<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04498468</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00246348</org_study_id>
    <nct_id>NCT04498468</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Dexamethasone Ophthalmic Insert (Dextenza®) in the Management of Clinically Significant Dry Eye</brief_title>
  <official_title>Safety and Efficacy of Dexamethasone Ophthalmic Insert (Dextenza®) in the Management of Clinically Significant Dry Eye</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine efficacy and safety profile of dexamethasone 0.4mg lacrimal insert in dry eye&#xD;
      related ocular surface inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Previous studies showed that dexamethasone and loteprednol topical drops have led to&#xD;
      favorable results. However, the requirement of frequent instillation of drops by the patients&#xD;
      is problematic causing discomfort and blurring of vision and requires remembering and&#xD;
      dexterity for instillation, poor compliance is not uncommon. In addition Investigators&#xD;
      believe that instillation of drops disturbs the homeostasis of the natural tear film due to&#xD;
      physical and chemical trauma due to large drop volume (50 microliters) hammering on the eye&#xD;
      surface (which can only hold 7 to 10 microliters). Particularly washing away of the mucin&#xD;
      layer that holds all the &quot;good ingredients&quot; in the tears is harmful to the ocular surface.&#xD;
      Therefore, &quot;dropless&quot; treatment of dry eye is desirable.&#xD;
&#xD;
      Dextenza® (dexamethasone ophthalmic insert, Ocular Therapeutix Inc., Bedford, MA) is a&#xD;
      corticosteroid intracanalicular insert approved by US-FDA in November 2018 for the treatment&#xD;
      of post-surgical ocular inflammation and pain. It is inserted into the lower lacrimal punctum&#xD;
      and into the canaliculus. A single insert releases a 0.4 mg dose of dexamethasone for up to&#xD;
      30 days following insertion. Dextenza® is resorbable and does not require removal.&#xD;
      Investigators hypothesize that Dextenza® could mimic short-term topical steroid use in a&#xD;
      tapering manner in patients with clinically significant dry eye and show efficacy in&#xD;
      improving its symptoms and signs, as was previously shown with other steroid preparations. If&#xD;
      proven, the use of Dextenza® may shift paradigms in the management of the clinically&#xD;
      significant ocular surface disease. To test this hypothesis, investigators propose to study&#xD;
      the effects of Dextenza® in the treatment of clinically significant dry eye.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The enrollment is complete and all patients have finished their follow-up visits. We are&#xD;
    currently writing up the manuscript before study is fully complete.&#xD;
  </why_stopped>
  <start_date type="Actual">March 16, 2021</start_date>
  <completion_date type="Actual">March 3, 2023</completion_date>
  <primary_completion_date type="Actual">March 3, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Prospective, Double Masked, Interventional Study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The patient and the examining physician/outcomes accessor will be masked. The treating physician cannot be masked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy Endpoint as assessed by dry eye sign using Ocular Surface Scale (OSS)</measure>
    <time_frame>28 days</time_frame>
    <description>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.&#xD;
The difference between the average corneal staining in the treated arm versus the average corneal staining in the sham arm will be compared statistically.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient reported symptom</measure>
    <time_frame>42 Days</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving 1 severity grade improvement in corneal staining</measure>
    <time_frame>42 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a 30% improvement in their most bothersome symptom</measure>
    <time_frame>42 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Safety Endpoint as assessed by Intraocular pressure</measure>
    <time_frame>At day 30 and day 42</time_frame>
    <description>Intraocular Pressure (IOP) measurement using applanation tonometry</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Dry Eye</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Commercially available EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL) (Vera90™ - Elkridge, MD)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sustained Release Dexamethasone, 0.4 mg</intervention_name>
    <description>dexamethasone 0.4mg lacrimal insert</description>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>E-Caprolactone-L-Lactide copolymer (PCL) punctal plug</intervention_name>
    <description>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)</description>
    <arm_group_label>Control Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        A patient's study eye must meet the following criteria to be eligible for inclusion in the&#xD;
        study:&#xD;
&#xD;
          -  Male or Female Age 18-100&#xD;
&#xD;
          -  Capacity to give informed consent&#xD;
&#xD;
          -  Ability to follow study direction and complete all study visits&#xD;
&#xD;
          -  A previous or current diagnosis of dry eye by an eye care specialist, whereas&#xD;
             treatment is requiring the use of a topical steroid&#xD;
&#xD;
          -  Able to have a lacrimal plug placement into both lower puncta. If lower puncta are&#xD;
             already plugged or cauterized/sealed, upper puncta will be used&#xD;
&#xD;
          -  Females of childbearing potential unwilling to use reliable form(s) of birth control&#xD;
             throughout study period&#xD;
&#xD;
          -  Clinical diagnosis of dry eye syndrome (DES) or keratoconjunctivitis sicca (KCS), in&#xD;
             which the following has been bilaterally documented in the ophthalmic and medical&#xD;
             histories:&#xD;
&#xD;
             i. history/diagnosis of dry eye ii. has taken or is on prescription drops (including&#xD;
             but not limited to topical steroids, cyclosporine or lifitegrast)&#xD;
&#xD;
          -  Presence of all of the following in both eyes at Baseline (Day 1):&#xD;
&#xD;
             i. Total OSS of 3 or more with at least 2+ corneal staining (0-6) ii. Unanesthetized&#xD;
             Schirmer level of &lt;10 mm at 5 minutes iii. Presence of significant symptoms defined as&#xD;
             30mm or higher score of (1) eye dryness, or (2) eye fatigue, or (3) eye discomfort as&#xD;
             measured using VAS, in both eyes. At the baseline visit, the most bothersome symptom&#xD;
             (of the three) will be determined and used as the main symptom outcome measure&#xD;
             throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A patient who meets any of the following criteria will be excluded from the study:&#xD;
&#xD;
          -  Use of Contact lenses within 1 week of screening visit or during the study&#xD;
&#xD;
          -  Any ocular surgery (including tear duct cauterization) within the 3 months&#xD;
&#xD;
          -  Inability to place a lacrimal device into upper or lower puncta of both eyes (if upper&#xD;
             in R eye should be upper in the left eye and vice versa)&#xD;
&#xD;
          -  Inability to participate in the wash out period&#xD;
&#xD;
          -  Use of topical glaucoma medications (With exception of rescue medication)&#xD;
&#xD;
          -  Pregnancy, nursing or intention of pregnancy or nursing in the study period.&#xD;
&#xD;
          -  Monocular patients&#xD;
&#xD;
          -  Uncontrolled systemic disease (defined as frequent or recent change in the medication&#xD;
             regimen)&#xD;
&#xD;
          -  Patients who are currently on with stable doses of oral steroids, topical cyclosporine&#xD;
             or lifitigrast, topical tacrolimus or pimecrolimus are eligible as long as there has&#xD;
             been no change in the dose in the last 3 months&#xD;
&#xD;
          -  Patients who are on topical steroids (With exception of rescue medication) (Patients&#xD;
             who have used steroids recently but have been off for at least 2 weeks will be&#xD;
             eligible.)&#xD;
&#xD;
          -  Current enrollment in any other investigational drug or device study or participation&#xD;
             of study within 30 days of baseline visit.&#xD;
&#xD;
          -  Known allergy or sensitivity to any of the clinical or experimental drugs used in this&#xD;
             study including history of steroid response.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Esen Akpek, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wilmer Eye Institute, Johns Hopkins School of Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>June 8, 2023</last_update_submitted>
  <last_update_submitted_qc>June 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ocular surface disease</keyword>
  <keyword>dexamethasone</keyword>
  <keyword>ophthalmic steroids</keyword>
  <keyword>keratoconjuntivitis sicca</keyword>
  <keyword>dry eye</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Aggregated information only will be shared with sponsor</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04498468
org study id: IRB00246348
nct id: NCT04498468
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
To determine efficacy and safety profile of dexamethasone 0.4mg lacrimal insert in dry eye
      related ocular surface inflammation.
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.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: Prospective, Double Masked, Interventional Study.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The patient and the examining physician/outcomes accessor will be masked. The treating physician cannot be masked.
measure: Efficacy Endpoint as assessed by dry eye sign using Ocular Surface Scale (OSS)
time frame: 28 days
description: 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.
measure: Patient reported symptom
time frame: 42 Days
description: 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.
measure: Percentage of subjects achieving 1 severity grade improvement in corneal staining
time frame: 42 days
description: 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.
measure: Percentage of subjects achieving a 30% improvement in their most bothersome symptom
time frame: 42 days
description: 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.
measure: Change in Safety Endpoint as assessed by Intraocular pressure
time frame: At day 30 and day 42
description: Intraocular Pressure (IOP) measurement using applanation tonometry
arm group label: Treatment Arm
arm group type: Experimental
description: Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)
arm group label: Control Arm
arm group type: Sham Comparator
description: Commercially available EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL) (Vera90™ - Elkridge, MD)
intervention type: Drug
intervention name: Sustained Release Dexamethasone, 0.4 mg
description: dexamethasone 0.4mg lacrimal insert
arm group label: Treatment Arm
intervention type: Other
intervention name: E-Caprolactone-L-Lactide copolymer (PCL) punctal plug
description: 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)
arm group label: Control Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Esen Akpek, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Dexamethasone
sharing ipd: No
ipd description: Aggregated information only will be shared with sponsor