<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/NCT03041038</url>
  </required_header>
  <id_info>
    <org_study_id>CAIN457AUS05T</org_study_id>
    <nct_id>NCT03041038</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of Secukinumab in Patients With Ichthyoses</brief_title>
  <official_title>A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Period, Followed by an Open-Label Maintenance Dosing Period to Evaluate the Efficacy and Safety of Secukinumab in Patients With Ichthyoses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The ichthyoses are a group of lifelong genetic disorders which share characteristics of&#xD;
      generalized skin thickening, scaling and underlying cutaneous inflammation. There are no&#xD;
      therapies based on growing understanding of what causes the disease. However, there have been&#xD;
      recent discoveries of marked elevations in expression of interleukin-17A (IL-17A) and&#xD;
      IL-17-related cytokines in the skin of individuals with ichthyosis, which may explain the&#xD;
      inflammation. Investigators propose that IL-17-targeting therapeutics will safely suppress&#xD;
      the inflammation and possibly the other features of ichthyosis, improving quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The ichthyoses are a group of lifelong genetic disorders which share characteristics of&#xD;
      generalized skin thickening, scaling and underlying cutaneous inflammation. The vast majority&#xD;
      are orphan disorders and are associated with extremely poor quality of life related to social&#xD;
      ostracism from altered appearance, associated itchiness and discomfort, and functional&#xD;
      limitations from the skin disease. Among the most common of these orphan disorders are&#xD;
      autosomal recessive congenital ichthyosis (ARCI) with its phenotypic subsets of lamellar&#xD;
      ichthyosis (ARCI-LI) and congenital ichthyosiform erythroderma (ARCI-CIE), epidermolytic&#xD;
      ichthyosis (EI) and Netherton syndrome (NS). Therapy is time-consuming for patients or&#xD;
      parents and is supportive, focusing on clearance of the scaling. There are no therapies based&#xD;
      on growing understanding of what causes the disease. There have been recent discoveries of&#xD;
      marked elevations in expression of interleukin-17A (IL-17A) and IL-17-related cytokines in&#xD;
      the skin of individuals with ichthyosis, which may explain the inflammation. Psoriasis,&#xD;
      another inflammatory skin disorder with redness and scaling, has now been shown to result&#xD;
      from IL-17 pathway activation and IL-17A inhibition is the most effective therapy known to&#xD;
      treat psoriasis. Investigators propose that IL-17-targeting therapeutics will safely suppress&#xD;
      the inflammation and possibly the other features of ichthyosis, improving quality of life. In&#xD;
      this long-term, open-label extension, Investigators propose to treat adults with ichthyosis&#xD;
      and at least moderate erythema with subcutaneously administered anti-IL-17 antibody&#xD;
      (secukinumab) and to serially assess clinical response to this therapy and its safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 31, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI)</measure>
    <time_frame>16 Weeks</time_frame>
    <description>Primary Efficacy Endpoint. The IASI score was modelled after the Eczema Area and Severity Index (EASI) and Psoriasis Area and Severity Index (PASI), commonly used in clinical trials for atopic dermatitis and psoriasis, respectively. This scale measures erythema and scaling and has a range of 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. Mean difference IASI total score at Baseline was compared to IASI total score at Week 16.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16</measure>
    <time_frame>16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment</time_frame>
    <description>Primary Safety Endpoint</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Ichthyosis</condition>
  <condition>Autosomal Recessive Congenital Ichthyosis</condition>
  <condition>Lamellar Ichthyosis</condition>
  <condition>Congenital Ichthyosiform Erythroderma</condition>
  <condition>Epidermolytic Ichthyosis</condition>
  <condition>Netherton Syndrome</condition>
  <arm_group>
    <arm_group_label>Secukinumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>Anti IL-17A antibody</description>
    <arm_group_label>Secukinumab</arm_group_label>
    <other_name>Cosentyx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sterile Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject has provided informed consent&#xD;
&#xD;
          -  Subjects are at least 18 years of age or older at the time of screening&#xD;
&#xD;
          -  Female subjects must not be pregnant or breast-feeding&#xD;
&#xD;
          -  Female subjects of child-bearing potential with a negative urine pregnancy test and&#xD;
             using at least one form of contraception (abstinence allowed)&#xD;
&#xD;
          -  Subjects must have a confirmed diagnosis of ARCI (divided phenotypically into ARCI-LI&#xD;
             or ARCI-CIE), EI or NS (by genotype or willingness to be genotyped)&#xD;
&#xD;
          -  Subjects must be clinically judged to be immunocompetent.&#xD;
&#xD;
          -  Subjects will have no allergy to secukinumab or components of the product.&#xD;
&#xD;
          -  Subjects will have normal baseline laboratory testing (CMP, CBC, HIV negative,&#xD;
             hepatitis B, C negative, QuantiFERON®-TB gold negative)&#xD;
&#xD;
          -  Subjects must have an erythema score of at least 18 on IASI and an IASI-E score of 12&#xD;
             (at least moderate severity of erythema) at baseline&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who are unable to give informed consent or assent.&#xD;
&#xD;
          -  Subjects without a confirmed diagnosis ARCI, EI, or NS.&#xD;
&#xD;
          -  Subjects who have a known allergy to secukinumab.&#xD;
&#xD;
          -  Female subjects who are pregnant, considering becoming pregnant, or will breastfeed.&#xD;
&#xD;
          -  Subjects who have prior biologic use targeting IL-17A/IL-17 receptor A or IL-12/IL-23&#xD;
             or who have prior use of TNF-alpha blockers.&#xD;
&#xD;
          -  Subjects who have used a systemic retinoid within one month prior to initiation.&#xD;
&#xD;
          -  Subjects who have used topical retinoids or keratolytics within one week prior to&#xD;
             initiation.&#xD;
&#xD;
          -  Subjects who have used emollient on the area to be biopsied in the previous 24 hours&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amy Paller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University Department of Dermatology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emma Guttman-Yassky, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mt. Sinai Hospital Department of Dermatology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Dermatology, Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <results_first_submitted>July 7, 2021</results_first_submitted>
  <results_first_submitted_qc>August 2, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 25, 2021</results_first_posted>
  <last_update_submitted>August 2, 2021</last_update_submitted>
  <last_update_submitted_qc>August 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Amy Paller</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ichthyosis</mesh_term>
    <mesh_term>Ichthyosis, Lamellar</mesh_term>
    <mesh_term>Netherton Syndrome</mesh_term>
    <mesh_term>Ichthyosiform Erythroderma, Congenital</mesh_term>
    <mesh_term>Hyperkeratosis, Epidermolytic</mesh_term>
    <mesh_term>Dermatitis, Exfoliative</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 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT03041038/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Secukinumab</title>
          <description>Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Secukinumab: Anti IL-17A antibody</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Week 16</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Week 32</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Secukinumab</title>
          <description>Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Secukinumab: Anti IL-17A antibody</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Placebo</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="11"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.2" spread="11.7"/>
                    <measurement group_id="B2" value="35.5" spread="12.7"/>
                    <measurement group_id="B3" value="34.7" spread="12.9"/>
                  </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="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </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>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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ichthyosis Subtype</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>CIE</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>EI</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>LI</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>NS</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Site</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Mount Sinai</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Northwestern</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.9" spread="13.5"/>
                    <measurement group_id="B2" value="75.5" spread="30.4"/>
                    <measurement group_id="B3" value="72.4" spread="22.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ichthyosis Area Severity Index (IASI)</title>
          <description>The IASI score was modelled after the Eczema Area and Severity Index (EASI) and Psoriasis Area and Severity Index (PASI), commonly used in clinical trials for atopic dermatitis and psoriasis, respectively. This scale measures erythema and scaling and has a range of 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.7" spread="6.5"/>
                    <measurement group_id="B2" value="36.2" spread="4.7"/>
                    <measurement group_id="B3" value="34.8" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI)</title>
        <description>Primary Efficacy Endpoint. The IASI score was modelled after the Eczema Area and Severity Index (EASI) and Psoriasis Area and Severity Index (PASI), commonly used in clinical trials for atopic dermatitis and psoriasis, respectively. This scale measures erythema and scaling and has a range of 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. Mean difference IASI total score at Baseline was compared to IASI total score at Week 16.</description>
        <time_frame>16 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Secukinumab</title>
            <description>Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Secukinumab: Anti IL-17A antibody</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI)</title>
          <description>Primary Efficacy Endpoint. The IASI score was modelled after the Eczema Area and Severity Index (EASI) and Psoriasis Area and Severity Index (PASI), commonly used in clinical trials for atopic dermatitis and psoriasis, respectively. This scale measures erythema and scaling and has a range of 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. Mean difference IASI total score at Baseline was compared to IASI total score at Week 16.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="-7.8" upper_limit="12.7"/>
                    <measurement group_id="O2" value="4.3" lower_limit="-6.5" upper_limit="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16</title>
        <description>Primary Safety Endpoint</description>
        <time_frame>16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Secukinumab</title>
            <description>Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Secukinumab: Anti IL-17A antibody</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Placebo</description>
          </group>
          <group group_id="O3">
            <title>Open Label</title>
            <description>Participants transitioned to open label treatment with Secukinumab300mg monthly after week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16</title>
          <description>Primary Safety Endpoint</description>
          <units>infections</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>56 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Secukinumab</title>
          <description>Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Secukinumab: Anti IL-17A antibody</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial&#xD;
Placebo</description>
        </group>
        <group group_id="E3">
          <title>Open Label</title>
          <description>Participants transitioned to open label treatment with Secukinumab300mg monthly after week 16.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hospitalization-GERD</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hospitalization-pyelonephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Otitis externa bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Amy Paller</name_or_title>
      <organization>Northwestern University</organization>
      <phone>3126953721</phone>
      <email>NUderm-research@northwestern.edu</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/NCT03041038
org study id: CAIN457AUS05T
nct id: NCT03041038
lead sponsor: 
collaborator: 
has dmc: Yes
The ichthyoses are a group of lifelong genetic disorders which share characteristics of
      generalized skin thickening, scaling and underlying cutaneous inflammation. There are no
      therapies based on growing understanding of what causes the disease. However, there have been
      recent discoveries of marked elevations in expression of interleukin-17A (IL-17A) and
      IL-17-related cytokines in the skin of individuals with ichthyosis, which may explain the
      inflammation. Investigators propose that IL-17-targeting therapeutics will safely suppress
      the inflammation and possibly the other features of ichthyosis, improving quality of life.
The ichthyoses are a group of lifelong genetic disorders which share characteristics of
      generalized skin thickening, scaling and underlying cutaneous inflammation. The vast majority
      are orphan disorders and are associated with extremely poor quality of life related to social
      ostracism from altered appearance, associated itchiness and discomfort, and functional
      limitations from the skin disease. Among the most common of these orphan disorders are
      autosomal recessive congenital ichthyosis (ARCI) with its phenotypic subsets of lamellar
      ichthyosis (ARCI-LI) and congenital ichthyosiform erythroderma (ARCI-CIE), epidermolytic
      ichthyosis (EI) and Netherton syndrome (NS). Therapy is time-consuming for patients or
      parents and is supportive, focusing on clearance of the scaling. There are no therapies based
      on growing understanding of what causes the disease. There have been recent discoveries of
      marked elevations in expression of interleukin-17A (IL-17A) and IL-17-related cytokines in
      the skin of individuals with ichthyosis, which may explain the inflammation. Psoriasis,
      another inflammatory skin disorder with redness and scaling, has now been shown to result
      from IL-17 pathway activation and IL-17A inhibition is the most effective therapy known to
      treat psoriasis. Investigators propose that IL-17-targeting therapeutics will safely suppress
      the inflammation and possibly the other features of ichthyosis, improving quality of life. In
      this long-term, open-label extension, Investigators propose to treat adults with ichthyosis
      and at least moderate erythema with subcutaneously administered anti-IL-17 antibody
      (secukinumab) and to serially assess clinical response to this therapy and its safety.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Reduction at Week 16 in the Ichthyosis Area Severity Index (IASI)
time frame: 16 Weeks
description: Primary Efficacy Endpoint. The IASI score was modelled after the Eczema Area and Severity Index (EASI) and Psoriasis Area and Severity Index (PASI), commonly used in clinical trials for atopic dermatitis and psoriasis, respectively. This scale measures erythema and scaling and has a range of 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. Mean difference IASI total score at Baseline was compared to IASI total score at Week 16.
measure: Total Number of Bacterial or Fungal Mucocutaneous Infections Through Week 16
time frame: 16 weeks of secukinumab/placebo double blind followed by 32 week open label treatment
description: Primary Safety Endpoint
arm group label: Secukinumab
arm group type: Experimental
description: Secukinumab 300mg (liquid formation) administered subcutaneously weekly for 5 weeks then monthly until end of trial
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo (sterile saline) 2ml administered subcutaneously weekly for 5 weeks then monthly until end of trial
intervention type: Drug
intervention name: Secukinumab
description: Anti IL-17A antibody
arm group label: Secukinumab
other name: Cosentyx
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
other name: Sterile Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Amy Paller, MD
role: Principal Investigator
affiliation: Northwestern University Department of Dermatology
last name: Emma Guttman-Yassky, MD, PhD
role: Principal Investigator
affiliation: Mt. Sinai Hospital Department of Dermatology
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Northwestern University
investigator full name: Amy Paller
investigator title: Principal Investigator
mesh term: Ichthyosis
mesh term: Ichthyosis, Lamellar
mesh term: Netherton Syndrome
mesh term: Ichthyosiform Erythroderma, Congenital
mesh term: Hyperkeratosis, Epidermolytic
mesh term: Dermatitis, Exfoliative
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 