<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/NCT03250663</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00045841</org_study_id>
    <nct_id>NCT03250663</nct_id>
  </id_info>
  <brief_title>Eucrisa for Atopic Dermatitis</brief_title>
  <official_title>Eucrisa for Atopic Dermatitis: Measuring and Improving Adherence to Topical Eucrisa in Patients With Atopic Dermatitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with mild to moderate atopic dermatitis will be asked to participate in helping the&#xD;
      study team determine how well the medication works for atopic dermatitis. Participants will&#xD;
      not be told that adherence will be monitored. Patients will be dispensed topical crisaborole&#xD;
      2% ointment (Eucrisa®) in a medication tube fitted with a Medication Event Monitoring System&#xD;
      (MEMS) cap if they agree to participate. This cap records dates and times the bottle is&#xD;
      opened and this data can be downloaded and tabulated with the associated software.&#xD;
&#xD;
      Investigators and subjects will be blinded to the adherence data until the final treatment&#xD;
      (12 month) session. The study subjects will be randomized to two groups. After baseline&#xD;
      visit, both groups will come for a follow-up visit at 1 month, 3 months, 6 months, and 12&#xD;
      months. The intervention group will also be asked to complete an online treatment response&#xD;
      survey designed to improve adherence at weekly intervals for 6 weeks, then monthly&#xD;
      thereafter.&#xD;
&#xD;
      The study will consist of a 12-month Treatment Phase. Study subjects will be instructed to&#xD;
      apply the medication twice daily (morning and evening) to all of their AD lesions. They will&#xD;
      be instructed to apply the smallest amount of study medication possible that is sufficient to&#xD;
      cover all lesions. These instructions are standard-of-care for patients with AD.&#xD;
&#xD;
      Subjects will be asked to bring their medication tubes with them at each visit. At each&#xD;
      visit, the study coordinator will weigh the medication tube and download the MEMS cap data.&#xD;
      Disclosure of the adherence monitoring will occur at the 12 month visit (or end of&#xD;
      treatment), at which time the results of the subject's adherence behavior will be used to&#xD;
      supply individualized treatment options for each subject (feedback session).&#xD;
&#xD;
      At each visit, drug tubes will be measured for weight to determine the amount of study&#xD;
      medication used. This data will be correlated with the extent of BSA involved and the&#xD;
      response of the disease. The MEMS caps will be downloaded at each visit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atopic Dermatitis (AD) affects between 10% and 30% of all children, making it one of the most&#xD;
      common childhood diseases. Recent epidemiological studies report a trend toward the&#xD;
      increasing prevalence of AD in children. Symptoms of AD include dry, scaly, and intensely&#xD;
      itchy skin. A number of treatments are available for these patients. Topical corticosteroids&#xD;
      are commonly prescribed. Topical immunomodulators without the potential for steroid atrophy&#xD;
      are also used. A non-steroidal topical, Eucrisa (crisaborole) ointment, is specifically&#xD;
      indicated for mild to moderate atopic dermatitis and was approved for marketing in the U.S.&#xD;
      for the treatment atopic dermatitis in December 2016. The 2% ointment is approved for use in&#xD;
      patients ages 2 and older. Unfortunately, many people with atopic dermatitis do not&#xD;
      adequately respond to topical treatment.&#xD;
&#xD;
      It is widely recognized that adherence to oral medications is poor. Adherence to medication&#xD;
      in chronic disease is worse. Adherence to topical medication for chronic disease in children&#xD;
      is horrible. In a previous study, the investigator found that the adherence of children to&#xD;
      topical triamcinolone for atopic dermatitis was poor. Adherence dropped by roughly 60-70%&#xD;
      over the first 3 days of treatment. While that study analyzed adherence over 8 weeks, the&#xD;
      long-term adherence to topical treatment in patients with atopic dermatitis is not well&#xD;
      characterized.&#xD;
&#xD;
      Measures to improve adherence have the potential to improve treatment outcomes. Adherence to&#xD;
      topical treatment tends to improve around the time of office visits (so called, &quot;white coat&#xD;
      compliance&quot;), much as tooth flossing behavior improves around the time of dental visits.&#xD;
      Standard-of-care treatment of atopic dermatitis generally involves having patients return in&#xD;
      roughly 4 weeks to assess treatment efficacy. Clinical trials generally have more frequent&#xD;
      visits. The investigator's recent studies have suggested that adherence may be improved with&#xD;
      virtual medical visits, alleviating the need for more frequent in-person office visits that&#xD;
      can be costly and negatively impact access to care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>All subjects will receive study medication. Groups will be randomized to receive online treatment response surveys.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>adherence data of the randomized subjects</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Adherence to topical Therapy</measure>
    <time_frame>12 months</time_frame>
    <description>Difference in adherence between standard-of-care and intervention with use of the impact of an internet reporting intervention on adherence. Asking 50% of the enrolled subjects to complete internet-based surveys on their use of the study medication.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adherence to topical therapy #1</measure>
    <time_frame>12 months</time_frame>
    <description>Difference in adherence between standard-of-care and intervention with use of MEMS Caps: The Medical Events Monitoring System (MEMS) by MWV formerly Aardex Corporation in Switzerland will be used. The MEMS incorporates a microprocessor into the cap of a standard medication tube. Each time the tube is opened for at least 3 seconds, the time and date are recorded. The Eucrisa 2% ointment will be fitted with a MEMS cap using a specially designed adaptor. Subjects will be asked to bring the unused portion of the medication tube to each visit so that the medication can be &quot;checked and redispensed&quot;. At each visit the information is downloaded via the MEMS communicator onto a computer database by the study staff to ensure the blinding of the primary physician performing the severity measures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to topical therapy #2</measure>
    <time_frame>12 months</time_frame>
    <description>Difference in adherence between standard-of-care and intervention with use of Eczema Area and Severity Index (EASI): Disease severity will be assessed by a physician with the Eczema Area and Severity Index (EASI). This measure is a commonly used and well-validated instrument of eczema severity. It is weighted for area in each of the four body regions (which differs for adults and children under 7) and scores erythema, excoriation, induration/papulation, and lichenification. The total scores range from 0-72.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to topical therapy #3</measure>
    <time_frame>12 months</time_frame>
    <description>Difference in adherence between standard-of-care and intervention with use Visual Analog Scale (VAS) for Itching. A 100mm VAS will be used to measure itch intensity at each visit. VAS is a self-report tool that is designed to present to the respondent a rating scale with minimum constraints. VAS data is recorded as the number of mm from the left of the line with the range 0-100mm. The Visual Analog Scale is anchored with the verbal descriptions of &quot;no itching&quot; on the left and &quot;the most intense itching imaginable&quot; on the right. VAS is considered a useful tool for the measurement of symptoms such as itch.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to topical therapy #4</measure>
    <time_frame>12 months</time_frame>
    <description>difference in adherence between the standard-of-care and intervention with use of the Investigator Global Assessment(IGA) This measure is commonly used as a quick and simple way to quantify disease severity both for clinical studies and in a non-study clinic setting. Score ranges from '0' = clear or &quot;No inflammatory signs of AD&quot; to '4' = Very Severe Disease with &quot;severe erythema and severe papulation/infiltration with oozing/crusting</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Mild to Moderate Atopic Dermatitis</condition>
  <arm_group>
    <arm_group_label>Arm 1 - Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects receive study medication, EUCRISA (crisaborole) ointment 2%, and follow standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 - Online Treatment Response</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive study medication, EUCRISA (crisaborole) ointment 2%, and electronic treatment response emails</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Online Treatment response</intervention_name>
    <description>Electronic treatment response survey to track use of study medication, EUCRISA (crisaborole) ointment 2%.</description>
    <arm_group_label>Arm 2 - Online Treatment Response</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EUCRISA</intervention_name>
    <description>Participants are given EUCRISA (crisaborole) ointment 2%.</description>
    <arm_group_label>Arm 1 - Standard of Care</arm_group_label>
    <arm_group_label>Arm 2 - Online Treatment Response</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects age 2-64.&#xD;
&#xD;
          -  Stable or worsening atopic dermatitis affecting 5% or greater body surface area. Face&#xD;
             and genital areas can be included in the body surface area determination and treatment&#xD;
             area.&#xD;
&#xD;
          -  The ability and willingness to follow all study procedures, attend all scheduled&#xD;
             visits, and successfully complete the study.&#xD;
&#xD;
          -  The ability to understand and sign a written informed consent/assent form, which must&#xD;
             be obtained prior to treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy to crisaborole or to any component of the formulations.&#xD;
&#xD;
          -  The use of systemic therapy for atopic dermatitis within the past 4 weeks.&#xD;
&#xD;
          -  Use of prescription topical therapy for atopic dermatitis (e.g., corticosteroids or&#xD;
             retinoids) within the past 2 weeks.&#xD;
&#xD;
          -  Use of any investigational therapy within the past 4 weeks.&#xD;
&#xD;
          -  Pregnant females, females who are breast feeding, or females of childbearing potential&#xD;
             who are not practicing an acceptable method of birth control (abstinence, birth&#xD;
             control pill/patch, barrier with spermicidal jelly, IUD, etc.), as determined by the&#xD;
             investigator. Acceptable contraception must be used during the entire study. A&#xD;
             pregnancy test will be performed on females of childbearing potential at baseline and&#xD;
             at 6 month and 12 month.&#xD;
&#xD;
          -  Any other condition, which, in the judgment of the investigator, would put the subject&#xD;
             at unacceptable risk for participation in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lindsay C Strowd, MD, FAAD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wake Forest University Heath Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>topical therapy, atopic dermatitis,</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatitis, Atopic</mesh_term>
    <mesh_term>Dermatitis</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Study team does not plan to make individual participant data available; only the total outcome</ipd_description>
  </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/NCT03250663
org study id: IRB00045841
nct id: NCT03250663
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Patients with mild to moderate atopic dermatitis will be asked to participate in helping the
      study team determine how well the medication works for atopic dermatitis. Participants will
      not be told that adherence will be monitored. Patients will be dispensed topical crisaborole
      2% ointment (Eucrisa®) in a medication tube fitted with a Medication Event Monitoring System
      (MEMS) cap if they agree to participate. This cap records dates and times the bottle is
      opened and this data can be downloaded and tabulated with the associated software.

      Investigators and subjects will be blinded to the adherence data until the final treatment
      (12 month) session. The study subjects will be randomized to two groups. After baseline
      visit, both groups will come for a follow-up visit at 1 month, 3 months, 6 months, and 12
      months. The intervention group will also be asked to complete an online treatment response
      survey designed to improve adherence at weekly intervals for 6 weeks, then monthly
      thereafter.

      The study will consist of a 12-month Treatment Phase. Study subjects will be instructed to
      apply the medication twice daily (morning and evening) to all of their AD lesions. They will
      be instructed to apply the smallest amount of study medication possible that is sufficient to
      cover all lesions. These instructions are standard-of-care for patients with AD.

      Subjects will be asked to bring their medication tubes with them at each visit. At each
      visit, the study coordinator will weigh the medication tube and download the MEMS cap data.
      Disclosure of the adherence monitoring will occur at the 12 month visit (or end of
      treatment), at which time the results of the subject's adherence behavior will be used to
      supply individualized treatment options for each subject (feedback session).

      At each visit, drug tubes will be measured for weight to determine the amount of study
      medication used. This data will be correlated with the extent of BSA involved and the
      response of the disease. The MEMS caps will be downloaded at each visit.
Atopic Dermatitis (AD) affects between 10% and 30% of all children, making it one of the most
      common childhood diseases. Recent epidemiological studies report a trend toward the
      increasing prevalence of AD in children. Symptoms of AD include dry, scaly, and intensely
      itchy skin. A number of treatments are available for these patients. Topical corticosteroids
      are commonly prescribed. Topical immunomodulators without the potential for steroid atrophy
      are also used. A non-steroidal topical, Eucrisa (crisaborole) ointment, is specifically
      indicated for mild to moderate atopic dermatitis and was approved for marketing in the U.S.
      for the treatment atopic dermatitis in December 2016. The 2% ointment is approved for use in
      patients ages 2 and older. Unfortunately, many people with atopic dermatitis do not
      adequately respond to topical treatment.

      It is widely recognized that adherence to oral medications is poor. Adherence to medication
      in chronic disease is worse. Adherence to topical medication for chronic disease in children
      is horrible. In a previous study, the investigator found that the adherence of children to
      topical triamcinolone for atopic dermatitis was poor. Adherence dropped by roughly 60-70%
      over the first 3 days of treatment. While that study analyzed adherence over 8 weeks, the
      long-term adherence to topical treatment in patients with atopic dermatitis is not well
      characterized.

      Measures to improve adherence have the potential to improve treatment outcomes. Adherence to
      topical treatment tends to improve around the time of office visits (so called, "white coat
      compliance"), much as tooth flossing behavior improves around the time of dental visits.
      Standard-of-care treatment of atopic dermatitis generally involves having patients return in
      roughly 4 weeks to assess treatment efficacy. Clinical trials generally have more frequent
      visits. The investigator's recent studies have suggested that adherence may be improved with
      virtual medical visits, alleviating the need for more frequent in-person office visits that
      can be costly and negatively impact access to care.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: All subjects will receive study medication. Groups will be randomized to receive online treatment response surveys.
primary purpose: Health Services Research
masking: Double (Participant, Investigator)
masking description: adherence data of the randomized subjects
measure: Adherence to topical Therapy
time frame: 12 months
description: Difference in adherence between standard-of-care and intervention with use of the impact of an internet reporting intervention on adherence. Asking 50% of the enrolled subjects to complete internet-based surveys on their use of the study medication.
measure: Adherence to topical therapy #1
time frame: 12 months
description: Difference in adherence between standard-of-care and intervention with use of MEMS Caps: The Medical Events Monitoring System (MEMS) by MWV formerly Aardex Corporation in Switzerland will be used. The MEMS incorporates a microprocessor into the cap of a standard medication tube. Each time the tube is opened for at least 3 seconds, the time and date are recorded. The Eucrisa 2% ointment will be fitted with a MEMS cap using a specially designed adaptor. Subjects will be asked to bring the unused portion of the medication tube to each visit so that the medication can be "checked and redispensed". At each visit the information is downloaded via the MEMS communicator onto a computer database by the study staff to ensure the blinding of the primary physician performing the severity measures.
measure: Adherence to topical therapy #2
time frame: 12 months
description: Difference in adherence between standard-of-care and intervention with use of Eczema Area and Severity Index (EASI): Disease severity will be assessed by a physician with the Eczema Area and Severity Index (EASI). This measure is a commonly used and well-validated instrument of eczema severity. It is weighted for area in each of the four body regions (which differs for adults and children under 7) and scores erythema, excoriation, induration/papulation, and lichenification. The total scores range from 0-72.
measure: Adherence to topical therapy #3
time frame: 12 months
description: Difference in adherence between standard-of-care and intervention with use Visual Analog Scale (VAS) for Itching. A 100mm VAS will be used to measure itch intensity at each visit. VAS is a self-report tool that is designed to present to the respondent a rating scale with minimum constraints. VAS data is recorded as the number of mm from the left of the line with the range 0-100mm. The Visual Analog Scale is anchored with the verbal descriptions of "no itching" on the left and "the most intense itching imaginable" on the right. VAS is considered a useful tool for the measurement of symptoms such as itch.
measure: Adherence to topical therapy #4
time frame: 12 months
description: difference in adherence between the standard-of-care and intervention with use of the Investigator Global Assessment(IGA) This measure is commonly used as a quick and simple way to quantify disease severity both for clinical studies and in a non-study clinic setting. Score ranges from '0' = clear or "No inflammatory signs of AD" to '4' = Very Severe Disease with "severe erythema and severe papulation/infiltration with oozing/crusting
arm group label: Arm 1 - Standard of Care
arm group type: Active Comparator
description: Subjects receive study medication, EUCRISA (crisaborole) ointment 2%, and follow standard of care
arm group label: Arm 2 - Online Treatment Response
arm group type: Experimental
description: Subjects receive study medication, EUCRISA (crisaborole) ointment 2%, and electronic treatment response emails
intervention type: Behavioral
intervention name: Online Treatment response
description: Electronic treatment response survey to track use of study medication, EUCRISA (crisaborole) ointment 2%.
arm group label: Arm 2 - Online Treatment Response
intervention type: Drug
intervention name: EUCRISA
description: Participants are given EUCRISA (crisaborole) ointment 2%.
arm group label: Arm 1 - Standard of Care
arm group label: Arm 2 - Online Treatment Response
criteria: 
gender: All
minimum age: 2 Years
maximum age: 64 Years
healthy volunteers: No
last name: Lindsay C Strowd, MD, FAAD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dermatitis, Atopic
mesh term: Dermatitis
mesh term: Eczema
sharing ipd: No
ipd description: Study team does not plan to make individual participant data available; only the total outcome