<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/NCT04435665</url>
  </required_header>
  <id_info>
    <org_study_id>NFX-179-NF1-201</org_study_id>
    <nct_id>NCT04435665</nct_id>
  </id_info>
  <brief_title>NFX-179 Topical Gel Treatment in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF)</brief_title>
  <official_title>A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2a Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of NFX-179 Gel in Subjects With Cutaneous Neurofibromas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NFlection Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NFlection Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will enroll and treat subjects with cutaneous neurofibromas with NFX-179, a&#xD;
      topical study drug. Eligible subjects will receive treatment for 28 days and be observed by a&#xD;
      study doctor for approximately 56 days. Subjects will be randomly assigned to 1 of 4&#xD;
      treatment groups. 3 of the treatment groups will receive a specific dose NFX-179, and 1 group&#xD;
      will receive placebo. The subject, study doctor, and NFlection Therapeutics will not know&#xD;
      what treatment group each subject is assigned. Study participation requires at least 7 clinic&#xD;
      visits, blood, urine, and tissue collection, images of the treated cutaneous neurofibromas,&#xD;
      electrocardiograms, and information regarding the subject's medical and disease history.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 21, 2020</start_date>
  <completion_date type="Actual">April 14, 2021</completion_date>
  <primary_completion_date type="Actual">April 8, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phospho-erk (p-ERK) Levels of Target cNF Tumors in NFX-179 Gel Group and Vehicle Gel Group After 28 Days of Once-daily (QD) Application</measure>
    <time_frame>Baseline through Week 4</time_frame>
    <description>Pharmacodynamic activity (biochemical and physiologic effects of drugs) of NFX-179 Gel as defined by suppression of phospho-ERK (p-ERK) levels in Target cNF Tumors in each NFX-179 Gel group compared with the Vehicle Gel group after 28 days of once-daily (QD) application will be measured at Week 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment</measure>
    <time_frame>Baseline through Week 4</time_frame>
    <description>Safety and tolerability will be measured via a local tolerability assessment. The investigator will assess erythema, edema, scabbing/crusting, vesiculation, and erosion. The subject will assess stinging, burning, and pruritus. All assessments are performed using a 4-point scale (0 none, 1 mild, 2 moderate, 3 severe).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of Adverse Events</measure>
    <time_frame>Baseline through Week 8</time_frame>
    <description>Assessment of adverse events (AEs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change in cNF Tumor Volume (Cubic Millimeters)</measure>
    <time_frame>Baseline through Week 4</time_frame>
    <description>Percent change in cNF tumor volume after 28 days of QD applications of NFX-179 gel based on tumor volume derived from ruler measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration</measure>
    <time_frame>Baseline through Week 4</time_frame>
    <description>Systemic exposure of NFX-179 will be measured during the 28 days of QD applications at select investigative sites. Pharmacokinetic samples will be drawn at the baseline visit and week 4 visit. 5 time point samples will be collected at the week 4 visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Physician Assessment of Tumor Severity Score</measure>
    <time_frame>Baseline through Week 4</time_frame>
    <description>Effect of treatment with The Physician Tumor Assessment is the investigator's assessment of the average overall severity of each Target cNF tumor at a particular time point. The Physician Tumor Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Subject Self-Assessment of Tumor Severity Score</measure>
    <time_frame>Baseline through Week 4</time_frame>
    <description>The Subject Self-Assessment is the subject's assessment of the average overall severity of each Target cNF at a particular time point and is not a comparison with any other time point. The Subject Self-Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Neurofibromatosis 1</condition>
  <condition>Cutaneous Neurofibroma</condition>
  <arm_group>
    <arm_group_label>NFX-179 Gel Low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NFX-179 Gel for topical administration, once daily for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NFX-179 Gel Mid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NFX-179 Gel for topical administration, once daily for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NFX-179 Gel High</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NFX-179 Gel for topical administration, once daily for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vehicle Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vehicle Gel, for topical administration, once daily for 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NFX-179 Gel</intervention_name>
    <description>gel for topical administration</description>
    <arm_group_label>NFX-179 Gel High</arm_group_label>
    <arm_group_label>NFX-179 Gel Low</arm_group_label>
    <arm_group_label>NFX-179 Gel Mid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vehicle Gel</intervention_name>
    <description>vehicle gel for topical administration</description>
    <arm_group_label>Vehicle Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is at least 18 years of age&#xD;
&#xD;
          2. Subject must provide written informed consent prior to any study procedures&#xD;
&#xD;
          3. Subject must have a clinical diagnosis of NF1&#xD;
&#xD;
          4. Subject has 6 Study cNF Tumors (5 Target cNF Tumors [1 on the face; 4 on the anterior&#xD;
             trunk or upper extremities] that will be treated with the assigned study medication;1&#xD;
             Untreated cNF Tumor on the anterior trunk or upper extremities) that each meet the&#xD;
             following criteria:&#xD;
&#xD;
               -  Has, in the investigator's opinion, a clinically typical appearance&#xD;
&#xD;
               -  Is dome shaped&#xD;
&#xD;
               -  Is not pedunculated&#xD;
&#xD;
               -  Is a discrete tumor&#xD;
&#xD;
               -  Is not irritated&#xD;
&#xD;
               -  Is not in an area subject to repeated trauma (e.g., area that is shaved, on the&#xD;
                  beltline, under a bra strap, etc.)&#xD;
&#xD;
               -  Does not have an active cutaneous infection&#xD;
&#xD;
               -  Has a diameter that is ≥5mm and ≤10mm&#xD;
&#xD;
               -  Has a height of ≥2mm&#xD;
&#xD;
               -  Is, when centered in the center of the provided template, the only cNF tumor&#xD;
                  visible&#xD;
&#xD;
               -  Is not within 5mm of the orbital rim.&#xD;
&#xD;
          5. Subject is willing to have the 5 Target cNF Tumors and the 1 Untreated cNF Tumor&#xD;
             excised at the end of the treatment period&#xD;
&#xD;
          6. Subject is willing to have hair in the area surrounding the Target cNF Tumors shaved,&#xD;
             if necessary, to obtain photographs&#xD;
&#xD;
          7. Subject is willing to minimize exposure of each Target cNF to natural and artificial&#xD;
             ultraviolet radiation&#xD;
&#xD;
          8. Subject is willing to forego treatment of the Target cNF Tumors, except protocol&#xD;
             specified therapy, during the study&#xD;
&#xD;
          9. Female subjects who are women of childbearing potential must have a negative urine&#xD;
             pregnancy test result and be willing to use a protocol approved, contraceptive method&#xD;
             for the duration of the study&#xD;
&#xD;
         10. Subject is willing and able to follow all study instructions and to attend all study&#xD;
             visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has applied any of the following topical products in the previous 30 days on&#xD;
             or in proximity to any Study cNF Tumor that, in the investigator's opinion, impairs&#xD;
             evaluation of any the tumor or which exposes the subject to an unacceptable risk by&#xD;
             study participation:&#xD;
&#xD;
               -  Corticosteroids&#xD;
&#xD;
               -  Retinoids (e.g., tazarotene, tretinoin, adapalene)&#xD;
&#xD;
               -  &gt; 5% of an alpha-hydroxy acid (e.g., glycolic acid, lactic acid)&#xD;
&#xD;
               -  Fluorouracil&#xD;
&#xD;
               -  Imiquimod&#xD;
&#xD;
          2. Any Study cNF Tumor has ever been treated with an MEK inhibitor or a BRAF inhibitor&#xD;
&#xD;
          3. The subject has used any of the following systemic medications in the noted time&#xD;
             period:&#xD;
&#xD;
               -  Retinoids (e.g., etretinate, isotretinoin) within the previous 90 days&#xD;
&#xD;
               -  MEK inhibitors within the previous 180 days&#xD;
&#xD;
               -  BRAF inhibitors within the previous 180 days&#xD;
&#xD;
          4. Subject has a history of hypersensitivity to any of the ingredients in the study&#xD;
             medications&#xD;
&#xD;
          5. Subject has any known intercurrent illness or physical condition that would, in the&#xD;
             investigator's opinion, impair evaluation of a Target cNF Tumor or which exposes the&#xD;
             subject to an unacceptable risk by study participation&#xD;
&#xD;
          6. Subject has, in the investigator's opinion, clinically relevant history of liver&#xD;
             disease, including viral hepatitis, current alcohol abuse, or cirrhosis&#xD;
&#xD;
          7. Subject has a history of metastatic disease, or active cancer (excluding nonmelanoma&#xD;
             skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the breast, or Stage&#xD;
             0 chronic lymphocytic lymphoma) within the previous 5 years&#xD;
&#xD;
          8. Subject has any condition (e.g., other skin conditions or diseases, metabolic&#xD;
             dysfunction, physical examination findings, clinical laboratory findings) or situation&#xD;
             (e.g., vacation, scheduled surgery) that would, in the investigator's opinion, impair&#xD;
             evaluation of a Target cNF Tumor or which exposes the subject to an unacceptable risk&#xD;
             by study participation&#xD;
&#xD;
          9. Subject has participated in an investigational drug trial in which administration of&#xD;
             an investigational study medication occurred within the previous 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guy Webster, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>NFlection Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Dermatology Clinical Research, Inc.</name>
      <address>
        <city>Fremont</city>
        <state>California</state>
        <zip>94538</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Clinical Study Center</name>
      <address>
        <city>New Brighton</city>
        <state>Minnesota</state>
        <zip>55112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skin Search of Rochester, Inc.</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14623</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DermResearch</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Education &amp; Research Foundation, Inc.</name>
      <address>
        <city>Lynchburg</city>
        <state>Virginia</state>
        <zip>24501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <results_first_submitted>August 25, 2021</results_first_submitted>
  <results_first_submitted_qc>July 13, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 9, 2022</results_first_posted>
  <last_update_submitted>July 13, 2022</last_update_submitted>
  <last_update_submitted_qc>July 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NFX-179</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurofibromatoses</mesh_term>
    <mesh_term>Neurofibromatosis 1</mesh_term>
    <mesh_term>Neurofibroma</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Full Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT04435665/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Amendment 1</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 20, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT04435665/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Amendment 2</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 25, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT04435665/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Amendment 3</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT04435665/Prot_003.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 3, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT04435665/ICF_004.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>NFX-179 Gel Low (0.05%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="P2">
          <title>NFX-179 Gel Mid (0.15%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="P3">
          <title>NFX-179 Gel High (0.50%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="P4">
          <title>Vehicle Arm (Placebo)</title>
          <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NFX-179 Gel Low (0.05%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="B2">
          <title>NFX-179 Gel Mid (0.15%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="B3">
          <title>NFX-179 Gel High (0.50%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="B4">
          <title>Vehicle Arm (Placebo)</title>
          <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
        </group>
        <group group_id="B5">
          <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="12"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="13"/>
            <count group_id="B5" value="48"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.1" lower_limit="31" upper_limit="69"/>
                    <measurement group_id="B2" value="49.5" lower_limit="29" upper_limit="73"/>
                    <measurement group_id="B3" value="43.5" lower_limit="25" upper_limit="63"/>
                    <measurement group_id="B4" value="45.2" lower_limit="33" upper_limit="72"/>
                    <measurement group_id="B5" value="47.8" lower_limit="25" upper_limit="73"/>
                  </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="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Non-white</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black/African American</title>
              <category_list>
                <category>
                  <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="1"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not reported</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phospho-erk (p-ERK) Levels of Target cNF Tumors in NFX-179 Gel Group and Vehicle Gel Group After 28 Days of Once-daily (QD) Application</title>
        <description>Pharmacodynamic activity (biochemical and physiologic effects of drugs) of NFX-179 Gel as defined by suppression of phospho-ERK (p-ERK) levels in Target cNF Tumors in each NFX-179 Gel group compared with the Vehicle Gel group after 28 days of once-daily (QD) application will be measured at Week 4</description>
        <time_frame>Baseline through Week 4</time_frame>
        <population>The p-ERK analysis included all available p-ERK data from tumors determined by histology to be cNF tumors. Missing data were due to missing or non-analyzable tumor samples or tumor samples shown to come from non-cNF tumors upon histologic review. Therefore the number of participants is not the same as those in the participant flow.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle Arm (Placebo)</title>
            <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
          </group>
          <group group_id="O2">
            <title>NFX-179 Gel Low (0.05%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O3">
            <title>NFX-179 Gel Mid (0.15%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O4">
            <title>NFX-179 Gel High (0.50%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
        </group_list>
        <measure>
          <title>Phospho-erk (p-ERK) Levels of Target cNF Tumors in NFX-179 Gel Group and Vehicle Gel Group After 28 Days of Once-daily (QD) Application</title>
          <description>Pharmacodynamic activity (biochemical and physiologic effects of drugs) of NFX-179 Gel as defined by suppression of phospho-ERK (p-ERK) levels in Target cNF Tumors in each NFX-179 Gel group compared with the Vehicle Gel group after 28 days of once-daily (QD) application will be measured at Week 4</description>
          <population>The p-ERK analysis included all available p-ERK data from tumors determined by histology to be cNF tumors. Missing data were due to missing or non-analyzable tumor samples or tumor samples shown to come from non-cNF tumors upon histologic review. Therefore the number of participants is not the same as those in the participant flow.</population>
          <units>% reduction in pERK to total ERK</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Tumors</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="11"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Tumors</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="53"/>
                <count group_id="O3" value="47"/>
                <count group_id="O4" value="53"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3054" spread="0.1369"/>
                    <measurement group_id="O2" value="0.2734" spread="0.1257"/>
                    <measurement group_id="O3" value="0.2267" spread="0.1272"/>
                    <measurement group_id="O4" value="0.1627" spread="0.0686"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment</title>
        <description>Safety and tolerability will be measured via a local tolerability assessment. The investigator will assess erythema, edema, scabbing/crusting, vesiculation, and erosion. The subject will assess stinging, burning, and pruritus. All assessments are performed using a 4-point scale (0 none, 1 mild, 2 moderate, 3 severe).</description>
        <time_frame>Baseline through Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vehicle Arm (Placebo)</title>
            <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
          </group>
          <group group_id="O2">
            <title>NFX-179 Gel Low (0.05%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O3">
            <title>NFX-179 Gel Mid (0.15%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O4">
            <title>NFX-179 Gel High (0.50%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment</title>
          <description>Safety and tolerability will be measured via a local tolerability assessment. The investigator will assess erythema, edema, scabbing/crusting, vesiculation, and erosion. The subject will assess stinging, burning, and pruritus. All assessments are performed using a 4-point scale (0 none, 1 mild, 2 moderate, 3 severe).</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>subject reported instances of mild pruritus</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>subject reported instances of moderate pruritus</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>subject reported instances of mild burning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>subject reported instances of mild stinging</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>investigator reported instances of mild erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>investigator reported instances of moderate erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>investigator reported instances of mild edema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>investigator reported instances of scabbing/crusting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Assessment of Adverse Events</title>
        <description>Assessment of adverse events (AEs)</description>
        <time_frame>Baseline through Week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vehicle Arm (Placebo)</title>
            <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
          </group>
          <group group_id="O2">
            <title>NFX-179 Gel Low (0.05%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O3">
            <title>NFX-179 Gel Mid (0.15%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O4">
            <title>NFX-179 Gel High (0.50%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of Adverse Events</title>
          <description>Assessment of adverse events (AEs)</description>
          <units>Subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of subjects with treatment-emergent AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of subects with related treatment-emergent AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of subjects withdrawn due to AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subjects with mild treatment-emergent AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subjects with moderate treatment-emergent AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subjects with severe treatment-emergent AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in cNF Tumor Volume (Cubic Millimeters)</title>
        <description>Percent change in cNF tumor volume after 28 days of QD applications of NFX-179 gel based on tumor volume derived from ruler measurements.</description>
        <time_frame>Baseline through Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vehicle Arm (Placebo)</title>
            <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
          </group>
          <group group_id="O2">
            <title>NFX-179 Gel Low (0.05%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O3">
            <title>NFX-179 Gel Mid (0.15%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O4">
            <title>NFX-179 Gel High (0.50%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in cNF Tumor Volume (Cubic Millimeters)</title>
          <description>Percent change in cNF tumor volume after 28 days of QD applications of NFX-179 gel based on tumor volume derived from ruler measurements.</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.0" spread="18.2"/>
                    <measurement group_id="O2" value="-1.6" spread="22.1"/>
                    <measurement group_id="O3" value="-11.9" spread="29.4"/>
                    <measurement group_id="O4" value="-16.7" spread="30.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration</title>
        <description>Systemic exposure of NFX-179 will be measured during the 28 days of QD applications at select investigative sites. Pharmacokinetic samples will be drawn at the baseline visit and week 4 visit. 5 time point samples will be collected at the week 4 visit.</description>
        <time_frame>Baseline through Week 4</time_frame>
        <population>Pharmacokinetic data from subjects treated with active NFX-179 gel was performed, which does not include samples from subjects treated with Vehicle gel (placebo). As such, no analysis pharmacokinetic analysis was performed in the Vehicle Arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle Arm (Placebo)</title>
            <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
          </group>
          <group group_id="O2">
            <title>NFX-179 Gel Low (0.05%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O3">
            <title>NFX-179 Gel Mid (0.15%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O4">
            <title>NFX-179 Gel High (0.50%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
        </group_list>
        <measure>
          <title>Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration</title>
          <description>Systemic exposure of NFX-179 will be measured during the 28 days of QD applications at select investigative sites. Pharmacokinetic samples will be drawn at the baseline visit and week 4 visit. 5 time point samples will be collected at the week 4 visit.</description>
          <population>Pharmacokinetic data from subjects treated with active NFX-179 gel was performed, which does not include samples from subjects treated with Vehicle gel (placebo). As such, no analysis pharmacokinetic analysis was performed in the Vehicle Arm.</population>
          <units>ng/mL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline, pre dose (0 hour)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O3" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O4" value="NA">below the lower limit of quantification</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4, pre dose (0 hour)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O3" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O4" value="0.439"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4, post dose 30 min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O3" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O4" value="0.887"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4, post dose 1 hour</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O3" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O4" value="0.573"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4, post dose 2 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O3" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O4" value="0.718"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4, post dose 4 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O3" value="NA">below the lower limit of quantification</measurement>
                    <measurement group_id="O4" value="0.528"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Physician Assessment of Tumor Severity Score</title>
        <description>Effect of treatment with The Physician Tumor Assessment is the investigator's assessment of the average overall severity of each Target cNF tumor at a particular time point. The Physician Tumor Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.</description>
        <time_frame>Baseline through Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vehicle Arm (Placebo)</title>
            <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
          </group>
          <group group_id="O2">
            <title>NFX-179 Gel Low (0.05%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O3">
            <title>NFX-179 Gel Mid (0.15%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O4">
            <title>NFX-179 Gel High (0.50%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Physician Assessment of Tumor Severity Score</title>
          <description>Effect of treatment with The Physician Tumor Assessment is the investigator's assessment of the average overall severity of each Target cNF tumor at a particular time point. The Physician Tumor Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.</description>
          <units>Change in Investigator Assessment score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.74" spread="0.53"/>
                    <measurement group_id="O2" value="2.46" spread="0.62"/>
                    <measurement group_id="O3" value="2.60" spread="0.57"/>
                    <measurement group_id="O4" value="2.65" spread="0.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.51" spread="0.58"/>
                    <measurement group_id="O2" value="3.58" spread="0.62"/>
                    <measurement group_id="O3" value="2.50" spread="0.59"/>
                    <measurement group_id="O4" value="2.70" spread="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Subject Self-Assessment of Tumor Severity Score</title>
        <description>The Subject Self-Assessment is the subject's assessment of the average overall severity of each Target cNF at a particular time point and is not a comparison with any other time point. The Subject Self-Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.</description>
        <time_frame>Baseline through Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vehicle Arm (Placebo)</title>
            <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
          </group>
          <group group_id="O2">
            <title>NFX-179 Gel Low (0.05%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O3">
            <title>NFX-179 Gel Mid (0.15%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
          <group group_id="O4">
            <title>NFX-179 Gel High (0.50%)</title>
            <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Subject Self-Assessment of Tumor Severity Score</title>
          <description>The Subject Self-Assessment is the subject's assessment of the average overall severity of each Target cNF at a particular time point and is not a comparison with any other time point. The Subject Self-Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.</description>
          <units>change in subject assessment score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.75" spread="0.73"/>
                    <measurement group_id="O2" value="2.81" spread="0.53"/>
                    <measurement group_id="O3" value="2.71" spread="0.38"/>
                    <measurement group_id="O4" value="2.38" spread="0.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.50" spread="0.60"/>
                    <measurement group_id="O2" value="2.76" spread="0.55"/>
                    <measurement group_id="O3" value="2.50" spread="0.56"/>
                    <measurement group_id="O4" value="2.39" spread="0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 56 Days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vehicle Arm (Placebo)</title>
          <description>Vehicle Gel, for topical administration, once daily for 28 days&#xD;
Vehicle Gel placebo&#xD;
Vehicle Gel: vehicle gel for topical administration</description>
        </group>
        <group group_id="E2">
          <title>NFX-179 Gel Low (0.05%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.05%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="E3">
          <title>NFX-179 Gel Mid (0.15%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.15%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
        <group group_id="E4">
          <title>NFX-179 Gel High (0.50%)</title>
          <description>NFX-179 Gel for topical administration, once daily for 28 days&#xD;
NFX-179 Gel 0.50%&#xD;
NFX-179 Gel: gel for topical administration</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.0</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="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Multiple allergies</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Corona test positive</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep apnea syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Menopause</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Operations</name_or_title>
      <organization>NFlection</organization>
      <phone>7078532199</phone>
      <email>comara@nflectionrx.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/NCT04435665
org study id: NFX-179-NF1-201
nct id: NCT04435665
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will enroll and treat subjects with cutaneous neurofibromas with NFX-179, a
      topical study drug. Eligible subjects will receive treatment for 28 days and be observed by a
      study doctor for approximately 56 days. Subjects will be randomly assigned to 1 of 4
      treatment groups. 3 of the treatment groups will receive a specific dose NFX-179, and 1 group
      will receive placebo. The subject, study doctor, and NFlection Therapeutics will not know
      what treatment group each subject is assigned. Study participation requires at least 7 clinic
      visits, blood, urine, and tissue collection, images of the treated cutaneous neurofibromas,
      electrocardiograms, and information regarding the subject's medical and disease history.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Phospho-erk (p-ERK) Levels of Target cNF Tumors in NFX-179 Gel Group and Vehicle Gel Group After 28 Days of Once-daily (QD) Application
time frame: Baseline through Week 4
description: Pharmacodynamic activity (biochemical and physiologic effects of drugs) of NFX-179 Gel as defined by suppression of phospho-ERK (p-ERK) levels in Target cNF Tumors in each NFX-179 Gel group compared with the Vehicle Gel group after 28 days of once-daily (QD) application will be measured at Week 4
measure: Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment
time frame: Baseline through Week 4
description: Safety and tolerability will be measured via a local tolerability assessment. The investigator will assess erythema, edema, scabbing/crusting, vesiculation, and erosion. The subject will assess stinging, burning, and pruritus. All assessments are performed using a 4-point scale (0 none, 1 mild, 2 moderate, 3 severe).
measure: Assessment of Adverse Events
time frame: Baseline through Week 8
description: Assessment of adverse events (AEs)
measure: Percent Change in cNF Tumor Volume (Cubic Millimeters)
time frame: Baseline through Week 4
description: Percent change in cNF tumor volume after 28 days of QD applications of NFX-179 gel based on tumor volume derived from ruler measurements.
measure: Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration
time frame: Baseline through Week 4
description: Systemic exposure of NFX-179 will be measured during the 28 days of QD applications at select investigative sites. Pharmacokinetic samples will be drawn at the baseline visit and week 4 visit. 5 time point samples will be collected at the week 4 visit.
measure: Change in Physician Assessment of Tumor Severity Score
time frame: Baseline through Week 4
description: Effect of treatment with The Physician Tumor Assessment is the investigator's assessment of the average overall severity of each Target cNF tumor at a particular time point. The Physician Tumor Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.
measure: Change in Subject Self-Assessment of Tumor Severity Score
time frame: Baseline through Week 4
description: The Subject Self-Assessment is the subject's assessment of the average overall severity of each Target cNF at a particular time point and is not a comparison with any other time point. The Subject Self-Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). The assessment is performed at the Baseline visit and week 4 visit.
arm group label: NFX-179 Gel Low
arm group type: Experimental
description: NFX-179 Gel for topical administration, once daily for 28 days
arm group label: NFX-179 Gel Mid
arm group type: Experimental
description: NFX-179 Gel for topical administration, once daily for 28 days
arm group label: NFX-179 Gel High
arm group type: Experimental
description: NFX-179 Gel for topical administration, once daily for 28 days
arm group label: Vehicle Arm
arm group type: Placebo Comparator
description: Vehicle Gel, for topical administration, once daily for 28 days
intervention type: Drug
intervention name: NFX-179 Gel
description: gel for topical administration
arm group label: NFX-179 Gel High
arm group label: NFX-179 Gel Low
arm group label: NFX-179 Gel Mid
intervention type: Drug
intervention name: Vehicle Gel
description: vehicle gel for topical administration
arm group label: Vehicle Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Guy Webster, MD, PhD
role: Study Director
affiliation: NFlection Therapeutics
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neurofibromatoses
mesh term: Neurofibromatosis 1
mesh term: Neurofibroma
provided document: 
provided document: 
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 