<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/NCT03826628</url>
  </required_header>
  <id_info>
    <org_study_id>DSLP-01</org_study_id>
    <nct_id>NCT03826628</nct_id>
  </id_info>
  <brief_title>Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex</brief_title>
  <official_title>A Phase 2/3, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Dose-Response Comparison of the Efficacy and Safety of a Topical Rapamycin Cream for the Treatment of Facial Angiofibromas (FA) Associated With Tuberous Sclerosis Complex (TSC) in Patients 6 Years of Age and Over</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dermatology Specialties Limited Partnership</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dermatology Specialties Limited Partnership</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>
      The study aims to compare the safety and efficacy of two different strengths of Rapamycin&#xD;
      cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA)&#xD;
      associated with Tuberous Sclerosis Complex (TSC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Topical rapamycin has previously been used to treat FA associated with TSC, reducing&#xD;
      erythema, papule size, while flattening lesions and improving skin texture. Topical rapamycin&#xD;
      has been reported to be well tolerated.&#xD;
&#xD;
      The efficacy and safety of a topical rapamycin cream at two strengths (0.5% and 1.0%) will be&#xD;
      assessed during a 26 week double-blind treatment phase with assessments made at clinical&#xD;
      visits at baseline, 2, 8, 14, 20 and 26 weeks, and at follow-up (4 weeks after the last dose&#xD;
      of study drug).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 28, 2019</start_date>
  <completion_date type="Actual">September 1, 2022</completion_date>
  <primary_completion_date type="Actual">September 1, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Obtaining Successful Treatment</measure>
    <time_frame>After 26 weeks treatment</time_frame>
    <description>Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Treatment Success</measure>
    <time_frame>From first dose to 26 weeks (± 2 weeks)</time_frame>
    <description>The time elapsed from the first dose to the time of treatment success, according to the Investigator's Global Assessment (IGA) scale. The total time of treatment was 26 weeks, although Covid-19 visit delays led to an extension of up to 2 weeks (28 weeks total) for some patients. Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Investigator's Global Assessment</measure>
    <time_frame>At baseline and after 26 weeks treatment</time_frame>
    <description>The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.&#xD;
IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Facial Angiofibroma Severity Index (FASI)</measure>
    <time_frame>At baseline and after 26 weeks treatment</time_frame>
    <description>The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline. FASI grades lesions according to their erythema, size and extent by summing the scores of each category. The final FASI scores range from (mild) 2-9 (severe).&#xD;
Erythema Skin color 0 Light Red 1 Red 2 Dark Red/purple 3 Size None 0 Small (&lt; 5mm) 1 Large (&gt; 5mm) 2 Confluent 3 Extension &lt;50 % cheek surface 2 &gt;50% cheek surface 3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale</measure>
    <time_frame>After 26 weeks treatment</time_frame>
    <description>Percentage change in facial angiofibroma since beginning treatment, as assessed by the participant or parent/caregiver. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where the participant or parent/caregiver estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective (Clinician) Percentage Change Rating Scale</measure>
    <time_frame>After 26 weeks treatment</time_frame>
    <description>Percentage improvement in facial angiofibroma since beginning treatment, as assessed by the clinician. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where clinicians estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Categorical Change in Facial Angiofibroma</measure>
    <time_frame>After 26 weeks treatment</time_frame>
    <description>Change in facial angiofibroma since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver. This was a single assessment time-point, where the participant or parent/caregiver evaluated the change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Facial Angiofibroma</condition>
  <condition>Tuberous Sclerosis</condition>
  <arm_group>
    <arm_group_label>0.5% Rapamycin cream, topical</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1.0% Rapamycin cream, topical</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rapamycin</intervention_name>
    <description>Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
    <arm_group_label>0.5% Rapamycin cream, topical</arm_group_label>
    <arm_group_label>1.0% Rapamycin cream, topical</arm_group_label>
    <other_name>sirolimus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients aged ≥ 6 years and ≤ 65 years on the day informed consent is&#xD;
             obtained&#xD;
&#xD;
          2. Patients diagnosed with TSC based on the clinical diagnostic criteria of International&#xD;
             Tuberous Sclerosis Complex Consensus Conference 2012 and presenting visible facial&#xD;
             angiofibroma&#xD;
&#xD;
          3. An FA severity score of 2 or 3 on the IGA scale&#xD;
&#xD;
          4. Patients or their legal representatives capable of understanding the explanation of&#xD;
             the clinical trial and who give written informed consent for participation&#xD;
&#xD;
          5. Patients or their legal representatives able to maintain patient diaries following the&#xD;
             instructions of the investigator or sub-investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who cannot carry out the treatment plan or follow-up assessment&#xD;
&#xD;
          2. Patients with serious skin lesions such as erosions or ulcers&#xD;
&#xD;
          3. Patients with known hypersensitivity to any component of the study product&#xD;
&#xD;
          4. Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3&#xD;
             months of enrolment&#xD;
&#xD;
          5. Patients who received laser therapy or surgical therapy within 6 months prior to trial&#xD;
             enrolment&#xD;
&#xD;
          6. Patients who participated in any other clinical trial within 3 months prior to the day&#xD;
             of enrolment&#xD;
&#xD;
          7. Patients judged unsuitable for this clinical trial by the investigator or&#xD;
             sub-investigator&#xD;
&#xD;
          8. Pregnant or lactating females&#xD;
&#xD;
          9. Sexually active females of childbearing potential not using adequate contraception and&#xD;
             sexually active males not using adequate contraception&#xD;
&#xD;
         10. Patients with immune dysfunction or receiving any form of immunosuppression&#xD;
&#xD;
         11. Patients with severe FA, with a score of 4 on the IGA scale&#xD;
&#xD;
         12. Patients with an FA severity score of less than 2 on the IGA scale&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ioana Stanescu</last_name>
    <role>Study Director</role>
    <affiliation>Dermatology Specialties Limited Partnership</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Phoenix Children's Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>All Children's Research Institute</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Health Queensland</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Brno</name>
      <address>
        <city>Brno</city>
        <zip>5HG9+4W</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bethesda Children's Hospital of the Hungarian Reformed Church</name>
      <address>
        <city>Budapest</city>
        <zip>G39Q+49</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pécs</name>
      <address>
        <city>Pécs</city>
        <zip>H-7624</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Canterbury District Health Board</name>
      <address>
        <city>Christchurch</city>
        <state>Canterbury</state>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinic of Neurology and Psychiatry for Children and Youth</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center of Serbia</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodný ústav detských chorȏb</name>
      <address>
        <city>Bratislava</city>
        <zip>83340</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universidad de Navarra</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Universidad de Navarra</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>New Zealand</country>
    <country>Serbia</country>
    <country>Slovakia</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>United Kingdom</country>
  </removed_countries>
  <results_reference>
    <citation>Aitken P, Stanescu I, Boddington L, Mahon C, Fogarasi A, Liao YH, Ivars M, Moreno-Artero E, Trauner D, DeRoos ST, Jancic J, Nikolic M, Balazova P, Price HN, Hadzsiev K, Riney K, Stapleton S, Tollefson MM, Bauer D, Pinkova B, Atkinson H. A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blinded, randomised, placebo-controlled trial. Br J Dermatol. 2023 Jul 18:ljad243. doi: 10.1093/bjd/ljad243. Online ahead of print.</citation>
    <PMID>37463422</PMID>
  </results_reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <results_first_submitted>July 19, 2023</results_first_submitted>
  <results_first_submitted_qc>August 9, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 14, 2023</results_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</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>Tuberous Sclerosis</mesh_term>
    <mesh_term>Angiofibroma</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
    <mesh_term>Facies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual Participant Data is not planned to be shared with other researchers</ipd_description>
  </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>March 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03826628/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>0.5% Rapamycin Cream, Topical</title>
          <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
        <group group_id="P2">
          <title>1.0% Rapamycin Cream, Topical</title>
          <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="33"/>
                <participants group_id="P3" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="31"/>
                <participants group_id="P3" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>0.5% Rapamycin Cream, Topical</title>
          <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
        <group group_id="B2">
          <title>1.0% Rapamycin Cream, Topical</title>
          <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</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="36"/>
            <count group_id="B2" value="33"/>
            <count group_id="B3" value="38"/>
            <count group_id="B4" value="107"/>
          </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="27.8" spread="15"/>
                    <measurement group_id="B2" value="25.5" spread="15"/>
                    <measurement group_id="B3" value="26.3" spread="13.8"/>
                    <measurement group_id="B4" value="26.6" spread="14.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Age group</title>
              <category_list>
                <category>
                  <title>6-11 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>12-17 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>18-65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="71"/>
                  </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="14"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="49"/>
                  </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="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="94"/>
                  </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>
          <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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="18"/>
                  </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="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="84"/>
                  </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="2"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Study Site</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Site #00 - ACRI Johns Hopkins</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #01 - University Hospital Brno</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>Site #02 - Children's Health Queensland</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #03 - Christchurch Hospital</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #04 - University of Navarra</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #05 - Mayo Clinic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #06 - Phoenix Children's Hospital</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #07 - Spectrum Health, Michigan</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #08 - University of California, San Diego</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #09 - University of Virginia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #10 - University of Pecs</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #11 - Slovakia National Institute of Children's Diseases</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #12 - Bethesda Children's Hospital</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #13 - University of Szeged</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>Site #14 - Clinic of Neurology and Psychiatry for Children and Youth, Belgrade</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #15 - Clinical Center of Serbia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Site #16 - National Taiwan University</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="164" spread="17"/>
                    <measurement group_id="B2" value="165" spread="16"/>
                    <measurement group_id="B3" value="161" spread="17"/>
                    <measurement group_id="B4" value="163" spread="17"/>
                  </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="68.1" spread="22.8"/>
                    <measurement group_id="B2" value="68.9" spread="24.3"/>
                    <measurement group_id="B3" value="68.4" spread="25.8"/>
                    <measurement group_id="B4" value="68.5" spread="24.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.7" spread="5.6"/>
                    <measurement group_id="B2" value="24.8" spread="6.6"/>
                    <measurement group_id="B3" value="25.4" spread="6.4"/>
                    <measurement group_id="B4" value="25" spread="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Rapamycin concentration</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Below limit of detection</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="38"/>
                    <measurement group_id="B4" value="107"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Above limit of detection</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>
          <title>Investigator's Global Assessment (IGA)</title>
          <description>The Investigator's Global Assessment (IGA) measures the severity of facial angiofibroma, with scores between 0 (clear) and 4 (severe).&#xD;
0 = Clear&#xD;
= Almost Clear&#xD;
= Mild&#xD;
= Moderate&#xD;
= Severe</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>2 - Mild</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3 - Moderate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Facial Angiofibroma Severity Index (FASI)</title>
          <description>Facial Angiofibroma Severity Index (FASI) grades lesions according to their erythema, size and extent. Scores range between 2 and 9. Scores are summed from the following measures:&#xD;
Erythema Skin color 0 Light Red 1 Red 2 Dark Red/purple 3 Size None 0 Small (&lt; 5mm) 1 Large (&gt; 5mm) 2 Confluent 3 Extension &lt;50 % cheek surface 2 &gt;50% cheek surface 3</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>5</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>6</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>7</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>8</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>9</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Obtaining Successful Treatment</title>
        <description>Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
        <time_frame>After 26 weeks treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O2">
            <title>1.0% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Obtaining Successful Treatment</title>
          <description>Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</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="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Treatment Success</title>
        <description>The time elapsed from the first dose to the time of treatment success, according to the Investigator's Global Assessment (IGA) scale. The total time of treatment was 26 weeks, although Covid-19 visit delays led to an extension of up to 2 weeks (28 weeks total) for some patients. Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
        <time_frame>From first dose to 26 weeks (± 2 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O2">
            <title>1.0% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Treatment Success</title>
          <description>The time elapsed from the first dose to the time of treatment success, according to the Investigator's Global Assessment (IGA) scale. The total time of treatment was 26 weeks, although Covid-19 visit delays led to an extension of up to 2 weeks (28 weeks total) for some patients. Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.89" spread="0.7"/>
                    <measurement group_id="O2" value="26.71" spread="0.28"/>
                    <measurement group_id="O3" value="19.7" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Investigator's Global Assessment</title>
        <description>The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.&#xD;
IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
        <time_frame>At baseline and after 26 weeks treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O2">
            <title>1.0% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Investigator's Global Assessment</title>
          <description>The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.&#xD;
IGA scores range from 0-4:&#xD;
0=Clear&#xD;
Almost Clear&#xD;
Mild&#xD;
Moderate&#xD;
Severe</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="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>-2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>-1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>+1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Facial Angiofibroma Severity Index (FASI)</title>
        <description>The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline. FASI grades lesions according to their erythema, size and extent by summing the scores of each category. The final FASI scores range from (mild) 2-9 (severe).&#xD;
Erythema Skin color 0 Light Red 1 Red 2 Dark Red/purple 3 Size None 0 Small (&lt; 5mm) 1 Large (&gt; 5mm) 2 Confluent 3 Extension &lt;50 % cheek surface 2 &gt;50% cheek surface 3</description>
        <time_frame>At baseline and after 26 weeks treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O2">
            <title>1.0% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Facial Angiofibroma Severity Index (FASI)</title>
          <description>The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline. FASI grades lesions according to their erythema, size and extent by summing the scores of each category. The final FASI scores range from (mild) 2-9 (severe).&#xD;
Erythema Skin color 0 Light Red 1 Red 2 Dark Red/purple 3 Size None 0 Small (&lt; 5mm) 1 Large (&gt; 5mm) 2 Confluent 3 Extension &lt;50 % cheek surface 2 &gt;50% cheek surface 3</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="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>-5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>-4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>-3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>-2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>-1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>+1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>+2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale</title>
        <description>Percentage change in facial angiofibroma since beginning treatment, as assessed by the participant or parent/caregiver. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where the participant or parent/caregiver estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
        <time_frame>After 26 weeks treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O2">
            <title>1.0% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale</title>
          <description>Percentage change in facial angiofibroma since beginning treatment, as assessed by the participant or parent/caregiver. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where the participant or parent/caregiver estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
          <units>Percentage Change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.06" spread="4.36"/>
                    <measurement group_id="O2" value="54.06" spread="5.21"/>
                    <measurement group_id="O3" value="30.84" spread="3.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective (Clinician) Percentage Change Rating Scale</title>
        <description>Percentage improvement in facial angiofibroma since beginning treatment, as assessed by the clinician. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where clinicians estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
        <time_frame>After 26 weeks treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O2">
            <title>1.0% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Objective (Clinician) Percentage Change Rating Scale</title>
          <description>Percentage improvement in facial angiofibroma since beginning treatment, as assessed by the clinician. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where clinicians estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
          <units>Percentage Change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.83" spread="3.88"/>
                    <measurement group_id="O2" value="49.39" spread="5.22"/>
                    <measurement group_id="O3" value="20.76" spread="4.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Categorical Change in Facial Angiofibroma</title>
        <description>Change in facial angiofibroma since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver. This was a single assessment time-point, where the participant or parent/caregiver evaluated the change in the facial angiofibroma lesion appearance from their perspective since baseline.</description>
        <time_frame>After 26 weeks treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O2">
            <title>1.0% Rapamycin Cream, Topical</title>
            <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Categorical Change in Facial Angiofibroma</title>
          <description>Change in facial angiofibroma since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver. This was a single assessment time-point, where the participant or parent/caregiver evaluated the change in the facial angiofibroma lesion appearance from their perspective since baseline.</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="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>-1 - Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>0 - No Difference</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>+1 - Slightly Better</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>+2 - Moderately Better</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>+3 - Significantly Better</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 weeks</time_frame>
      <desc>Adverse events were collected during each clinical visit and follow-up visit. Patients or their parents/guardians were questioned by the investigator regarding any adverse events experienced since the previous clinical visit.</desc>
      <group_list>
        <group group_id="E1">
          <title>0.5% Rapamycin Cream, Topical</title>
          <description>Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
        <group group_id="E2">
          <title>1.0% Rapamycin Cream, Topical</title>
          <description>Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks&#xD;
rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Placebo cream topical, applied once daily before bed on affected area for 26 weeks&#xD;
placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (24.0)</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="0" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation, nausea, malnutrition, diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Collapsed lung</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney bleeding</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (24.0)</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="29" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="27" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin burning sensation</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="36"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="33"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="36"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="36"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="33"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="36"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Skin haemorrhage</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Skin tightness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="38"/>
              </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 only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Covid-19 pandemic halted recruitment, leading to a smaller number of patients recruited than intended (107/120).</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Ioana Stanescu</name_or_title>
      <organization>AFT Pharmaceuticals Ltd.</organization>
      <phone>+64 9 488 0232 ext 712</phone>
      <email>ioana.stanescu@aftpharm.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/NCT03826628
org study id: DSLP-01
nct id: NCT03826628
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study aims to compare the safety and efficacy of two different strengths of Rapamycin
      cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA)
      associated with Tuberous Sclerosis Complex (TSC).
Topical rapamycin has previously been used to treat FA associated with TSC, reducing
      erythema, papule size, while flattening lesions and improving skin texture. Topical rapamycin
      has been reported to be well tolerated.

      The efficacy and safety of a topical rapamycin cream at two strengths (0.5% and 1.0%) will be
      assessed during a 26 week double-blind treatment phase with assessments made at clinical
      visits at baseline, 2, 8, 14, 20 and 26 weeks, and at follow-up (4 weeks after the last dose
      of study drug).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Obtaining Successful Treatment
time frame: After 26 weeks treatment
description: Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:
0=Clear
Almost Clear
Mild
Moderate
Severe
measure: Time to Treatment Success
time frame: From first dose to 26 weeks (± 2 weeks)
description: The time elapsed from the first dose to the time of treatment success, according to the Investigator's Global Assessment (IGA) scale. The total time of treatment was 26 weeks, although Covid-19 visit delays led to an extension of up to 2 weeks (28 weeks total) for some patients. Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:
0=Clear
Almost Clear
Mild
Moderate
Severe
measure: Change From Baseline in Investigator's Global Assessment
time frame: At baseline and after 26 weeks treatment
description: The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.
IGA scores range from 0-4:
0=Clear
Almost Clear
Mild
Moderate
Severe
measure: Change From Baseline in Facial Angiofibroma Severity Index (FASI)
time frame: At baseline and after 26 weeks treatment
description: The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline. FASI grades lesions according to their erythema, size and extent by summing the scores of each category. The final FASI scores range from (mild) 2-9 (severe).
Erythema Skin color 0 Light Red 1 Red 2 Dark Red/purple 3 Size None 0 Small (< 5mm) 1 Large (> 5mm) 2 Confluent 3 Extension <50 % cheek surface 2 >50% cheek surface 3
measure: Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale
time frame: After 26 weeks treatment
description: Percentage change in facial angiofibroma since beginning treatment, as assessed by the participant or parent/caregiver. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where the participant or parent/caregiver estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.
measure: Objective (Clinician) Percentage Change Rating Scale
time frame: After 26 weeks treatment
description: Percentage improvement in facial angiofibroma since beginning treatment, as assessed by the clinician. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where clinicians estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.
measure: Categorical Change in Facial Angiofibroma
time frame: After 26 weeks treatment
description: Change in facial angiofibroma since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver. This was a single assessment time-point, where the participant or parent/caregiver evaluated the change in the facial angiofibroma lesion appearance from their perspective since baseline.
arm group label: 0.5% Rapamycin cream, topical
arm group type: Experimental
description: Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks
arm group label: 1.0% Rapamycin cream, topical
arm group type: Experimental
description: Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo cream topical, applied once daily before bed on affected area for 26 weeks
intervention type: Drug
intervention name: rapamycin
description: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks
arm group label: 0.5% Rapamycin cream, topical
arm group label: 1.0% Rapamycin cream, topical
other name: sirolimus
intervention type: Drug
intervention name: placebo
description: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ioana Stanescu
role: Study Director
affiliation: Dermatology Specialties Limited Partnership
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Czechia
country: Hungary
country: New Zealand
country: Serbia
country: Slovakia
country: Spain
country: Taiwan
country: United States
country: United Kingdom
citation: Aitken P, Stanescu I, Boddington L, Mahon C, Fogarasi A, Liao YH, Ivars M, Moreno-Artero E, Trauner D, DeRoos ST, Jancic J, Nikolic M, Balazova P, Price HN, Hadzsiev K, Riney K, Stapleton S, Tollefson MM, Bauer D, Pinkova B, Atkinson H. A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blinded, randomised, placebo-controlled trial. Br J Dermatol. 2023 Jul 18:ljad243. doi: 10.1093/bjd/ljad243. Online ahead of print.
PMID: 37463422
responsible party type: Sponsor
mesh term: Tuberous Sclerosis
mesh term: Angiofibroma
mesh term: Sclerosis
mesh term: Facies
mesh term: Sirolimus
sharing ipd: No
ipd description: Individual Participant Data is not planned to be shared with other researchers
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Covid-19 pandemic halted recruitment, leading to a smaller number of patients recruited than intended (107/120).
point of contact: 