<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/NCT02975102</url>
  </required_header>
  <id_info>
    <org_study_id>2016-A01121-50</org_study_id>
    <nct_id>NCT02975102</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Performance and Safety of CBL-101 Versus Vismed® Multi Eye Drops in the Management of Dry Eye</brief_title>
  <official_title>A Study to Evaluate the Performance and Safety of CBL-101 Versus Vismed® Multi Eye Drops in the Management of Dry Eye</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laboratoire Chauvin</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Laboratoire Chauvin</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 primary objectives of this investigation are to show that the performance of CBL-101 Eye&#xD;
      Drops is non-inferior to that of Vismed® Multi eye drops in subjects with moderate to severe&#xD;
      keratoconjunctivitis sicca after 28 days, and to assess the safety of CBL-101 Eye Drops&#xD;
      during a 90-day period with treatment administered 3 to 6 times per day.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study duration will be approximately 15 weeks from screening to the last visit. Subjects will&#xD;
      visit the clinic approximately 5 times.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">September 17, 2019</completion_date>
  <primary_completion_date type="Actual">September 17, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ocular surface fluorescein staining score at Visit 4</measure>
    <time_frame>Baseline (Day 0), Visit 4 (Day 28)</time_frame>
    <description>The primary performance endpoint for this study is the mean change from baseline (CFB) in the study eye in ocular surface fluorescein staining score according to a scale from 0 to 15, combining corneal, nasal and temporal bulbar conjunctival fluorescein staining, each graded 0 to 5, according to the Oxford Scheme.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total ocular surface fluorescein staining score at Visit 3</measure>
    <time_frame>Baseline (Day 0), Visit 3 (Day 7)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total ocular surface fluorescein staining score at Visit 5</measure>
    <time_frame>Baseline (Day 0), Visit 5 (Day 90)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corneal fluorescein staining score at Visit 3</measure>
    <time_frame>Baseline (Day 0), Visit 3 (Day 7)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corneal fluorescein staining score at Visit 4</measure>
    <time_frame>Baseline (Day 0), Visit 4 (Day 28)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corneal fluorescein staining score at Visit 5</measure>
    <time_frame>Baseline (Day 0), Visit 5 (Day 90)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nasal conjunctival fluorescein staining score at Visit 3</measure>
    <time_frame>Baseline (Day 0), Visit 3 (Day 7)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nasal conjunctival fluorescein staining score at Visit 4</measure>
    <time_frame>Baseline (Day 0), Visit 4 (Day 28)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nasal conjunctival fluorescein staining score at Visit 5</measure>
    <time_frame>Baseline (Day 0), Visit 5 (Day 90)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Temporal conjunctival fluorescein staining score at Visit 3</measure>
    <time_frame>Baseline (Day 0), Visit 3 (Day 7)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Temporal conjunctival fluorescein staining score at Visit 4</measure>
    <time_frame>Baseline (Day 0), Visit 4 (Day 28)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Temporal conjunctival fluorescein staining score at Visit 5</measure>
    <time_frame>Baseline (Day 0), Visit 5 (Day 90)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tear Film Break Up Time (TFBUT) at Visit 3</measure>
    <time_frame>Baseline (Day 0), Visit 3 (day 7)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFBUT at Visit 4</measure>
    <time_frame>Baseline (Day 0), Visit 4 (Day 28)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFBUT at Visit 5</measure>
    <time_frame>Baseline (Day 0), Visit 5 (Day 90)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ocular Surface Disease-Quality of Life (OSD-QoL®) at Visit 5</measure>
    <time_frame>Baseline (Day 0), Visit 5 (Day 90)</time_frame>
    <description>Evolution from baseline of OSD-QoL® questionnaire scores for all 7 dimensions: Daily Activities, Handicap and Work Difficulties, Giving up Make-up, Acknowledgement, Acceptance, Fear for the Future, Emotional Well-Being, and Global Question.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global sum score of dry eye symptoms at Visit 4</measure>
    <time_frame>Baseline, Visit 4 (Day 28)</time_frame>
    <description>Mean change from baseline in the global sum score of dry eye symptoms: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 to 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global sum score of dry eye symptoms at Visit 5</measure>
    <time_frame>Baseline, Visit 5 (Day 90)</time_frame>
    <description>Mean change from baseline in the global sum score of dry eye symptoms: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 to 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of tear fluid secretion as assessed by the unanaesthetized Schirmer test at Visit 4</measure>
    <time_frame>Baseline (Day 0), Visit 4 (Day 28)</time_frame>
    <description>Mean change from baseline in the study eye</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Dry Eye</condition>
  <arm_group>
    <arm_group_label>CBL-101 Eye Drops</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The test article, CBL-101 Eye Drops, is a CE-marked medical device containing 0.15% hyaluronic acid. An oxide (Oxyd®) used as mild preservative, rapidly turns into oxygen, water and ions on contact with the eye. The formula is presented in 10 mL bottles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vismed® Multi</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The comparator product, Vismed® Multi ophthalmic solution (CE marked), contains 0.18% sodium hyaluronate, is unpreserved and presented in 10 mL bottles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CBL-101 Eye Drops</intervention_name>
    <description>CBL-101 Eye Drops 3 to 6 times per day for 3 months.</description>
    <arm_group_label>CBL-101 Eye Drops</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Vismed® Multi</intervention_name>
    <description>Vismed® Multi 3 to 6 times per day for 3 months.</description>
    <arm_group_label>Vismed® Multi</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects must be of legal age (at least 18) on the date the Informed Consent Form&#xD;
             (ICF) is signed and with the capacity to provide voluntary informed consent&#xD;
&#xD;
          2. Subjects must be able to read, understand, and provide written informed consent on the&#xD;
             Ethics Committee (EC) approved ICF&#xD;
&#xD;
          3. Subjects who are able and willing to comply with all treatment and follow-up, study&#xD;
             procedures&#xD;
&#xD;
          4. Subjects who have been using tear substitutes for at least 3 months prior to&#xD;
             inclusion, and who will use multidose preservative-free ART (Aqualarm U.P. povidone 2%&#xD;
             eye drops in 10 mL bottles) up to 6 times a day for at least 2 weeks immediately prior&#xD;
             to randomization&#xD;
&#xD;
          5. Subjects with a score ≥ 1 for at least 2 out of the 7 following symptoms (rated 0 to&#xD;
             4): sensation of dryness, foreign body, burning, stinging, itching, blurred vision,&#xD;
             sensitivity to light&#xD;
&#xD;
          6. Subjects with at least 1 eye with the following signs of keratoconjunctivitis sicca :&#xD;
&#xD;
               -  Tear break-up time of ≤ 10sec (mean of 3 measurements) at both screening visit&#xD;
                  and inclusion visit&#xD;
&#xD;
               -  Total ocular surface staining score ≥ 4 and ≤ 9 at both screening visit and&#xD;
                  inclusion visit. This assessment combines corneal, nasal and temporal bulbar&#xD;
                  conjunctival fluorescein staining, each graded 0-5 according to the Oxford Scheme&#xD;
&#xD;
          7. Subjects who have a decimal visual acuity (VA) with habitual correction equal to or&#xD;
             better than 0.1 (Monoyer chart) in both eyes&#xD;
&#xD;
          8. Subjects with no systemic treatment or who are receiving stable systemic treatment&#xD;
             (unchanged for 1 month or longer)&#xD;
&#xD;
          9. Female subjects who are not of childbearing potential or who have a negative urine&#xD;
             pregnancy test result at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Ocular Exclusion Criteria&#xD;
&#xD;
          1. Subjects with moderate or severe blepharitis defined by at least moderate (a score of&#xD;
             ≥ 2 from a range of 0 to 3) eyelid margin hyperemia or moderate eyelid swelling or&#xD;
             both and at least moderate eyelid debris or moderate plugging of meibomian glands or&#xD;
             both&#xD;
&#xD;
          2. Subjects who have severe ocular dryness accompanied by one of the following:&#xD;
&#xD;
               -  Lid abnormality (except mild blepharitis)&#xD;
&#xD;
               -  Corneal disease&#xD;
&#xD;
               -  Ocular surface metaplasia&#xD;
&#xD;
               -  Filamentary keratitis&#xD;
&#xD;
               -  Corneal neovascularization&#xD;
&#xD;
          3. Subjects who currently wear contact lenses or have worn contact lenses within 90 days&#xD;
             prior to study start&#xD;
&#xD;
          4. Subjects who have received ocular surgery, including laser surgery, in either eye&#xD;
             within 180 days prior to study start&#xD;
&#xD;
          5. Subjects with a history of ocular trauma, non-dry eye ocular inflammation, or ocular&#xD;
             infection within 90 days prior to study start&#xD;
&#xD;
          6. Subjects with a history of ocular allergic disease or ocular herpes within 1 year&#xD;
             prior to study start&#xD;
&#xD;
          7. Subjects with a history of any inflammatory ulcerative keratitis, recurrent corneal&#xD;
             erosion, or uveitis&#xD;
&#xD;
             Treatment Exclusion Criteria&#xD;
&#xD;
          8. Subjects with known hypersensitivity or contraindications to any of the ingredients in&#xD;
             the test or comparator products or ART&#xD;
&#xD;
          9. Subjects with initiation of, or changes to, concomitant medication that could affect&#xD;
             dry eye within 30 days prior to Visit 1 (Screening) or with planned initiation or&#xD;
             changes of such medications during the study&#xD;
&#xD;
         10. Subjects who have received ocular therapy (either eye) with any ophthalmic medication,&#xD;
             except tear substitutes, within 2 weeks prior to study start&#xD;
&#xD;
         11. Subjects expected to receive ocular therapy during the study&#xD;
&#xD;
         12. Subjects treated with topical ocular steroidal or non-steroidal antiinflammatory&#xD;
             medication within 30 days prior to study start&#xD;
&#xD;
         13. Subjects expected to receive ocular therapy with immunosuppressants (e.g.&#xD;
             cyclosporine) during the study or who have used ocular immunosuppressants within 90&#xD;
             days prior to study start&#xD;
&#xD;
         14. Subjects who have received occlusion therapy with lacrimal or punctum plugs within 90&#xD;
             days prior to study start&#xD;
&#xD;
             General Exclusion Criteria&#xD;
&#xD;
         15. Female subjects who are sexually active and who do not fall into 1 of the following&#xD;
             categories:&#xD;
&#xD;
               -  Post-menopausal&#xD;
&#xD;
               -  Surgically sterile&#xD;
&#xD;
               -  Using one of the following birth control methods throughout the duration of the&#xD;
                  study: Intrauterine device (at least for 14 days prior to study start) or Barrier&#xD;
                  method (condom or diaphragm) with spermicide (at least for 14 days prior to study&#xD;
                  start) or Hormonal contraception (same dose and same formulation for at least 6&#xD;
                  months)&#xD;
&#xD;
         16. Females who are breastfeeding&#xD;
&#xD;
         17. Subjects participating in any drug or device clinical investigation within 30 days&#xD;
             prior to entry into this study and, or during the period of study participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raphaele Siou Mermet, MD</last_name>
    <role>Study Director</role>
    <affiliation>Laboratoire Chauvin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pr Mortemousque private office</name>
      <address>
        <city>Bordeaux</city>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>April 24, 2020</last_update_submitted>
  <last_update_submitted_qc>April 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2020</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ophthalmic Solutions</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>January 27, 2023</submitted>
  </pending_results>
  <!-- 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/NCT02975102
org study id: 2016-A01121-50
nct id: NCT02975102
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objectives of this investigation are to show that the performance of CBL-101 Eye
      Drops is non-inferior to that of Vismed® Multi eye drops in subjects with moderate to severe
      keratoconjunctivitis sicca after 28 days, and to assess the safety of CBL-101 Eye Drops
      during a 90-day period with treatment administered 3 to 6 times per day.
Study duration will be approximately 15 weeks from screening to the last visit. Subjects will
      visit the clinic approximately 5 times.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Ocular surface fluorescein staining score at Visit 4
time frame: Baseline (Day 0), Visit 4 (Day 28)
description: The primary performance endpoint for this study is the mean change from baseline (CFB) in the study eye in ocular surface fluorescein staining score according to a scale from 0 to 15, combining corneal, nasal and temporal bulbar conjunctival fluorescein staining, each graded 0 to 5, according to the Oxford Scheme.
measure: Total ocular surface fluorescein staining score at Visit 3
time frame: Baseline (Day 0), Visit 3 (Day 7)
description: Mean change from baseline in the study eye
measure: Total ocular surface fluorescein staining score at Visit 5
time frame: Baseline (Day 0), Visit 5 (Day 90)
description: Mean change from baseline in the study eye
measure: Corneal fluorescein staining score at Visit 3
time frame: Baseline (Day 0), Visit 3 (Day 7)
description: Mean change from baseline in the study eye
measure: Corneal fluorescein staining score at Visit 4
time frame: Baseline (Day 0), Visit 4 (Day 28)
description: Mean change from baseline in the study eye
measure: Corneal fluorescein staining score at Visit 5
time frame: Baseline (Day 0), Visit 5 (Day 90)
description: Mean change from baseline in the study eye
measure: Nasal conjunctival fluorescein staining score at Visit 3
time frame: Baseline (Day 0), Visit 3 (Day 7)
description: Mean change from baseline in the study eye
measure: Nasal conjunctival fluorescein staining score at Visit 4
time frame: Baseline (Day 0), Visit 4 (Day 28)
description: Mean change from baseline in the study eye
measure: Nasal conjunctival fluorescein staining score at Visit 5
time frame: Baseline (Day 0), Visit 5 (Day 90)
description: Mean change from baseline in the study eye
measure: Temporal conjunctival fluorescein staining score at Visit 3
time frame: Baseline (Day 0), Visit 3 (Day 7)
description: Mean change from baseline in the study eye
measure: Temporal conjunctival fluorescein staining score at Visit 4
time frame: Baseline (Day 0), Visit 4 (Day 28)
description: Mean change from baseline in the study eye
measure: Temporal conjunctival fluorescein staining score at Visit 5
time frame: Baseline (Day 0), Visit 5 (Day 90)
description: Mean change from baseline in the study eye
measure: Tear Film Break Up Time (TFBUT) at Visit 3
time frame: Baseline (Day 0), Visit 3 (day 7)
description: Mean change from baseline in the study eye
measure: TFBUT at Visit 4
time frame: Baseline (Day 0), Visit 4 (Day 28)
description: Mean change from baseline in the study eye
measure: TFBUT at Visit 5
time frame: Baseline (Day 0), Visit 5 (Day 90)
description: Mean change from baseline in the study eye
measure: Ocular Surface Disease-Quality of Life (OSD-QoL®) at Visit 5
time frame: Baseline (Day 0), Visit 5 (Day 90)
description: Evolution from baseline of OSD-QoL® questionnaire scores for all 7 dimensions: Daily Activities, Handicap and Work Difficulties, Giving up Make-up, Acknowledgement, Acceptance, Fear for the Future, Emotional Well-Being, and Global Question.
measure: Global sum score of dry eye symptoms at Visit 4
time frame: Baseline, Visit 4 (Day 28)
description: Mean change from baseline in the global sum score of dry eye symptoms: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 to 4
measure: Global sum score of dry eye symptoms at Visit 5
time frame: Baseline, Visit 5 (Day 90)
description: Mean change from baseline in the global sum score of dry eye symptoms: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 to 4
measure: Volume of tear fluid secretion as assessed by the unanaesthetized Schirmer test at Visit 4
time frame: Baseline (Day 0), Visit 4 (Day 28)
description: Mean change from baseline in the study eye
arm group label: CBL-101 Eye Drops
arm group type: Experimental
description: The test article, CBL-101 Eye Drops, is a CE-marked medical device containing 0.15% hyaluronic acid. An oxide (Oxyd®) used as mild preservative, rapidly turns into oxygen, water and ions on contact with the eye. The formula is presented in 10 mL bottles.
arm group label: Vismed® Multi
arm group type: Active Comparator
description: The comparator product, Vismed® Multi ophthalmic solution (CE marked), contains 0.18% sodium hyaluronate, is unpreserved and presented in 10 mL bottles.
intervention type: Device
intervention name: CBL-101 Eye Drops
description: CBL-101 Eye Drops 3 to 6 times per day for 3 months.
arm group label: CBL-101 Eye Drops
intervention type: Device
intervention name: Vismed® Multi
description: Vismed® Multi 3 to 6 times per day for 3 months.
arm group label: Vismed® Multi
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Raphaele Siou Mermet, MD
role: Study Director
affiliation: Laboratoire Chauvin
facility: 
country: France
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Ophthalmic Solutions
sharing ipd: No
submitted: January 27, 2023