<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/NCT02260180</url>
  </required_header>
  <id_info>
    <org_study_id>A-101-SEBK-203</org_study_id>
    <nct_id>NCT02260180</nct_id>
  </id_info>
  <brief_title>Study of A-101 for the Treatment of Seborrheic Keratosis</brief_title>
  <official_title>A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the Dose-Response Profile of A-101 Topical Solution in Subjects With Seborrheic Keratosis of the Face</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aclaris Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aclaris Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and dose-response of 2 concentrations of&#xD;
      A-101 versus a vehicle control in the treatment of seborrheic keratosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main objective of this study is to evaluate the dose-response relationship of 2&#xD;
      concentrations of A-101 Solution and its matching A-101 Solution Vehicle when applied to&#xD;
      seborrheic Keratosis (SK) target lesions on the face. A further objective is to evaluate the&#xD;
      safety and efficacy of 2 concentrations of A-101 Solution and its matching A-101 Solution&#xD;
      Vehicle when applied topically up to 2 times to SK target lesions on the face.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8.</measure>
    <time_frame>Day 106</time_frame>
    <description>The primary effectiveness analysis was a comparison between each A-101 group and the vehicle group based on the percentage with target lesions judged to be clear on the PLA (PLA = 0) at Visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline PLA Score at Visit 8</measure>
    <time_frame>Day 106</time_frame>
    <description>A secondary efficacy analysis was the mean change from baseline PLA Score at visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better. A lower (more negative) mean change is a better outcome.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">119</enrollment>
  <condition>Seborrheic Keratosis</condition>
  <arm_group>
    <arm_group_label>A-101 40%</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A-101 40% Topical Solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A-101 32.5%</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A-101 32.5% Topical Solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A-101 Vehicle Topical Solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A-101 0% Topical Solution (vehicle)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>A-101</intervention_name>
    <description>Topical Solution</description>
    <arm_group_label>A-101 32.5%</arm_group_label>
    <arm_group_label>A-101 40%</arm_group_label>
    <arm_group_label>A-101 Vehicle Topical Solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is at least 18 years of age&#xD;
&#xD;
          2. Subject has a Fitzpatrick skin type of 1-4&#xD;
&#xD;
          3. Subject has a clinical diagnosis of stable clinically typical seborrheic keratosis&#xD;
&#xD;
          4. Subject has 1 appropriate seborrheic keratosis target lesion, as defined below&#xD;
             (Section 5.4), on the face:&#xD;
&#xD;
               -  Have a clinically typical appearance&#xD;
&#xD;
               -  Be treatment naïve&#xD;
&#xD;
               -  Have a Physician's Lesion Assessment (PLA) of ≥2 (Section 6.1.2)&#xD;
&#xD;
               -  Have a longest axis that is ≥7mm and ≤15mm (Section 5.4)&#xD;
&#xD;
               -  Have a longest dimension perpendicular to the longest axis that is ≥7mm and ≤15mm&#xD;
                  (Section 5.4)&#xD;
&#xD;
               -  Have a thickness that is ≤2mm&#xD;
&#xD;
               -  Be a discrete lesion&#xD;
&#xD;
               -  Be, when centered in the area outlined by the provided 3cm diameter circular&#xD;
                  template, the only seborrheic keratosis lesion present&#xD;
&#xD;
               -  Not be on the eyelids&#xD;
&#xD;
               -  Not be within 5mm of the orbital rim&#xD;
&#xD;
               -  Not be covered with hair which, in the investigator's opinion, would interfere&#xD;
                  with the study medication application or the study evaluations (NB: the study&#xD;
                  medication may bleach hair)&#xD;
&#xD;
               -  Not be in an intertriginous fold&#xD;
&#xD;
               -  Not be pedunculated.&#xD;
&#xD;
          5. If the subject is a woman of childbearing potential, she has a negative urine&#xD;
             pregnancy test and agrees to use an approved effective method of birth control&#xD;
             (Section 8) for the duration of the study&#xD;
&#xD;
          6. Subject is non-pregnant and non-lactating&#xD;
&#xD;
          7. Subject is in good general health and free of any known disease state or physical&#xD;
             condition which, in the investigator's opinion, might impair evaluation of the target&#xD;
             lesion or which exposes the subject to an unacceptable risk by study participation&#xD;
&#xD;
          8. Subject is willing and able to follow all study instructions and to attend all study&#xD;
             visits&#xD;
&#xD;
          9. Subject is able to comprehend and willing to sign an Informed Consent Form (ICF).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has clinically atypical and/or rapidly growing seborrheic keratosis lesions&#xD;
&#xD;
          2. Subject has presence of multiple eruptive seborrheic keratosis lesions (Sign of&#xD;
             Leser-Trelat)&#xD;
&#xD;
          3. Subject has a current systemic malignancy&#xD;
&#xD;
          4. Subject has a history of keloid formation or hypertrophic scarring&#xD;
&#xD;
          5. Subject has used any of the following systemic therapies within the specified period&#xD;
             prior to Visit 1:&#xD;
&#xD;
               -  Retinoids; 180 days&#xD;
&#xD;
               -  Glucocortico-steroids; 28 days&#xD;
&#xD;
               -  Anti-metabolites (e.g., methotrexate); 28 days&#xD;
&#xD;
          6. Subject has used any of the following topical therapies within the specified period&#xD;
             prior to Visit 1 on, or in a proximity to the target lesion, which in the&#xD;
             investigator's opinion, interferes with the application of the study medication or the&#xD;
             study assessments:&#xD;
&#xD;
               -  LASER, light (e.g., intense pulsed light (IPL), photo-dynamic therapy(PDT)) or&#xD;
                  other energy based therapy; 180 days&#xD;
&#xD;
               -  Retinoids; 28 days&#xD;
&#xD;
               -  Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-fluorouracil, or&#xD;
                  ingenol mebutate; 60 days&#xD;
&#xD;
               -  Glucocortico-steroids or antibiotics; 14 days&#xD;
&#xD;
          7. Subject currently has or has had any of the following within the specified period&#xD;
             prior to Visit 1 on, or in a proximity to the target lesion, which in the&#xD;
             investigator's opinion, interferes with the application of the study medication or the&#xD;
             study assessments :&#xD;
&#xD;
               -  A cutaneous malignancy; 180 days&#xD;
&#xD;
               -  Experienced a sunburn; 28 days&#xD;
&#xD;
               -  A pre-malignancy (e.g., actinic keratosis); currently&#xD;
&#xD;
               -  Body art (e.g., tattoos, piercing, etc.); currently&#xD;
&#xD;
               -  Excessive tan; currently&#xD;
&#xD;
          8. Subject has a history of sensitivity to any of the ingredients in the study&#xD;
             medications&#xD;
&#xD;
          9. Subject has any current skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun&#xD;
             damage, etc.), or condition (e.g., sunburn, excessive hair, open wounds) which, in the&#xD;
             investigator's opinion, might put the subject at undue risk by study participation or&#xD;
             interfere with the study conduct or evaluations&#xD;
&#xD;
         10. Subject has participated in an investigational drug trial in which administration of&#xD;
             an investigational study medication occurred within 30 days prior to Visit 1.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brian Beger, BS</last_name>
    <role>Study Director</role>
    <affiliation>Aclaris Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Medical Research Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97223</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Philadelphia Institute of Dermatology</name>
      <address>
        <city>Fort Washington</city>
        <state>Pennsylvania</state>
        <zip>19034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DermReseach, Inc.</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78759</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Education &amp; Research Foundation, Inc.</name>
      <address>
        <city>Lynchburg</city>
        <state>Virginia</state>
        <zip>24501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <results_first_submitted>September 30, 2018</results_first_submitted>
  <results_first_submitted_qc>November 5, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 6, 2018</results_first_posted>
  <last_update_submitted>November 17, 2020</last_update_submitted>
  <last_update_submitted_qc>November 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 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>Keratosis, Actinic</mesh_term>
    <mesh_term>Keratosis</mesh_term>
    <mesh_term>Keratosis, Seborrheic</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 1, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT02260180/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>A-101 40% Topical Solution</title>
          <description>A-101 40% Topical Solution&#xD;
A-101: Topical Solution</description>
        </group>
        <group group_id="P2">
          <title>A-101 32.5% Topical Solution</title>
          <description>A-101 32.5% Topical Solution&#xD;
A-101: Topical Solution</description>
        </group>
        <group group_id="P3">
          <title>A-101 Vehicle Topical Solution</title>
          <description>A-101 0% Topical Solution (vehicle)&#xD;
A-101: Topical 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="39"/>
                <participants group_id="P2" count="39"/>
                <participants group_id="P3" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="39"/>
                <participants group_id="P3" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>A-101 40%</title>
          <description>A-101 40% Topical Solution</description>
        </group>
        <group group_id="B2">
          <title>A-101 32.5%</title>
          <description>A-101 32.5% Topical Solution</description>
        </group>
        <group group_id="B3">
          <title>A-101 Vehicle Topical Solution</title>
          <description>A-101 0% Topical Solution (vehicle)</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="39"/>
            <count group_id="B2" value="39"/>
            <count group_id="B3" value="41"/>
            <count group_id="B4" value="119"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <title>Age</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71" lower_limit="53" upper_limit="93"/>
                    <measurement group_id="B2" value="71" lower_limit="33" upper_limit="88"/>
                    <measurement group_id="B3" value="67" lower_limit="47" upper_limit="87"/>
                    <measurement group_id="B4" value="70" lower_limit="33" upper_limit="93"/>
                  </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="21"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="54"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="41"/>
                    <measurement group_id="B4" value="118"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8.</title>
        <description>The primary effectiveness analysis was a comparison between each A-101 group and the vehicle group based on the percentage with target lesions judged to be clear on the PLA (PLA = 0) at Visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better.</description>
        <time_frame>Day 106</time_frame>
        <group_list>
          <group group_id="O1">
            <title>A-101 40%</title>
            <description>A-101 40% Topical Solution</description>
          </group>
          <group group_id="O2">
            <title>A-101 32.5%</title>
            <description>A-101 32.5% Topical Solution</description>
          </group>
          <group group_id="O3">
            <title>A-101 Vehicle Topical Solution</title>
            <description>A-101 0% Topical Solution (vehicle)</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8.</title>
          <description>The primary effectiveness analysis was a comparison between each A-101 group and the vehicle group based on the percentage with target lesions judged to be clear on the PLA (PLA = 0) at Visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>2-tail alpha was set to 0.05 with no adjustment for multiple comparisons.</non_inferiority_desc>
            <p_value>&lt;0.0001</p_value>
            <method>Chi-squared</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Chi-squared</method>
            <method_desc>2-tail alpha was set to 0.05 with no adjustment for multiple comparisons.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline PLA Score at Visit 8</title>
        <description>A secondary efficacy analysis was the mean change from baseline PLA Score at visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better. A lower (more negative) mean change is a better outcome.</description>
        <time_frame>Day 106</time_frame>
        <population>Participants completing the study.</population>
        <group_list>
          <group group_id="O1">
            <title>A-101 40%</title>
            <description>A-101 40% Topical Solution</description>
          </group>
          <group group_id="O2">
            <title>A-101 32.5%</title>
            <description>A-101 32.5% Topical Solution</description>
          </group>
          <group group_id="O3">
            <title>A-101 Vehicle Topical Solution</title>
            <description>A-101 0% Topical Solution (vehicle)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline PLA Score at Visit 8</title>
          <description>A secondary efficacy analysis was the mean change from baseline PLA Score at visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better. A lower (more negative) mean change is a better outcome.</description>
          <population>Participants completing the study.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="1.11"/>
                    <measurement group_id="O2" value="-1.4" spread="1.14"/>
                    <measurement group_id="O3" value="-0.1" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>No adjustment for multiple comparisons were made.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>Baseline PLA was the covariate. Comparisons were performed within the model using least-squares means and the common error term.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The primary efficacy analysis of mean change from baseline to Visit 8 PLA was performed using analysis of covariance (ANCOVA) with baseline PLA as the covariate. Comparisons between vehicle and each A-101 group were performed within the model using least-squares means and the common error term.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>No adjustment for multiple comparisons were conducted.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>Baseline PLA was the covariate. Comparisons were performed within the model using least-squares means and the common error term.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events (TEAEs) had a start date on or after the date of Visit 2 (study day 1) and treatment-emergent serious adverse events (TESAEs) had a start date on or after the date of Visit 1 (Screening). Collection continued through the patients last visit or the end of the study, visit 8 (Day 106.)</time_frame>
      <desc>An adverse event (AE) was any untoward medical occurrence in a patient or clinical investigation subject administered a study medication(s) and that did not necessarily have a causal relationship with the study medication.&#xD;
Safety summaries by study medication group will include listings by study medication of adverse events incidences within each MedDRA System Organ Class, and changes from pre-application values in vital signs.</desc>
      <group_list>
        <group group_id="E1">
          <title>A-101 40%</title>
          <description>A-101 40% Topical Solution&#xD;
A-101: Topical Solution</description>
        </group>
        <group group_id="E2">
          <title>A-101 32.5%</title>
          <description>A-101 32.5% Topical Solution&#xD;
A-101: Topical Solution</description>
        </group>
        <group group_id="E3">
          <title>A-101 Vehicle Topical Solution</title>
          <description>A-101 0% Topical Solution (vehicle)&#xD;
A-101: Topical Solution</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (14.2)</default_vocab>
        <default_assessment>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="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>metastatic neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (14.2)</default_vocab>
        <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="13" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="39"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Eustacian Tube Obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal Allergy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Onychomycosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Oral Herpes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Tooth abcess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Face injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypocholestersterolaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carpal tunnel syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Sinus Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Actinic Keratosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Skin Haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </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>The Institution and Investigator agree not to publish the results of this study without the prior written consent of the Sponsor.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Judith Schnyder, Senior Director of Clinical Operations</name_or_title>
      <organization>Aclaris Therapeutics, Inc.</organization>
      <phone>1-484-329-2144</phone>
      <email>jschnyder@aclaristx.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/NCT02260180
org study id: A-101-SEBK-203
nct id: NCT02260180
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the safety and dose-response of 2 concentrations of
      A-101 versus a vehicle control in the treatment of seborrheic keratosis.
The main objective of this study is to evaluate the dose-response relationship of 2
      concentrations of A-101 Solution and its matching A-101 Solution Vehicle when applied to
      seborrheic Keratosis (SK) target lesions on the face. A further objective is to evaluate the
      safety and efficacy of 2 concentrations of A-101 Solution and its matching A-101 Solution
      Vehicle when applied topically up to 2 times to SK target lesions on the face.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8.
time frame: Day 106
description: The primary effectiveness analysis was a comparison between each A-101 group and the vehicle group based on the percentage with target lesions judged to be clear on the PLA (PLA = 0) at Visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better.
measure: Mean Change From Baseline PLA Score at Visit 8
time frame: Day 106
description: A secondary efficacy analysis was the mean change from baseline PLA Score at visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better. A lower (more negative) mean change is a better outcome.
arm group label: A-101 40%
arm group type: Active Comparator
description: A-101 40% Topical Solution
arm group label: A-101 32.5%
arm group type: Active Comparator
description: A-101 32.5% Topical Solution
arm group label: A-101 Vehicle Topical Solution
arm group type: Placebo Comparator
description: A-101 0% Topical Solution (vehicle)
intervention type: Drug
intervention name: A-101
description: Topical Solution
arm group label: A-101 32.5%
arm group label: A-101 40%
arm group label: A-101 Vehicle Topical Solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Brian Beger, BS
role: Study Director
affiliation: Aclaris Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Keratosis, Actinic
mesh term: Keratosis
mesh term: Keratosis, Seborrheic
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 