<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/NCT03029104</url>
  </required_header>
  <id_info>
    <org_study_id>CXL-005</org_study_id>
    <nct_id>NCT03029104</nct_id>
  </id_info>
  <brief_title>Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas</brief_title>
  <official_title>Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cxlusa</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cxlusa</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess changes in visual acuity and corneal symmetry after corneal collagen&#xD;
      cross-linking (CXL) of asymmetric corneas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the results of Corneal Collagen Crosslinking (CXL) in patients with&#xD;
      conditions that include keratoconus, forme fruste keratoconus, post-LASIK ectasia, pellucid&#xD;
      marginal degeneration, forme fruste pellucid marginal degeneration, diurnal fluctuation&#xD;
      post-radial keratotomy, or Terrien's marginal degeneration. This is an outcomes study, all&#xD;
      patients receive treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sufficient clinical results obtained to support study endpoints.&#xD;
  </why_stopped>
  <start_date type="Actual">December 21, 2016</start_date>
  <completion_date type="Actual">December 27, 2020</completion_date>
  <primary_completion_date type="Actual">December 27, 2020</primary_completion_date>
  <phase>Phase 2</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 (Outcomes Assessor)</masking>
    <masking_description>Visual acuity will be evaluated by an observer who is masked as to the treatment protocol to which study subjects have been assigned.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Corrected Distance Visual Acuity (CDVA)</measure>
    <time_frame>Baseline and 6 and 12 months</time_frame>
    <description>Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Uncorrected Distance Visual Acuity (UCVA)</measure>
    <time_frame>Baseline and 6 and 12 months</time_frame>
    <description>Changes in UCVA are reported as the value at 6 and 12 months minus the value at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Maximum Keratometry (KMax)</measure>
    <time_frame>Baseline and 6 and 12 months</time_frame>
    <description>Kmax is the maximum value of corneal curvature in Diopters. Changes in Kmax are reported as the value at 6 and 12 months minus the value at baseline.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">2228</enrollment>
  <condition>Keratoconus</condition>
  <condition>Corneal Diseases</condition>
  <condition>Eye Diseases</condition>
  <condition>Photosensitizing Agents</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>CXLO Corneal Strengthening Solution and UVA Illumination Device</intervention_name>
    <description>CXLO Corneal Strengthening Solution</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A diagnosis of at least one of the following conditions:&#xD;
&#xD;
               1. Keratoconus&#xD;
&#xD;
               2. Forme fruste keratoconus&#xD;
&#xD;
               3. Post-LASIK ectasia&#xD;
&#xD;
               4. Pellucid marginal degeneration&#xD;
&#xD;
               5. Forme fruste pellucid marginal degeneration&#xD;
&#xD;
               6. Diurnal fluctuation post-radial keratotomy&#xD;
&#xD;
               7. Terrien's marginal degeneration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Corneal thickness &lt; 375 microns measured by ultrasound or Pentacam.&#xD;
&#xD;
          2. Contraindications or hypersensitivities to any study medications or their components.&#xD;
&#xD;
          3. Pregnancy or breastfeeding.&#xD;
&#xD;
          4. Any history of herpes simplex corneal disease in an eye to be treated.&#xD;
&#xD;
          5. Nystagmus or any other condition that would, in the judgement of the investigator,&#xD;
             prevent a steady gaze during the treatment.&#xD;
&#xD;
          6. Inability to cooperate with diagnostic tests.&#xD;
&#xD;
          7. Enrollment in another ophthalmic clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gregg J Berdy, MD, FACS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ophthalmology Associates, St. Louis, MO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Schwartz Laser Eye Center</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goodman Eye Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cornea Consultants of Colorado</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120-4508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Woolfson Eye Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chicago Cornea Consultants</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60035</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chicago Cornea Consultants, Ltd.</name>
      <address>
        <city>Hoffman Estates</city>
        <state>Illinois</state>
        <zip>60169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmology Associates</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Eye Clinic</name>
      <address>
        <city>Brecksville</city>
        <state>Ohio</state>
        <zip>44141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cornea Associates of Texas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <results_first_submitted>November 14, 2021</results_first_submitted>
  <results_first_submitted_qc>December 15, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 12, 2022</results_first_posted>
  <last_update_submitted>December 15, 2021</last_update_submitted>
  <last_update_submitted_qc>December 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Keratoconus</keyword>
  <keyword>Forme fruste keratoconus</keyword>
  <keyword>Post-LASIK ectasia</keyword>
  <keyword>Pellucid marginal degeneration</keyword>
  <keyword>Forme fruste pellucid marginal degeneration</keyword>
  <keyword>Diurnal fluctuation post-radial keratotomy</keyword>
  <keyword>Terrien's marginal degeneration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eye Diseases</mesh_term>
    <mesh_term>Keratoconus</mesh_term>
    <mesh_term>Corneal Diseases</mesh_term>
    <mesh_term>Dermatitis, Phototoxic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03029104/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03029104/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Group 1</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
        <group group_id="P2">
          <title>Group 2</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
        <group group_id="P3">
          <title>Group 3</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="745"/>
                <participants group_id="P2" count="735"/>
                <participants group_id="P3" count="748"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="612"/>
                <participants group_id="P2" count="597"/>
                <participants group_id="P3" count="623"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="133"/>
                <participants group_id="P2" count="138"/>
                <participants group_id="P3" count="125"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group 1</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
        <group group_id="B2">
          <title>Group 2</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
        <group group_id="B3">
          <title>Group 3</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="745"/>
            <count group_id="B2" value="735"/>
            <count group_id="B3" value="748"/>
            <count group_id="B4" value="2228"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.6" spread="13.04"/>
                    <measurement group_id="B2" value="32.4" spread="13.11"/>
                    <measurement group_id="B3" value="32.6" spread="12.94"/>
                    <measurement group_id="B4" value="32.5" spread="13.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>≤21 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="175"/>
                    <measurement group_id="B2" value="163"/>
                    <measurement group_id="B3" value="175"/>
                    <measurement group_id="B4" value="513"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="221"/>
                    <measurement group_id="B2" value="217"/>
                    <measurement group_id="B3" value="220"/>
                    <measurement group_id="B4" value="658"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="524"/>
                    <measurement group_id="B2" value="518"/>
                    <measurement group_id="B3" value="528"/>
                    <measurement group_id="B4" value="1570"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="142"/>
                    <measurement group_id="B2" value="118"/>
                    <measurement group_id="B3" value="138"/>
                    <measurement group_id="B4" value="398"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="603"/>
                    <measurement group_id="B2" value="617"/>
                    <measurement group_id="B3" value="609"/>
                    <measurement group_id="B4" value="1829"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="101"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="92"/>
                    <measurement group_id="B2" value="89"/>
                    <measurement group_id="B3" value="99"/>
                    <measurement group_id="B4" value="280"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="582"/>
                    <measurement group_id="B2" value="573"/>
                    <measurement group_id="B3" value="584"/>
                    <measurement group_id="B4" value="1739"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="745"/>
                    <measurement group_id="B2" value="735"/>
                    <measurement group_id="B3" value="748"/>
                    <measurement group_id="B4" value="2228"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diagnosis of Keratoconus</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="644"/>
                    <measurement group_id="B2" value="635"/>
                    <measurement group_id="B3" value="643"/>
                    <measurement group_id="B4" value="1922"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Corrected Distance Visual Acuity (CDVA)</title>
        <description>Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline</description>
        <time_frame>Baseline and 6 and 12 months</time_frame>
        <population>Keratoconus subjects completing assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Corrected Distance Visual Acuity (CDVA)</title>
          <description>Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline</description>
          <population>Keratoconus subjects completing assessment</population>
          <units>logMAR</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="542"/>
                <count group_id="O2" value="534"/>
                <count group_id="O3" value="529"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="472"/>
                    <count group_id="O2" value="461"/>
                    <count group_id="O3" value="467"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.058" spread="0.0088"/>
                    <measurement group_id="O2" value="-0.068" spread="0.0094"/>
                    <measurement group_id="O3" value="-0.064" spread="0.0104"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="264"/>
                    <count group_id="O2" value="247"/>
                    <count group_id="O3" value="273"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.074" spread="0.0119"/>
                    <measurement group_id="O2" value="-0.060" spread="0.0127"/>
                    <measurement group_id="O3" value="-0.071" spread="0.0176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Uncorrected Distance Visual Acuity (UCVA)</title>
        <description>Changes in UCVA are reported as the value at 6 and 12 months minus the value at baseline</description>
        <time_frame>Baseline and 6 and 12 months</time_frame>
        <population>Keratoconus subjects completing assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Uncorrected Distance Visual Acuity (UCVA)</title>
          <description>Changes in UCVA are reported as the value at 6 and 12 months minus the value at baseline</description>
          <population>Keratoconus subjects completing assessment</population>
          <units>logMAR</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="541"/>
                <count group_id="O2" value="533"/>
                <count group_id="O3" value="528"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="469"/>
                    <count group_id="O2" value="461"/>
                    <count group_id="O3" value="468"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0853" spread="0.0150"/>
                    <measurement group_id="O2" value="-0.1099" spread="0.0150"/>
                    <measurement group_id="O3" value="-0.0990" spread="0.0155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="263"/>
                    <count group_id="O2" value="247"/>
                    <count group_id="O3" value="272"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0875" spread="0.0191"/>
                    <measurement group_id="O2" value="-0.0696" spread="0.0197"/>
                    <measurement group_id="O3" value="-0.1243" spread="0.0212"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Maximum Keratometry (KMax)</title>
        <description>Kmax is the maximum value of corneal curvature in Diopters. Changes in Kmax are reported as the value at 6 and 12 months minus the value at baseline.</description>
        <time_frame>Baseline and 6 and 12 months</time_frame>
        <population>Keratoconus subjects completing assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Maximum Keratometry (KMax)</title>
          <description>Kmax is the maximum value of corneal curvature in Diopters. Changes in Kmax are reported as the value at 6 and 12 months minus the value at baseline.</description>
          <population>Keratoconus subjects completing assessment</population>
          <units>Diopters</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="542"/>
                <count group_id="O2" value="533"/>
                <count group_id="O3" value="527"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="471"/>
                    <count group_id="O2" value="460"/>
                    <count group_id="O3" value="465"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1979" spread="0.1069"/>
                    <measurement group_id="O2" value="-0.4033" spread="0.1228"/>
                    <measurement group_id="O3" value="-0.3673" spread="0.1125"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="263"/>
                    <count group_id="O2" value="246"/>
                    <count group_id="O3" value="270"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2859" spread="0.1204"/>
                    <measurement group_id="O2" value="-0.5268" spread="0.1716"/>
                    <measurement group_id="O3" value="-0.5256" spread="0.1707"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <desc>A total of 2,228 subjects were randomized and treated in this study (Treated Analysis Set). 1,583 (71%) of these subjects received bilateral, simultaneous treatments. The Safety Analysis Set (SAS) is larger than the Treated Analysis Set because subjects who had an initial unilateral treatment and then had a subsequent procedure, appear in the SAS under two different treatment groups, if the subsequent treatment differs from the initial treatment. This occurred in 19 subjects.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group 1</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
        <group group_id="E2">
          <title>Group 2</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
        <group group_id="E3">
          <title>Group 3</title>
          <description>Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.&#xD;
CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (16.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="750"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="745"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="752"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="750"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="745"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="752"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <description>Subject developed diverticulitis 208 days post-procedure; not related; treated and resolved.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="750"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="745"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="752"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="750"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="745"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="752"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Clinical Development Officer</name_or_title>
      <organization>CXL Ophthalmics, LLC</organization>
      <phone>339-234-6020</phone>
      <email>info@cxlophthalmics.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03029104
org study id: CXL-005
nct id: NCT03029104
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
This study will assess changes in visual acuity and corneal symmetry after corneal collagen
      cross-linking (CXL) of asymmetric corneas.
This study will evaluate the results of Corneal Collagen Crosslinking (CXL) in patients with
      conditions that include keratoconus, forme fruste keratoconus, post-LASIK ectasia, pellucid
      marginal degeneration, forme fruste pellucid marginal degeneration, diurnal fluctuation
      post-radial keratotomy, or Terrien's marginal degeneration. This is an outcomes study, all
      patients receive treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Visual acuity will be evaluated by an observer who is masked as to the treatment protocol to which study subjects have been assigned.
measure: Change From Baseline in Corrected Distance Visual Acuity (CDVA)
time frame: Baseline and 6 and 12 months
description: Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline
measure: Change From Baseline in Uncorrected Distance Visual Acuity (UCVA)
time frame: Baseline and 6 and 12 months
description: Changes in UCVA are reported as the value at 6 and 12 months minus the value at baseline
measure: Change From Baseline in Maximum Keratometry (KMax)
time frame: Baseline and 6 and 12 months
description: Kmax is the maximum value of corneal curvature in Diopters. Changes in Kmax are reported as the value at 6 and 12 months minus the value at baseline.
arm group label: Group 1
arm group type: Active Comparator
description: Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.
arm group label: Group 2
arm group type: Active Comparator
description: Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.
arm group label: Group 3
arm group type: Active Comparator
description: Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.
intervention type: Combination Product
intervention name: CXLO Corneal Strengthening Solution and UVA Illumination Device
description: CXLO Corneal Strengthening Solution
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
criteria: 
gender: All
minimum age: 8 Years
maximum age: N/A
healthy volunteers: No
last name: Gregg J Berdy, MD, FACS
role: Principal Investigator
affiliation: Ophthalmology Associates, St. Louis, MO
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Eye Diseases
mesh term: Keratoconus
mesh term: Corneal Diseases
mesh term: Dermatitis, Phototoxic
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 