A Study to Evaluate AXR-159 Ophthalmic Solution in Patients With Dry Eye Disease

Study Overview
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Brief Summary
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Protocol AXR201701 is a multicenter, double-masked, vehicle-controlled, randomized, parallel group study carried out in 2 stages (Stage 1: AXR-159 Ophthalmic Solution (30 mg/mL or 50 mg/mL); Stage 2: AXR-159 Ophthalmic Solution (3 mg/mL, 30 mg/mL or 50 mg/mL) in approximately 430 patients diagnosed with dry eye disease (DED).

Detailed Description
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Protocol AXR201701 is designed with 2 stages. For both Stages 1 and 2, patients with signs and symptoms of DED will be randomly assigned to receive either a single concentration of AXR-159 Ophthalmic Solution or AXR-159 Ophthalmic Solution Vehicle. A screening visit will be followed by a baseline period where subjects will dose with AXR-159 Ophthalmic Solution Vehicle for 14 days. At the end of the baseline period patients who still exhibit signs and symptoms of DED will be enrolled into a 3-month double-masked treatment period.

Official Title
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A Multicenter, Vehicle-controlled, Randomized Study to Evaluate the Safety, Tolerability, Systemic Pharmacokinetics, and Pharmacodynamics of AXR-159 Ophthalmic Solution 3 mg/mL, 30 mg/mL, and 50 mg/mL in Patients With Dry Eye Disease (DED)

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: AXR-159
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years of age or older at screening visit Best-corrected visual acuity (BCVA) of 20/100 or better (Snellen equivalent), using the logarithm of the minimum angle of resolution (LogMAR) in each eye Reported history of dry eye for at least 6 months Corneal fluorescein staining score ≥ 2 Eye dryness score ≥ 40 Total Ocular Surface Disease Index (OSDI) score > 18 Exclusion Criteria: Uncontrolled ocular disease (except for dry eye disease/keratoconjunctivitis sicca) or uncontrolled systemic disease Patient has glaucoma, ocular hypertension, on IOP-lowering medications or have previously undergone any glaucoma laser or surgical procedure. Corneal abnormality or disorder that impacts normal spreading of the tear film (keratoconus, pterygia, scarring) or compromised corneal integrity BCVA worse than 20/100 in either eye Current use of punctal plugs, anticipated insertion during the study, or a history of punctal cautery in either eye Keratoconjunctivitis sicca secondary to destruction of conjunctival goblet cells Patients with clinically significant inflammation of the lid margin such as anterior blepharitis or ocular rosacea Recent (within the past 3 months) ocular surgery, trauma or herpes Use of contact lenses in either eye within one month prior to the screening visit or anticipated use during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AXR-159 Ophthalmic Solution 3 mg/mL<br>AXR-159 Low Dose | Drug: AXR-159<br>* AXR-159 Ophthalmic Solution<br>|
| Experimental: AXR-159 Ophthalmic Solution 30 mg/mL<br>AXR-159 Mid Dose | Drug: AXR-159<br>* AXR-159 Ophthalmic Solution<br>|
| Experimental: AXR-159 Ophthalmic Solution 50 mg/mL<br>AXR-159 High Dose | Drug: AXR-159<br>* AXR-159 Ophthalmic Solution<br>|
| Placebo Comparator: AXR-159 Ophthalmic Solution Vehicle<br>Control Group | Drug: Vehicle<br>* AXR-159 Ophthalmic Solution Vehicle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inferior Corneal Staining Score | Change from Baseline in Ora Calibra® Corneal and Conjunctival Staining Scale with a range from 0 to 4 (0=None, 1=Trace, 2=Mild, 3=Moderate, 4=Severe) in the study eye. Higher negative scores mean a better outcome. | Month 3 | 
| Eye Dryness | Change from baseline in Eye Dryness score on a subject level across both eyes. Using the visual analogue scale (VAS) subjects rated eye dryness by placing a vertical mark on the horizontal line to indicate the level of discomfort with a range of 0 to 100. 0% corresponds to no dryness (no discomfort) and 100% corresponds to maximal dryness indicating maximal discomfort. A greater negative change from baseline score means a better outcome. | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Ocular Surface and Disease Index (OSDI) © for Dry Eye | Change from baseline in OSDI © score on a subject level. The 12-question OSDI © is assessed on a total scale from 0 to 100, where higher scores represent greater disability. A greater negative change from baseline indicates a better outcome. | Month 3 | 
| Schirmer's Test | Change from baseline in Schirmer's Test score in the study eye. Unanesthetized Schirmer's Test measures the length of the moistened area of a test strip, placed in the lower temporal lid margin of each eye, in mm following a 5-minute exposure period. Greater positive numbers indicate a better outcome. | Month 3 | 
| Tear Film Break-up Time (TBUT) | Change from baseline in the study eye with a greater positive increase indicating a better outcome. Following the instillation of a sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye and several blinks over 30 seconds, the examiner monitored the integrity of the tear film with the aid of a slit lamp, noting the time it takes to form micelles from the time that the eye is opened. TBUT was measured in seconds using a stopwatch and a digital image recording system for the right eye followed by the left eye. Values reported are for the study eye. | Month 3 | 
| Conjunctival Redness Score | Change from baseline of Ora Calibra® Conjunctival Redness Scale for Dry Eye. Scores range from 0 to 4 with 0=None, 1=Trace, 2=Mild, 3=Moderate, 4=Severe; with higher numbers indicating more conjunctival redness. Greater negative numbers indicate a better outcome. Values reported are for the study eye. | Month 3 | 
| Total Lissamine Green Conjunctival Staining | Change from baseline of Oxford Grading Scale measuring staining within a range from 0-5 (0=None, 1=Trace, 2=Mild, 3=Moderate, 4=Severe, 5=Confluent) for each panel (temporal and nasal) and 0-10 as the sum of both panel scores for the total exposed inter-palpebral conjunctiva. Larger negative numbers indicate reduced staining and a better outcome. Values reported are for the study eye. | Month 3 |