<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/NCT03292588</url>
  </required_header>
  <id_info>
    <org_study_id>DAIT ICAC-30</org_study_id>
    <secondary_id>UM1AI114271</secondary_id>
    <secondary_id>NIAID CRMS ID#: 38189</secondary_id>
    <nct_id>NCT03292588</nct_id>
  </id_info>
  <brief_title>A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children</brief_title>
  <acronym>MUPPITS-2</acronym>
  <official_title>Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (ICAC-30)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Inner-City Asthma Consortium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rho Federal Systems Division, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see if treatment with a medication called Nucala®&#xD;
      (mepolizumab), given along with standard asthma care, makes children less likely to have&#xD;
      asthma attacks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Asthma is a growing problem, especially in children. It causes frequent wheezing, shortness&#xD;
      of breath, chest tightness, and cough. Asthma attacks, or exacerbations, are problems for&#xD;
      children with asthma.&#xD;
&#xD;
      The purpose of this study is to see if treatment with a medication called mepolizumab&#xD;
      (Nucala®), given along with standard asthma care, makes children less likely to have asthma&#xD;
      attacks. Mepolizumab is a new drug that is approved by the Food and Drug Administration (FDA)&#xD;
      for use in children with asthma who are aged 12 years and older. Mepolizumab is given by&#xD;
      injection. It is being studied by other researchers in children aged 6-11 years.&#xD;
&#xD;
      All participants will be prescribed standard asthma medications by a clinician who is trained&#xD;
      in asthma care. Medications will include controller medications, a rescue medication, and a&#xD;
      medication for severe asthma attacks (prednisone). The amount of medication that participants&#xD;
      receive may be increased or decreased during the study based on their symptoms and breathing&#xD;
      test results. Study clinicians will treat all participants according to the same guidelines.&#xD;
      These treatment guidelines are based on recommendations from a group of national experts in&#xD;
      asthma. This study has been designed this way so that all participants will have safe and&#xD;
      effective standard asthma care.&#xD;
&#xD;
      In order to enroll in this study, participants must be willing to have their asthma managed&#xD;
      by the study clinician during the entire study period. Participants must also be willing to&#xD;
      bring study medications to all study visits.&#xD;
&#xD;
      This study will include up to 20 study visits. Participant involvement in the study will&#xD;
      endure for approximately 1 year.&#xD;
&#xD;
      During the treatment period, participants will be placed in one of two treatment groups:&#xD;
&#xD;
        -  Mepolizumab injection and guidelines-based asthma care or&#xD;
&#xD;
        -  Placebo injection and guidelines-based asthma care.&#xD;
&#xD;
      Participants will not be able to choose which group they are assigned. This assignment is&#xD;
      random and by chance, much like flipping a coin. Participants will not know if they are&#xD;
      receiving mepolizumab or placebo. Investigators will compare the study results between the&#xD;
      participants of each group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 7, 2017</start_date>
  <completion_date type="Actual">April 20, 2021</completion_date>
  <primary_completion_date type="Actual">April 20, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Asthma Exacerbations During the Treatment Period</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Exacerbations were defined as a prescription of a course of systemic corticosteroids by a clinician, initiation of a course of systemic corticosteroids by a participant, or as a hospitalization for asthma. If a participant initiated and completed a course of systemic corticosteroids without clinician involvement, this course was counted only if the study clinician agreed the treatment was warranted, and it met the following dosage: the course for prednisone, prednisolone, or methylprednisolone was at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone was at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation was prescribed by a non-ICAC clinician, it was counted regardless of dose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite Asthma Severity Index (CASI)</measure>
    <time_frame>Week 12, 24, 36, 48, 52 after randomization</time_frame>
    <description>Composite Asthma Severity Index (CASI) scores included 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. The minimum composite score was 0 while the maximum was 20. The higher the score the more allergy symptoms a subject has.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Quality of Life Measured Using the Physician Global Assessment Tool</measure>
    <time_frame>Week 56</time_frame>
    <description>The Physician Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the physician to evaluate how the participant's quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14</measure>
    <time_frame>Week 56</time_frame>
    <description>The Patient Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the participant to evaluate how their quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung Function as Assessed by Spirometry</measure>
    <time_frame>Weeks 12, 24, 36, 48, 52 after randomization</time_frame>
    <description>A generalized mixed model was used to analyze spirometry parameter at each visit where the lung function was collected. The ratio of the forced expiratory volume to the forced vital capacity of the lungs (FEV1/FVC) is the outcome that measured lung function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung Function as Assessed by Impulse Oscillometry</measure>
    <time_frame>Weeks 12, 24, 36, 48, 52 after randomization</time_frame>
    <description>A generalized mixed model was used to analyze impulse oscillometry parameter at each visit where the lung function was collected. The Percent Predicted FEV1 (%) is the outcome that measured lung function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Asthma Exacerbation</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>A Cox PH model was also used to model the time to first asthma exacerbation during the treatment period. The Cox PH model included treatment arm as the primary exposure but was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (above or below 400 cells/μl), BMI (above or below 95th percentile for age) and total serum IgE (above or below 540 kUA/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Reported Adverse Events (AEs), Including Their Severity</measure>
    <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
    <description>The number of AEs by severity was used to assess safety. Please refer to the Adverse Event tables for specifics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness</measure>
    <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
    <description>The number of AEs by relationship to study drug was used to assess safety. Please refer to the Adverse Event tables for specifics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics.</measure>
    <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
    <description>The number of SAEs by severity and relationship to study drug was used to assess safety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics.</measure>
    <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
    <description>The number of SAEs by relationship to study drug was used to assess safety.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation</measure>
    <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
    <description>As measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations</measure>
    <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
    <description>Measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT</measure>
    <time_frame>Visits (V) 4 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment)</time_frame>
    <description>A validated tool to assess overall asthma control (over the last 4 weeks) in participants.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY:Maximum Number of Asthma Symptom Days</measure>
    <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
    <description>Defined as the highest value among the following variables over a two-week period:&#xD;
number of days with wheezing, tightness in the chest, or cough;&#xD;
number of nights with disturbed sleep as a result of asthma; and&#xD;
number of days on which the participant had to slow down or discontinue play/physical activities.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY:Bronchodilator Responsiveness</measure>
    <time_frame>Baseline (prior to treatment initiation), Week 56 (Completion of Treatment)</time_frame>
    <description>A measure to determine whether mepolizumab improves pulmonary outcomes.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY: Gene Expression in Nasal Lavage Samples</measure>
    <time_frame>Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)</time_frame>
    <description>Whole genome transcriptomics of nasal lavage samples to identify inflammatory pathways affected by mepolizumab.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY: Gene Expression in Whole Blood RNA Samples</measure>
    <time_frame>Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)</time_frame>
    <description>Whole genome transcriptomics of whole blood RNA samples to identify inflammatory pathways affected by mepolizumab..</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY:Levels of Antibody to Mepolizumab</measure>
    <time_frame>Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)</time_frame>
    <description>An assay for detection/measurement of levels of antibody to mepolizumab. Analysis will include participants randomized to mepolizumab.</description>
  </other_outcome>
  <other_outcome>
    <measure>EXPLORATORY:Other Potential Biomarkers Not Specified to Date</measure>
    <time_frame>Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)</time_frame>
    <description>Plasma, nasal samples, RNA and DNA will be banked for possible future study of potential biomarkers associated with asthma and asthma exacerbations.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">335</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Mepolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Mepolizumab</intervention_name>
    <description>Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.</description>
    <arm_group_label>Mepolizumab</arm_group_label>
    <other_name>Nucala®</other_name>
    <other_name>anti-Interleukin 5 (IL5) antagonist monoclonal antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo for Mepolizumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Study applicant(s) that fulfill all of the inclusion criteria and none of the exclusion&#xD;
        criteria are eligible for the study-&#xD;
&#xD;
          -  Participant and/or parent guardian must be able to understand and provide informed&#xD;
             consent and age-appropriate assent;&#xD;
&#xD;
          -  Must have a primary place of residence in one of the pre-selected recruitment census&#xD;
             tracts as outlined in the study's Manual of Procedures (MOP);&#xD;
&#xD;
          -  Has had a diagnosis of asthma made &gt;1 year prior to recruitment;&#xD;
&#xD;
             --Those who received an asthma diagnosis by a clinician ≤1 year prior to recruitment&#xD;
             must report that their respiratory symptoms were present for more than 1 year prior to&#xD;
             recruitment.&#xD;
&#xD;
          -  Has had ≥2 asthma exacerbations in the prior year (defined as a requirement for&#xD;
             systemic corticosteroids and/or hospitalization);&#xD;
&#xD;
          -  At Visit 0 (Screening), has the following requirement for asthma controller&#xD;
             medication:&#xD;
&#xD;
               -  For those ages 6 to 11 years, treatments with at least fluticasone 250 mcg dry&#xD;
                  powder inhaler (DPI) one puff twice daily or its equivalent and,&#xD;
&#xD;
               -  For those ≥12 years of age, treatment with at least Advair 250/50 mcg dry powder&#xD;
                  inhaler (DPI), one puff twice daily or its equivalent.&#xD;
&#xD;
          -  Has peripheral blood eosinophils ≥150 cells/µl obtained at Visit 0 (Screening) or in&#xD;
             another Inner-City Asthma Consortium (ICAC) clinical research study within 6 months;&#xD;
&#xD;
          -  Is able to perform spirometry at randomization (Visit for treatment assignment);&#xD;
&#xD;
          -  Has documentation of current medical insurance with prescription coverage at&#xD;
             randomization; and&#xD;
&#xD;
          -  Has had varicella or the varicella vaccination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Individual(s) who meets any of the following criteria are not eligible for enrollment or&#xD;
        randomization-&#xD;
&#xD;
          -  Is not able or willing to give written informed consent or comply with the study&#xD;
             protocol;&#xD;
&#xD;
          -  Has concurrent (existing) medical problems that would require systemic corticosteroids&#xD;
             or other immunomodulator treatments during the study;&#xD;
&#xD;
          -  Is currently receiving immunotherapy;&#xD;
&#xD;
          -  Is currently receiving treatment with omalizumab or has had omalizumab treatment&#xD;
             within 6 months prior to planned participant randomization to treatment assignment;&#xD;
&#xD;
          -  Is currently requiring greater than fluticasone 500 mcg administered twice daily plus&#xD;
             a long-acting beta agonist (LABA) one puff twice daily or its equivalent, and/or&#xD;
&#xD;
             --Individuals using oral corticosteroids daily or every other day for more than 14&#xD;
             days at the time of Visit 0 (Screening).&#xD;
&#xD;
          -  Is currently pregnant or lactating, or plans to become pregnant during the time of&#xD;
             study participation&#xD;
&#xD;
             --Note: Females of child-bearing potential (post-menarche) must be abstinent or use a&#xD;
             medically acceptable birth control method throughout the study (e.g. oral&#xD;
             subcutaneous, mechanical, or surgical contraception).&#xD;
&#xD;
          -  Has a known, pre-existing clinically important lung condition other than asthma;&#xD;
&#xD;
          -  Has a current malignancy or previous history of cancer in remission for less than 12&#xD;
             months prior to randomization;&#xD;
&#xD;
          -  Has known, pre-existing, unstable liver disease;&#xD;
&#xD;
          -  Is a current smoker or has a smoking history of 10 or more pack years;&#xD;
&#xD;
          -  Has a known immunodeficiency disease;&#xD;
&#xD;
          -  Has other conditions that could lead to elevated eosinophils such as hypereosinophilic&#xD;
             syndromes, including eosinophilic granulomatosis with polyangiitis;&#xD;
&#xD;
          -  Has a known, active pre-existing parasitic infestation or is undergoing treatment for&#xD;
             a parasitic infestation&#xD;
&#xD;
             --Note: Once the individual has been successfully treated, the interested study&#xD;
             applicant may be reevaluated for study eligibility.&#xD;
&#xD;
          -  Positive for use of investigational drugs within 4 weeks of randomization;&#xD;
&#xD;
          -  Has a past or current medical problems or findings from physical examination or&#xD;
             laboratory testing that are not listed above, which, in the opinion of the study&#xD;
             clinician,&#xD;
&#xD;
               -  May pose additional risks from participation in this study,&#xD;
&#xD;
               -  May interfere with the participant's ability to comply with study requirements,&#xD;
                  or&#xD;
&#xD;
               -  May impact the quality or interpretation of the data obtained from the study.&#xD;
&#xD;
          -  In the event that the study applicant will not allow the study clinician, an asthma&#xD;
             specialist, to manage their disease for the duration of the study or who are not&#xD;
             willing to change their asthma medications to follow the protocol;&#xD;
&#xD;
          -  Has a known history of allergic reaction to previous biologic therapy for asthma; or&#xD;
&#xD;
          -  Has had a life threatening asthma exacerbation in the last 2 years requiring&#xD;
             intubation, mechanical ventilation or resulting in a hypoxic seizure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel J Jackson, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <overall_official>
    <last_name>William W Busse, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann and Robert Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Children's Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.niaid.nih.gov/</url>
    <description>National Institute of Allergy and Infectious Diseases (NIAID) website</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/about/dait</url>
    <description>Division of Allergy, Immunology, and Transplantation (DAIT) website</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <results_first_submitted>April 20, 2022</results_first_submitted>
  <results_first_submitted_qc>May 23, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 21, 2022</results_first_posted>
  <last_update_submitted>June 23, 2022</last_update_submitted>
  <last_update_submitted_qc>June 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>urban setting</keyword>
  <keyword>children and adolescents</keyword>
  <keyword>double-masked, placebo-controlled randomized trial</keyword>
  <keyword>asthma exacerbations (attacks)</keyword>
  <keyword>mepolizumab adjunctive therapy</keyword>
  <keyword>asthma exacerbations prevention</keyword>
  <keyword>difficult-to-control exacerbation-prone asthma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Participant level data access and additional relevant materials will be made available upon completion of the trial.</ipd_description>
    <ipd_time_frame>After completion of the trial, within 24 months status post database lock.</ipd_time_frame>
    <ipd_access_criteria>Registration is available for the Immunology Database and Analysis Portal (ImmPort) at: https://www.immport.org/registration. Submit a rationale for the purpose of requesting study data access.&#xD;
ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.</ipd_access_criteria>
    <ipd_url>https://www.immport.org/home</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT03292588/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>335 people were enrolled in the study (signed a consent and were assigned a unique participant number). However, 45 participants dropped out before receiving treatment bringing the total to 290 participants who started treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Mepolizumab</title>
          <description>Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.&#xD;
Mepolizumab: Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.&#xD;
Placebo: Placebo administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during 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="146"/>
                <participants group_id="P2" count="144"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="122"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Move out of town</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>&gt;3 bursts of systemic corticosteroids for asthma during treatment period (Starting Nov 2020)</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat population with available data</population>
      <group_list>
        <group group_id="B1">
          <title>Mepolizumab</title>
          <description>Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.&#xD;
Mepolizumab: Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.&#xD;
Placebo: Placebo administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during 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="146"/>
            <count group_id="B2" value="144"/>
            <count group_id="B3" value="290"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="146"/>
                    <measurement group_id="B2" value="144"/>
                    <measurement group_id="B3" value="290"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="10.8" spread="2.87"/>
                    <measurement group_id="B2" value="10.8" spread="2.88"/>
                    <measurement group_id="B3" value="10.8" spread="2.87"/>
                  </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="71"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="126"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                    <measurement group_id="B2" value="89"/>
                    <measurement group_id="B3" value="164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="72"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="111"/>
                    <measurement group_id="B2" value="107"/>
                    <measurement group_id="B3" value="218"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="146"/>
                    <measurement group_id="B2" value="144"/>
                    <measurement group_id="B3" value="290"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Asthma Exacerbations During the Treatment Period</title>
        <description>Exacerbations were defined as a prescription of a course of systemic corticosteroids by a clinician, initiation of a course of systemic corticosteroids by a participant, or as a hospitalization for asthma. If a participant initiated and completed a course of systemic corticosteroids without clinician involvement, this course was counted only if the study clinician agreed the treatment was warranted, and it met the following dosage: the course for prednisone, prednisolone, or methylprednisolone was at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone was at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation was prescribed by a non-ICAC clinician, it was counted regardless of dose.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>All participants who were randomized and received at least one dose of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.&#xD;
Mepolizumab: Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.&#xD;
Placebo: Placebo administered every 4 weeks by subcutaneous injection at a dose of:&#xD;
100 mg for participants ≥12 years of age and&#xD;
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.&#xD;
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.&#xD;
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Asthma Exacerbations During the Treatment Period</title>
          <description>Exacerbations were defined as a prescription of a course of systemic corticosteroids by a clinician, initiation of a course of systemic corticosteroids by a participant, or as a hospitalization for asthma. If a participant initiated and completed a course of systemic corticosteroids without clinician involvement, this course was counted only if the study clinician agreed the treatment was warranted, and it met the following dosage: the course for prednisone, prednisolone, or methylprednisolone was at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone was at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation was prescribed by a non-ICAC clinician, it was counted regardless of dose.</description>
          <population>All participants who were randomized and received at least one dose of study treatment</population>
          <units>Exacerbations during treatment</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
                <count group_id="O2" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.96" spread="0.10"/>
                    <measurement group_id="O2" value="1.30" spread="0.13"/>
                  </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</non_inferiority_type>
            <non_inferiority_desc>Negative binomial model for the rate of exacerbations in the first year. The model included an offset term to account for differential follow-up among participants. To account for adaptive randomization, the model was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (&lt; or ≥400 cells/μl), BMI (&lt; or ≥95th percentile for age), total serum IgE (&lt; or ≥540 kUA/L) and treatment dose (40 mg or 100 mg).</non_inferiority_desc>
            <p_value>0.027</p_value>
            <method>Regression, Negative Binomial</method>
            <method_desc>Adjusted relative rate of exacerbations in the first year.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.73</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.56</ci_lower_limit>
            <ci_upper_limit>0.96</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Asthma Severity Index (CASI)</title>
        <description>Composite Asthma Severity Index (CASI) scores included 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. The minimum composite score was 0 while the maximum was 20. The higher the score the more allergy symptoms a subject has.</description>
        <time_frame>Week 12, 24, 36, 48, 52 after randomization</time_frame>
        <population>All participants who were randomized and received at least one dose of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Asthma Severity Index (CASI)</title>
          <description>Composite Asthma Severity Index (CASI) scores included 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. The minimum composite score was 0 while the maximum was 20. The higher the score the more allergy symptoms a subject has.</description>
          <population>All participants who were randomized and received at least one dose of study treatment</population>
          <units>Composite Asthma Severity Index</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
                <count group_id="O2" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.17" spread="0.2"/>
                    <measurement group_id="O2" value="6.45" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.94" spread="0.23"/>
                    <measurement group_id="O2" value="6.01" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.48" spread="0.22"/>
                    <measurement group_id="O2" value="5.99" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.16" spread="0.22"/>
                    <measurement group_id="O2" value="5.23" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.03" spread="0.23"/>
                    <measurement group_id="O2" value="5.00" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 12</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.290</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>The difference in least square mean of CASI scores for week 12.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.28</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.81</ci_lower_limit>
            <ci_upper_limit>0.24</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.820</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>The difference in least square mean of CASI scores for week 24.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.07</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.69</ci_lower_limit>
            <ci_upper_limit>0.55</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.096</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>The difference in least square mean of CASI scores for week 36.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.51</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.11</ci_lower_limit>
            <ci_upper_limit>0.09</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.831</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>The difference in least square mean of CASI scores for week 48.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.65</ci_lower_limit>
            <ci_upper_limit>0.52</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 52</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.947</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>The difference in least square mean of CASI scores for week 52.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>0.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.60</ci_lower_limit>
            <ci_upper_limit>0.64</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participant Quality of Life Measured Using the Physician Global Assessment Tool</title>
        <description>The Physician Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the physician to evaluate how the participant's quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.</description>
        <time_frame>Week 56</time_frame>
        <population>All participants who were randomized and received at least one dose of study treatment and completed the quality of life questionnaire at visit 14.</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Participant Quality of Life Measured Using the Physician Global Assessment Tool</title>
          <description>The Physician Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the physician to evaluate how the participant's quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.</description>
          <population>All participants who were randomized and received at least one dose of study treatment and completed the quality of life questionnaire at visit 14.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="129"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Physician Global Assessment Tool - Significantly Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Physician Global Assessment Tool - Moderately Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Physician Global Assessment Tool - Mildly Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Physician Global Assessment Tool - No Change</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Physician Global Assessment Tool - Mildly Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Physician Global Assessment Tool - Moderately Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Physician Global Assessment Tool - Significantly Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Physician Global Assessment Tool</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A generalized logit model was used to analyze Physician Global Assessment Tool at Visit 14. The model included treatment arm as fixed effect as primary exposure but was also adjusted for study site, # of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils ((&lt; or ≥400 cells/μl), BMI (&lt; or ≥95th percentile for age) &amp; total serum IgE (&lt; or ≥540 kUA/L). No imputation of missing data was used for participants who weren't assessed for quality of life measurements at Visit 14.</non_inferiority_desc>
            <p_value>0.974</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>1.64</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14</title>
        <description>The Patient Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the participant to evaluate how their quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.</description>
        <time_frame>Week 56</time_frame>
        <population>All participants who were randomized and received at least one dose of study treatment and completed the quality of life questionnaire at visit 14.</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14</title>
          <description>The Patient Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the participant to evaluate how their quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.</description>
          <population>All participants who were randomized and received at least one dose of study treatment and completed the quality of life questionnaire at visit 14.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="129"/>
                <count group_id="O2" value="124"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Patient Global Assessment Tool - Significantly Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82"/>
                    <measurement group_id="O2" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient Global Assessment Tool - Moderately Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient Global Assessment Tool - Mildly Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient Global Assessment Tool - No Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient Global Assessment Tool - Mildly Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient Global Assessment Tool - Moderately Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient Global Assessment Tool - Significantly Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Patient Global Assessment Tool</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A generalized logit model was used to analyze the Patient Global Assessment Tool at Visit 14. The model included treatment arm as fixed effect as the primary exposure but was adjusted for study site, # of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils ((&lt; or ≥400 cells/μl), BMI (&lt; or ≥95th percentile for age) &amp; total serum IgE (&lt; or ≥540 kUA/L). No imputation of missing data was used for participants who weren't assessed for quality of life measurements at Visit 14.</non_inferiority_desc>
            <p_value>0.238</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.72</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.42</ci_lower_limit>
            <ci_upper_limit>1.24</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lung Function as Assessed by Spirometry</title>
        <description>A generalized mixed model was used to analyze spirometry parameter at each visit where the lung function was collected. The ratio of the forced expiratory volume to the forced vital capacity of the lungs (FEV1/FVC) is the outcome that measured lung function.</description>
        <time_frame>Weeks 12, 24, 36, 48, 52 after randomization</time_frame>
        <population>All participants who were randomized and received at least one dose of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Lung Function as Assessed by Spirometry</title>
          <description>A generalized mixed model was used to analyze spirometry parameter at each visit where the lung function was collected. The ratio of the forced expiratory volume to the forced vital capacity of the lungs (FEV1/FVC) is the outcome that measured lung function.</description>
          <population>All participants who were randomized and received at least one dose of study treatment</population>
          <units>FEV1/FVC</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
                <count group_id="O2" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FEV1/FVC - Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.747" spread="0.007"/>
                    <measurement group_id="O2" value="0.752" spread="0.007"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1/FVC - Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.755" spread="0.007"/>
                    <measurement group_id="O2" value="0.766" spread="0.007"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1/FVC - Week 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.758" spread="0.008"/>
                    <measurement group_id="O2" value="0.747" spread="0.008"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1/FVC - Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.755" spread="0.008"/>
                    <measurement group_id="O2" value="0.742" spread="0.008"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1/FVC - Week 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.761" spread="0.008"/>
                    <measurement group_id="O2" value="0.763" spread="0.008"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1/FVC Week 12</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A generalized mixed model as described in section 8.3.1 was used to analyze each spirometry and impulse oscillometry parameter, separately, at each visit where the lung function was collected.</non_inferiority_desc>
            <p_value>0.591</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.005</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.023</ci_lower_limit>
            <ci_upper_limit>0.013</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1/FVC Week 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.265</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.011</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.031</ci_lower_limit>
            <ci_upper_limit>0.008</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1/FVC Week 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.345</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>0.011</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.012</ci_lower_limit>
            <ci_upper_limit>0.033</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1/FVC Week 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.248</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>0.013</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.009</ci_lower_limit>
            <ci_upper_limit>0.036</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1/FVC Week 52</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.864</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.002</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.023</ci_lower_limit>
            <ci_upper_limit>0.020</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lung Function as Assessed by Impulse Oscillometry</title>
        <description>A generalized mixed model was used to analyze impulse oscillometry parameter at each visit where the lung function was collected. The Percent Predicted FEV1 (%) is the outcome that measured lung function.</description>
        <time_frame>Weeks 12, 24, 36, 48, 52 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Lung Function as Assessed by Impulse Oscillometry</title>
          <description>A generalized mixed model was used to analyze impulse oscillometry parameter at each visit where the lung function was collected. The Percent Predicted FEV1 (%) is the outcome that measured lung function.</description>
          <units>Percent Predicted FEV1 (%)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
                <count group_id="O2" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FEV1PP - Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.9" spread="1.27"/>
                    <measurement group_id="O2" value="92.3" spread="1.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1PP - Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.8" spread="1.46"/>
                    <measurement group_id="O2" value="94.2" spread="1.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1PP - Week 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.5" spread="1.45"/>
                    <measurement group_id="O2" value="89.9" spread="1.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1PP - Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.4" spread="1.46"/>
                    <measurement group_id="O2" value="89.8" spread="1.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1PP - Week 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.9" spread="1.45"/>
                    <measurement group_id="O2" value="93.5" spread="1.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1PP Week 12</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.816</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.8</ci_lower_limit>
            <ci_upper_limit>3.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1PP Week 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.095</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-3.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.4</ci_lower_limit>
            <ci_upper_limit>0.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1PP Week 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.444</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.4</ci_lower_limit>
            <ci_upper_limit>5.5</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1PP Week 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.751</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.3</ci_lower_limit>
            <ci_upper_limit>4.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FEV1PP Week 52</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.184</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-2.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.5</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.</title>
        <description>Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE</description>
        <time_frame>Up to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.</title>
          <description>Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE</description>
          <units>Exacerbations during treatment</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.11" spread="0.21"/>
                    <measurement group_id="O2" value="1.31" spread="0.25"/>
                  </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>
            <groups_desc>Did not meet FDA-approved dosing</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Negative binomial model for the rate of exacerbations (per year. The model included an offset term to account for differential follow-up among participants. To account for adaptive randomization, the model was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (&lt; or ≥400 cells/μl), BMI (&lt; or ≥95th percentile for age), total serum IgE (&lt; or ≥540 kUA/L) and treatment dose (40 mg or 100 mg).</non_inferiority_desc>
            <p_value>0.458</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.85</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.55</ci_lower_limit>
            <ci_upper_limit>1.31</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.</title>
        <description>Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE</description>
        <time_frame>Up to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.</title>
          <description>Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE</description>
          <units>Exacerbations during treatment</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.87" spread="0.13"/>
                    <measurement group_id="O2" value="1.30" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Fit FDA-approved dosing</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Negative binomial model for the rate of exacerbations (per year. The model included an offset term to account for differential follow-up among participants. To account for adaptive randomization, the model was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (&lt; or ≥400 cells/μl), BMI (&lt; or ≥95th percentile for age), total serum IgE (&lt; or ≥540 kUA/L) and treatment dose (40 mg or 100 mg).</non_inferiority_desc>
            <p_value>0.025</p_value>
            <method>Regression, Negative Binomial</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.67</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.47</ci_lower_limit>
            <ci_upper_limit>0.95</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Asthma Exacerbation</title>
        <description>A Cox PH model was also used to model the time to first asthma exacerbation during the treatment period. The Cox PH model included treatment arm as the primary exposure but was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (above or below 400 cells/μl), BMI (above or below 95th percentile for age) and total serum IgE (above or below 540 kUA/L).</description>
        <time_frame>Up to 12 months</time_frame>
        <population>All participants who were randomized and received at least one dose of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Asthma Exacerbation</title>
          <description>A Cox PH model was also used to model the time to first asthma exacerbation during the treatment period. The Cox PH model included treatment arm as the primary exposure but was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (above or below 400 cells/μl), BMI (above or below 95th percentile for age) and total serum IgE (above or below 540 kUA/L).</description>
          <population>All participants who were randomized and received at least one dose of study treatment</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
                <count group_id="O2" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="241" lower_limit="1" upper_limit="380"/>
                    <measurement group_id="O2" value="224" lower_limit="1" upper_limit="378"/>
                  </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</non_inferiority_type>
            <p_value>0.3587</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.63</ci_lower_limit>
            <ci_upper_limit>1.18</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Reported Adverse Events (AEs), Including Their Severity</title>
        <description>The number of AEs by severity was used to assess safety. Please refer to the Adverse Event tables for specifics.</description>
        <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
        <population>Number of Subjects with at Least One AE by severity</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Reported Adverse Events (AEs), Including Their Severity</title>
          <description>The number of AEs by severity was used to assess safety. Please refer to the Adverse Event tables for specifics.</description>
          <population>Number of Subjects with at Least One AE by severity</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Severity: Grade 1 - Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                    <measurement group_id="O2" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severity: Grade 2 - Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severity: Grade 3 - Severe and undesirable</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severity: Grade 4 - Life-threatening or disabling</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severity: Grade 5 - Death</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness</title>
        <description>The number of AEs by relationship to study drug was used to assess safety. Please refer to the Adverse Event tables for specifics.</description>
        <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
        <population>Number of Subjects with any study procedures related AEs</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness</title>
          <description>The number of AEs by relationship to study drug was used to assess safety. Please refer to the Adverse Event tables for specifics.</description>
          <population>Number of Subjects with any study procedures related AEs</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
                <count group_id="O2" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics.</title>
        <description>The number of SAEs by severity and relationship to study drug was used to assess safety.</description>
        <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
        <population>Number of subjects with Serious Adverse Events</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics.</title>
          <description>The number of SAEs by severity and relationship to study drug was used to assess safety.</description>
          <population>Number of subjects with Serious Adverse Events</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Severity: Grade 2 - Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severity: Grade 3 - Severe and undesirable</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severity: Grade 4 - Life threatening</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severity: Grade 5 - Death</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation</title>
        <description>As measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.</description>
        <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations</title>
        <description>Measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.</description>
        <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT</title>
        <description>A validated tool to assess overall asthma control (over the last 4 weeks) in participants.</description>
        <time_frame>Visits (V) 4 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY:Maximum Number of Asthma Symptom Days</title>
        <description>Defined as the highest value among the following variables over a two-week period:&#xD;
number of days with wheezing, tightness in the chest, or cough;&#xD;
number of nights with disturbed sleep as a result of asthma; and&#xD;
number of days on which the participant had to slow down or discontinue play/physical activities.</description>
        <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY:Bronchodilator Responsiveness</title>
        <description>A measure to determine whether mepolizumab improves pulmonary outcomes.</description>
        <time_frame>Baseline (prior to treatment initiation), Week 56 (Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY: Gene Expression in Nasal Lavage Samples</title>
        <description>Whole genome transcriptomics of nasal lavage samples to identify inflammatory pathways affected by mepolizumab.</description>
        <time_frame>Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY: Gene Expression in Whole Blood RNA Samples</title>
        <description>Whole genome transcriptomics of whole blood RNA samples to identify inflammatory pathways affected by mepolizumab..</description>
        <time_frame>Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY:Levels of Antibody to Mepolizumab</title>
        <description>An assay for detection/measurement of levels of antibody to mepolizumab. Analysis will include participants randomized to mepolizumab.</description>
        <time_frame>Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EXPLORATORY:Other Potential Biomarkers Not Specified to Date</title>
        <description>Plasma, nasal samples, RNA and DNA will be banked for possible future study of potential biomarkers associated with asthma and asthma exacerbations.</description>
        <time_frame>Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics.</title>
        <description>The number of SAEs by relationship to study drug was used to assess safety.</description>
        <time_frame>Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)</time_frame>
        <population>Number of subjects with any study procedures related Serious Adverse Events</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab</title>
            <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics.</title>
          <description>The number of SAEs by relationship to study drug was used to assess safety.</description>
          <population>Number of subjects with any study procedures related Serious Adverse Events</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
                <count group_id="O2" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the time of consent until 1 year and the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.</time_frame>
      <desc>The safety population was used for reporting adverse events, which was defined as: participants who were randomized and received at least one dose of study treatment. Participants were analyzed according to the medication they actually received, regardless of the treatment arm to which they were randomized. Non-treatment emergent adverse events were summarized in all participants who were enrolled, while treatment emergent adverse events were summarized in the safety sample</desc>
      <group_list>
        <group group_id="E1">
          <title>Mepolizumab</title>
          <description>Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="144"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="146"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="146"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>All-Cause Mortality</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="146"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA 18.1</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="146"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="146"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="14" subjects_affected="13" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="146"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="144"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="146"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="19" subjects_affected="15" subjects_at_risk="146"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="144"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="146"/>
                <counts group_id="E2" events="14" subjects_affected="8" subjects_at_risk="144"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Clinical Research Operations Program</name_or_title>
      <organization>DAIT/NIAID</organization>
      <phone>301-594-7669</phone>
      <email>DAITClinicalTrialsGov@niaid.nih.gov</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03292588
org study id: DAIT ICAC-30
secondary id: UM1AI114271
secondary id: NIAID CRMS ID#: 38189
nct id: NCT03292588
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to see if treatment with a medication called Nucala®
      (mepolizumab), given along with standard asthma care, makes children less likely to have
      asthma attacks.
Asthma is a growing problem, especially in children. It causes frequent wheezing, shortness
      of breath, chest tightness, and cough. Asthma attacks, or exacerbations, are problems for
      children with asthma.

      The purpose of this study is to see if treatment with a medication called mepolizumab
      (Nucala®), given along with standard asthma care, makes children less likely to have asthma
      attacks. Mepolizumab is a new drug that is approved by the Food and Drug Administration (FDA)
      for use in children with asthma who are aged 12 years and older. Mepolizumab is given by
      injection. It is being studied by other researchers in children aged 6-11 years.

      All participants will be prescribed standard asthma medications by a clinician who is trained
      in asthma care. Medications will include controller medications, a rescue medication, and a
      medication for severe asthma attacks (prednisone). The amount of medication that participants
      receive may be increased or decreased during the study based on their symptoms and breathing
      test results. Study clinicians will treat all participants according to the same guidelines.
      These treatment guidelines are based on recommendations from a group of national experts in
      asthma. This study has been designed this way so that all participants will have safe and
      effective standard asthma care.

      In order to enroll in this study, participants must be willing to have their asthma managed
      by the study clinician during the entire study period. Participants must also be willing to
      bring study medications to all study visits.

      This study will include up to 20 study visits. Participant involvement in the study will
      endure for approximately 1 year.

      During the treatment period, participants will be placed in one of two treatment groups:

        -  Mepolizumab injection and guidelines-based asthma care or

        -  Placebo injection and guidelines-based asthma care.

      Participants will not be able to choose which group they are assigned. This assignment is
      random and by chance, much like flipping a coin. Participants will not know if they are
      receiving mepolizumab or placebo. Investigators will compare the study results between the
      participants of each group.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Asthma Exacerbations During the Treatment Period
time frame: Up to 12 months
description: Exacerbations were defined as a prescription of a course of systemic corticosteroids by a clinician, initiation of a course of systemic corticosteroids by a participant, or as a hospitalization for asthma. If a participant initiated and completed a course of systemic corticosteroids without clinician involvement, this course was counted only if the study clinician agreed the treatment was warranted, and it met the following dosage: the course for prednisone, prednisolone, or methylprednisolone was at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone was at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation was prescribed by a non-ICAC clinician, it was counted regardless of dose.
measure: Composite Asthma Severity Index (CASI)
time frame: Week 12, 24, 36, 48, 52 after randomization
description: Composite Asthma Severity Index (CASI) scores included 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. The minimum composite score was 0 while the maximum was 20. The higher the score the more allergy symptoms a subject has.
measure: Participant Quality of Life Measured Using the Physician Global Assessment Tool
time frame: Week 56
description: The Physician Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the physician to evaluate how the participant's quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.
measure: Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14
time frame: Week 56
description: The Patient Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the participant to evaluate how their quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.
measure: Lung Function as Assessed by Spirometry
time frame: Weeks 12, 24, 36, 48, 52 after randomization
description: A generalized mixed model was used to analyze spirometry parameter at each visit where the lung function was collected. The ratio of the forced expiratory volume to the forced vital capacity of the lungs (FEV1/FVC) is the outcome that measured lung function.
measure: Lung Function as Assessed by Impulse Oscillometry
time frame: Weeks 12, 24, 36, 48, 52 after randomization
description: A generalized mixed model was used to analyze impulse oscillometry parameter at each visit where the lung function was collected. The Percent Predicted FEV1 (%) is the outcome that measured lung function.
measure: Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.
time frame: Up to 12 months
description: Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE
measure: Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.
time frame: Up to 12 months
description: Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE
measure: Time to First Asthma Exacerbation
time frame: Up to 12 months
description: A Cox PH model was also used to model the time to first asthma exacerbation during the treatment period. The Cox PH model included treatment arm as the primary exposure but was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (above or below 400 cells/μl), BMI (above or below 95th percentile for age) and total serum IgE (above or below 540 kUA/L).
measure: Number of Reported Adverse Events (AEs), Including Their Severity
time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
description: The number of AEs by severity was used to assess safety. Please refer to the Adverse Event tables for specifics.
measure: Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness
time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
description: The number of AEs by relationship to study drug was used to assess safety. Please refer to the Adverse Event tables for specifics.
measure: Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics.
time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
description: The number of SAEs by severity and relationship to study drug was used to assess safety.
measure: Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics.
time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
description: The number of SAEs by relationship to study drug was used to assess safety.
measure: EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation
time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
description: As measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.
measure: EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations
time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
description: Measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.
measure: EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT
time frame: Visits (V) 4 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment)
description: A validated tool to assess overall asthma control (over the last 4 weeks) in participants.
measure: EXPLORATORY:Maximum Number of Asthma Symptom Days
time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
description: Defined as the highest value among the following variables over a two-week period:
number of days with wheezing, tightness in the chest, or cough;
number of nights with disturbed sleep as a result of asthma; and
number of days on which the participant had to slow down or discontinue play/physical activities.
measure: EXPLORATORY:Bronchodilator Responsiveness
time frame: Baseline (prior to treatment initiation), Week 56 (Completion of Treatment)
description: A measure to determine whether mepolizumab improves pulmonary outcomes.
measure: EXPLORATORY: Gene Expression in Nasal Lavage Samples
time frame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)
description: Whole genome transcriptomics of nasal lavage samples to identify inflammatory pathways affected by mepolizumab.
measure: EXPLORATORY: Gene Expression in Whole Blood RNA Samples
time frame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)
description: Whole genome transcriptomics of whole blood RNA samples to identify inflammatory pathways affected by mepolizumab..
measure: EXPLORATORY:Levels of Antibody to Mepolizumab
time frame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)
description: An assay for detection/measurement of levels of antibody to mepolizumab. Analysis will include participants randomized to mepolizumab.
measure: EXPLORATORY:Other Potential Biomarkers Not Specified to Date
time frame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)
description: Plasma, nasal samples, RNA and DNA will be banked for possible future study of potential biomarkers associated with asthma and asthma exacerbations.
arm group label: Mepolizumab
arm group type: Experimental
description: Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.
arm group label: Placebo
arm group type: Placebo Comparator
description: Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.
intervention type: Biological
intervention name: Mepolizumab
description: Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of:
100 mg for participants ≥12 years of age and
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.
arm group label: Mepolizumab
other name: Nucala®
other name: anti-Interleukin 5 (IL5) antagonist monoclonal antibody
intervention type: Drug
intervention name: Placebo
description: Placebo administered every 4 weeks by subcutaneous injection at a dose of:
100 mg for participants ≥12 years of age and
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.
arm group label: Placebo
other name: Placebo for Mepolizumab
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
last name: Daniel J Jackson, MD
role: Study Chair
affiliation: University of Wisconsin, Madison
last name: William W Busse, MD
role: Study Chair
affiliation: University of Wisconsin, Madison
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.niaid.nih.gov/
description: National Institute of Allergy and Infectious Diseases (NIAID) website
url: https://www.niaid.nih.gov/about/dait
description: Division of Allergy, Immunology, and Transplantation (DAIT) website
responsible party type: Sponsor
mesh term: Asthma
sharing ipd: Yes
ipd description: Participant level data access and additional relevant materials will be made available upon completion of the trial.
ipd time frame: After completion of the trial, within 24 months status post database lock.
ipd access criteria: Registration is available for the Immunology Database and Analysis Portal (ImmPort) at: https://www.immport.org/registration. Submit a rationale for the purpose of requesting study data access.
ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.
ipd url: https://www.immport.org/home
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 