<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/NCT03239106</url>
  </required_header>
  <id_info>
    <org_study_id>CIP-ApremilastCC-10004</org_study_id>
    <nct_id>NCT03239106</nct_id>
  </id_info>
  <brief_title>A Study Examining the Medication Apremilast as Treatment for Chronic Itch</brief_title>
  <official_title>An Open Label Study of Apremilast in Chronic Idiopathic Pruritus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</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>
      Chronic Itch is a debilitating condition affecting many people. Currently, there are no&#xD;
      FDA-approved treatments. Apremilast is an FDA-approved oral medication used to successfully&#xD;
      treat the inflammatory skin disorder psoriasis and the inflammatory disorder psoriatic&#xD;
      arthritis. This study examines if apremiliast taken twice daily relieves chronic itch.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is no FDA-approved medication for chronic idiopathic pruritus (CIP). Apremilast has&#xD;
      demonstrated notable activity and is approved for treatment in other pruritic inflammatory&#xD;
      skin conditions such as psoriasis. The drug is currently being investigated as therapy for&#xD;
      atopic dermatitis. Additionally, the investigators have preliminary data to suggest that&#xD;
      apremilast's anti-inflammatory properties may work via neuromodulation targeting neuronal&#xD;
      cytokine pathways. The proposed study plans to assess the efficacy of apremilast 30 mg BID in&#xD;
      the setting of CIP. Durable response to a medication is typically seen within one to two&#xD;
      months of starting an efficacious medication in subjects who respond. Therefore, the&#xD;
      investigators have designed this study to end at Week 16 to definitively determine efficacy&#xD;
      and conclude the study with confidence with regard to both efficacy and failure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Actual">September 19, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2018</primary_completion_date>
  <phase>Phase 2</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>Absolute NRS Itch Score at Week 16 (End of Treatment)</measure>
    <time_frame>Week 16</time_frame>
    <description>Participants will complete a Numeric Rating Scale for itch (0 representing &quot;no itching&quot; through 10 representing &quot;worst itch imaginable&quot;) will be recalled from prior 24 hours and the prior week.&#xD;
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute DLQI at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16&#xD;
The DLQI is a numerical scale that scores multiple parameters of skin symptoms on a scale from 0 to 30. 0-1 = no effect at all on a patient's life (most favorable clinical outcome and minimum score), 1-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life (worse clinical outcome and maximum score).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NRS at Screening, Baseline and Weeks 2,4,8,12,16,and 18</measure>
    <time_frame>Screening through Week 18 (follow up visit)</time_frame>
    <description>Participants' itch will be measured utilizing the Numeric Rating Scale for itch (0 representing &quot;no itching&quot; through 10 representing &quot;worst itch imaginable&quot;) will be recalled from prior 24 hours and the prior week.&#xD;
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLQI at Screening, Baseline, and Weeks 2,4,8,12,16 and 18</measure>
    <time_frame>Screening through Week 18 (follow up visit)</time_frame>
    <description>Participants will complete a 10 question Dermatology Life Quality Index questionnaire at Screening, Baseline, and Weeks 2,4,8,12,16,18.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Itch</condition>
  <arm_group>
    <arm_group_label>open label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive Apremilast 30 mg BID.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast</intervention_name>
    <description>Apremilast 30 mg BID daily</description>
    <arm_group_label>open label</arm_group_label>
    <other_name>Otezla</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Key Inclusion Criteria: A subject who meets all of the following criteria may be included&#xD;
        in the study:&#xD;
&#xD;
          -  Male and non-pregnant, non-lactating female subjects aged 18 years or older&#xD;
&#xD;
          -  Diagnosed with chronic idiopathic pruritus (CIP) with an NRS Itch Score of ≥ 7 at both&#xD;
             Screening and Baseline&#xD;
&#xD;
          -  Diagnosis of CIP for at least 6 weeks prior to screening&#xD;
&#xD;
          -  Willingness to avoid pregnancy or fathering of children&#xD;
&#xD;
          -  Ability and willingness to provide written informed consent&#xD;
&#xD;
          -  Willing and able to comply with all study requirements and restrictions&#xD;
&#xD;
          -  Willing to not participate in any other interventional trial for the duration of their&#xD;
             participation&#xD;
&#xD;
          -  Subjects must be in good health as determined by medical history, physical&#xD;
             examination, electrocardiogram, clinical laboratory tests and vital signs&#xD;
&#xD;
          -  Failure of a course 2-week course of treatment with topical triamcinolone 0.1%&#xD;
             ointment BID&#xD;
&#xD;
          -  Histopathological demonstration of skin eosinophils, mast cell activation, lymphocytic&#xD;
             infiltration, and/or dermal edema&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Key Exclusion Criteria: A subject who meets any of the following criteria will be excluded&#xD;
        from the study:&#xD;
&#xD;
          -  Chronic pruritus due to a defined primary dermatologic disorder (e.g., atopic&#xD;
             dermatitis, psoriasis, etc.)&#xD;
&#xD;
          -  Patients with a prior diagnosis of excoriation disorder&#xD;
&#xD;
          -  Use of topical treatments for CIP (other than bland emollients) within 1 week of&#xD;
             Baseline&#xD;
&#xD;
          -  Systemic immunosuppressive or immunomodulating drugs within 4 weeks of Baseline&#xD;
&#xD;
          -  Subjects with cytopenias at screening, defined as:&#xD;
&#xD;
               -  Leukocytes &lt; 3 × 109/L.&#xD;
&#xD;
               -  Neutrophils &lt; lower limit of normal.&#xD;
&#xD;
               -  Lymphocytes &lt; 0.5 × 109/L&#xD;
&#xD;
               -  Hemoglobin &lt; 10 g/dL.&#xD;
&#xD;
               -  Platelets &lt; 100 × 109/L.&#xD;
&#xD;
          -  Unwilling or unable to follow medication restrictions described in Section 5.6.3, or&#xD;
             unwilling or unable to sufficiently washout from use of restricted medication&#xD;
&#xD;
          -  Under medical treatment for a skin disease with a therapy listed in the prohibited&#xD;
             medications section that may influence the results of the study&#xD;
&#xD;
          -  Current clinically significant cardiovascular, respiratory, neurologic, hepatic,&#xD;
             hematopoietic, renal gastrointestinal, endocrine or metabolic dysfunction unless&#xD;
             currently controlled and stable, including (but not limited to) the following:&#xD;
             Positive for Hepatitis C antibody test (anti-HCF) Positive for hepatitis B surface&#xD;
             antigen (HBsAg) or hepatitis B core antibody (HBcAb) Positive for HIV (DUO test, p24&#xD;
             antigen)&#xD;
&#xD;
          -  Active malignancy&#xD;
&#xD;
          -  Active substance abuse or history of substance abuse within 6 months of screening&#xD;
&#xD;
          -  History (including family history) or current evidence of congenital long QT syndrome&#xD;
             or known acquired QT prolongation&#xD;
&#xD;
          -  Exposure to any investigational medication, including placebo, within 60 days of the&#xD;
             Baseline Visit&#xD;
&#xD;
          -  Subjects who had previously received apremilast&#xD;
&#xD;
          -  Subjects with severely impaired liver function (Child-Pugh Class C) or end-stage renal&#xD;
             disease on dialysis or at least 1 of the following:&#xD;
&#xD;
               -  Serum creatinine &gt; 1.5 mg/dL&#xD;
&#xD;
               -  Alanine aminotransferase or aspartate aminotransferase ≥ 1.5 × upper limit of&#xD;
                  normal&#xD;
&#xD;
          -  Anyone affiliated with the site or sponsor and/or anyone who may consent under duress&#xD;
&#xD;
          -  Any other sound medical reason as determined by the Investigator including any&#xD;
             condition which may lead to an unfavorable risk-benefit of study participation, may&#xD;
             interfere with study compliance or may confound results.&#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>Brian S. Kim, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University Division of Dermatology</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <results_first_submitted>March 16, 2020</results_first_submitted>
  <results_first_submitted_qc>April 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 20, 2020</results_first_posted>
  <last_update_submitted>June 23, 2021</last_update_submitted>
  <last_update_submitted_qc>June 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>itch</keyword>
  <keyword>pruritus</keyword>
  <keyword>CIP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pruritus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apremilast</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 29, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT03239106/Prot_SAP_000.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>August 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT03239106/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Open Label</title>
          <description>All participants will received apremilast 30 mg PO BID.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Key inclusion criteria included age &gt;18 years, diagnosis of chronic pruritus of unknown origin (CPUO) for &gt;6 weeks, Numerical Rating Scale (NRS) itch score of &gt;7, failure of topical triamcinolone 0.1% ointment twice daily (BID) for at least 2 weeks.</population>
      <group_list>
        <group group_id="B1">
          <title>Open Label</title>
          <description>All participants will receive apremilast 30 mg PO BID.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.5" spread="11.7"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>24 hour numerical rating scale (NRS) itch score</title>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.25" lower_limit="7.75" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>1 week NRS itch score</title>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Dermatology Life Quality Index</title>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.5" lower_limit="8" upper_limit="20.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Absolute NRS Itch Score at Week 16 (End of Treatment)</title>
        <description>Participants will complete a Numeric Rating Scale for itch (0 representing &quot;no itching&quot; through 10 representing &quot;worst itch imaginable&quot;) will be recalled from prior 24 hours and the prior week.&#xD;
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.</description>
        <time_frame>Week 16</time_frame>
        <population>All patients met criteria for chronic pruritus of unknown origin.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label</title>
            <description>All participants will receive apremilast 30 mg PO BID.&#xD;
The data were analyzed in an intent-to-treat manner with key primary and secondary endpoints measured as an absolute reduction in NRS itch and DLQI scores, respectively at week 16 from baseline. Thirty percent of the patients completed the study, which did not allow for meaningful intent-to-treat statistical analysis. As an alternative approach, we undertook a LOCF analysis by carrying forward to week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute NRS Itch Score at Week 16 (End of Treatment)</title>
          <description>Participants will complete a Numeric Rating Scale for itch (0 representing &quot;no itching&quot; through 10 representing &quot;worst itch imaginable&quot;) will be recalled from prior 24 hours and the prior week.&#xD;
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.</description>
          <population>All patients met criteria for chronic pruritus of unknown origin.</population>
          <units>Units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Hour NRS Itch Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="1.5" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 Week NRS Itch Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" lower_limit="2" upper_limit="9.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute DLQI at Week 16</title>
        <description>Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16&#xD;
The DLQI is a numerical scale that scores multiple parameters of skin symptoms on a scale from 0 to 30. 0-1 = no effect at all on a patient's life (most favorable clinical outcome and minimum score), 1-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life (worse clinical outcome and maximum score).</description>
        <time_frame>Week 16</time_frame>
        <population>Patients who met inclusion criteria with a diagnosis of chronic pruritus of unknown origin</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label</title>
            <description>All participants will receive apremilast 30 mg PO BID.&#xD;
The data were analyzed in an intent-to-treat manner with key primary and secondary endpoints measured as an absolute reduction in NRS itch and DLQI scores, respectively at week 16 from baseline. Thirty percent of the patients completed the study, which did not allow for meaningful intent-to-treat statistical analysis. As an alternative approach, we undertook a LOCF analysis by carrying forward to week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute DLQI at Week 16</title>
          <description>Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16&#xD;
The DLQI is a numerical scale that scores multiple parameters of skin symptoms on a scale from 0 to 30. 0-1 = no effect at all on a patient's life (most favorable clinical outcome and minimum score), 1-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life (worse clinical outcome and maximum score).</description>
          <population>Patients who met inclusion criteria with a diagnosis of chronic pruritus of unknown origin</population>
          <units>Score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13" lower_limit="2.5" upper_limit="18.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NRS at Screening, Baseline and Weeks 2,4,8,12,16,and 18</title>
        <description>Participants' itch will be measured utilizing the Numeric Rating Scale for itch (0 representing &quot;no itching&quot; through 10 representing &quot;worst itch imaginable&quot;) will be recalled from prior 24 hours and the prior week.&#xD;
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.</description>
        <time_frame>Screening through Week 18 (follow up visit)</time_frame>
        <population>Although we started with 10 patients, patients dropped out of the study as it progressed.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label</title>
            <description>All participants will receive Apremilast 30 mg BID.&#xD;
Apremilast: Apremilast 30 mg BID daily</description>
          </group>
        </group_list>
        <measure>
          <title>NRS at Screening, Baseline and Weeks 2,4,8,12,16,and 18</title>
          <description>Participants' itch will be measured utilizing the Numeric Rating Scale for itch (0 representing &quot;no itching&quot; through 10 representing &quot;worst itch imaginable&quot;) will be recalled from prior 24 hours and the prior week.&#xD;
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.</description>
          <population>Although we started with 10 patients, patients dropped out of the study as it progressed.</population>
          <units>Numerical Rating Scale Itch 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="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.9" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline (Week 0)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.9" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.5" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLQI at Screening, Baseline, and Weeks 2,4,8,12,16 and 18</title>
        <description>Participants will complete a 10 question Dermatology Life Quality Index questionnaire at Screening, Baseline, and Weeks 2,4,8,12,16,18.</description>
        <time_frame>Screening through Week 18 (follow up visit)</time_frame>
        <population>Although we started with 10 patients, patients dropped out of the study as it progressed.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label</title>
            <description>All participants will receive apremilast 30 mg PO BID.&#xD;
The data were analyzed in an intent-to-treat manner with key primary and secondary endpoints measured as an absolute reduction in NRS itch and DLQI scores, respectively at week 16 from baseline. Thirty percent of the patients completed the study, which did not allow for meaningful intent-to-treat statistical analysis. As an alternative approach, we undertook a LOCF analysis by carrying forward to week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>DLQI at Screening, Baseline, and Weeks 2,4,8,12,16 and 18</title>
          <description>Participants will complete a 10 question Dermatology Life Quality Index questionnaire at Screening, Baseline, and Weeks 2,4,8,12,16,18.</description>
          <population>Although we started with 10 patients, patients dropped out of the study as it progressed.</population>
          <units>Dermatology Life Quality Index 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="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.3" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline (Week 0)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.7" spread="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3" spread="9.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8" spread="9.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" spread="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected until the end of the study visit at Week 18 or earlier if the subject dropped out of the study.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Open Label</title>
          <description>All participants will receive apremilast 30 mg PO BID.</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="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="5" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to the high dropout rate in this study a meaningful intent-to-treat analysis was not possible. Therefore, in addition, we attempted a last observation carried forward (LOCF) analysis as well.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Brian Kim, Associate Professor of Medicine</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-273-1376</phone>
      <email>briankim@wustl.edu</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/NCT03239106
org study id: CIP-ApremilastCC-10004
nct id: NCT03239106
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Chronic Itch is a debilitating condition affecting many people. Currently, there are no
      FDA-approved treatments. Apremilast is an FDA-approved oral medication used to successfully
      treat the inflammatory skin disorder psoriasis and the inflammatory disorder psoriatic
      arthritis. This study examines if apremiliast taken twice daily relieves chronic itch.
There is no FDA-approved medication for chronic idiopathic pruritus (CIP). Apremilast has
      demonstrated notable activity and is approved for treatment in other pruritic inflammatory
      skin conditions such as psoriasis. The drug is currently being investigated as therapy for
      atopic dermatitis. Additionally, the investigators have preliminary data to suggest that
      apremilast's anti-inflammatory properties may work via neuromodulation targeting neuronal
      cytokine pathways. The proposed study plans to assess the efficacy of apremilast 30 mg BID in
      the setting of CIP. Durable response to a medication is typically seen within one to two
      months of starting an efficacious medication in subjects who respond. Therefore, the
      investigators have designed this study to end at Week 16 to definitively determine efficacy
      and conclude the study with confidence with regard to both efficacy and failure.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: open label
primary purpose: Treatment
masking: None (Open Label)
measure: Absolute NRS Itch Score at Week 16 (End of Treatment)
time frame: Week 16
description: Participants will complete a Numeric Rating Scale for itch (0 representing "no itching" through 10 representing "worst itch imaginable") will be recalled from prior 24 hours and the prior week.
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.
measure: Absolute DLQI at Week 16
time frame: Week 16
description: Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16
The DLQI is a numerical scale that scores multiple parameters of skin symptoms on a scale from 0 to 30. 0-1 = no effect at all on a patient's life (most favorable clinical outcome and minimum score), 1-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life (worse clinical outcome and maximum score).
measure: NRS at Screening, Baseline and Weeks 2,4,8,12,16,and 18
time frame: Screening through Week 18 (follow up visit)
description: Participants' itch will be measured utilizing the Numeric Rating Scale for itch (0 representing "no itching" through 10 representing "worst itch imaginable") will be recalled from prior 24 hours and the prior week.
0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.
measure: DLQI at Screening, Baseline, and Weeks 2,4,8,12,16 and 18
time frame: Screening through Week 18 (follow up visit)
description: Participants will complete a 10 question Dermatology Life Quality Index questionnaire at Screening, Baseline, and Weeks 2,4,8,12,16,18.
arm group label: open label
arm group type: Experimental
description: All participants will receive Apremilast 30 mg BID.
intervention type: Drug
intervention name: Apremilast
description: Apremilast 30 mg BID daily
arm group label: open label
other name: Otezla
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Brian S. Kim, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pruritus
mesh term: Apremilast
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to the high dropout rate in this study a meaningful intent-to-treat analysis was not possible. Therefore, in addition, we attempted a last observation carried forward (LOCF) analysis as well.
point of contact: 