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

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

Study Overview

• Status: Terminated
• Conditions: Dry Eye
• Intervention / Treatment: Drug: Sustained Release Dexamethasone, 0.4 mg; Other: E-Caprolactone-L-Lactide copolymer (PCL) punctal plug

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shanna M VanCourt, BS; Phone Number: 410-502-4026; Email: singrod1@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute, Johns Hopkins School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)	Drug: Sustained Release Dexamethasone, 0.4 mg; dexamethasone 0.4mg lacrimal insert; Other Names: Dextenza
Sham Comparator: Control Arm; 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; 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); Other Names: EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG

What is the study measuring?

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. 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. Maximum possible conjunctival staining score (the punctate epithelial erosions grade on the temporal and nasal sides) 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, and minimum OSS will be 0. Higher corneal, conjunctival, and staining scores represent worse outcomes. 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	(1)eye dryness, (2)eye discomfort, or (3)eye fatigue will be measured using visual analogue scale (0 to 100). The difference between the average bothersome symptom in the treated arm versus the average most bothersome symptom in the sham arm will be compared statistically. Higher VAS scores indicate worse eye dryness, discomfort, or fatigue.	28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving 2 Severity Grade Improvement in Corneal Staining	Corneal staining responder analysis. Responder is defined as two full severity grade improvement in corneal staining. The percentage of subjects achieving two severity grades improvement in corneal staining (responders) in the treated arm versus sham arm will be compared statistically.	42 days
Percentage of Subjects Achieving Improvement in Their Most Bothersome Symptom	Symptom responder analysis. Responder is defined as 30% or more improvement in the most bothersome symptom (VAS score is decreased by 30 points or more). 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Intraocular Pressure Increase	Intraocular Pressure (IOP) measurement obtained using applanation tonometry	At day 30 and day 42

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Esen Akpek, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Actual): March 3, 2023
• Study Completion (Actual): March 3, 2023

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: dexamethasone; dry eye; ocular surface disease; ophthalmic steroids; keratoconjuntivitis sicca
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: IRB00246348

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Aggregated information only will be shared with sponsor

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No