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

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)

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).

Study Overview

• Status: Completed
• Conditions: Dry Eye
• Intervention / Treatment: Drug: AXR-159; Drug: Vehicle

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Andover, Massachusetts, United States, 01810
      • Andover Eye Associates
    • Raynham, Massachusetts, United States, 02767
      • Andover Eye Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care, P.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AxeroVision, Inc.
• Collaborators: ORA, Inc.
• Investigators: Principal Investigator: Gail L Torkildson, MD, Andover Eye Associates, 138 Haverhill Street, Andover MA 01810; Principal Investigator: Kenneth R Kenyon, MD, Andover Eye Associates, 675 Paramount Drive, Raynham, MA 02767; Principal Investigator: Eugene McLaurin, MD, Total Eye Care, P.A., 6060 Primacy Parkway, Memphis, TN 38119

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2018
• Primary Completion (Actual): December 28, 2018
• Study Completion (Actual): January 9, 2019

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Other Study ID Numbers: AXR201701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No