<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/NCT02245516</url>
  </required_header>
  <id_info>
    <org_study_id>KPI-121-C-004</org_study_id>
    <nct_id>NCT02245516</nct_id>
  </id_info>
  <brief_title>Exploratory Study of KPI-121 Effect on Intra- or Subretinal Fluid Due to Retinal Vein Occlusion/Diabetic Macular Edema</brief_title>
  <acronym>Molokini</acronym>
  <official_title>An Exploratory, Multi-Center, Randomized, Single-Masked Study Evaluating the Effect of KPI-121 on Intraretinal or Subretinal Fluid Secondary to Retinal Vein Occlusion or Diabetic Macular Edema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kala Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kala Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objectives of the study are to evaluate the safety and effect of KPI-121 0.25%&#xD;
      ophthalmic suspension and KPI-121 1.0% ophthalmic suspension on intraretinal or subretinal&#xD;
      fluid secondary to Retinal Vein Occlusion or Diabetic Macular Edema.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, randomized, single-masked study evaluating the safety and effect of&#xD;
      topical ocular administration of either KPI-121 0.25% ophthalmic suspension or KPI-121 1.0%&#xD;
      ophthalmic suspension in subjects with intraretinal or subretinal fluid secondary to Retinal&#xD;
      Vein Occlusion or Diabetic Macular Edema.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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 (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)</measure>
    <time_frame>Day 1 to Day 57</time_frame>
    <description>Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Macular Volume by SD-OCT</measure>
    <time_frame>Day 1 to Day 57</time_frame>
    <description>Change in measurement (in microns) in macular volume as measured by Spectral Domain Optical Coherence Tomography (OCT)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Center Subfield Retinal Thickness by SD-OCT</measure>
    <time_frame>Day 1 to Day 57</time_frame>
    <description>Change in measurement (in microns) in the central subfield retinal thickness as measured by Spectral Domain Optical Coherence Tomography (OCT)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Investigator's Assessment of Leakage on the Fluorescein Angiogram</measure>
    <time_frame>Day 1 to Day 57</time_frame>
    <description>Change in leakage by investigator's assessment of the fluorescein angiogram</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Retinal Vein Occlusion</condition>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>KPI-121 0.25% Ophthalmic Suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema</description>
  </arm_group>
  <arm_group>
    <arm_group_label>KPI-121 1.0% Ophthalmic Suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KPI-121 0.25% Ophthalmic Suspension</intervention_name>
    <description>KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
    <arm_group_label>KPI-121 0.25% Ophthalmic Suspension</arm_group_label>
    <other_name>Loteprednol etabonate 0.25%</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KPI-121 1.0% Ophthalmic Suspension</intervention_name>
    <description>KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
    <arm_group_label>KPI-121 1.0% Ophthalmic Suspension</arm_group_label>
    <other_name>Loteprednol etabonate 1.0%</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have documented presence of intraretinal or subretinal fluid secondary to Retinal Vein&#xD;
             Occlusion or Diabetic Macular Edema at Screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with topical, intravitreal injection, posterior sub-Tenon's, or periocular&#xD;
             corticosteroids within 120 days prior to Visit 1 and for the duration of the study&#xD;
&#xD;
          -  History of uncontrolled glaucoma, IOP over 21 mmHg at Visit 1, or are being treated&#xD;
             for glaucoma in the study eye&#xD;
&#xD;
          -  Any significant ocular disease that could compromise vision in the study eye&#xD;
             (including ongoing ocular infection, wet age-related macular degeneration, myopic&#xD;
             degeneration with active subfoveal choroidal neovascularization)&#xD;
&#xD;
          -  Known hypersensitivity or contraindication to the investigational product(s) or their&#xD;
             components&#xD;
&#xD;
          -  Diagnosis of severe/serious ocular condition that in the judgment of the Investigator&#xD;
             could confound study assessments or limit compliance; or severe/serious systemic&#xD;
             disease or uncontrolled medical condition that in the judgment of the Investigator&#xD;
             could confound study assessments or limit compliance&#xD;
&#xD;
          -  Exposed to an investigational drug within 30 days prior to Visit 1 and for the&#xD;
             duration of the study&#xD;
&#xD;
          -  In the opinion of the Investigator or study coordinator, an unwillingness or inability&#xD;
             to comply with the study protocol or inability to successfully instill eye drops&#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>Retina-Vitreous Associates Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmic Consultants of Boston</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>September 4, 2014</study_first_submitted>
  <study_first_submitted_qc>September 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <results_first_submitted>August 18, 2020</results_first_submitted>
  <results_first_submitted_qc>December 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 10, 2020</results_first_posted>
  <disposition_first_submitted>July 8, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>July 8, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">July 12, 2016</disposition_first_posted>
  <last_update_submitted>December 9, 2020</last_update_submitted>
  <last_update_submitted_qc>December 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intraretinal Fluid</keyword>
  <keyword>Subretinal Fluid</keyword>
  <keyword>Retinal Vein Occlusion</keyword>
  <keyword>Diabetic Macular Edema</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Retinal Vein Occlusion</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Loteprednol Etabonate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>KPI-121 1.0% Ophthalmic Suspension</title>
          <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
        <group group_id="P2">
          <title>KPI-121 0.25% Ophthalmic Suspension</title>
          <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>KPI-121 1.0% Ophthalmic Suspension</title>
          <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
        <group group_id="B2">
          <title>KPI-121 0.25% Ophthalmic Suspension</title>
          <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
        <group group_id="B3">
          <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="9"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Age (years)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.2" spread="12.93"/>
                    <measurement group_id="B2" value="65.4" spread="10.34"/>
                    <measurement group_id="B3" value="64.2" spread="11.54"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </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_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="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)</title>
        <description>Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.</description>
        <time_frame>Day 1 to Day 57</time_frame>
        <population>Intent to treat- all subjects randomized</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 1.0% Ophthalmic Suspension</title>
            <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)</title>
          <description>Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.</description>
          <population>Intent to treat- all subjects randomized</population>
          <units>ETDRS letters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="7.83"/>
                    <measurement group_id="O2" value="-2.0" spread="2.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Macular Volume by SD-OCT</title>
        <description>Change in measurement (in microns) in macular volume as measured by Spectral Domain Optical Coherence Tomography (OCT)</description>
        <time_frame>Day 1 to Day 57</time_frame>
        <population>Intent to Treat (all randomized subjects) minus subjects in each treatment group that discontinued the study prior to this time point or otherwise did not have this assessment completed</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 1.0% Ophthalmic Suspension</title>
            <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Macular Volume by SD-OCT</title>
          <description>Change in measurement (in microns) in macular volume as measured by Spectral Domain Optical Coherence Tomography (OCT)</description>
          <population>Intent to Treat (all randomized subjects) minus subjects in each treatment group that discontinued the study prior to this time point or otherwise did not have this assessment completed</population>
          <units>mm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.237" spread="1.1607"/>
                    <measurement group_id="O2" value="-0.377" spread="0.8190"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Center Subfield Retinal Thickness by SD-OCT</title>
        <description>Change in measurement (in microns) in the central subfield retinal thickness as measured by Spectral Domain Optical Coherence Tomography (OCT)</description>
        <time_frame>Day 1 to Day 57</time_frame>
        <population>Intent to Treat (all randomized subjects) minus subjects in each treatment group that discontinued the study prior to this time point or otherwise did not have this assessment completed</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 1.0% Ophthalmic Suspension</title>
            <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Center Subfield Retinal Thickness by SD-OCT</title>
          <description>Change in measurement (in microns) in the central subfield retinal thickness as measured by Spectral Domain Optical Coherence Tomography (OCT)</description>
          <population>Intent to Treat (all randomized subjects) minus subjects in each treatment group that discontinued the study prior to this time point or otherwise did not have this assessment completed</population>
          <units>micrometers (μm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.2" spread="52.37"/>
                    <measurement group_id="O2" value="4.8" spread="13.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Investigator's Assessment of Leakage on the Fluorescein Angiogram</title>
        <description>Change in leakage by investigator's assessment of the fluorescein angiogram</description>
        <time_frame>Day 1 to Day 57</time_frame>
        <population>Unable to analyze the FA data for efficacy. The efficacy variable defined in the protocol was the mean change from baseline in total area of fluorescein leakage and unfortunately the total area was not collected during the study.</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 1.0% Ophthalmic Suspension</title>
            <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Investigator's Assessment of Leakage on the Fluorescein Angiogram</title>
          <description>Change in leakage by investigator's assessment of the fluorescein angiogram</description>
          <population>Unable to analyze the FA data for efficacy. The efficacy variable defined in the protocol was the mean change from baseline in total area of fluorescein leakage and unfortunately the total area was not collected during the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the time a subjects signed the informed consent until they exited the study at the end of Visit 5 (up to 57 days).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>KPI-121 1.0% Ophthalmic Suspension</title>
          <description>KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
        <group group_id="E2">
          <title>KPI-121 0.25% Ophthalmic Suspension</title>
          <description>KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema&#xD;
KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>generalized weakness</sub_title>
                <description>1 Subject had a non-ocular SAE hospitalization of generalized weakness starting on Day 7 resolved Day 28. It was mild in severity, was not considered by the Investigator to be related to study treatment and the subject discontinued from the trial.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Increase in floaters</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Punctate Epithelial Erosions</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Soreness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>generalized weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Worsening of Hypercholesterolemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </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>No submission for publication or public disclosure will be made by the PI until after the publication of the results of the multi-center clinical trial by the Sponsor. Thereafter, PI shall provide KALA with an advance copy of any proposed publication or public disclosure at least sixty (60) days prior to the planned date of submission or disclosure and KALA shall have forty-five (45) days from the date of its receipt to recommend changes.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>VP, Clinical Development</name_or_title>
      <organization>Kala Pharmaceuticals Inc</organization>
      <email>results004@kalarx.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/NCT02245516
org study id: KPI-121-C-004
nct id: NCT02245516
lead sponsor: 
has dmc: No
The primary objectives of the study are to evaluate the safety and effect of KPI-121 0.25%
      ophthalmic suspension and KPI-121 1.0% ophthalmic suspension on intraretinal or subretinal
      fluid secondary to Retinal Vein Occlusion or Diabetic Macular Edema.
This is a multicenter, randomized, single-masked study evaluating the safety and effect of
      topical ocular administration of either KPI-121 0.25% ophthalmic suspension or KPI-121 1.0%
      ophthalmic suspension in subjects with intraretinal or subretinal fluid secondary to Retinal
      Vein Occlusion or Diabetic Macular Edema.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)
time frame: Day 1 to Day 57
description: Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.
measure: Macular Volume by SD-OCT
time frame: Day 1 to Day 57
description: Change in measurement (in microns) in macular volume as measured by Spectral Domain Optical Coherence Tomography (OCT)
measure: Center Subfield Retinal Thickness by SD-OCT
time frame: Day 1 to Day 57
description: Change in measurement (in microns) in the central subfield retinal thickness as measured by Spectral Domain Optical Coherence Tomography (OCT)
measure: Investigator's Assessment of Leakage on the Fluorescein Angiogram
time frame: Day 1 to Day 57
description: Change in leakage by investigator's assessment of the fluorescein angiogram
arm group label: KPI-121 0.25% Ophthalmic Suspension
arm group type: Active Comparator
description: KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema
arm group label: KPI-121 1.0% Ophthalmic Suspension
arm group type: Active Comparator
description: KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema
intervention type: Drug
intervention name: KPI-121 0.25% Ophthalmic Suspension
description: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
arm group label: KPI-121 0.25% Ophthalmic Suspension
other name: Loteprednol etabonate 0.25%
intervention type: Drug
intervention name: KPI-121 1.0% Ophthalmic Suspension
description: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
arm group label: KPI-121 1.0% Ophthalmic Suspension
other name: Loteprednol etabonate 1.0%
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Retinal Vein Occlusion
mesh term: Edema
mesh term: Loteprednol Etabonate
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 