<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/NCT03792516</url>
  </required_header>
  <id_info>
    <org_study_id>J18169</org_study_id>
    <secondary_id>IRB00196703</secondary_id>
    <secondary_id>IRB 19 1353</secondary_id>
    <nct_id>NCT03792516</nct_id>
  </id_info>
  <brief_title>Artesunate Ointment for the Treatment of High Grade Vulvar Intraepithelial Neoplasia (HSIL VIN2/3)</brief_title>
  <acronym>ART-VIN</acronym>
  <official_title>A Phase I Proof-of-Concept Study of Artesunate Ointment for the Treatment of Patients With High-Grade Vulvar Intraepithelial Neoplasia (HSIL VIN 2/3)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Frantz Viral Therapeutics, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
  <oversight_info>
    <has_dmc>Yes</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 is a Phase I, proof-of-concept treatment study to evaluate the safety, tolerability and&#xD;
      feasibility of topical artesunate ointment to treat high grade vulvar intraepithelial&#xD;
      neoplasia (HSIL VIN2/3).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase I open-label dose escalation study of topical artesunate, formulated as ointment, in&#xD;
      the treatment of adult females with biopsy-confirmed HSIL VIN2/3. Fifteen (15) subjects will&#xD;
      undergo up to a total of three cycles of topical artesunate. The first cycle will be&#xD;
      initiated on Day 0, the second at Week 2, and the third and final cycle at week 4.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      To evaluate the safety and tolerability of artesunate ointment applied topically on VIN2/3&#xD;
      lesions&#xD;
&#xD;
      To measure the effect of artesunate ointment on histologic regression of HSIL/VIN2/3 to VIN1&#xD;
      or less, confirmed by a colposcopically-directed biopsy, at study week 15.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 17, 2019</start_date>
  <completion_date type="Anticipated">October 31, 2024</completion_date>
  <primary_completion_date type="Actual">August 31, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of artesunate ointment applied topically on VIN2/3 lesions as assessed by number of participants experiencing serious adverse events or dose-limiting toxicities</measure>
    <time_frame>15 weeks</time_frame>
    <description>Number of participants with study-related serious adverse events or dose-limiting toxicities assessed using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of artesunate ointment as assessed by number of participants with regression to VIN1 or less at week 15</measure>
    <time_frame>15 weeks</time_frame>
    <description>Number of participants with histologic regression of HSIL/VIN2/3 to VIN1 or less on colposcopically-directed biopsy, at study week 15 after receiving artesunate ointment therapy.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Vulvar Dysplasia</condition>
  <condition>HPV-Related Vulvar Intraepithelial Neoplasia</condition>
  <condition>Preinvasive Vulvar Disease</condition>
  <condition>Vulva Intraepithelial Neoplasia</condition>
  <condition>Vulvar Diseases</condition>
  <arm_group>
    <arm_group_label>Artesunate ointment 40%, 1 cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients enrolled in this treatment group will receive one 5-day cycle of artesunate ointment applied topically to the vulva at week 0.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Artesunate ointment 40%, 2 cycles</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients enrolled in this treatment group will receive two 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0 and 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Artesunate ointment 40%, 3 cycles</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients enrolled in this treatment group will receive three 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0, 2, and 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>artesunate ointment 40%</intervention_name>
    <description>artesunate formulated as an ointment to be applied topically to the vulva</description>
    <arm_group_label>Artesunate ointment 40%, 1 cycle</arm_group_label>
    <arm_group_label>Artesunate ointment 40%, 2 cycles</arm_group_label>
    <arm_group_label>Artesunate ointment 40%, 3 cycles</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Colposcopically-directed biopsy diagnosis of high-grade vulvar dysplasia (VIN2, VIN3,&#xD;
             VIN2/3, HSIL), including both new and recurrent disease.&#xD;
&#xD;
          -  Females of childbearing potential: negative urine pregnancy test&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
          -  Ability to collaborate with planned follow-up (transportation, compliance history,&#xD;
             etc.)&#xD;
&#xD;
          -  Use of contraception through the study exit visit (week 28)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant use of any topical immune modulating agents e.g. imiquimod, Aldara ®&#xD;
&#xD;
          -  Cluster of differentiation 4 (CD4) count &lt; 200 at the time of screening for&#xD;
             eligibility.&#xD;
&#xD;
          -  Unable to provide informed consent&#xD;
&#xD;
          -  Currently receiving systemic chemotherapy or radiation therapy for another cancer.&#xD;
&#xD;
          -  Pregnant females&#xD;
&#xD;
          -  Concurrent dermatological disorders involving the vulva (i.e., herpes, ulceration&#xD;
             secondary to Crohn's disease) or vulvar dermatosis (i.e., lichen planus, lichen&#xD;
             sclerosus, or lichen simplex chronicus);&#xD;
&#xD;
          -  Women weighing less than 50 kg&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>This study is for vulvar intraepithelial neoplasia, therefore it is only offerred to women.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cornelia L Trimble, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Outpatient Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Fairview Hospital</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation - Main Campus</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic - Hillcrest Hospital</name>
      <address>
        <city>Mayfield Heights</city>
        <state>Ohio</state>
        <zip>44124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>artesunate</keyword>
  <keyword>pre-invasive disease</keyword>
  <keyword>treatment</keyword>
  <keyword>alternative</keyword>
  <keyword>non-surgical</keyword>
  <keyword>cancer prevention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Carcinoma in Situ</mesh_term>
    <mesh_term>Vulvar Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Artesunate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03792516
org study id: J18169
secondary id: IRB00196703
secondary id: IRB 19 1353
nct id: NCT03792516
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I, proof-of-concept treatment study to evaluate the safety, tolerability and
      feasibility of topical artesunate ointment to treat high grade vulvar intraepithelial
      neoplasia (HSIL VIN2/3).
Phase I open-label dose escalation study of topical artesunate, formulated as ointment, in
      the treatment of adult females with biopsy-confirmed HSIL VIN2/3. Fifteen (15) subjects will
      undergo up to a total of three cycles of topical artesunate. The first cycle will be
      initiated on Day 0, the second at Week 2, and the third and final cycle at week 4.

      Primary Objective:

      To evaluate the safety and tolerability of artesunate ointment applied topically on VIN2/3
      lesions

      To measure the effect of artesunate ointment on histologic regression of HSIL/VIN2/3 to VIN1
      or less, confirmed by a colposcopically-directed biopsy, at study week 15.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of artesunate ointment applied topically on VIN2/3 lesions as assessed by number of participants experiencing serious adverse events or dose-limiting toxicities
time frame: 15 weeks
description: Number of participants with study-related serious adverse events or dose-limiting toxicities assessed using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) criteria
measure: Effect of artesunate ointment as assessed by number of participants with regression to VIN1 or less at week 15
time frame: 15 weeks
description: Number of participants with histologic regression of HSIL/VIN2/3 to VIN1 or less on colposcopically-directed biopsy, at study week 15 after receiving artesunate ointment therapy.
arm group label: Artesunate ointment 40%, 1 cycle
arm group type: Experimental
description: Patients enrolled in this treatment group will receive one 5-day cycle of artesunate ointment applied topically to the vulva at week 0.
arm group label: Artesunate ointment 40%, 2 cycles
arm group type: Experimental
description: Patients enrolled in this treatment group will receive two 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0 and 2.
arm group label: Artesunate ointment 40%, 3 cycles
arm group type: Experimental
description: Patients enrolled in this treatment group will receive three 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0, 2, and 4.
intervention type: Drug
intervention name: artesunate ointment 40%
description: artesunate formulated as an ointment to be applied topically to the vulva
arm group label: Artesunate ointment 40%, 1 cycle
arm group label: Artesunate ointment 40%, 2 cycles
arm group label: Artesunate ointment 40%, 3 cycles
criteria: 
gender: Female
gender based: Yes
gender description: This study is for vulvar intraepithelial neoplasia, therefore it is only offerred to women.
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cornelia L Trimble, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Carcinoma in Situ
mesh term: Vulvar Diseases
mesh term: Artesunate
sharing ipd: No