<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/NCT04492618</url>
  </required_header>
  <id_info>
    <org_study_id>19-004087</org_study_id>
    <nct_id>NCT04492618</nct_id>
  </id_info>
  <brief_title>Ruxolitinib Cream in the Treatment of Cutaneous Necrobiosis Lipoidica</brief_title>
  <official_title>Ruxolitinib Cream in the Treatment of Cutaneous Necrobiosis Lipoidica</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aaron R. Mangold</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is evaluating the safety and efficacy of a topical drug treatment&#xD;
      &quot;Ruxolitinib&quot; in treating Necrobiosis Lipoidica (NL).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 29, 2020</start_date>
  <completion_date type="Actual">March 16, 2022</completion_date>
  <primary_completion_date type="Actual">March 16, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mean Necrobiosis Lipoidica (NL) Lesion Score</measure>
    <time_frame>Baseline, week 12</time_frame>
    <description>The NL skin scoring system examines the index treatment lesion on a scale from 0 (none) to 3 (severe) for each of the following areas: erythema, infiltration, ulceration, and pain. A total possible score of 0-12, with lower scores indicating none and higher scores indicating more severe.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Necrobiosis Lipoidica</condition>
  <arm_group>
    <arm_group_label>Necrobiosis Lipoidica</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adults with cutaneous Necrobiosis Lipoidica (NL) up to 10% of the body surface area (BSA) treated with Ruxolitinib cream</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Ruxolitinib cream 1.5%, topical application will be used twice daily on lesions of Necrobiosis Lipoidica</description>
    <arm_group_label>Necrobiosis Lipoidica</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must be able to understand and comply with the requirements of the study and&#xD;
             communicate with the investigator. Subjects must give written, signed, and dated&#xD;
             informed consent before any study related activity is performed. When appropriate, a&#xD;
             legal representative will sign the informed consent according to local laws and&#xD;
             regulation&#xD;
&#xD;
          -  Both men and women must be at least 18 years of age at the time of screening&#xD;
&#xD;
          -  Subjects must have clinical and histological features of NL&#xD;
&#xD;
          -  Subjects must have at least one NL lesion measuring at least 1.7 cm&#xD;
&#xD;
          -  NL must not affect greater than 10% BSA&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  On excluded therapies, not on a stable dose of a therapy, or incompletely washed out&#xD;
             for a therapy (Table-1).&#xD;
&#xD;
          -  Known hypersensitivity to Ruxolitinib formulation.&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women (pregnancy is defined as the state of a female&#xD;
             after conception and until the termination of gestation, confirmed by a positive human&#xD;
             chorionic gonadotropin (hCG) laboratory test).&#xD;
&#xD;
          -  Women of childbearing potential [Post-menopausal or not of child-bearing potential is&#xD;
             defined by: 1 year of natural (spontaneous) amenorrhea or Surgical bilateral&#xD;
             oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at&#xD;
             least 6 weeks ago. Oophorectomy alone must be confirmed by follow up hormone level&#xD;
             assessment to be considered not of child-bearing potential, defined as all women&#xD;
             physiologically capable of becoming pregnant, unless they are using medically&#xD;
             acceptable methods of contraception which includes:&#xD;
&#xD;
               -  Total abstinence (periodic abstinence and withdrawal are not acceptable methods&#xD;
                  of contraception).&#xD;
&#xD;
               -  Female sterilization (bilateral oophorectomy with or without hysterectomy), total&#xD;
                  hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.&#xD;
                  Oophorectomy alone requires follow up hormone level assessment for fertility.&#xD;
&#xD;
               -  Male sterilization (at least 6 months prior to screening). The vasectomized male&#xD;
                  partner should be the sole partner for that subject.&#xD;
&#xD;
               -  Barrier methods of contraception: condom or occlusive cap.&#xD;
&#xD;
               -  Use of oral, injected or implanted hormonal methods of contraception or other&#xD;
                  forms or hormonal contraception that have complete efficacy (failure &lt;1%). (The&#xD;
                  dose of the contraceptive should be stable for 3 months).&#xD;
&#xD;
          -  Active ongoing inflammatory diseases of the skin other than NL that might confound the&#xD;
             evaluation of the benefit of ruxolitinib cream.&#xD;
&#xD;
          -  Underlying condition (including, but not limited to metabolic, hematologic, renal,&#xD;
             hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal&#xD;
             conditions) which, in the opinion of the investigator, significantly immunocompromised&#xD;
             the subject and/or places the subject at unacceptable risk for receiving an&#xD;
             immunomodulatory therapy.&#xD;
&#xD;
          -  Active systemic infections during the 2 weeks prior to randomization (common cold&#xD;
             viruses not included) or any infection that reoccurs on a regular basis.&#xD;
&#xD;
          -  Current severe progressive or uncontrolled disease which the investigator renders the&#xD;
             subject unsuitable for the trial or puts the subject at increased risk.&#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>Aaron R Mangold</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <results_first_submitted>January 12, 2023</results_first_submitted>
  <results_first_submitted_qc>January 12, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 8, 2023</results_first_posted>
  <last_update_submitted>January 12, 2023</last_update_submitted>
  <last_update_submitted_qc>January 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Aaron R. Mangold</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>Necrobiotic Disorders</mesh_term>
    <mesh_term>Necrobiosis Lipoidica</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>January 29, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT04492618/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Necrobiosis Lipoidica</title>
          <description>Adults with cutaneous Necrobiosis Lipoidica (NL) up to 10% of the body surface area (BSA) were treated with Ruxolitinib cream&#xD;
Ruxolitinib: Ruxolitinib cream 1.5%, topical application was used twice daily on lesions of Necrobiosis Lipoidica</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Necrobiosis Lipoidica</title>
          <description>Adults with cutaneous Necrobiosis Lipoidica (NL) up to 10% of the body surface area (BSA) were treated with Ruxolitinib cream&#xD;
Ruxolitinib: Ruxolitinib cream 1.5%, topical application was used twice daily on lesions of Necrobiosis Lipoidica</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </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="43.6" 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="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Mean Necrobiosis Lipoidica (NL) Lesion Score</title>
        <description>The NL skin scoring system examines the index treatment lesion on a scale from 0 (none) to 3 (severe) for each of the following areas: erythema, infiltration, ulceration, and pain. A total possible score of 0-12, with lower scores indicating none and higher scores indicating more severe.</description>
        <time_frame>Baseline, week 12</time_frame>
        <population>1 Subject withdrew. Week 12 data was not collected nor analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Necrobiosis Lipoidica</title>
            <description>Adults with cutaneous Necrobiosis Lipoidica (NL) up to 10% of the body surface area (BSA) were treated with Ruxolitinib cream&#xD;
Ruxolitinib: Ruxolitinib cream 1.5%, topical application was used twice daily on lesions of Necrobiosis Lipoidica</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Necrobiosis Lipoidica (NL) Lesion Score</title>
          <description>The NL skin scoring system examines the index treatment lesion on a scale from 0 (none) to 3 (severe) for each of the following areas: erythema, infiltration, ulceration, and pain. A total possible score of 0-12, with lower scores indicating none and higher scores indicating more severe.</description>
          <population>1 Subject withdrew. Week 12 data was not collected nor analyzed</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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.7" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected for all subjects from baseline to end of study, approximately 16 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Necrobiosis Lipoidica</title>
          <description>Adults with cutaneous Necrobiosis Lipoidica (NL) up to 10% of the body surface area (BSA) were treated with Ruxolitinib cream&#xD;
Ruxolitinib: Ruxolitinib cream 1.5%, topical application was used twice daily on lesions of Necrobiosis Lipoidica</description>
        </group>
      </group_list>
      <serious_events>
        <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="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Heaviness Bilateral legs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Leg pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lower extremity aches</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tingling feeling left shin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcimona removal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cold Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Burning sensation on NL spots</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Heightened sensitivity on lesions</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Aaron R. Mangold, M.D.</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>480-301-4256</phone>
      <email>Mangold.Aaron@mayo.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/NCT04492618
org study id: 19-004087
nct id: NCT04492618
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This research study is evaluating the safety and efficacy of a topical drug treatment
      "Ruxolitinib" in treating Necrobiosis Lipoidica (NL).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Mean Necrobiosis Lipoidica (NL) Lesion Score
time frame: Baseline, week 12
description: The NL skin scoring system examines the index treatment lesion on a scale from 0 (none) to 3 (severe) for each of the following areas: erythema, infiltration, ulceration, and pain. A total possible score of 0-12, with lower scores indicating none and higher scores indicating more severe.
arm group label: Necrobiosis Lipoidica
arm group type: Experimental
description: Adults with cutaneous Necrobiosis Lipoidica (NL) up to 10% of the body surface area (BSA) treated with Ruxolitinib cream
intervention type: Drug
intervention name: Ruxolitinib
description: Ruxolitinib cream 1.5%, topical application will be used twice daily on lesions of Necrobiosis Lipoidica
arm group label: Necrobiosis Lipoidica
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Aaron R Mangold
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Sponsor-Investigator
investigator affiliation: Mayo Clinic
investigator full name: Aaron R. Mangold
investigator title: Principal Investigator
mesh term: Necrobiotic Disorders
mesh term: Necrobiosis Lipoidica
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 