<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/NCT03810183</url>
  </required_header>
  <id_info>
    <org_study_id>CQAW039E12201</org_study_id>
    <secondary_id>2018-004267-32</secondary_id>
    <nct_id>NCT03810183</nct_id>
  </id_info>
  <brief_title>A Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia</brief_title>
  <official_title>A Multi-center, Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled,&#xD;
      parallel group, proof-of-mechanism study of multiple oral doses of fevipiprant (QAW039) in&#xD;
      chronic obstructive pulmonary disease (COPD) patients with eosinophilia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled,&#xD;
      parallel group, proof-of-mechanism study in COPD subjects with eosinophilia, on standard of&#xD;
      care therapy. Standard of care (SoC) treatment in subjects with COPD typically includes a&#xD;
      regimen of inhaled corticosteroid (ICS) plus one or more long acting bronchodilator&#xD;
      (long-acting beta2-agonist (LABA) or long-acting antimuscarinic antagonist (LAMA)).&#xD;
&#xD;
      The study consisted of a screening period (including an optional pre-screen visit) during&#xD;
      which the subject's phenotype and eligibility for the study were assessed. All subjects who&#xD;
      met the eligibility criteria after the screening visit were to undergo induction of their&#xD;
      sputum to examine the baseline sputum cell counts. Subjects were required to demonstrate both&#xD;
      blood and sputum eosinophilia to be eligible for participation in the study.&#xD;
&#xD;
      Eligible subjects were randomized 3:2 to active (fevipiprant 450 mg oral daily) vs. placebo&#xD;
      arms. Randomization was stratified by current smoking status (current vs. ex-smoker).&#xD;
      Subjects were to continue their COPD standard of care and other medications during the entire&#xD;
      course of the study. Subjects were to receive multiple doses of fevipiprant or placebo for&#xD;
      six weeks.&#xD;
&#xD;
      Sputum induction was to be repeated at the end of the treatment period and at the end of the&#xD;
      study (approximately 4 weeks after the last dose).&#xD;
&#xD;
      The primary purpose of the proof-of-mechanism study was to determine whether fevipiprant&#xD;
      (QAW039), when administered to COPD patients with eosinophilic airway inflammation on&#xD;
      standard of care therapy, reduced the burden of sputum eosinophilia. Data from other trials&#xD;
      did not confirm efficacy of fevipiprant and did not warrant the continuation of treatment in&#xD;
      this study. As a result, this study was terminated early.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Company decision&#xD;
  </why_stopped>
  <start_date type="Actual">May 21, 2019</start_date>
  <completion_date type="Actual">January 16, 2020</completion_date>
  <primary_completion_date type="Actual">January 16, 2020</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, Care Provider, Investigator)</masking>
    <masking_description>This was a subject and investigator-blinded study. Subjects, investigators and all site staff remained blinded to study treatment throughout the study.&#xD;
The identity of the treatments was concealed by the use of study drugs that were all identical in packaging, labeling, schedule of administration, appearance, and odor.&#xD;
The sponsor could be unblinded to the study treatment at any time, especially in case of a safety concern.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6</measure>
    <time_frame>Baseline, Week 6</time_frame>
    <description>Sputum eosinophil percentage of the total cell count was obtained from induced sputum samples. Sputum was processed to include preparation of slides for differential cellular count.&#xD;
As sputum eosinophil percentage has been found to follow a log-normal distribution, the analysis of this outcome measure was based on log10-transformed scale. The baseline measurement was defined as sputum eosinophil percentage prior to the first dosing (on log10-transformed scale).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>QAW039 450 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo once daily for 6 weeks administered orally as a tablet.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QAW039</intervention_name>
    <description>QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet + Standard of Care</description>
    <arm_group_label>QAW039 450 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo once daily for 6 weeks administered orally as a tablet + Standard of Care</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Acceptable and reproducible spirometry with post-bronchodilator FEV1/FVC &lt; 0.7 and&#xD;
             post-bronchodilator FEV1≥ 30 and ≤ 80% of predicted at the screening and baseline&#xD;
             visits (GOLD stage II or III COPD).&#xD;
&#xD;
          2. Patients with a physician-diagnosed history of COPD for at least 1 year prior to&#xD;
             screening visit, and a documented history of at least one COPD exacerbation within the&#xD;
             year prior to screening visit and on a stable therapy regimen for COPD for at least 4&#xD;
             weeks prior to screening visit with inhaled glucocorticoid + one or more long acting&#xD;
             bronchodilator.&#xD;
&#xD;
          3. Current or ex-smokers who have a smoking history of at least 10 pack-years (10&#xD;
             pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for&#xD;
             20 years, or equivalent).&#xD;
&#xD;
          4. Circulating eosinophils ≥ 300 cells/µL blood AND sputum eosinophils ≥ 3% of total cell&#xD;
             count during screening period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a past or current medical history of asthma.&#xD;
&#xD;
          2. Patients with a past or current medical history of conditions other than COPD or&#xD;
             allergic rhinitis that could result in elevated sputum eosinophils (e.g., asthma,&#xD;
             hypereosinophilic syndrome, Churg-Strauss Syndrome). Patients with known parasitic&#xD;
             infestation within 6 months prior to screening are also excluded.&#xD;
&#xD;
          3. Patients who have had a respiratory tract infection or COPD worsening or systemic&#xD;
             steroid use within 4 weeks prior to screening visit or between screening and&#xD;
             randomization visits.&#xD;
&#xD;
          4. Patients with history of concomitant chronic or severe pulmonary disease (e.g.,&#xD;
             sarcoidosis, interstitial lung disease, cystic fibrosis, tuberculosis). Exception:&#xD;
             patients with concomitant mild or moderate pulmonary hypertension or bronchiectasis&#xD;
             are permitted to participate.&#xD;
&#xD;
          5. Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unless they are using effective contraception (also called basic&#xD;
             contraception)methods during the study.&#xD;
&#xD;
          6. Patients on any statin therapy with a CK level &gt; 2 X ULN at screening.&#xD;
&#xD;
          7. Patients who have a clinically significant laboratory abnormality at the screening&#xD;
             visit including (but not limited to):&#xD;
&#xD;
               -  Total white blood cell count &lt;2500 cells/uL&#xD;
&#xD;
               -  AST or ALT &gt; 2.0 X ULN or total bilirubin &gt; 1.3 X ULN&#xD;
&#xD;
               -  Estimated Glomerular Filtration Rate (eGFR) by the Modification of Diet in Renal&#xD;
                  Disease (MDRD) equation or Bedside Schwartz equation &lt;55 mL/minute/1.73 m2.&#xD;
&#xD;
          8. Patients with any of the following cardiac related concerns:&#xD;
&#xD;
               -  A resting QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female) at screening&#xD;
                  visit&#xD;
&#xD;
               -  A history of familial long QT syndrome or known family history of Torsades de&#xD;
                  Pointe&#xD;
&#xD;
               -  Receiving any medications or other agents known to prolong the QT interval&#xD;
&#xD;
               -  patients with a history of moderate or severe uncontrolled tachyarrhythmias&#xD;
&#xD;
               -  History of a clinically significant cardiovascular event within 1 year prior to&#xD;
                  the screening visit, such as acute myocardial infarction, congestive heart&#xD;
                  failure, unstable arrhythmia&#xD;
&#xD;
               -  Patients who, in the judgment of the investigator have a clinically significant&#xD;
                  ECG abnormality such as (but not limited to) sustained ventricular tachycardia,&#xD;
                  or clinically significant second or third degree AV block without a pacemaker&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hamburg</city>
        <zip>20354</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bradford</city>
        <state>West Yorkshire</state>
        <zip>BD9 6RJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Belgium</country>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=709</url>
    <description>A Plain Language Trial Summary is available on novartisclinicaltrials.com</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <results_first_submitted>January 4, 2021</results_first_submitted>
  <results_first_submitted_qc>January 4, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 25, 2021</results_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>QAW039</keyword>
  <keyword>Chronic obstructive pulmonary disease</keyword>
  <keyword>COPD</keyword>
  <keyword>sputum</keyword>
  <keyword>eosinophillic</keyword>
  <keyword>eosinophilia</keyword>
  <keyword>prostaglandin D2 receptor</keyword>
  <keyword>DP2</keyword>
  <keyword>CRTh2</keyword>
  <keyword>fevipiprant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Eosinophilia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 5, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03810183/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 28, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03810183/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in 4 investigative sites in 2 countries (Germany and United Kingdom).</recruitment_details>
      <pre_assignment_details>Participants were randomized 3:2 to active (QAW039 450 mg orally daily) vs. placebo arms. Randomization was stratified by current smoking status (current vs. ex-smoker).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>QAW039 450 mg</title>
          <description>QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo once daily for 6 weeks administered orally as a tablet.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>QAW039 450 mg</title>
          <description>QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo once daily for 6 weeks administered orally as a tablet.</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="6"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.5" spread="9.71"/>
                    <measurement group_id="B2" value="67.3" spread="6.35"/>
                    <measurement group_id="B3" value="64.8" spread="8.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </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>
              <category_list>
                <category>
                  <title>Asian</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>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6</title>
        <description>Sputum eosinophil percentage of the total cell count was obtained from induced sputum samples. Sputum was processed to include preparation of slides for differential cellular count.&#xD;
As sputum eosinophil percentage has been found to follow a log-normal distribution, the analysis of this outcome measure was based on log10-transformed scale. The baseline measurement was defined as sputum eosinophil percentage prior to the first dosing (on log10-transformed scale).</description>
        <time_frame>Baseline, Week 6</time_frame>
        <population>All subjects with available data and no protocol deviations with relevant impact on data.</population>
        <group_list>
          <group group_id="O1">
            <title>QAW039 450 mg</title>
            <description>QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo once daily for 6 weeks administered orally as a tablet.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6</title>
          <description>Sputum eosinophil percentage of the total cell count was obtained from induced sputum samples. Sputum was processed to include preparation of slides for differential cellular count.&#xD;
As sputum eosinophil percentage has been found to follow a log-normal distribution, the analysis of this outcome measure was based on log10-transformed scale. The baseline measurement was defined as sputum eosinophil percentage prior to the first dosing (on log10-transformed scale).</description>
          <population>All subjects with available data and no protocol deviations with relevant impact on data.</population>
          <units>Percentage</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.43373" spread="0.39740"/>
                    <measurement group_id="O2" value="-0.06689" spread="0.43094"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from first dose of study treatment until last dose plus 30 days, up to a maximum of 72 days.</time_frame>
      <desc>Any signs or symptoms that occurs during study treatment plus the 30 days post treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>QAW039 450mg</title>
          <description>QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo once daily for 6 weeks administered orally as a tablet.</description>
        </group>
        <group group_id="E3">
          <title>Total</title>
          <description>Total</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (22.0)</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="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Joint injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
              </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 terms and conditions of Novartis' agreements with its investigators may vary. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>Novartis.email@novartis.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/NCT03810183
org study id: CQAW039E12201
secondary id: 2018-004267-32
nct id: NCT03810183
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled,
      parallel group, proof-of-mechanism study of multiple oral doses of fevipiprant (QAW039) in
      chronic obstructive pulmonary disease (COPD) patients with eosinophilia.
This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled,
      parallel group, proof-of-mechanism study in COPD subjects with eosinophilia, on standard of
      care therapy. Standard of care (SoC) treatment in subjects with COPD typically includes a
      regimen of inhaled corticosteroid (ICS) plus one or more long acting bronchodilator
      (long-acting beta2-agonist (LABA) or long-acting antimuscarinic antagonist (LAMA)).

      The study consisted of a screening period (including an optional pre-screen visit) during
      which the subject's phenotype and eligibility for the study were assessed. All subjects who
      met the eligibility criteria after the screening visit were to undergo induction of their
      sputum to examine the baseline sputum cell counts. Subjects were required to demonstrate both
      blood and sputum eosinophilia to be eligible for participation in the study.

      Eligible subjects were randomized 3:2 to active (fevipiprant 450 mg oral daily) vs. placebo
      arms. Randomization was stratified by current smoking status (current vs. ex-smoker).
      Subjects were to continue their COPD standard of care and other medications during the entire
      course of the study. Subjects were to receive multiple doses of fevipiprant or placebo for
      six weeks.

      Sputum induction was to be repeated at the end of the treatment period and at the end of the
      study (approximately 4 weeks after the last dose).

      The primary purpose of the proof-of-mechanism study was to determine whether fevipiprant
      (QAW039), when administered to COPD patients with eosinophilic airway inflammation on
      standard of care therapy, reduced the burden of sputum eosinophilia. Data from other trials
      did not confirm efficacy of fevipiprant and did not warrant the continuation of treatment in
      this study. As a result, this study was terminated early.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: This was a subject and investigator-blinded study. Subjects, investigators and all site staff remained blinded to study treatment throughout the study.
The identity of the treatments was concealed by the use of study drugs that were all identical in packaging, labeling, schedule of administration, appearance, and odor.
The sponsor could be unblinded to the study treatment at any time, especially in case of a safety concern.
measure: Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6
time frame: Baseline, Week 6
description: Sputum eosinophil percentage of the total cell count was obtained from induced sputum samples. Sputum was processed to include preparation of slides for differential cellular count.
As sputum eosinophil percentage has been found to follow a log-normal distribution, the analysis of this outcome measure was based on log10-transformed scale. The baseline measurement was defined as sputum eosinophil percentage prior to the first dosing (on log10-transformed scale).
arm group label: QAW039 450 mg
arm group type: Experimental
description: QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo once daily for 6 weeks administered orally as a tablet.
intervention type: Drug
intervention name: QAW039
description: QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet + Standard of Care
arm group label: QAW039 450 mg
intervention type: Drug
intervention name: Placebo
description: Placebo once daily for 6 weeks administered orally as a tablet + Standard of Care
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: Germany
country: United Kingdom
country: Belgium
country: United States
url: https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=709
description: A Plain Language Trial Summary is available on novartisclinicaltrials.com
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Eosinophilia
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 