<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/NCT04400318</url>
  </required_header>
  <id_info>
    <org_study_id>LPS15834</org_study_id>
    <secondary_id>2019-004647-74</secondary_id>
    <secondary_id>U1111-1238-4679</secondary_id>
    <nct_id>NCT04400318</nct_id>
  </id_info>
  <brief_title>The Effect of Dupilumab on Lung Inflammation and Related Changes in Airway Volumes Detectable by Functional Respiratory Imaging in Patients With Moderate-severe Asthma</brief_title>
  <acronym>VESTIGE</acronym>
  <official_title>Randomized, Double Blind, Placebo Controlled Study to Evaluate the Effect of Dupilumab on Airway Inflammation Through Assessments of Lung Function, Mucus Plugging and Other Lung Imaging Parameters in Patients With Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective: • To assess the effect of dupilumab on lung inflammation and related&#xD;
      changes in airway volumes detectable by functional respiratory imaging Secondary Objective: •&#xD;
      To evaluate the effect of dupilumab at Week 24 on bronchodynamics, hyperinflation, airway&#xD;
      resistance, airway wall thickness, ventilation defects and mucus plugging derived from&#xD;
      high-resolution computed tomography (HRCT) scans, patient-reported outcomes, FeNO and&#xD;
      spirometry. • To evaluate safety of dupilumab&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study duration for each participant will be a total of minimum 29 weeks and up to 41&#xD;
      weeks. This includes 4 weeks +/-1 week screening period, 24 weeks of treatment period and a&#xD;
      follow-up period up to 12 weeks or until the patients switch to commercialized dupilumab (or&#xD;
      other biologic products), whatever comes first.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 22, 2020</start_date>
  <completion_date type="Anticipated">September 15, 2023</completion_date>
  <primary_completion_date type="Actual">June 26, 2023</primary_completion_date>
  <phase>Phase 4</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, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of participants achieving FeNO &lt;25 parts per billion (ppb) at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>Proportion of participants achieving FeNO &lt;25 parts per billion (ppb) at Week 24</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at TLC</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at TLC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at FRC</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at FRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in global lung lobar volumes (iVlobes) at TLC</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Absolute change from baseline to Week 24 in global lung lobar volumes (iVlobes) at TLC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD) for each lung zone</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Absolute Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD) for each lung zone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC for each lung zone</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Absolute change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC for each lung zone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in global lung mucus scoring (UCSF mucus scoring)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>University of California, San Francisco (UCSF) mucus scoring is a scoring system to quantify mucus plugs in lung images generated using computerized tomography. The scoring system is based on bronchopulmonary segmental anatomy. Each bronchopulmonary segment is given a score of 1 (mucus plug(s) present) or 0 (mucus plug(s) absent). The segment scores of each lobe are summed to generate a total mucus score for both lungs, yielding a mucus score ranging from 0-20.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in FeNO</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Absolute change from baseline to Week 24 in FeNO.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in pre-bronchodilator FEV1</measure>
    <time_frame>Week 24</time_frame>
    <description>Change from baseline to Week 24 in pre-bronchodilator FEV1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in post-bronchodilator FEV1</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Change from baseline to Week 24 in post-bronchodilator FEV1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to Week 24 in Asthma Control Questionnaire 7 (ACQ-7)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>The ACQ-7 is a validated asthma assessment tool that consists of 6 self-assessment questions. The overall scale ranges from 0 = 'totally controlled' to 6 = 'severely uncontrolled.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE) including clinically significant changes in vital signs and laboratory abnormalities</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>The incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) including clinically significant changes in vital signs and laboratory abnormalities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events of special interest (AESI )</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>The incidence of AESI.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">298</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Dupilumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 x loading dose on Day 1, followed by 1 x maintenance dose every 2 weeks (Q2W) during 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>2 x placebo injections on Day 1, then 1 placebo injection Q2W during 24 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dupilumab</intervention_name>
    <description>solution for injection subcutaneous</description>
    <arm_group_label>Dupilumab</arm_group_label>
    <other_name>SAR231893 Dupixent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Solution for injection subcutaneous</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 to 70 years of age inclusive with the diagnosis of asthma based on Global Strategy&#xD;
             for Asthma Management and Prevention (GINA) 2019 at the time of signing the informed&#xD;
             consent&#xD;
&#xD;
          -  History of ≥1 exacerbation(s) in the previous year&#xD;
&#xD;
          -  Uncontrolled moderate to severe asthma (ACQ-5 ≥1.5) at V1 and V2, prior to&#xD;
             randomization&#xD;
&#xD;
          -  Pre-bronchodilator FEV1 ≤80% of predicted normal at V1 and V2, prior to randomization&#xD;
&#xD;
          -  Exhibit bronchodilator reversibility (≥12% and 200 mL improvement in FEV1 post SABA&#xD;
             administration) during screening, prior to randomization&#xD;
&#xD;
          -  Blood eosinophil ≥300 cells /µL and FeNO ≥25 ppb during screening, prior to&#xD;
             randomization&#xD;
&#xD;
        NOTES:&#xD;
&#xD;
          -  Historical values of blood eosinophil count meeting the eligibility criterion measured&#xD;
             within 6 months prior to SV1 in the absence of OCS treatment are allowed.&#xD;
&#xD;
          -  FeNO value to be checked for eligibility at V2 as well. -Existing treatment with&#xD;
             medium to high dose ICS in combination with a second controller (e.g. LABA, LTRA) ± a&#xD;
             third controller. The dose regimen should be stable ≥1 month prior V1 and during&#xD;
             screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -Current smoker (cigarette or e-cigarette) or cessation of smoking within 1 year prior&#xD;
        randomization -Previous smoker with a smoking history &amp;gt;10 pack-years -Known&#xD;
        hypersensitivity to dupilumab or any of its excipients -A subject who experiences an asthma&#xD;
        exacerbation (defined as a deterioration of asthma that results in emergency treatment,&#xD;
        hospitalization due to asthma, or treatment with systemic steroids) during screening&#xD;
        -Current acute bronchospasm or status asthmaticus -Diagnosed pulmonary (other than asthma)&#xD;
        or systemic disease associated with elevated peripheral eosinophil counts -History or&#xD;
        clinical evidence of chronic obstructive pulmonary disease (COPD) including Asthma-COPD&#xD;
        Overlap Syndrome (ACOS) or any other significant lung disease (eg, lung fibrosis,&#xD;
        sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis,&#xD;
        Churg-Strauss Syndrome, etc) -Active tuberculosis, latent untreated tuberculosis or a&#xD;
        history of incompletely treated tuberculosis or non-tuberculous mycobacterial infection&#xD;
        unless it is well documented by a specialist that the participants has been adequately&#xD;
        treated and the treatment with a biologic agent can be initiated, in the medical judgment&#xD;
        of the Investigator and/or infectious disease specialist. Tuberculosis testing would only&#xD;
        be performed on a country by country basis according to the routine clinical practice and&#xD;
        the local guidelines, if required by regulatory authorities or ethics committees -History&#xD;
        of or current evidence of clinically significant disease in any non-respiratory system&#xD;
        (e.g. cardiovascular, hepatic, nervous system, gastrointestinal, endocrinological,&#xD;
        rheumatological, dermatological), which, in the judgment of the Investigator, could&#xD;
        interfere with the study or require treatment that might interfere with the study -Current&#xD;
        evidence of clinically significant oncological disease, which in the opinion of the&#xD;
        investigator may interfere with the objectives of the study or put the subject at undue&#xD;
        risk -Participants with any of the following results at Visit (V) 1: -Positive (or&#xD;
        indeterminate) hepatitis B surface antigen (HBs Ag) or -Positive Hepatitis B IgM core&#xD;
        antibody (IgM HBc Ab) or -Positive total hepatitis B core antibody (total HBc Ab) confirmed&#xD;
        by positive HBV DNA or -Positive hepatitis C antibody (HCV Ab) confirmed by positive HCV&#xD;
        RNA -History of human immunodeficiency virus (HIV) infection or positive HIV serology at V&#xD;
        1 -Any biologic therapy (including experimental treatments and dupilumab) or any other&#xD;
        biologic therapy/immunosuppressant within 3 months prior to V1 -Treatment with live&#xD;
        (attenuated) vaccine within 4 weeks before V1. For participants who have vaccination with&#xD;
        live, attenuated vaccines planned during the course of the study (based on national&#xD;
        vaccination schedule/local guidelines), it will be determined, after consultation with a&#xD;
        physician, whether the administration of vaccine can be postponed until after the end of&#xD;
        the study, or preponed to before the start of the study without compromising the health of&#xD;
        the participant: - Participants for whom administration of live (attenuated) vaccine can be&#xD;
        safely postponed would be eligible to enroll into the study. - Participants who have their&#xD;
        vaccination preponed can enroll in the study only after a gap of 4 weeks following&#xD;
        administration of the vaccine. -Treatment with oral corticosteroids (OCS) within 2 weeks&#xD;
        prior to V1 -Enrolled in other ongoing studies regardless of the investigational product&#xD;
        -Treatment with an investigational drug within 1 month or within 5 half-lives (if known),&#xD;
        whichever is longer, prior to V1 -Suspected or high risk of parasitic infection (helminthic&#xD;
        infection), unless clinical and (if necessary) laboratory assessments have ruled out active&#xD;
        infection prior to randomization -Females who are lactating, breastfeeding, or who are&#xD;
        pregnant -Individuals accommodated in an institution because of regulatory or legal order;&#xD;
        prisoners or subjects who are legally institutionalized -Participants are dependent on the&#xD;
        Sponsor or Investigator (in conjunction with Section 1.61 of the ICH GCP Ordinance E6)&#xD;
        -Participants are employees of the clinical study site or other individuals directly&#xD;
        involved in the conduct of the study, or immediate family members of such individuals&#xD;
        -Sensitivity to any of the study interventions, or components thereof, or drug or other&#xD;
        allergy that, in the opinion of the Investigator, contraindicates participation in the&#xD;
        study -Any country-related specific regulation that would prevent the subject from entering&#xD;
        the study The above information is not intended to contain all considerations relevant to a&#xD;
        patient's potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Allianz Research Institute-Site Number:8400020</name>
      <address>
        <city>Westminster</city>
        <state>California</state>
        <zip>92683</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas School of Medicine-Site Number:8400008</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan-Site Number:8400002</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Lung Research Center-Site Number:8400010</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <zip>63017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Research-Site Number:8400005</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28277</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velocity Clinical Research, Medford-Site Number:8400014</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina - Pulmonary &amp; Critical Care Clinical Research Program-Site Number:8400009</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VitaLink Research-Greenville-Site Number:8400013</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VitaLink Research - Spartanburg-Site Number:8400011</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>~Spartanburg Medical Research-Site Number:8400004</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000013</name>
      <address>
        <city>Dupnitsa</city>
        <zip>2600</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000004</name>
      <address>
        <city>Montana</city>
        <zip>3400</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000018</name>
      <address>
        <city>Plovdiv</city>
        <zip>4000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000012</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000008</name>
      <address>
        <city>Ruse</city>
        <zip>7002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000015</name>
      <address>
        <city>Sofia</city>
        <zip>1000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000005</name>
      <address>
        <city>Sofia</city>
        <zip>1202</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000003</name>
      <address>
        <city>Sofia</city>
        <zip>1233</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000006</name>
      <address>
        <city>Sofia</city>
        <zip>1233</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000011</name>
      <address>
        <city>Sofia</city>
        <zip>1407</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000010</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000002</name>
      <address>
        <city>Sofia</city>
        <zip>1680</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1000007</name>
      <address>
        <city>Stara Zagora</city>
        <zip>6001</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2080004</name>
      <address>
        <city>Aalborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2080006</name>
      <address>
        <city>Aarhus N</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2080003</name>
      <address>
        <city>Copenhagen Nv</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2080002</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2080005</name>
      <address>
        <city>Hellerup</city>
        <zip>2900</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2080001</name>
      <address>
        <city>Hvidovre</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500002</name>
      <address>
        <city>Lyon</city>
        <zip>69317</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500003</name>
      <address>
        <city>Marseille</city>
        <zip>13015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500001</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800003</name>
      <address>
        <city>Cona</city>
        <state>Ferrara</state>
        <zip>44124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800004</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800001</name>
      <address>
        <city>Pisa</city>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200004</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-075</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200005</name>
      <address>
        <city>Guimarães</city>
        <zip>4810-061</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200006</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200003</name>
      <address>
        <city>Porto</city>
        <zip>4100-180</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200001</name>
      <address>
        <city>Porto</city>
        <zip>4202-451</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6420005</name>
      <address>
        <city>Bragadiru</city>
        <zip>769764</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6420008</name>
      <address>
        <city>Brasov</city>
        <zip>500283</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6420006</name>
      <address>
        <city>Cluj-Napoca</city>
        <zip>400275</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6420001</name>
      <address>
        <city>Cluj-Napoca</city>
        <zip>400371</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6420007</name>
      <address>
        <city>Oradea</city>
        <zip>410169</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6420003</name>
      <address>
        <city>Timisoara</city>
        <zip>300134</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6820008</name>
      <address>
        <city>Dammam</city>
        <zip>31952</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6820004</name>
      <address>
        <city>Jeddah</city>
        <zip>21423</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6820006</name>
      <address>
        <city>Riyadh</city>
        <zip>11426</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6820001</name>
      <address>
        <city>Riyadh</city>
        <zip>11525</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6820002</name>
      <address>
        <city>Riyadh</city>
        <zip>12372</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6820010</name>
      <address>
        <city>Riyadh</city>
        <zip>12746</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240001</name>
      <address>
        <city>Barcelona</city>
        <state>Barcelona [Barcelona]</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240002</name>
      <address>
        <city>Santiago de Compostela</city>
        <state>Galicia [Galicia]</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240004</name>
      <address>
        <city>Madrid / Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240005</name>
      <address>
        <city>Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240003</name>
      <address>
        <city>Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7520001</name>
      <address>
        <city>Lund</city>
        <zip>221 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580004</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580002</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580003</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580001</name>
      <address>
        <city>Taipei</city>
        <zip>110</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040003</name>
      <address>
        <city>Chernivtsi</city>
        <zip>58001</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040001</name>
      <address>
        <city>Ivano-Frankivsk</city>
        <zip>76018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040002</name>
      <address>
        <city>Kharkiv</city>
        <zip>61124</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040004</name>
      <address>
        <city>Kyiv</city>
        <zip>01023</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040005</name>
      <address>
        <city>Odesa</city>
        <zip>65025</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8040007</name>
      <address>
        <city>Ternopil</city>
        <zip>46000</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8260001</name>
      <address>
        <city>Leicester</city>
        <state>Leicestershire</state>
        <zip>LE3 9QP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :8260002</name>
      <address>
        <city>Bradford</city>
        <zip>BD9 6RJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Italy</country>
    <country>Portugal</country>
    <country>Romania</country>
    <country>Saudi Arabia</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
  </removed_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>July 14, 2023</last_update_submitted>
  <last_update_submitted_qc>July 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04400318
org study id: LPS15834
secondary id: 2019-004647-74
secondary id: U1111-1238-4679
nct id: NCT04400318
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Primary Objective: • To assess the effect of dupilumab on lung inflammation and related
      changes in airway volumes detectable by functional respiratory imaging Secondary Objective: •
      To evaluate the effect of dupilumab at Week 24 on bronchodynamics, hyperinflation, airway
      resistance, airway wall thickness, ventilation defects and mucus plugging derived from
      high-resolution computed tomography (HRCT) scans, patient-reported outcomes, FeNO and
      spirometry. • To evaluate safety of dupilumab
The study duration for each participant will be a total of minimum 29 weeks and up to 41
      weeks. This includes 4 weeks +/-1 week screening period, 24 weeks of treatment period and a
      follow-up period up to 12 weeks or until the patients switch to commercialized dupilumab (or
      other biologic products), whatever comes first.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Proportion of participants achieving FeNO <25 parts per billion (ppb) at Week 24
time frame: Week 24
description: Proportion of participants achieving FeNO <25 parts per billion (ppb) at Week 24
measure: Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC)
time frame: Baseline to Week 24
description: Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC).
measure: Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC)
time frame: Baseline to Week 24
description: Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC).
measure: Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at TLC
time frame: Baseline to Week 24
description: Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at TLC.
measure: Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at FRC
time frame: Baseline to Week 24
description: Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at FRC.
measure: Change from baseline to Week 24 in global lung lobar volumes (iVlobes) at TLC
time frame: Baseline to Week 24
description: Absolute change from baseline to Week 24 in global lung lobar volumes (iVlobes) at TLC.
measure: Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD) for each lung zone
time frame: Baseline to Week 24
description: Absolute Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD) for each lung zone.
measure: Change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC for each lung zone
time frame: Baseline to Week 24
description: Absolute change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC for each lung zone.
measure: Change from baseline to Week 24 in global lung mucus scoring (UCSF mucus scoring)
time frame: Baseline to Week 24
description: University of California, San Francisco (UCSF) mucus scoring is a scoring system to quantify mucus plugs in lung images generated using computerized tomography. The scoring system is based on bronchopulmonary segmental anatomy. Each bronchopulmonary segment is given a score of 1 (mucus plug(s) present) or 0 (mucus plug(s) absent). The segment scores of each lobe are summed to generate a total mucus score for both lungs, yielding a mucus score ranging from 0-20.
measure: Change from baseline to Week 24 in FeNO
time frame: Baseline to Week 24
description: Absolute change from baseline to Week 24 in FeNO.
measure: Change from baseline to Week 24 in pre-bronchodilator FEV1
time frame: Week 24
description: Change from baseline to Week 24 in pre-bronchodilator FEV1
measure: Change from baseline to Week 24 in post-bronchodilator FEV1
time frame: Baseline to Week 24
description: Change from baseline to Week 24 in post-bronchodilator FEV1.
measure: Change from baseline to Week 24 in Asthma Control Questionnaire 7 (ACQ-7)
time frame: Baseline to Week 24
description: The ACQ-7 is a validated asthma assessment tool that consists of 6 self-assessment questions. The overall scale ranges from 0 = 'totally controlled' to 6 = 'severely uncontrolled.
measure: Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE) including clinically significant changes in vital signs and laboratory abnormalities
time frame: Baseline to Week 36
description: The incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) including clinically significant changes in vital signs and laboratory abnormalities.
measure: Incidence of adverse events of special interest (AESI )
time frame: Baseline to Week 36
description: The incidence of AESI.
arm group label: Dupilumab
arm group type: Experimental
description: 2 x loading dose on Day 1, followed by 1 x maintenance dose every 2 weeks (Q2W) during 24 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: 2 x placebo injections on Day 1, then 1 placebo injection Q2W during 24 weeks.
intervention type: Drug
intervention name: Dupilumab
description: solution for injection subcutaneous
arm group label: Dupilumab
other name: SAR231893 Dupixent
intervention type: Drug
intervention name: Placebo
description: Solution for injection subcutaneous
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
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country: Bulgaria
country: Denmark
country: France
country: Italy
country: Portugal
country: Romania
country: Saudi Arabia
country: Spain
country: Sweden
country: Taiwan
country: Ukraine
country: United Kingdom
country: United States
country: Canada
responsible party type: Sponsor
mesh term: Asthma
mesh term: Inflammation
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org