<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/NCT03802799</url>
  </required_header>
  <id_info>
    <org_study_id>ZYN2-CL-017</org_study_id>
    <nct_id>NCT03802799</nct_id>
  </id_info>
  <brief_title>Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS</brief_title>
  <official_title>An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zynerba Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zynerba Pharmaceuticals, 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>
      ZYN002 is a pharmaceutically manufactured Cannabidiol that is developed as a clear gel that&#xD;
      can be applied to the skin (called transdermal delivery).&#xD;
&#xD;
      The gel will be applied to clean, dry, intact skin of the shoulders and/or upper arms.&#xD;
&#xD;
      Participants from the ZYN2-CL-016 and ZYN2-CL-033 studies who meet the inclusion criteria and&#xD;
      none of the exclusion criteria for study ZYN2-CL-017 are eligible.&#xD;
&#xD;
      Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label extension, multiple-center study, to assess the long-term safety and&#xD;
      tolerability of cannabidiol administered as ZYN002, a transdermal gel, for the treatment of&#xD;
      child and adolescent patients with Fragile X Syndrome (FXS). Male and female patients with&#xD;
      FXS will be treated for up to 72 months. Up to 450 male and female patients, ages 3 to 18&#xD;
      years will be enrolled.&#xD;
&#xD;
      Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.&#xD;
&#xD;
      Participants from study ZYN-CL-016 who weigh less than or equal to 35 kg, will receive 1&#xD;
      sachet of ZYN002, applied every 12 hours (± 2 hours).&#xD;
&#xD;
      Participants from study ZYN-CL-016 who weigh more than 35 kg will receive 2 sachets of&#xD;
      ZYN002, applied every 12 hours (± 2 hours).&#xD;
&#xD;
      Participants from study ZYN-CL-033 who weigh less than or equal to 30 kg, will receive 1&#xD;
      sachet of ZYN002, applied every 12 hours (± 2 hours).&#xD;
&#xD;
      Participants from study ZYN-CL-033 who weigh more than 30 kg will receive 2 sachets of&#xD;
      ZYN002, applied every 12 hours (± 2 hours).&#xD;
&#xD;
      Participants from study ZYN-CL-033 who weigh more than 50 kg will receive 3 sachets of&#xD;
      ZYN002, applied every 12 hours (± 2 hours).&#xD;
&#xD;
      At the Investigator's discretion, the dose may be increased or decreased at any time after&#xD;
      the first month of treatment (for example due to weight changes during the course of the&#xD;
      study).&#xD;
&#xD;
      Participants who are taking anti-epileptic drugs may have an additional one or two weeks of&#xD;
      treatment after the 52 week treatment period to taper off study treatment.&#xD;
&#xD;
      Blood samples will be collected for safety analysis of ZYN002. Additionally, the&#xD;
      parents/caregivers will be asked to complete some questionnaires. There will be other&#xD;
      questionnaires and scales that will be completed at the site by the study doctor and/or with&#xD;
      the participant and their parents/caregivers.&#xD;
&#xD;
      Patients that complete Month 12 will be allowed to continue for another 12 months of&#xD;
      treatment if they qualify. Patients will be evaluated again annually at Months 24 and 36, and&#xD;
      48 in order to remain in the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">November 9, 2018</start_date>
  <completion_date type="Anticipated">August 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2027</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Open-Label</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the long-term safety and tolerability of ZYN002 administered as a transdermal gel formulation.</measure>
    <time_frame>Up to 72 month.</time_frame>
    <description>Safety assessment will include collection of any treatment emergent adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the long-term efficacy of ZYN002 in the treatment of symptoms of FXS.</measure>
    <time_frame>Change from baseline to end of treatment</time_frame>
    <description>Change from Baseline (last assessment prior to the first dose of ZYN002) in the ABC-CFXS subscale scores.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">450</enrollment>
  <condition>Fragile X Syndrome</condition>
  <arm_group>
    <arm_group_label>ZYN002</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ZYN002 - cannabidiol Transdermal Gel</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ZYN002 - Cannabidiol Transdermal Gel</intervention_name>
    <description>Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)</description>
    <arm_group_label>ZYN002</arm_group_label>
    <other_name>Cannabidiol Transdermal Gel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participated in study ZYN2-CL-016 or Study ZYN2-CL-033.&#xD;
&#xD;
          -  Patients and parents/caregivers agree to abide by all study restrictions and comply&#xD;
             with all study procedures.&#xD;
&#xD;
          -  Patients and parents/caregivers must be adequately informed of the nature, risks of&#xD;
             the study, and give written informed consent prior to enrollment in ZYN2-CL-017.&#xD;
&#xD;
          -  In the Investigator's opinion, the patients and parents/caregivers are reliable and&#xD;
             are willing and able to comply with all protocol requirements and procedures.&#xD;
&#xD;
          -  Females of childbearing potential must have a negative pregnancy test at all&#xD;
             designated visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient is receiving any investigational drugs (not ZYN002) or using any experimental&#xD;
             devices.&#xD;
&#xD;
          -  Patient has an ongoing serious adverse event (SAE) or has experienced a SAE in&#xD;
             ZYN2-CL-016 or ZYN2-CL-033, which in the opinion of the Investigator, should exclude&#xD;
             them from participation.&#xD;
&#xD;
          -  Females who are pregnant, nursing, or planning a pregnancy; females of childbearing&#xD;
             potential and male patients with a partner of childbearing potential who are unwilling&#xD;
             or unable to use an acceptable method of contraception for the duration of therapy and&#xD;
             for three months after the last dose of trial drug.&#xD;
&#xD;
          -  Patients who have alanine aminotransferase (ALT), aspartate aminotransferase (AST), or&#xD;
             total bilirubin levels ≥ 2 times the upper limit of normal (ULN) or has alkaline&#xD;
             phosphatase levels ≥ 3 times the ULN as determined from patient safety laboratories.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Southwest Autism Research and Resource Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Davis Health System, MIND Institute</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Colorado</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Han Phan</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kennedy Krieger Institute</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Masonic Institute of Developing Brain</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississipi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fragile X Center of Atlantic Health System</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central States Research</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S. Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suburban Research Associates</name>
      <address>
        <city>Media</city>
        <state>Pennsylvania</state>
        <zip>19063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenwood Genetic Center</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Children's Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Center for Human Development and Disability</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Children's Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lady Cilento Children's Hospital - South Brisbane</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Genetics Clinics Australia</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3161</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Hospital</name>
      <address>
        <city>Wellington</city>
        <zip>6021</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Space</name>
      <address>
        <city>Leicester</city>
        <state>Leicestershire</state>
        <zip>LE15WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manchester University NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>New Zealand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fragile X Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cannabidiol</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/NCT03802799
org study id: ZYN2-CL-017
nct id: NCT03802799
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
ZYN002 is a pharmaceutically manufactured Cannabidiol that is developed as a clear gel that
      can be applied to the skin (called transdermal delivery).

      The gel will be applied to clean, dry, intact skin of the shoulders and/or upper arms.

      Participants from the ZYN2-CL-016 and ZYN2-CL-033 studies who meet the inclusion criteria and
      none of the exclusion criteria for study ZYN2-CL-017 are eligible.

      Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.
This is an open-label extension, multiple-center study, to assess the long-term safety and
      tolerability of cannabidiol administered as ZYN002, a transdermal gel, for the treatment of
      child and adolescent patients with Fragile X Syndrome (FXS). Male and female patients with
      FXS will be treated for up to 72 months. Up to 450 male and female patients, ages 3 to 18
      years will be enrolled.

      Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.

      Participants from study ZYN-CL-016 who weigh less than or equal to 35 kg, will receive 1
      sachet of ZYN002, applied every 12 hours (± 2 hours).

      Participants from study ZYN-CL-016 who weigh more than 35 kg will receive 2 sachets of
      ZYN002, applied every 12 hours (± 2 hours).

      Participants from study ZYN-CL-033 who weigh less than or equal to 30 kg, will receive 1
      sachet of ZYN002, applied every 12 hours (± 2 hours).

      Participants from study ZYN-CL-033 who weigh more than 30 kg will receive 2 sachets of
      ZYN002, applied every 12 hours (± 2 hours).

      Participants from study ZYN-CL-033 who weigh more than 50 kg will receive 3 sachets of
      ZYN002, applied every 12 hours (± 2 hours).

      At the Investigator's discretion, the dose may be increased or decreased at any time after
      the first month of treatment (for example due to weight changes during the course of the
      study).

      Participants who are taking anti-epileptic drugs may have an additional one or two weeks of
      treatment after the 52 week treatment period to taper off study treatment.

      Blood samples will be collected for safety analysis of ZYN002. Additionally, the
      parents/caregivers will be asked to complete some questionnaires. There will be other
      questionnaires and scales that will be completed at the site by the study doctor and/or with
      the participant and their parents/caregivers.

      Patients that complete Month 12 will be allowed to continue for another 12 months of
      treatment if they qualify. Patients will be evaluated again annually at Months 24 and 36, and
      48 in order to remain in the study.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open-Label
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate the long-term safety and tolerability of ZYN002 administered as a transdermal gel formulation.
time frame: Up to 72 month.
description: Safety assessment will include collection of any treatment emergent adverse events
measure: To evaluate the long-term efficacy of ZYN002 in the treatment of symptoms of FXS.
time frame: Change from baseline to end of treatment
description: Change from Baseline (last assessment prior to the first dose of ZYN002) in the ABC-CFXS subscale scores.
arm group label: ZYN002
arm group type: Experimental
description: ZYN002 - cannabidiol Transdermal Gel
intervention type: Drug
intervention name: ZYN002 - Cannabidiol Transdermal Gel
description: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)
arm group label: ZYN002
other name: Cannabidiol Transdermal Gel
criteria: 
gender: All
minimum age: 3 Years
maximum age: 18 Years
healthy volunteers: No
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country: Australia
country: New Zealand
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Fragile X Syndrome
mesh term: Syndrome
mesh term: Cannabidiol
sharing ipd: No