<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/NCT02210780</url>
  </required_header>
  <id_info>
    <org_study_id>R668-AD-1314</org_study_id>
    <nct_id>NCT02210780</nct_id>
  </id_info>
  <brief_title>Study of Dupilumab and Immune Responses in Adults With Atopic Dermatitis (AD)</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Study Investigating Vaccine Responses in Adults With Moderate to Severe Atopic Dermatitis Treated With Dupilumab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Regeneron Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was a 32-week, randomized, double-blind, placebo-controlled, parallel-group study&#xD;
      assessing immunization responses to vaccination in adults with moderate to severe atopic&#xD;
      dermatitis who are treated with subcutaneous dupilumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 5, 2014</start_date>
  <completion_date type="Actual">September 15, 2015</completion_date>
  <primary_completion_date type="Actual">September 15, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With a Positive Response (≥4-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>A positive response was defined as a ≥ 4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G (IgG) titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of &lt;0.1 IU/ml. There was no planned statistical hypothesis testing regarding the difference in immune response between the 2 treatment groups for this study, therefore no formal statistical hypothesis between groups was performed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Positive Response (≥2-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>Participants with positive response defined as a ≥2-fold increase from pre-vaccination baseline in anti-tetanus IgG titer for participants with pre-vaccination tetanus antibody titers ≥0.1 IU/ml or a titer of ≥0.2 IU/ml for participants with pre-vaccination titers of &lt;0.1 IU/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Positive Response (SBA Antibody Titer of ≥8 for Serogroup C) to Menomune Vaccine at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>A positive response to the Menomune vaccine was a serum bactericidal antibody (SBA) titer of ≥8 for serogroup C.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of &quot;0&quot; or &quot;1&quot; at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were counted as non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving an Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving an Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peak Weekly Averaged Pruritis Numerical Rating Scale (NRS) Scores at Week 16</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>Pruritus NRS was an assessment tool that was used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Weekly average obtained in the 7-day period prior to the baseline visit. Values after first rescue medication use were set to missing and missing values were imputed by Last observation carried forward (LOCF).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Body Surface Area (BSA) Affected by AD at Week 16</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations and Lichenification) at Week 16</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue treatment were set to missing. Analysis was completed using MMRM model which includes treatment, randomization strata, visit, baseline value, treatment-by-visit interaction, and baseline-by-visit interaction as covariates. These results are observed results without imputation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline in GISS Cumulative Score to Week 16</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Patient Oriented Eczema Measure (POEM) Score From Baseline to Week 16</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>The POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">194</enrollment>
  <condition>Atopic Dermatitis</condition>
  <arm_group>
    <arm_group_label>Placebo qw</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dupilumab 300 mg qw</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dupilumab</intervention_name>
    <description>Administered via subcutaneous injection.</description>
    <arm_group_label>Dupilumab 300 mg qw</arm_group_label>
    <other_name>REGN668</other_name>
    <other_name>SAR231893</other_name>
    <other_name>Dupixent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>An inactive substance containing no medicine administered via subcutaneous injection.</description>
    <arm_group_label>Placebo qw</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Male or female adults ages 18 to 64 years with Chronic AD (according to the American&#xD;
             Academy of Dermatology Consensus Criteria, [Eichenfeld 2004])that has been present for&#xD;
             at least 3 years before the screening visit&#xD;
&#xD;
          2. Participants with documented recent history (within 6 months before the screening&#xD;
             visit) of inadequate response to a sufficient course of outpatient treatment with&#xD;
             topical AD medication(s), or for whom topical AD therapies are otherwise inadvisable&#xD;
             (e.g., because of side effects or safety risks).&#xD;
&#xD;
          3. Eczema Area and Severity Index (EASI) score ≥16 at the screening visit and the&#xD;
             baseline visit&#xD;
&#xD;
          4. Investigator's Global Assessment (IGA) score ≥3 (on the 0-4 IGA scale) at the&#xD;
             screening and baseline visits&#xD;
&#xD;
          5. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Prior treatment with dupilumab (REGN668/ SAR231893)&#xD;
&#xD;
          2. Patients needing &gt;10 mg of daily prednisone (including equivalent doses of other&#xD;
             steroids) or high dose systemic corticosteroids (≥2 mg/kg) for 14 days or longer&#xD;
             during the 16 week treatment period of the study&#xD;
&#xD;
          3. History of Guillain-Barre syndrome&#xD;
&#xD;
          4. History of severe allergic reaction to either vaccine or to vaccine components&#xD;
             including alum, thimerosal, phenol&#xD;
&#xD;
          5. Patients with a severe reaction to natural rubber latex products (some packaging&#xD;
             components of the vaccines contain rubber latex and may cause a reaction in&#xD;
             susceptible individuals)&#xD;
&#xD;
          6. Treatment with biologics within 4 months of baseline visit&#xD;
&#xD;
          7. Chronic or acute infection requiring treatment with antibiotics, antivirals,&#xD;
             antiparasitics, antifungals within 4 weeks before screening visit or superficial skin&#xD;
             infections within 1 week of screening visit&#xD;
&#xD;
        The information listed above is not intended to contain all considerations relevant to a&#xD;
        patient's potential participation in a clinical trial and not all inclusion/ exclusion&#xD;
        criteria are listed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trial Management</last_name>
    <role>Study Director</role>
    <affiliation>Regeneron Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Smith</city>
        <state>Arkansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mission Viejo</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rolling Hills Estates</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Macon</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>West Dundee</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plainfield</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Forest Hills</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Norman</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Webster</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <results_first_submitted>March 20, 2020</results_first_submitted>
  <results_first_submitted_qc>April 23, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 7, 2020</results_first_posted>
  <disposition_first_submitted>February 7, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>February 7, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">February 8, 2017</disposition_first_posted>
  <last_update_submitted>April 23, 2020</last_update_submitted>
  <last_update_submitted_qc>April 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2020</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>Dermatitis, Atopic</mesh_term>
    <mesh_term>Dermatitis</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at approximately 50 study sites in United States (US) between 05 August 2014 and 15 September 2015. A total of 243 participants were screened in the study.</recruitment_details>
      <pre_assignment_details>Out of 243 participants, 194 were randomized and treated in the study. Participants were randomized in 1:1 ratio to receive 600 mg subcutaneous (SC) dupilumab loading dose on day 1 and then dupilumab 300 mg once weekly (qw) or placebo qw.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo qw</title>
          <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
        </group>
        <group group_id="P2">
          <title>Dupilumab 300 mg qw</title>
          <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="92"/>
                <participants group_id="P2" count="89"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than specified above</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set (SAF) included all randomized participants who received any study drug, and was analyzed as treated. Any participant given at least 1 dupilumab injection was assigned to the dupilumab group. The safety analysis was based on the SAF.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo qw</title>
          <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
        </group>
        <group group_id="B2">
          <title>Dupilumab 300 mg qw</title>
          <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="97"/>
            <count group_id="B2" value="97"/>
            <count group_id="B3" value="194"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.9" spread="14.04"/>
                    <measurement group_id="B2" value="39.2" spread="13.55"/>
                    <measurement group_id="B3" value="39.6" spread="13.77"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="165"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="60"/>
                    <measurement group_id="B3" value="127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anti-tetanus Immunoglobulin G (IgG) Titer</title>
          <description>Immune responses to vaccines included anti-tetanus IgG (Adacel [Tdap] vaccine) titre: A ≥ 2-fold or ≥ 4-fold increase from pre-vaccination at baseline in IgG titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of &lt;0.1 IU/ml.</description>
          <units>IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.74" spread="1.908"/>
                    <measurement group_id="B2" value="1.51" spread="1.328"/>
                    <measurement group_id="B3" value="1.62" spread="1.644"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eczema Area and Severity Index (EASI) Score</title>
          <description>The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.23" spread="13.771"/>
                    <measurement group_id="B2" value="29.04" spread="13.085"/>
                    <measurement group_id="B3" value="30.14" spread="13.442"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Investigator Global Assessment (IGA) Score</title>
          <description>IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.4" spread="0.49"/>
                    <measurement group_id="B2" value="3.4" spread="0.49"/>
                    <measurement group_id="B3" value="3.4" spread="0.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weekly Peak Pruritus Numeric Rating Scale (NRS)</title>
          <population>Pruritus NRS was a tool used to report intensity of participant's pruritus (itch)--max &amp; average intensity. Participants were asked: how would you rate the itch at worst moment during previous 24 hrs (max itch intensity, scale of 0-10 [0=no itch;10=worst itch imaginable]). Participants were excluded if baseline values were missed.</population>
          <units>Units on a Scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="90"/>
                    <count group_id="B2" value="94"/>
                    <count group_id="B3" value="184"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.3" spread="2.19"/>
                    <measurement group_id="B2" value="7.4" spread="2.20"/>
                    <measurement group_id="B3" value="7.3" spread="2.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Global Individual Signs Score (GISS) Total Score</title>
          <description>Individual components of the AD lesions (erythema,infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.8" spread="1.80"/>
                    <measurement group_id="B2" value="8.8" spread="1.76"/>
                    <measurement group_id="B3" value="8.8" spread="1.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Patient Oriented Eczema Measure (POEM) Score</title>
          <description>The POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="97"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.6" spread="5.59"/>
                    <measurement group_id="B2" value="21.5" spread="6.04"/>
                    <measurement group_id="B3" value="21.1" spread="5.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With a Positive Response (≥4-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16</title>
        <description>A positive response was defined as a ≥ 4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G (IgG) titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of &lt;0.1 IU/ml. There was no planned statistical hypothesis testing regarding the difference in immune response between the 2 treatment groups for this study, therefore no formal statistical hypothesis between groups was performed.</description>
        <time_frame>Week 16</time_frame>
        <population>The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Positive Response (≥4-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16</title>
          <description>A positive response was defined as a ≥ 4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G (IgG) titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of &lt;0.1 IU/ml. There was no planned statistical hypothesis testing regarding the difference in immune response between the 2 treatment groups for this study, therefore no formal statistical hypothesis between groups was performed.</description>
          <population>The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.7"/>
                    <measurement group_id="O2" value="83.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Positive Response (≥2-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16</title>
        <description>Participants with positive response defined as a ≥2-fold increase from pre-vaccination baseline in anti-tetanus IgG titer for participants with pre-vaccination tetanus antibody titers ≥0.1 IU/ml or a titer of ≥0.2 IU/ml for participants with pre-vaccination titers of &lt;0.1 IU/ml.</description>
        <time_frame>Week 16</time_frame>
        <population>The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Positive Response (≥2-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16</title>
          <description>Participants with positive response defined as a ≥2-fold increase from pre-vaccination baseline in anti-tetanus IgG titer for participants with pre-vaccination tetanus antibody titers ≥0.1 IU/ml or a titer of ≥0.2 IU/ml for participants with pre-vaccination titers of &lt;0.1 IU/ml.</description>
          <population>The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.6"/>
                    <measurement group_id="O2" value="95.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Positive Response (SBA Antibody Titer of ≥8 for Serogroup C) to Menomune Vaccine at Week 16</title>
        <description>A positive response to the Menomune vaccine was a serum bactericidal antibody (SBA) titer of ≥8 for serogroup C.</description>
        <time_frame>Week 16</time_frame>
        <population>The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Positive Response (SBA Antibody Titer of ≥8 for Serogroup C) to Menomune Vaccine at Week 16</title>
          <description>A positive response to the Menomune vaccine was a serum bactericidal antibody (SBA) titer of ≥8 for serogroup C.</description>
          <population>The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87.0"/>
                    <measurement group_id="O2" value="86.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of &quot;0&quot; or &quot;1&quot; at Week 16</title>
        <description>IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were counted as non-responders.</description>
        <time_frame>Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of &quot;0&quot; or &quot;1&quot; at Week 16</title>
          <description>IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were counted as non-responders.</description>
          <population>Full analysis set (FAS) that included all randomized participants.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3"/>
                    <measurement group_id="O2" value="44.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using Cochran-Mantel-Haenszel test stratified by randomization strata (moderate [IGA=3] vs. severe [IGA=4] AD).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Percentage Difference</param_type>
            <param_value>34.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>24.29</ci_lower_limit>
            <ci_upper_limit>43.75</ci_upper_limit>
            <estimate_desc>Dupilumab 300 mg qw vs. Placebo qw</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving an Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16</title>
        <description>The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.</description>
        <time_frame>Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving an Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16</title>
          <description>The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.</description>
          <population>Full analysis set (FAS) that included all randomized participants.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.0"/>
                    <measurement group_id="O2" value="72.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using Cochran-Mantel-Haenszel test stratified by randomization strata (moderate [IGA=3] vs. severe [IGA=4] AD).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Percentage Difference</param_type>
            <param_value>40.2</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>29.40</ci_lower_limit>
            <ci_upper_limit>51.01</ci_upper_limit>
            <estimate_desc>Dupilumab 300 mg qw vs. Placebo qw</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving an Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16</title>
        <description>The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.</description>
        <time_frame>Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving an Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16</title>
          <description>The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.</description>
          <population>Full analysis set (FAS) that included all randomized participants.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.6"/>
                    <measurement group_id="O2" value="53.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using Cochran-Mantel-Haenszel test stratified by randomization strata (moderate [IGA=3] vs. severe [IGA=4] AD).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Percentage Difference</param_type>
            <param_value>34.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>23.38</ci_lower_limit>
            <ci_upper_limit>44.66</ci_upper_limit>
            <estimate_desc>Dupilumab 300 mg qw vs. Placebo qw</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peak Weekly Averaged Pruritis Numerical Rating Scale (NRS) Scores at Week 16</title>
        <description>Pruritus NRS was an assessment tool that was used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Weekly average obtained in the 7-day period prior to the baseline visit. Values after first rescue medication use were set to missing and missing values were imputed by Last observation carried forward (LOCF).</description>
        <time_frame>Baseline to Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak Weekly Averaged Pruritis Numerical Rating Scale (NRS) Scores at Week 16</title>
          <description>Pruritus NRS was an assessment tool that was used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Weekly average obtained in the 7-day period prior to the baseline visit. Values after first rescue medication use were set to missing and missing values were imputed by Last observation carried forward (LOCF).</description>
          <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="90"/>
                <count group_id="O2" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.11" spread="0.259"/>
                    <measurement group_id="O2" value="-4.24" spread="0.250"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using ANCOVA model which includes treatment, randomization strata, and baseline value as covariates.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-2.13</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.354</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.72</ci_lower_limit>
            <ci_upper_limit>-1.55</ci_upper_limit>
            <estimate_desc>Dupilumab 300 mg qw vs. Placebo qw</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Body Surface Area (BSA) Affected by AD at Week 16</title>
        <description>BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
        <time_frame>Baseline to Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Body Surface Area (BSA) Affected by AD at Week 16</title>
          <description>BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
          <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
          <units>Percentage of BSA</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.0" spread="2.11"/>
                    <measurement group_id="O2" value="-28.7" spread="2.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using ANCOVA model that includes treatment, randomization strata and baseline value as covariates.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-17.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>2.84</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-22.5</ci_lower_limit>
            <ci_upper_limit>-13.1</ci_upper_limit>
            <estimate_desc>Dupilumab 300 mg qw vs. Placebo qw</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations and Lichenification) at Week 16</title>
        <description>Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue treatment were set to missing. Analysis was completed using MMRM model which includes treatment, randomization strata, visit, baseline value, treatment-by-visit interaction, and baseline-by-visit interaction as covariates. These results are observed results without imputation.</description>
        <time_frame>Baseline to Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations and Lichenification) at Week 16</title>
          <description>Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue treatment were set to missing. Analysis was completed using MMRM model which includes treatment, randomization strata, visit, baseline value, treatment-by-visit interaction, and baseline-by-visit interaction as covariates. These results are observed results without imputation.</description>
          <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Erythema</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="79"/>
                    <count group_id="O2" value="87"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.08"/>
                    <measurement group_id="O2" value="-0.9" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infiltration/Papulation</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="79"/>
                    <count group_id="O2" value="87"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.08"/>
                    <measurement group_id="O2" value="-1.1" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Excoriations</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="79"/>
                    <count group_id="O2" value="87"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="0.09"/>
                    <measurement group_id="O2" value="-1.2" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lichenification</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="79"/>
                    <count group_id="O2" value="87"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.09"/>
                    <measurement group_id="O2" value="-1.0" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes From Baseline in GISS Cumulative Score to Week 16</title>
        <description>Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
        <time_frame>Baseline to Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes From Baseline in GISS Cumulative Score to Week 16</title>
          <description>Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
          <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="0.28"/>
                    <measurement group_id="O2" value="-4.1" spread="0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using the ANCOVA model which includes treatment, randomization strata, and baseline values as covariates.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-2.4</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.39</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.0</ci_lower_limit>
            <ci_upper_limit>-1.7</ci_upper_limit>
            <estimate_desc>Dupilumab 300 mg qw vs. Placebo qw</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Patient Oriented Eczema Measure (POEM) Score From Baseline to Week 16</title>
        <description>The POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
        <time_frame>Baseline to Week 16</time_frame>
        <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo qw</title>
            <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
          </group>
          <group group_id="O2">
            <title>Dupilumab 300 mg qw</title>
            <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Patient Oriented Eczema Measure (POEM) Score From Baseline to Week 16</title>
          <description>The POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.</description>
          <population>Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.</population>
          <units>Units on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.8" spread="0.72"/>
                    <measurement group_id="O2" value="-13.1" spread="0.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using the ANCOVA model which included treatment, randomization strata, and baseline value as covariates.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-8.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.99</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.9</ci_lower_limit>
            <ci_upper_limit>-6.6</ci_upper_limit>
            <estimate_desc>Dupilumab 300 mg qw vs. Placebo qw</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product</time_frame>
      <desc>Reported AEs are treatment-emergent adverse events which are AEs that developed/worsened during the 'on treatment period' (from the administration of first dose of study drug up to the final visit [Week 32]).</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo qw</title>
          <description>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.</description>
        </group>
        <group group_id="E2">
          <title>Dupilumab 300 mg qw</title>
          <description>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Serum sickness-like reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Mycosis fungoides stage iv</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis atopic</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </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 investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Management</name_or_title>
      <organization>Regeneron Pharmaceuticals, Inc.</organization>
      <phone>844-734-6643</phone>
      <email>clinicaltrials@regeneron.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02210780
org study id: R668-AD-1314
nct id: NCT02210780
lead sponsor: 
collaborator: 
has dmc: Yes
This was a 32-week, randomized, double-blind, placebo-controlled, parallel-group study
      assessing immunization responses to vaccination in adults with moderate to severe atopic
      dermatitis who are treated with subcutaneous dupilumab.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Percentage of Participants With a Positive Response (≥4-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16
time frame: Week 16
description: A positive response was defined as a ≥ 4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G (IgG) titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of <0.1 IU/ml. There was no planned statistical hypothesis testing regarding the difference in immune response between the 2 treatment groups for this study, therefore no formal statistical hypothesis between groups was performed.
measure: Percentage of Participants With a Positive Response (≥2-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16
time frame: Week 16
description: Participants with positive response defined as a ≥2-fold increase from pre-vaccination baseline in anti-tetanus IgG titer for participants with pre-vaccination tetanus antibody titers ≥0.1 IU/ml or a titer of ≥0.2 IU/ml for participants with pre-vaccination titers of <0.1 IU/ml.
measure: Percentage of Participants With a Positive Response (SBA Antibody Titer of ≥8 for Serogroup C) to Menomune Vaccine at Week 16
time frame: Week 16
description: A positive response to the Menomune vaccine was a serum bactericidal antibody (SBA) titer of ≥8 for serogroup C.
measure: Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of "0" or "1" at Week 16
time frame: Week 16
description: IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were counted as non-responders.
measure: Percentage of Participants Achieving an Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16
time frame: Week 16
description: The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.
measure: Percentage of Participants Achieving an Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
time frame: Week 16
description: The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.
measure: Change From Baseline in Peak Weekly Averaged Pruritis Numerical Rating Scale (NRS) Scores at Week 16
time frame: Baseline to Week 16
description: Pruritus NRS was an assessment tool that was used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Weekly average obtained in the 7-day period prior to the baseline visit. Values after first rescue medication use were set to missing and missing values were imputed by Last observation carried forward (LOCF).
measure: Change From Baseline in Body Surface Area (BSA) Affected by AD at Week 16
time frame: Baseline to Week 16
description: BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
measure: Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations and Lichenification) at Week 16
time frame: Baseline to Week 16
description: Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue treatment were set to missing. Analysis was completed using MMRM model which includes treatment, randomization strata, visit, baseline value, treatment-by-visit interaction, and baseline-by-visit interaction as covariates. These results are observed results without imputation.
measure: Changes From Baseline in GISS Cumulative Score to Week 16
time frame: Baseline to Week 16
description: Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
measure: Change in Patient Oriented Eczema Measure (POEM) Score From Baseline to Week 16
time frame: Baseline to Week 16
description: The POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
arm group label: Placebo qw
arm group type: Experimental
description: Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.
arm group label: Dupilumab 300 mg qw
arm group type: Experimental
description: Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15.
intervention type: Drug
intervention name: Dupilumab
description: Administered via subcutaneous injection.
arm group label: Dupilumab 300 mg qw
other name: REGN668
other name: SAR231893
other name: Dupixent
intervention type: Drug
intervention name: Placebo
description: An inactive substance containing no medicine administered via subcutaneous injection.
arm group label: Placebo qw
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: Clinical Trial Management
role: Study Director
affiliation: Regeneron Pharmaceuticals
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country: United States
responsible party type: Sponsor
mesh term: Dermatitis, Atopic
mesh term: Dermatitis
mesh term: Eczema
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 