<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/NCT02987686</url>
  </required_header>
  <id_info>
    <org_study_id>CE16.221</org_study_id>
    <nct_id>NCT02987686</nct_id>
  </id_info>
  <brief_title>Topical Infliximab for Sterile Corneal Melt</brief_title>
  <official_title>Topical Infliximab for the Treatment of Sterile Corneal Melt</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fonds de recherche en ophtalmologie de l'Université de Montréal</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre hospitalier de l'Université de Montréal (CHUM)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Corneal melt is a complication that could affect very ill eyes and lead to the thinning of&#xD;
      the cornea (the clear window covering of the eyes). This thinning can lead to severe&#xD;
      consequences such as the leakage of the liquid inside the eye (ocular perforation), or even&#xD;
      blindness. Corneal melt can be caused by certain infections or as a sterile process. This&#xD;
      project only includes patients with a sterile corneal melt (without an infection) caused by&#xD;
      diseases such as rosacea, Sjogren's syndrome, rheumatoid arthritis, Crohn's disease, Stevens&#xD;
      Johnson syndrome, as well as toxic epidermal necrolysis or mucous membrane pemphigoid.&#xD;
&#xD;
      Infliximab is an antibody against tumour necrosis factor alpha and has been used to treat or&#xD;
      prevent corneal melt in certain patients with inflammatory of auto-immune disease. In this&#xD;
      situation, infliximab was used intravenous (using veins) in order to treat the whole body.&#xD;
&#xD;
      This study's hypothesis is that infliximab can safely be used as eye drops for the treatment&#xD;
      of sterile corneal melt.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an unmasked, prospective, single-center trial of twelve patients with sterile corneal&#xD;
      melt and an underlying auto-immune or inflammatory disease, such as rosacea, Sjogren's&#xD;
      syndrome, rheumatoid arthritis, Crohn's disease, Stevens Johnson syndrome, as well as toxic&#xD;
      epidermal necrolysis or mucous membrane pemphigoid.&#xD;
&#xD;
      The aim of this phase I study is to evaluate the safety and tolerability of topical&#xD;
      infliximab 10mg/ml eye drops for the treatment of corneal melt. As such, six (6) subjects&#xD;
      will be recruited in the experimental treatment study and six (6) subjects will be enrolled&#xD;
      in the parallel observational study. Indeed, candidates having all inclusion criteria but one&#xD;
      exclusion criteria (which are contraindication to infliximab use), will be recruited in the&#xD;
      observational study, will receive the standard treatment without infliximab.&#xD;
&#xD;
      During the treatment period, subjects in the therapeutic study will receive topical&#xD;
      infliximab 10mg/ml four (4) times per day for four (4) weeks. In order to determine the&#xD;
      safety profile, potential side effects as well as the course of the disease, subjects will be&#xD;
      monitored while on the study medication as well as for 8 weeks following discontinuation of&#xD;
      the drug. The ophthalmological follow-up will be identical in the two groups. However, only&#xD;
      subjects enrolled in the experimental treatment study will receive additional laboratory&#xD;
      tests. The total study duration for each patient will be 12 weeks.&#xD;
&#xD;
      In terms of statistical analysis, the investigators will focus on describing the outcome&#xD;
      measured in the study. For instance, the investigators will describe the number and&#xD;
      proportion of side effects, the number of patients with a quiescent corneal melt at 4 weeks&#xD;
      and the patients who required a tectonic surgery at 12 weeks post-treatment. The&#xD;
      investigators will report the average and standard of deviation of the OSDI score, the&#xD;
      epithelial deficit surface as well as the minimal corneal thickness. Moreover, the&#xD;
      investigators will perform exploratory statistical analysis in order to study the disease&#xD;
      course of each subject and comparing the addition of infliximab to the standard.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 6, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number and type of adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of patients finishing 4 weeks of infliximab use</measure>
    <time_frame>4 weeks</time_frame>
    <description>Percentage of patients finishing 4 weeks of infliximab use</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual Acuity</measure>
    <time_frame>4 and 12 weeks</time_frame>
    <description>Visual Acuity is measured using a Snellen chart</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ocular surface symptoms as assessed by ocular disease index score</measure>
    <time_frame>4 and 12 weeks</time_frame>
    <description>Ocular surface symptoms as assessed by ocular disease index score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Conjunctival hyperemia using a slit-lamp photographs</measure>
    <time_frame>4 and 12 weeks</time_frame>
    <description>Conjunctival hyperemia using a slit-lamp photographs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corneal thickness as measured by anterior segment optical coherence tomography</measure>
    <time_frame>4 weeks</time_frame>
    <description>Corneal thickness as measured by anterior segment optical coherence tomography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surface area of the corneal melt using a slit-lamp photographs</measure>
    <time_frame>4 weeks</time_frame>
    <description>Surface area of the corneal melt using a slit-lamp photographs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quiescent corneal state</measure>
    <time_frame>4 weeks</time_frame>
    <description>Percentage of eyes presenting a quiescent corneal state at 4 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eyes requiring tectonic surgery</measure>
    <time_frame>12 weeks</time_frame>
    <description>Percentage of eyes requiring tectonic surgery at 12 weeks</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Sterile Corneal Melt</condition>
  <arm_group>
    <arm_group_label>Topical Infliximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Additionally to standard treatment, patients with all inclusive criteria and none exclusive criteria will be included in the therapeutic group and will receive topical infliximab QID for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observational group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients with all inclusive criteria and one exclusive criteria will receive the standard treatment, without topical infliximab.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topical Infliximab</intervention_name>
    <description>Aside from the standard treatment, patients will receive topical infliximab ( 10mg/ml) four (4) time per day for four (4) weeks.</description>
    <arm_group_label>Topical Infliximab</arm_group_label>
    <other_name>Remicade</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 to 80 years;&#xD;
&#xD;
          -  Any degree of active sterile corneal melting , as documented by slit-lamp examination,&#xD;
             showing an epithelial defect and stromal thinning;&#xD;
&#xD;
          -  Negative work-up for local and systemic infectious causes&#xD;
&#xD;
          -  Negative corneal cultures (may show growth of common contaminants)&#xD;
&#xD;
          -  Capable of providing informed consent;&#xD;
&#xD;
          -  Capable of administering eye drops either themselves or through a caregiver.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any active ocular or systemic infection including active or latent tuberculosis,&#xD;
             histoplasmosis, coccidiomycosis, cytomegalovirus, pneumocystosis, aspergillosis, or&#xD;
             hepatitis B.&#xD;
&#xD;
          -  History of neoplasia diagnosed within the last 5 years&#xD;
&#xD;
          -  Demyelinating disease&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Congestive heart failure&#xD;
&#xD;
          -  Significant anomalies on complete blood count, creatinine or hepatic enzymes&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  Allergy to infliximab or to the drug vehicle (Refresh liquigel)&#xD;
&#xD;
          -  Past or present use of anti-TNF-α medications or human interleukin-1 receptor&#xD;
             antagonist (anakinra, IL-1Ra)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie-Claude Robert, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marie-Claude Robert, MD</last_name>
    <phone>514 890-8000</phone>
    <phone_ext>11550</phone_ext>
    <email>marie-claude.robert.2@umontreal.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marie-Catherine Tessier</last_name>
    <phone>514 890-8000</phone>
    <phone_ext>11550</phone_ext>
    <email>marie-catherine.tessier.chum@ssss.gouv.qc.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marie-Catherine Tessier</last_name>
      <phone>5148908000</phone>
      <phone_ext>11550</phone_ext>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>October 26, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>December 12, 2022</last_update_submitted>
  <last_update_submitted_qc>December 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Topical Infliximab</keyword>
  <keyword>Cornea</keyword>
  <keyword>Keratolysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Corneal Ulcer</mesh_term>
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infliximab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02987686
org study id: CE16.221
nct id: NCT02987686
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Corneal melt is a complication that could affect very ill eyes and lead to the thinning of
      the cornea (the clear window covering of the eyes). This thinning can lead to severe
      consequences such as the leakage of the liquid inside the eye (ocular perforation), or even
      blindness. Corneal melt can be caused by certain infections or as a sterile process. This
      project only includes patients with a sterile corneal melt (without an infection) caused by
      diseases such as rosacea, Sjogren's syndrome, rheumatoid arthritis, Crohn's disease, Stevens
      Johnson syndrome, as well as toxic epidermal necrolysis or mucous membrane pemphigoid.

      Infliximab is an antibody against tumour necrosis factor alpha and has been used to treat or
      prevent corneal melt in certain patients with inflammatory of auto-immune disease. In this
      situation, infliximab was used intravenous (using veins) in order to treat the whole body.

      This study's hypothesis is that infliximab can safely be used as eye drops for the treatment
      of sterile corneal melt.
This is an unmasked, prospective, single-center trial of twelve patients with sterile corneal
      melt and an underlying auto-immune or inflammatory disease, such as rosacea, Sjogren's
      syndrome, rheumatoid arthritis, Crohn's disease, Stevens Johnson syndrome, as well as toxic
      epidermal necrolysis or mucous membrane pemphigoid.

      The aim of this phase I study is to evaluate the safety and tolerability of topical
      infliximab 10mg/ml eye drops for the treatment of corneal melt. As such, six (6) subjects
      will be recruited in the experimental treatment study and six (6) subjects will be enrolled
      in the parallel observational study. Indeed, candidates having all inclusion criteria but one
      exclusion criteria (which are contraindication to infliximab use), will be recruited in the
      observational study, will receive the standard treatment without infliximab.

      During the treatment period, subjects in the therapeutic study will receive topical
      infliximab 10mg/ml four (4) times per day for four (4) weeks. In order to determine the
      safety profile, potential side effects as well as the course of the disease, subjects will be
      monitored while on the study medication as well as for 8 weeks following discontinuation of
      the drug. The ophthalmological follow-up will be identical in the two groups. However, only
      subjects enrolled in the experimental treatment study will receive additional laboratory
      tests. The total study duration for each patient will be 12 weeks.

      In terms of statistical analysis, the investigators will focus on describing the outcome
      measured in the study. For instance, the investigators will describe the number and
      proportion of side effects, the number of patients with a quiescent corneal melt at 4 weeks
      and the patients who required a tectonic surgery at 12 weeks post-treatment. The
      investigators will report the average and standard of deviation of the OSDI score, the
      epithelial deficit surface as well as the minimal corneal thickness. Moreover, the
      investigators will perform exploratory statistical analysis in order to study the disease
      course of each subject and comparing the addition of infliximab to the standard.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: 12 weeks
description: Number and type of adverse events
measure: Percentage of patients finishing 4 weeks of infliximab use
time frame: 4 weeks
description: Percentage of patients finishing 4 weeks of infliximab use
measure: Visual Acuity
time frame: 4 and 12 weeks
description: Visual Acuity is measured using a Snellen chart
measure: Ocular surface symptoms as assessed by ocular disease index score
time frame: 4 and 12 weeks
description: Ocular surface symptoms as assessed by ocular disease index score
measure: Conjunctival hyperemia using a slit-lamp photographs
time frame: 4 and 12 weeks
description: Conjunctival hyperemia using a slit-lamp photographs
measure: Corneal thickness as measured by anterior segment optical coherence tomography
time frame: 4 weeks
description: Corneal thickness as measured by anterior segment optical coherence tomography
measure: Surface area of the corneal melt using a slit-lamp photographs
time frame: 4 weeks
description: Surface area of the corneal melt using a slit-lamp photographs
measure: Quiescent corneal state
time frame: 4 weeks
description: Percentage of eyes presenting a quiescent corneal state at 4 weeks
measure: Eyes requiring tectonic surgery
time frame: 12 weeks
description: Percentage of eyes requiring tectonic surgery at 12 weeks
arm group label: Topical Infliximab
arm group type: Experimental
description: Additionally to standard treatment, patients with all inclusive criteria and none exclusive criteria will be included in the therapeutic group and will receive topical infliximab QID for 4 weeks.
arm group label: Observational group
arm group type: No Intervention
description: Patients with all inclusive criteria and one exclusive criteria will receive the standard treatment, without topical infliximab.
intervention type: Drug
intervention name: Topical Infliximab
description: Aside from the standard treatment, patients will receive topical infliximab ( 10mg/ml) four (4) time per day for four (4) weeks.
arm group label: Topical Infliximab
other name: Remicade
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Marie-Claude Robert, MD
role: Principal Investigator
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
last name: Marie-Claude Robert, MD
phone: 514 890-8000
phone ext: 11550
email: marie-claude.robert.2@umontreal.ca
last name: Marie-Catherine Tessier
phone: 514 890-8000
phone ext: 11550
email: marie-catherine.tessier.chum@ssss.gouv.qc.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Corneal Ulcer
mesh term: Infertility
mesh term: Infliximab
sharing ipd: No