Safety and Efficacy of Dexamethasone Ophthalmic Insert (Dextenza®) in the Management of Clinically Significant Dry Eye

Study Overview
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Brief Summary
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To determine efficacy and safety profile of dexamethasone 0.4mg lacrimal insert in dry eye related ocular surface inflammation.

Detailed Description
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Previous studies showed that dexamethasone and loteprednol topical drops have led to favorable results. However, the requirement of frequent instillation of drops by the patients is problematic causing discomfort and blurring of vision and requires remembering and dexterity for instillation, poor compliance is not uncommon. In addition Investigators believe that instillation of drops disturbs the homeostasis of the natural tear film due to physical and chemical trauma due to large drop volume (50 microliters) hammering on the eye surface (which can only hold 7 to 10 microliters). Particularly washing away of the mucin layer that holds all the good ingredients in the tears is harmful to the ocular surface. Therefore, dropless treatment of dry eye is desirable. Dextenza® (dexamethasone ophthalmic insert, Ocular Therapeutix Inc., Bedford, MA) is a corticosteroid intracanalicular insert approved by US-FDA in November 2018 for the treatment of post-surgical ocular inflammation and pain. It is inserted into the lower lacrimal punctum and into the canaliculus. A single insert releases a 0.4 mg dose of dexamethasone for up to 30 days following insertion. Dextenza® is resorbable and does not require removal. Investigators hypothesize that Dextenza® could mimic short-term topical steroid use in a tapering manner in patients with clinically significant dry eye and show efficacy in improving its symptoms and signs, as was previously shown with other steroid preparations. If proven, the use of Dextenza® may shift paradigms in the management of the clinically significant ocular surface disease. To test this hypothesis, investigators propose to study the effects of Dextenza® in the treatment of clinically significant dry eye.

Official Title
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Safety and Efficacy of Dexamethasone Ophthalmic Insert (Dextenza®) in the Management of Clinically Significant Dry Eye

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: Sustained Release Dexamethasone, 0.4 mg
* Other: E-Caprolactone-L-Lactide copolymer (PCL) punctal plug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A patient's study eye must meet the following criteria to be eligible for inclusion in the study: Male or Female Age 18-100 Capacity to give informed consent Ability to follow study direction and complete all study visits A previous or current diagnosis of dry eye by an eye care specialist, whereas treatment is requiring the use of a topical steroid Able to have a lacrimal plug placement into both lower puncta. If lower puncta are already plugged or cauterized/sealed, upper puncta will be used Females of childbearing potential unwilling to use reliable form(s) of birth control throughout study period Clinical diagnosis of dry eye syndrome (DES) or keratoconjunctivitis sicca (KCS), in which the following has been bilaterally documented in the ophthalmic and medical histories: i. history/diagnosis of dry eye ii. has taken or is on prescription drops (including but not limited to topical steroids, cyclosporine or lifitegrast) Presence of all of the following in both eyes at Baseline (Day 1): i. Total OSS of 3 or more with at least 2+ corneal staining (0-6) ii. Unanesthetized Schirmer level of <10 mm at 5 minutes iii. Presence of significant symptoms defined as 30mm or higher score of (1) eye dryness, or (2) eye fatigue, or (3) eye discomfort as measured using VAS, in both eyes. At the baseline visit, the most bothersome symptom (of the three) will be determined and used as the main symptom outcome measure throughout the study. Exclusion Criteria: A patient who meets any of the following criteria will be excluded from the study: Use of Contact lenses within 1 week of screening visit or during the study Any ocular surgery (including tear duct cauterization) within the 3 months Inability to place a lacrimal device into upper or lower puncta of both eyes (if upper in R eye should be upper in the left eye and vice versa) Inability to participate in the wash out period Use of topical glaucoma medications (With exception of rescue medication) Pregnancy, nursing or intention of pregnancy or nursing in the study period. Monocular patients Uncontrolled systemic disease (defined as frequent or recent change in the medication regimen) Patients who are currently on with stable doses of oral steroids, topical cyclosporine or lifitigrast, topical tacrolimus or pimecrolimus are eligible as long as there has been no change in the dose in the last 3 months Patients who are on topical steroids (With exception of rescue medication) (Patients who have used steroids recently but have been off for at least 2 weeks will be eligible.) Current enrollment in any other investigational drug or device study or participation of study within 30 days of baseline visit. Known allergy or sensitivity to any of the clinical or experimental drugs used in this study including history of steroid response.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, Double Masked, Interventional Study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) | Drug: Sustained Release Dexamethasone, 0.4 mg<br>* dexamethasone 0.4mg lacrimal insert<br>|
| Sham Comparator: Control Arm<br>Commercially available EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL) (Vera90™ - Elkridge, MD) | Other: E-Caprolactone-L-Lactide copolymer (PCL) punctal plug<br>* Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Endpoint as assessed by dry eye sign using Ocular Surface Scale (OSS) | OSS will be graded according to the Sjögren's International Collaborative Clinical Alliance (SICCA) grading system. Conjunctival staining will be evaluated 1st, using a neutral density filter over the light source after instillation of lissamine green dye. The nasal and temporal conjunctiva, within the interpalpebral fissure, will be graded separately (maximum score of 3 and minimum of 0 for each area). Corneal staining will be evaluated using the cobalt blue filter at least 2 minutes after instillation of fluorescein dye. Maximum possible fluorescein score (the punctate epithelial erosions grade + any extra points for modifiers [central staining, confluent staining, and filaments]) will be 6 and minimum of 0. The total possible maximum OSS, derived by summing the corneal and conjunctival scores, will be 12 for each eye. The difference between the average corneal staining in the treated arm versus the average corneal staining in the sham arm will be compared statistically. | 28 days | 
| Patient reported symptom | Most bothersome symptom (any one of the (1)eye dryness, (2)eye discomfort, or (3)eye fatigue will be established as the most bothersome symptom at baseline for each eye) measured using visual analogue scale (0 to 100). The difference between the average most bothersome symptom in the treated arm versus the average most bothersome symptom in the sham arm will be compared statistically. | 42 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects achieving 1 severity grade improvement in corneal staining | Corneal staining responder analysis. Responder is defined as one full severity grade improvement in corneal staining. The percentage of subjects achieving 1 severity grade improvement in corneal staining (responders) in the treated arm versus sham arm will be compared statistically. | 42 days | 
| Percentage of subjects achieving a 30% improvement in their most bothersome symptom | Symptom responder analysis. Responder is defined as 30% improvement in the most bothersome symptom. The percentage of subjects achieving a 30% improvement in their most bothersome symptom (responders) in the treated arm versus the sham arm will be compared statistically. | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ocular surface disease, dexamethasone, ophthalmic steroids, keratoconjuntivitis sicca, dry eye