<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/NCT01691521</url>
  </required_header>
  <id_info>
    <org_study_id>115588</org_study_id>
    <nct_id>NCT01691521</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma</brief_title>
  <official_title>MEA115588 A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate two dose regimens of mepolizumab [75mg intravenous (i.v.) or 100mg&#xD;
      subcutaneous (SC) every 4 weeks] compared with placebo over a 32 week treatment period in&#xD;
      subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be&#xD;
      measured by a reduction in the frequency of asthma exacerbations. Additional efficacy&#xD;
      assessments will include measurements of lung function, symptom scores, and quality of life.&#xD;
      Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse&#xD;
      events.&#xD;
&#xD;
      This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588,&#xD;
      who meet all eligibility criteria at screening visit, will enter the run-in period. Those&#xD;
      subjects that are not able/eligible to be randomised at the end of the 6 week run-in period&#xD;
      will be deemed run-in failures. Subjects will remain on their current maintenance therapy&#xD;
      throughout the run-in, double-blind treatment administration and follow-up periods. Subjects&#xD;
      who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to&#xD;
      receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75&#xD;
      miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v.&#xD;
      and placebo SC.&#xD;
&#xD;
      Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility&#xD;
      criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to&#xD;
      participate in the OLE trial.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 8, 2012</start_date>
  <completion_date type="Actual">January 18, 2014</completion_date>
  <primary_completion_date type="Actual">January 1, 2014</primary_completion_date>
  <phase>Phase 3</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Clinically Significant Exacerbations of Asthma Per Year</measure>
    <time_frame>From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose</time_frame>
    <description>Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visits Per Year</measure>
    <time_frame>From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose</time_frame>
    <description>Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an ICU) Per Year</measure>
    <time_frame>From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose</time_frame>
    <description>Clinically significant exacerbations of asthma is defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 32</measure>
    <time_frame>Baseline, Week 32</time_frame>
    <description>FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using mixed model repeated measures with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in the St. George's Respiratory Questionnaire Total Score at Week 32</measure>
    <time_frame>Baseline, Week 32</time_frame>
    <description>The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health. The lowest possible value is zero and the highest possible value is 100. The higher values correspond to greater impairment in quality of life. The questionnaire was administered at Baseline (Visit 2) and at the Exit Visit (approximately 4 weeks after the last dose of study treatment). The change from baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using analysis of covariance with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), baseline % predicted FEV1, and treatment.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">580</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Mepolizumab IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mepolizumab 75 mg will be administered intravenously approximately every 4 weeks with the last dose at week 32. Subjects in the Mepolizumab IV arm will receive mepolizumab 75 mg intravenously and placebo SC once every 4 weeks with the last dose at Week 28 (total of 8 doses)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mepolizumab SC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in the Mepolizumab SC arm will receive mepolizumab 100 mg SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects in the Placebo arm will receive matching placebo SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mepolizumab IV</intervention_name>
    <description>Mepolizumab 75 mg IV will be administered every 4 weeks with the last dose at Week 28</description>
    <arm_group_label>Mepolizumab IV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mepolizumab SC</intervention_name>
    <description>Mepolizumab 100 mg SC will be administered every 4 weeks with the last dose at Week 28</description>
    <arm_group_label>Mepolizumab SC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IV Placebo</intervention_name>
    <description>Normal saline (placebo) will be administered IV every 4 weeks with the last dose at Week 28</description>
    <arm_group_label>Mepolizumab SC</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SC Placebo</intervention_name>
    <description>Normal saline (placebo) will be administered SC every 4 weeks with the last dose at Week 28</description>
    <arm_group_label>Mepolizumab IV</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to give written informed consent prior to participation in the study&#xD;
&#xD;
          -  At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)&#xD;
&#xD;
          -  A well-documented requirement for regular treatment with high dose inhaled&#xD;
             corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance&#xD;
             oral corticosteroids (OCS)&#xD;
&#xD;
          -  Current treatment with an additional controller medication, besides ICS, for at least&#xD;
             3 months or a documented failure in the past 12 months of an additional controller&#xD;
             medication for at least 3 successive months&#xD;
&#xD;
          -  Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma&#xD;
&#xD;
          -  At Visit 1, a pre-bronchodilator FEV1 &lt;80% (for subjects &gt;= 18 years of age), a&#xD;
             pre-bronchodilator FEV1 &lt;90% or FEV1:FVC ratio &lt;0.8 (for subjects 12-17 years of age).&#xD;
&#xD;
          -  Previously confirmed history of two or more exacerbations requiring treatment with&#xD;
             systemic CS&#xD;
&#xD;
          -  Male or Eligible Female (females of childbearing potential must commit to consistent&#xD;
             and correct use of an acceptable method of birth control)&#xD;
&#xD;
          -  French subjects will be included only if either affiliated to or a beneficiary of a&#xD;
             social security category.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current smokers or former smokers with a smoking history of &gt;=10 pack years&#xD;
&#xD;
          -  Presence of a known pre-existing, clinically important lung condition other than&#xD;
             asthma&#xD;
&#xD;
          -  A current malignancy or previous history of malignancy in less than 12 months&#xD;
&#xD;
          -  Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities&#xD;
&#xD;
          -  Known, pre-existing severe or clinically significant cardiovascular disease&#xD;
&#xD;
          -  known, pre-existing other concurrent clinically significant medical conditions that&#xD;
             are uncontrolled with standard treatment&#xD;
&#xD;
          -  Subjects with any eosinophilic diseases&#xD;
&#xD;
          -  QTc(F) ≥450msec or QTc(F) ≥480 msec&#xD;
&#xD;
          -  A history of alcohol/substance abuse&#xD;
&#xD;
          -  Subject with known immunodeficiency&#xD;
&#xD;
          -  Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal&#xD;
             antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of&#xD;
             Visit 1&#xD;
&#xD;
          -  Subjects who have received treatment with an investigational drug within the past 30&#xD;
             days or five terminal phase half-lives of the drug whichever is longer&#xD;
&#xD;
          -  Subjects with allergy/intolerance to a monoclonal antibody or biologic.&#xD;
&#xD;
          -  Subjects who are pregnant or breastfeeding&#xD;
&#xD;
          -  Subjects who have known evidence of lack of adherence to controller medications and/or&#xD;
             ability to follow physician's recommendations&#xD;
&#xD;
          -  Previously participated in any study with mepolizumab and received investigational&#xD;
             product (including placebo)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rolling Hills Estates</city>
        <state>California</state>
        <zip>90274</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Albany</city>
        <state>Georgia</state>
        <zip>31707</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132-2409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mar del Plata</city>
        <state>Buenos Aires</state>
        <zip>7600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mar del Plata</city>
        <state>Buenos Aires</state>
        <zip>B7600FZN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Rafael</city>
        <state>Mendoza</state>
        <zip>5600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>S2000DBS</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1424BSF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autónoma de Buenos Aires</city>
        <zip>C1426ABP</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mendoza</city>
        <zip>5500</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>New Lambton</city>
        <state>New South Wales</state>
        <zip>2305</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bedford Park</city>
        <state>South Australia</state>
        <zip>5042</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Parkville</city>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G2E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R2H 2A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Burlington</city>
        <state>Ontario</state>
        <zip>L7N 3V2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Windsor</city>
        <state>Ontario</state>
        <zip>N8X 5A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W 1T8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 2P4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4J 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>St-Charles-Borromée</city>
        <state>Quebec</state>
        <zip>J6E 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Trois Rivieres</city>
        <state>Quebec</state>
        <zip>G8T 7A1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rancagua</city>
        <state>Reg Del Libert Bern Ohiggins</state>
        <zip>2841959</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santiago</city>
        <zip>8380453</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Talcahuano</city>
        <zip>4270918</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Le Kremlin-Bicêtre Cedex</city>
        <zip>94275</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lille cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lyon cedex 04</city>
        <zip>69317</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Marseille cedex 20</city>
        <zip>13915</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Montpellier cedex 5</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Perpignan</city>
        <zip>66000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint Pierre cedex</city>
        <zip>97448</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Aschaffenburg</city>
        <state>Bayern</state>
        <zip>63739</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Potsdam</city>
        <state>Brandenburg</state>
        <zip>14478</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ruedersdorf</city>
        <state>Brandenburg</state>
        <zip>15562</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Frankfurt am Main</city>
        <state>Hessen</state>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60389</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gelnhausen</city>
        <state>Hessen</state>
        <zip>63571</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Neu isenburg</city>
        <state>Hessen</state>
        <zip>63263</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mainz</city>
        <state>Rheinland-Pfalz</state>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Magdeburg</city>
        <state>Sachsen-Anhalt</state>
        <zip>39112</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10367</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hamburg</city>
        <zip>22299</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Parma</city>
        <state>Emilia-Romagna</state>
        <zip>43125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pietra Ligure (SV)</city>
        <state>Liguria</state>
        <zip>17027</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Foggia</city>
        <state>Puglia</state>
        <zip>71100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Perugia</city>
        <state>Umbria</state>
        <zip>06156</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cittadella PD</city>
        <state>Veneto</state>
        <zip>35013</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chiba</city>
        <zip>296-8602</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fukuoka</city>
        <zip>802-0052</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fukuoka</city>
        <zip>811-1394</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fukuoka</city>
        <zip>832-0059</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gunma</city>
        <zip>370-0615</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hiroshima</city>
        <zip>732-0052</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hokkaido</city>
        <zip>062-8618</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hokkaido</city>
        <zip>070-8644</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hyogo</city>
        <zip>651-0072</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hyogo</city>
        <zip>672-8064</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ibaraki</city>
        <zip>319-1113</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kanagawa</city>
        <zip>252-0392</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kumamoto</city>
        <zip>861-1196</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mie</city>
        <zip>515-8544</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Okinawa</city>
        <zip>901-2132</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Okinawa</city>
        <zip>904-2293</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Osaka</city>
        <zip>560-8552</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Osaka</city>
        <zip>596-8501</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tokyo</city>
        <zip>102-0083</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tokyo</city>
        <zip>103-0027</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tokyo</city>
        <zip>171-0014</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tokyo</city>
        <zip>187-0024</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Anyang-Si</city>
        <zip>431-070</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bucheon-si,</city>
        <zip>420-767</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cheongju, Chungcheongbuk-do</city>
        <zip>361-711</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Daegu</city>
        <zip>705-717</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Donggu Gwangju</city>
        <zip>501757</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Incheon</city>
        <zip>405-760</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Jeonju-si, Jeollabuk-Do</city>
        <zip>561-712</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kangwon-do</city>
        <zip>220-701</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Suwon, Kyonggi-do</city>
        <zip>443-721</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Zapopan</city>
        <state>Jalisco</state>
        <zip>45040</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Zapopan</city>
        <state>Jalisco</state>
        <zip>45200</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo León</state>
        <zip>64020</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>México DF</city>
        <zip>14050</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454106</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>123182</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>194354</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>St. Petersburg</city>
        <zip>194356</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Alicante</city>
        <zip>03004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pozuelo De Alarcón/Madrid</city>
        <zip>28223</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kharkiv</city>
        <zip>61124</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kiev</city>
        <zip>03680</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mykolayiv</city>
        <zip>54003</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bradford</city>
        <zip>BD9 6RJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Glasgow</city>
        <zip>G11 6NT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>London</city>
        <zip>EC1M 6BQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Plymouth</city>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.clinicalstudydatarequest.com</url>
    <description>Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.</description>
  </link>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 20, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <results_first_submitted>November 5, 2015</results_first_submitted>
  <results_first_submitted_qc>December 17, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 26, 2016</results_first_posted>
  <disposition_first_submitted>April 22, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>April 22, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">May 8, 2015</disposition_first_posted>
  <last_update_submitted>August 2, 2018</last_update_submitted>
  <last_update_submitted_qc>August 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>safety</keyword>
  <keyword>SB-240563</keyword>
  <keyword>efficacy</keyword>
  <keyword>placebo</keyword>
  <keyword>eosinophils</keyword>
  <keyword>mepolizumab</keyword>
  <keyword>Severe refractory asthma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>115588</doc_id>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115588</doc_id>
      <doc_type>Annotated Case Report Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115588</doc_id>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115588</doc_id>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115588</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115588</doc_id>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115588</doc_id>
      <doc_type>Dataset Specification</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
  </study_docs>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Par. who met the eligibility criteria at screening, entered the Run-in period for a minimum of 1 week and a maximum of 6 weeks. Par. who received all 8 doses and met the eligibility criteria were offered the opportunity to participate in an open label extension (OLE) study. Par. not entering the OLE study completed the Follow-up Visit.</recruitment_details>
      <pre_assignment_details>A total of 802 participants (par.) were screened; 82 were Screen failures; 140 were Run-in failures; 580 were randomized, of which 576 received at least 1 dose of study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received placebo intravenously (IV) plus placebo subcutaneously (SC) every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
        <group group_id="P2">
          <title>Mepolizumab 75 mg IV</title>
          <description>Participants received mepolizumab 75 milligrams (mg) IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
        <group group_id="P3">
          <title>Mepolizumab 100 mg SC</title>
          <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="191"/>
                <participants group_id="P2" count="191"/>
                <participants group_id="P3" count="194"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="179"/>
                <participants group_id="P2" count="175"/>
                <participants group_id="P3" count="185"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
        <group group_id="B2">
          <title>Mepolizumab 75 mg IV</title>
          <description>Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
        <group group_id="B3">
          <title>Mepolizumab 100 mg SC</title>
          <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
        <group group_id="B4">
          <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="191"/>
            <count group_id="B2" value="191"/>
            <count group_id="B3" value="194"/>
            <count group_id="B4" value="576"/>
          </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="49.2" spread="14.26"/>
                    <measurement group_id="B2" value="50.0" spread="14.03"/>
                    <measurement group_id="B3" value="51.2" spread="14.55"/>
                    <measurement group_id="B4" value="50.1" spread="14.28"/>
                  </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="107"/>
                    <measurement group_id="B2" value="106"/>
                    <measurement group_id="B3" value="116"/>
                    <measurement group_id="B4" value="329"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                    <measurement group_id="B2" value="85"/>
                    <measurement group_id="B3" value="78"/>
                    <measurement group_id="B4" value="247"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>African American/African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaskan Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - Central/South Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - East Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - Japanese Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - South East Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - Arabic/North African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - White/Caucasian/European Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="144"/>
                    <measurement group_id="B2" value="148"/>
                    <measurement group_id="B3" value="148"/>
                    <measurement group_id="B4" value="440"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mixed Race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Clinically Significant Exacerbations of Asthma Per Year</title>
        <description>Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
        <time_frame>From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose</time_frame>
        <population>Modified Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of trial medication. 'Modified' implies that, in cases where there is is a discrepancy between randomized and actual treatment the analysis used the actual treatment received by the participant rather than the randomized treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O2">
            <title>Mepolizumab 75 mg IV</title>
            <description>Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O3">
            <title>Mepolizumab 100 mg SC</title>
            <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Clinically Significant Exacerbations of Asthma Per Year</title>
          <description>Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
          <population>Modified Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of trial medication. 'Modified' implies that, in cases where there is is a discrepancy between randomized and actual treatment the analysis used the actual treatment received by the participant rather than the randomized treatment.</population>
          <units>Number of exacerbations per year</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="191"/>
                <count group_id="O2" value="191"/>
                <count group_id="O3" value="194"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.74"/>
                    <measurement group_id="O2" value="0.93"/>
                    <measurement group_id="O3" value="0.83"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hochberg procedure with a gamma parameter of 1 used for multiplicity adjustment.</p_value_desc>
            <method>Negative binomial model</method>
            <param_type>Rate Ratio</param_type>
            <param_value>0.53</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.40</ci_lower_limit>
            <ci_upper_limit>0.72</ci_upper_limit>
            <estimate_desc>Number of exacerbations per year in the mepolizumab 75mg IV arm divided by the number of exacerbations per year in the placebo arm.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hochberg procedure with a gamma parameter of 1 used for multiplicity adjustment.</p_value_desc>
            <method>Negative binomial model</method>
            <param_type>Rate Ratio</param_type>
            <param_value>0.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.35</ci_lower_limit>
            <ci_upper_limit>0.64</ci_upper_limit>
            <estimate_desc>Number of exacerbations per year in the mepolizumab 100 mg SC arm divided by the number of exacerbations per year in the placebo arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visits Per Year</title>
        <description>Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
        <time_frame>From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O2">
            <title>Mepolizumab 75 mg IV</title>
            <description>Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O3">
            <title>Mepolizumab 100 mg SC</title>
            <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visits Per Year</title>
          <description>Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
          <population>ITT Population</population>
          <units>Number of exacerbations per year</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="191"/>
                <count group_id="O2" value="191"/>
                <count group_id="O3" value="194"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20"/>
                    <measurement group_id="O2" value="0.14"/>
                    <measurement group_id="O3" value="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an ICU) Per Year</title>
        <description>Clinically significant exacerbations of asthma is defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
        <time_frame>From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O2">
            <title>Mepolizumab 75 mg IV</title>
            <description>Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O3">
            <title>Mepolizumab 100 mg SC</title>
            <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an ICU) Per Year</title>
          <description>Clinically significant exacerbations of asthma is defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.</description>
          <population>ITT Population</population>
          <units>Number of exacerbations per year</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="191"/>
                <count group_id="O2" value="191"/>
                <count group_id="O3" value="194"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10"/>
                    <measurement group_id="O2" value="0.06"/>
                    <measurement group_id="O3" value="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 32</title>
        <description>FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using mixed model repeated measures with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.</description>
        <time_frame>Baseline, Week 32</time_frame>
        <population>ITT Population. Only participants with a Baseline FEV1 available and at least one post-Baseline FEV1 measurement were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O2">
            <title>Mepolizumab 75 mg IV</title>
            <description>Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O3">
            <title>Mepolizumab 100 mg SC</title>
            <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 32</title>
          <description>FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using mixed model repeated measures with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.</description>
          <population>ITT Population. Only participants with a Baseline FEV1 available and at least one post-Baseline FEV1 measurement were analyzed.</population>
          <units>Milliliters (mL)</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="189"/>
                <count group_id="O2" value="188"/>
                <count group_id="O3" value="192"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86" spread="31.4"/>
                    <measurement group_id="O2" value="186" spread="31.5"/>
                    <measurement group_id="O3" value="183" spread="31.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the St. George's Respiratory Questionnaire Total Score at Week 32</title>
        <description>The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health. The lowest possible value is zero and the highest possible value is 100. The higher values correspond to greater impairment in quality of life. The questionnaire was administered at Baseline (Visit 2) and at the Exit Visit (approximately 4 weeks after the last dose of study treatment). The change from baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using analysis of covariance with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), baseline % predicted FEV1, and treatment.</description>
        <time_frame>Baseline, Week 32</time_frame>
        <population>ITT Population. Note that only participants with a Baseline and Week 32 assessment were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O2">
            <title>Mepolizumab 75 mg IV</title>
            <description>Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
          </group>
          <group group_id="O3">
            <title>Mepolizumab 100 mg SC</title>
            <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the St. George's Respiratory Questionnaire Total Score at Week 32</title>
          <description>The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health. The lowest possible value is zero and the highest possible value is 100. The higher values correspond to greater impairment in quality of life. The questionnaire was administered at Baseline (Visit 2) and at the Exit Visit (approximately 4 weeks after the last dose of study treatment). The change from baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using analysis of covariance with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), baseline % predicted FEV1, and treatment.</description>
          <population>ITT Population. Note that only participants with a Baseline and Week 32 assessment were included in the analysis.</population>
          <units>Scores 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="177"/>
                <count group_id="O2" value="174"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.0" spread="1.16"/>
                    <measurement group_id="O2" value="-15.4" spread="1.16"/>
                    <measurement group_id="O3" value="-16.0" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 32 weeks.</time_frame>
      <desc>Serious adverse events (SAEs) and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
        <group group_id="E2">
          <title>Mepolizumab 75 mg IV</title>
          <description>Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.</description>
        </group>
        <group group_id="E3">
          <title>Mepolizumab 100 mg SC</title>
          <description>Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial lipoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal motility disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Large intestine perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Oesophageal spasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Gallbladder disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Croup infectious</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Vulval abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Fractured coccyx</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Heat stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Inflammation of wound</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Spinal osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Calculus ureteric</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Calculus urethral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Nephrogenic diabetes insipidus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Renal colic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Pulmonary fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Dyshidrotic eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA</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="143" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="142" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="132" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="194"/>
              </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="6" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="24" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="18" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="39" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="194"/>
              </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>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
    </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/NCT01691521
org study id: 115588
nct id: NCT01691521
lead sponsor: 
has dmc: Yes
This study will evaluate two dose regimens of mepolizumab [75mg intravenous (i.v.) or 100mg
      subcutaneous (SC) every 4 weeks] compared with placebo over a 32 week treatment period in
      subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be
      measured by a reduction in the frequency of asthma exacerbations. Additional efficacy
      assessments will include measurements of lung function, symptom scores, and quality of life.
      Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse
      events.

      This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588,
      who meet all eligibility criteria at screening visit, will enter the run-in period. Those
      subjects that are not able/eligible to be randomised at the end of the 6 week run-in period
      will be deemed run-in failures. Subjects will remain on their current maintenance therapy
      throughout the run-in, double-blind treatment administration and follow-up periods. Subjects
      who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to
      receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75
      miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v.
      and placebo SC.

      Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility
      criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to
      participate in the OLE trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of Clinically Significant Exacerbations of Asthma Per Year
time frame: From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
description: Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.
measure: Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visits Per Year
time frame: From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
description: Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.
measure: Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an ICU) Per Year
time frame: From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
description: Clinically significant exacerbations of asthma is defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.
measure: Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 32
time frame: Baseline, Week 32
description: FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using mixed model repeated measures with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.
measure: Mean Change From Baseline in the St. George's Respiratory Questionnaire Total Score at Week 32
time frame: Baseline, Week 32
description: The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health. The lowest possible value is zero and the highest possible value is 100. The higher values correspond to greater impairment in quality of life. The questionnaire was administered at Baseline (Visit 2) and at the Exit Visit (approximately 4 weeks after the last dose of study treatment). The change from baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using analysis of covariance with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), baseline % predicted FEV1, and treatment.
arm group label: Mepolizumab IV
arm group type: Experimental
description: Mepolizumab 75 mg will be administered intravenously approximately every 4 weeks with the last dose at week 32. Subjects in the Mepolizumab IV arm will receive mepolizumab 75 mg intravenously and placebo SC once every 4 weeks with the last dose at Week 28 (total of 8 doses)
arm group label: Mepolizumab SC
arm group type: Experimental
description: Subjects in the Mepolizumab SC arm will receive mepolizumab 100 mg SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects in the Placebo arm will receive matching placebo SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)
intervention type: Drug
intervention name: Mepolizumab IV
description: Mepolizumab 75 mg IV will be administered every 4 weeks with the last dose at Week 28
arm group label: Mepolizumab IV
intervention type: Drug
intervention name: Mepolizumab SC
description: Mepolizumab 100 mg SC will be administered every 4 weeks with the last dose at Week 28
arm group label: Mepolizumab SC
intervention type: Drug
intervention name: IV Placebo
description: Normal saline (placebo) will be administered IV every 4 weeks with the last dose at Week 28
arm group label: Mepolizumab SC
arm group label: Placebo
intervention type: Drug
intervention name: SC Placebo
description: Normal saline (placebo) will be administered SC every 4 weeks with the last dose at Week 28
arm group label: Mepolizumab IV
arm group label: Placebo
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
country: Australia
country: Belgium
country: Canada
country: Chile
country: France
country: Germany
country: Italy
country: Japan
country: Korea, Republic of
country: Mexico
country: Russian Federation
country: Spain
country: Ukraine
country: United Kingdom
country: United States
url: https://www.clinicalstudydatarequest.com
description: Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
responsible party type: Sponsor
mesh term: Asthma
sharing ipd: Yes
ipd description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 