<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/NCT01691508</url>
  </required_header>
  <id_info>
    <org_study_id>115575</org_study_id>
    <nct_id>NCT01691508</nct_id>
  </id_info>
  <brief_title>Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma</brief_title>
  <official_title>MEA115575: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of Mepolizumab Adjunctive Therapy to Reduce Steroid Use in Subjects With Severe 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 is a randomised, double-blind, placebo-controlled, parallel-group, multicenter study of&#xD;
      mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects&#xD;
      with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase&#xD;
      (Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase&#xD;
      (Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase&#xD;
      (Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS&#xD;
      (prednisone/prednisolone) dose according to the Optimisation titration schedule based on a&#xD;
      review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction Phase&#xD;
      subjects will be randomized 1:1 (approximately 60 per arm) to receive either mepolizumab (100&#xD;
      mg) administered subcutaneously (SC) or placebo every 4 weeks in addition to their existing&#xD;
      maintenance asthma therapy with the lowest dose of OCS from Optimisation Phase. The Induction&#xD;
      Phase will allow sufficient time for those subjects randomised to the mepolizumab arm to&#xD;
      achieve a decrease in the eosinophilic inflammation prior to the reduction in OCS. During the&#xD;
      Reduction Phase, subjects will continue receiving 100 mg mepolizumab/placebo every 4 weeks&#xD;
      and the OCS dose reduction will be done every 4 weeks using the reduction titration schedule&#xD;
      based on a review of eDiary parameters recorded by the subject, the subjects' exacerbation&#xD;
      history, and a review of the signs and symptoms of adrenal insufficiency. In the Maintenance&#xD;
      Phase subjects will be maintained without any further OCS dose adjustment. Subjects who&#xD;
      complete the 24 week double-blind period and meet the eligibility criteria, will be offered&#xD;
      the opportunity to participate in an open label extension (OLE) study otherwise they will&#xD;
      return for a Follow-up Visit 12 weeks after their last dose of double blind study treatment.&#xD;
      At each clinic visit, adverse events, safety labs, spirometery parameters and exacerbations&#xD;
      will be assessed. The pharmacokinetic samples will be collected in the beginning of the&#xD;
      treatment, prior to last dose, at the end of study (exit visit) and the follow up.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</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 Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control</measure>
    <time_frame>Baseline; Weeks 20 to 24</time_frame>
    <description>Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to &lt;90%; 50 to &lt;75%; &gt;0 to &lt;50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Achieved a Reduction of &gt;=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control</measure>
    <time_frame>Baseline; Weeks 20 to 24</time_frame>
    <description>Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to &lt;=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control</measure>
    <time_frame>Weeks 20 to 24</time_frame>
    <description>Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to &lt;=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control</measure>
    <time_frame>Weeks 20 to 24</time_frame>
    <description>MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control</measure>
    <time_frame>Baseline; Weeks 20 to 24</time_frame>
    <description>BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">135</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Mepolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mepolizumab 100 mg subcutaneous once every 4 weeks upto Week 20</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo subcutaneous once every 4 weeks upto Week 20</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mepolizumab</intervention_name>
    <description>Mepolizumab is a fully humanised Immunoglobulin G antibody (IgG1, kappa) with human heavy and light chain frameworks.</description>
    <arm_group_label>Mepolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Will be available as an equivalent volume of 0.9% sodium chloride.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OCS (prednisone/prednisolone)</intervention_name>
    <description>Oral Corticosteroid (prednisone/prednisolone)</description>
    <arm_group_label>Mepolizumab</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed Consent and Study Compliance: Subjects must be able to give written informed&#xD;
             consent prior to participation in the study, which will include the ability to comply&#xD;
             with the requirements and restrictions listed in the consent form.&#xD;
&#xD;
          -  Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic&#xD;
             corticosteroids in the 6 months prior to Visit 1 and using a stable oral&#xD;
             corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35&#xD;
             mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study&#xD;
             required prednisone/prednisolone as their oral corticosteroid and use it per protocol&#xD;
             for the duration of the study.&#xD;
&#xD;
          -  Inhaled Corticosteroids: Requirement for regular treatment with high dose inhaled&#xD;
             corticosteroid in the 6 months prior to Visit 1. For 18 years of age and older:&#xD;
             inhaled corticosteroid (ICS) dose must be &gt;=880 microgram (µg)/day fluticasone&#xD;
             propionate (FP) (ex-actuator) or equivalent daily. For ICS/ long acting beta2 agonist&#xD;
             (LABA) combination preparations, the highest approved maintenance dose in the local&#xD;
             country will meet this ICS criterion. For ages 12 to 17: ICS dose must be &gt;=440 μg/day&#xD;
             FP (ex-actuator) or equivalent daily.&#xD;
&#xD;
          -  Controller Medication: Current treatment with an additional controller medication for&#xD;
             at least 3 months OR documentation of having used and failed an additional controller&#xD;
             medication for at least 3 successive months during the prior 12 months [e.g., LABA,&#xD;
             leukotriene receptor antagonist (LTRA), or theophylline].&#xD;
&#xD;
          -  Eosinophilic Asthma: Prior documentation of eosinophilic asthma or high likelihood of&#xD;
             eosinophilic asthma.&#xD;
&#xD;
          -  FEV1: Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 &lt;80%&#xD;
             predicted.&#xD;
&#xD;
          -  Asthma: Evidence of asthma indicated by airway reversibility, hyperresponsiveness or&#xD;
             airway variability.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking history: Current smokers or former smokers with a smoking history of &gt;=10 pack&#xD;
             years.&#xD;
&#xD;
          -  Concurrent Respiratory Disease: Presence of a clinically important lung condition&#xD;
             other than asthma.&#xD;
&#xD;
          -  Malignancy: A current malignancy or previous history of cancer in remission for less&#xD;
             than 12 months prior screening&#xD;
&#xD;
          -  Liver Disease: Unstable liver disease&#xD;
&#xD;
          -  Cardiovascular: Subjects who have severe or clinically significant cardiovascular&#xD;
             disease uncontrolled with standard treatment.&#xD;
&#xD;
          -  Other Concurrent Medical Conditions: Subjects who have known, pre-existing, clinically&#xD;
             significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal,&#xD;
             hepatic, haematological or any other system abnormalities that are uncontrolled with&#xD;
             standard treatment.&#xD;
&#xD;
          -  Eosinophilic Diseases: Subjects with other conditions that could lead to elevated&#xD;
             eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or&#xD;
             Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic infestation&#xD;
             within 6 months prior to Visit 1 are also to be excluded.&#xD;
&#xD;
          -  ECG: ECG assessment QTcF &gt;=450 milliseconds (msec) or QTcF &gt;= 480 msec for subjects&#xD;
             with Bundle Branch Block.&#xD;
&#xD;
          -  Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus - HIV),&#xD;
             other than that explained by the use of corticosteroids taken as therapy for asthma.&#xD;
&#xD;
          -  Omalizumab Use: Subjects who have received omalizumab [Xolair] within 130 days of&#xD;
             Visit 1.&#xD;
&#xD;
          -  Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other&#xD;
             than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.&#xD;
&#xD;
          -  Investigational Medications: Subjects who have received treatment with an&#xD;
             investigational drug within the past 30 days or five terminal phase half-lives of the&#xD;
             drug whichever is longer, prior to Visit 1 (this also includes investigational&#xD;
             formulations of marketed products).&#xD;
&#xD;
          -  Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal&#xD;
             antibody or biologic.&#xD;
&#xD;
          -  Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled&#xD;
             if they plan to become pregnant during the time of study participation.&#xD;
&#xD;
          -  Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or&#xD;
             substance abuse within 2 years prior to Visit 1.&#xD;
&#xD;
          -  Adherence: Subjects who have known evidence of lack of adherence to controller&#xD;
             medications and/or ability to follow physician's recommendations.&#xD;
&#xD;
          -  Previous participation: Subjects who have previously any study of mepolizumab and&#xD;
             received Investigational Product.&#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>Long Beach</city>
        <state>California</state>
        <zip>90808</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>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <zip>63110</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>Pittsburg</city>
        <state>Pennsylvania</state>
        <zip>PA 15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</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>Parkville</city>
        <state>Victoria</state>
        <zip>3050</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>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 4A6</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>Brno</city>
        <zip>625 00</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Olomouc</city>
        <zip>775 20</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Praha 4</city>
        <zip>140 59</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Praha 8</city>
        <zip>180 01</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gières</city>
        <zip>38610</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>Nantes cedex 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Paris Cedex 18</city>
        <zip>75877</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Strasbourg</city>
        <zip>67091</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</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>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30173</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>Luebeck</city>
        <state>Schleswig-Holstein</state>
        <zip>23552</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44100</zip>
        <country>Mexico</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>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leeuwarden</city>
        <zip>8934 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rotterdam</city>
        <zip>3045 PM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bialystok</city>
        <zip>15-010</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bialystok</city>
        <zip>15-044</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Krakow</city>
        <zip>31-024</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lodz</city>
        <zip>90-153</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leicester</city>
        <state>Leicestershire</state>
        <zip>LE3 9QP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Liverpool</city>
        <zip>L9 7AL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <zip>NE1 4LP</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>Australia</country>
    <country>Canada</country>
    <country>Czech Republic</country>
    <country>France</country>
    <country>Germany</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Poland</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>March 2017</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>March 21, 2017</last_update_submitted>
  <last_update_submitted_qc>March 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Safety</keyword>
  <keyword>Steroid Reduction</keyword>
  <keyword>Efficacy</keyword>
  <keyword>SB-240563</keyword>
  <keyword>Eosinophils</keyword>
  <keyword>Quality of Life</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
  </intervention_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>115575</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>115575</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_doc>
      <doc_id>115575</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>115575</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>115575</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>115575</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>115575</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_docs>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study consisted 4 phases: oral corticosteroids (OCS) Optimization (Run-in); Induction; OCS Reduction and Maintenance. Participants (par.) who completed the 4 phases 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 185 par. were screened; 3 par. were Screen failures; 47 par. were Run-in failures; 135 par. were randomized and received &gt;=1 dose of study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100mg SC</title>
          <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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="66"/>
                <participants group_id="P2" count="69"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
                <participants group_id="P2" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </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 subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100 mg SC</title>
          <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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>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="66"/>
            <count group_id="B2" value="69"/>
            <count group_id="B3" value="135"/>
          </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="49.9" spread="10.30"/>
                    <measurement group_id="B2" value="49.8" spread="14.10"/>
                    <measurement group_id="B3" value="49.9" spread="12.34"/>
                  </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="30"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="74"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="61"/>
                  </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>American Indian or Alaskan Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - East Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - South East Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - Arabic/North African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - White/Caucasian/European Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="125"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mixed Race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control</title>
        <description>Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to &lt;90%; 50 to &lt;75%; &gt;0 to &lt;50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
        <time_frame>Baseline; Weeks 20 to 24</time_frame>
        <population>Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100 mg SC</title>
            <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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 Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control</title>
          <description>Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to &lt;90%; 50 to &lt;75%; &gt;0 to &lt;50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
          <population>Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of study medication.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>90 to 100%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>75 to &lt;90%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50 to &lt;75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;0 to &lt;50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No decrease /lack of asthma control/early WD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="25"/>
                  </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>0.008</p_value>
            <method>Proportional odds model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.39</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.25</ci_lower_limit>
            <ci_upper_limit>4.56</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Achieved a Reduction of &gt;=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control</title>
        <description>Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
        <time_frame>Baseline; Weeks 20 to 24</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100 mg SC</title>
            <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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 Participants Who Achieved a Reduction of &gt;=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control</title>
          <description>Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
          <population>ITT Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>50 to 100%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&lt;50% or no decrease/lack of asthma control/WD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to &lt;=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control</title>
        <description>Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to &lt;=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
        <time_frame>Weeks 20 to 24</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100 mg SC</title>
            <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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 Participants Who Achieved a Reduction of Their Daily OCS Dose to &lt;=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control</title>
          <description>Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to &lt;=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
          <population>ITT Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&lt;=5 mg/day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;5 mg/day or lack of asthma control or WD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control</title>
        <description>MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
        <time_frame>Weeks 20 to 24</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100 mg SC</title>
            <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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 Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control</title>
          <description>MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (&lt;5 years vs. &gt;=5 years) and BL OCS dose.</description>
          <population>ITT Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0 mg/day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OCS taken or lack of asthma control or WD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61"/>
                    <measurement group_id="O2" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control</title>
        <description>BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.</description>
        <time_frame>Baseline; Weeks 20 to 24</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100 mg SC</title>
            <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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>Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control</title>
          <description>BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.</description>
          <population>ITT Population</population>
          <units>Percentage reduction in OCS dose</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-33.3" upper_limit="20.0"/>
                    <measurement group_id="O2" value="-50.0" lower_limit="-75.0" upper_limit="-20.0"/>
                  </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 24 weeks.</time_frame>
      <desc>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 subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. 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 100 mg SC</title>
          <description>Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. 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="12" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Chronic sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Post gastric surgery syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Fistula</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basosquamous carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Prostatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </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="7" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </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="53" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="47" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </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="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injection related reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Sinus headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </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/NCT01691508
org study id: 115575
nct id: NCT01691508
lead sponsor: 
has dmc: Yes
This is a randomised, double-blind, placebo-controlled, parallel-group, multicenter study of
      mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects
      with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase
      (Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase
      (Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase
      (Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS
      (prednisone/prednisolone) dose according to the Optimisation titration schedule based on a
      review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction Phase
      subjects will be randomized 1:1 (approximately 60 per arm) to receive either mepolizumab (100
      mg) administered subcutaneously (SC) or placebo every 4 weeks in addition to their existing
      maintenance asthma therapy with the lowest dose of OCS from Optimisation Phase. The Induction
      Phase will allow sufficient time for those subjects randomised to the mepolizumab arm to
      achieve a decrease in the eosinophilic inflammation prior to the reduction in OCS. During the
      Reduction Phase, subjects will continue receiving 100 mg mepolizumab/placebo every 4 weeks
      and the OCS dose reduction will be done every 4 weeks using the reduction titration schedule
      based on a review of eDiary parameters recorded by the subject, the subjects' exacerbation
      history, and a review of the signs and symptoms of adrenal insufficiency. In the Maintenance
      Phase subjects will be maintained without any further OCS dose adjustment. Subjects who
      complete the 24 week double-blind period and meet the eligibility criteria, will be offered
      the opportunity to participate in an open label extension (OLE) study otherwise they will
      return for a Follow-up Visit 12 weeks after their last dose of double blind study treatment.
      At each clinic visit, adverse events, safety labs, spirometery parameters and exacerbations
      will be assessed. The pharmacokinetic samples will be collected in the beginning of the
      treatment, prior to last dose, at the end of study (exit visit) and the follow up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control
time frame: Baseline; Weeks 20 to 24
description: Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to <90%; 50 to <75%; >0 to <50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
measure: Number of Participants Who Achieved a Reduction of >=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control
time frame: Baseline; Weeks 20 to 24
description: Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
measure: Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to <=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control
time frame: Weeks 20 to 24
description: Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to <=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
measure: Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
time frame: Weeks 20 to 24
description: MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
measure: Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
time frame: Baseline; Weeks 20 to 24
description: BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.
arm group label: Mepolizumab
arm group type: Experimental
description: Mepolizumab 100 mg subcutaneous once every 4 weeks upto Week 20
arm group label: Placebo
arm group type: Experimental
description: Placebo subcutaneous once every 4 weeks upto Week 20
intervention type: Drug
intervention name: Mepolizumab
description: Mepolizumab is a fully humanised Immunoglobulin G antibody (IgG1, kappa) with human heavy and light chain frameworks.
arm group label: Mepolizumab
intervention type: Drug
intervention name: Placebo
description: Will be available as an equivalent volume of 0.9% sodium chloride.
arm group label: Placebo
intervention type: Drug
intervention name: OCS (prednisone/prednisolone)
description: Oral Corticosteroid (prednisone/prednisolone)
arm group label: Mepolizumab
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
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country: Australia
country: Canada
country: Czech Republic
country: France
country: Germany
country: Mexico
country: Netherlands
country: Poland
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
mesh term: Prednisone
mesh term: Prednisolone
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.
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