<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/NCT04492878</url>
  </required_header>
  <id_info>
    <org_study_id>IOBA-ImmunEyez_011-2018</org_study_id>
    <nct_id>NCT04492878</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Ikervis Under Controlled Environmental Conditions Environment</brief_title>
  <official_title>A Phase IV Open-Label Clinical Trial to Evaluate the Efficacy of Ikervis® on Clinical Parameters and Molecular/Cellular Biomarkers in Dry Eye Patients With Severe Keratitis Who Have Not Improved Despite Regular Use of Tear Substitutes Before and After Exposure to an Adverse Controlled Environment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Santen Oy</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA</source>
  <oversight_info>
    <has_dmc>No</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>
      The proposed study is a prospective, open-label, unicentric, phase IV clinical trial.&#xD;
&#xD;
      This study is design to find new efficacy biomarkers for IKERVIS® (1mg/mL ciclosporin) eye&#xD;
      drops after 1 and 3 month after initiation of therapy. Additionally, this study intends to&#xD;
      investigate whether IKERVIS® will help patients to better overcome situations of desiccating&#xD;
      stress by exposing them to an adverse controlled environment (ACE) and analyzing both&#xD;
      clinical and molecular parameters.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 4, 2020</start_date>
  <completion_date type="Actual">January 18, 2021</completion_date>
  <primary_completion_date type="Actual">January 18, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single Group Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Corneal fluoresceing staining</measure>
    <time_frame>V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment); V2 (30 days of treatment) vs V3 (90 days of treatment)</time_frame>
    <description>Significant reduction in corneal fluorescein staining</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response against adverse environmental conditions</measure>
    <time_frame>V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment)</time_frame>
    <description>Significant differences in the percentage of patients suffering a worsening in clinical signs and/or symptoms following exposure to adverse environmental conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular changes</measure>
    <time_frame>V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment)</time_frame>
    <description>Significant reduction in median expression of HLA-DR by conjunctival epithelial cells.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Dry Eye</condition>
  <condition>Dry Eye Syndromes</condition>
  <condition>Severe Keratitis</condition>
  <arm_group>
    <arm_group_label>IKERVIS® (1mg/mL ciclosporin) eye drops</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IKERVIS®1mg/mL</intervention_name>
    <description>One drop of study medication once daily in each eye at bedtime during 90 days.</description>
    <arm_group_label>IKERVIS® (1mg/mL ciclosporin) eye drops</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years.&#xD;
&#xD;
          -  Diagnosis of DED with Severe Keratitis who have not improved despite regular use of&#xD;
             tear substitutes by an ophthalmologist, at least 2 months previously.&#xD;
&#xD;
          -  Not stable (as defined by the two items below) under at least 2 months of constant and&#xD;
             regular use of artificial tears (at least 4 drops a day)&#xD;
&#xD;
          -  Fluorescein corneal staining ≥ 2 (Oxford scale) in both eyes.&#xD;
&#xD;
          -  DEQ-5 &gt; 6 points&#xD;
&#xD;
          -  Use of at least 4 times daily of an ocular artificial tears.&#xD;
&#xD;
          -  Any concomitant medication that may affect DED, ocular surface condition or vision,&#xD;
             must have a start date at least 3 months prior to baseline and dosage is not expected&#xD;
             to change during the study.&#xD;
&#xD;
          -  Best corrected visual acuity (BCVA) of at least 0.1 logMar at 6 meters with each eye.&#xD;
&#xD;
          -  Signature of written informed consent form and data protection form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy or sensitivity to the study product(s) or its components.&#xD;
&#xD;
          -  Any ocular pathology other than DED.&#xD;
&#xD;
          -  History of severe ocular inflammation other than that due to DED or infection in the 6&#xD;
             previous months to the study inclusion.&#xD;
&#xD;
          -  Any ocular surgery or trauma that may affect corneal sensitivity and/or normal tear&#xD;
             distribution in the 6 previous months or any ocular or systemic surgery or procedure&#xD;
             planned during the study duration that may affect the study as assessed by principal&#xD;
             investigator.&#xD;
&#xD;
          -  History of refractive surgery in the previous 18 months.&#xD;
&#xD;
          -  Contact lens use in the ONE previous month to study inclusion and during the duration&#xD;
             of the study.&#xD;
&#xD;
          -  Use of any ocular topical medication for pathologies other than DED.&#xD;
&#xD;
          -  Use of any other ocular topical medication for DED other than artificial tears during&#xD;
             the last ONE (steroids) or THREE months (ciclosporine, tacrolimus) .&#xD;
&#xD;
          -  Any uncontrolled severe systemic disease that may affect the eye (except for Sjögren's&#xD;
             syndrome)&#xD;
&#xD;
          -  The start date of any systemic medication that may affect DED, ocular surface&#xD;
             condition or vision is &lt; 3 months prior to baseline or a change in dosage is&#xD;
             anticipated during the study.&#xD;
&#xD;
          -  Occlusion of the lacrimal puncta either surgically or with plugs within one month&#xD;
             prior to study, or anticipated use of the same during the study.&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Current enrolments in an investigational drug or device study or participation in such&#xD;
             a study within 30 day of entry into this study at baseline.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Institute of Applied Ophthalmobiology (IOBA)</name>
      <address>
        <city>Valladolid</city>
        <zip>47011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>April 20, 2021</last_update_submitted>
  <last_update_submitted_qc>April 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
    <mesh_term>Keratitis</mesh_term>
  </condition_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/NCT04492878
org study id: IOBA-ImmunEyez_011-2018
nct id: NCT04492878
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The proposed study is a prospective, open-label, unicentric, phase IV clinical trial.

      This study is design to find new efficacy biomarkers for IKERVIS® (1mg/mL ciclosporin) eye
      drops after 1 and 3 month after initiation of therapy. Additionally, this study intends to
      investigate whether IKERVIS® will help patients to better overcome situations of desiccating
      stress by exposing them to an adverse controlled environment (ACE) and analyzing both
      clinical and molecular parameters.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Corneal fluoresceing staining
time frame: V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment); V2 (30 days of treatment) vs V3 (90 days of treatment)
description: Significant reduction in corneal fluorescein staining
measure: Response against adverse environmental conditions
time frame: V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment)
description: Significant differences in the percentage of patients suffering a worsening in clinical signs and/or symptoms following exposure to adverse environmental conditions
measure: Molecular changes
time frame: V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment)
description: Significant reduction in median expression of HLA-DR by conjunctival epithelial cells.
arm group label: IKERVIS® (1mg/mL ciclosporin) eye drops
arm group type: Experimental
intervention type: Drug
intervention name: IKERVIS®1mg/mL
description: One drop of study medication once daily in each eye at bedtime during 90 days.
arm group label: IKERVIS® (1mg/mL ciclosporin) eye drops
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Keratitis
sharing ipd: No