Calibra® | Efficacy assessment period (Week 2 through Week 12) | 
| Unanesthetized Schirmer's Test | The method of assessment for this outcome is the Schirmer test strip. | Efficacy assessment period (Week 2 through Week 12) |