xml: <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/NCT06023589</url>
    </required_header>
    <id_info>
      <org_study_id>D5180C00016</org_study_id>
      <nct_id>NCT06023589</nct_id>
    </id_info>
    <brief_title>A Study to Investigate the Efficacy and Safety of Tezepelumab Compared With Placebo in Children 5 to &lt; 12 Years Old With Severe Asthma</brief_title>
    <acronym>HORIZON</acronym>
    <official_title>A Multicentre, Randomised, Double-Blind, Parallel-Group Placebo-Controlled, Phase 3, Efficacy and Safety Study of Tezepelumab in 5 to &lt; 12 Year Old Children With Severe Uncontrolled Asthma (HORIZON)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Amgen</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>AstraZeneca</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        To assess the efficacy and safety of tezepelumab in pediatric participants with severe&#xD;
        uncontrolled asthma on medium to high-dose inhaled corticosteroids (ICS) and at least one&#xD;
        additional asthma controller medication with or without oral corticosteroids.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised&#xD;
        study.&#xD;
  &#xD;
        The study will comprise of:&#xD;
  &#xD;
          1. Screening/Run-in period of 4 to 6 weeks,&#xD;
  &#xD;
          2. 52-week double-blind Treatment period,&#xD;
  &#xD;
          3. Post-treatment Follow-up period of 12 weeks.&#xD;
  &#xD;
        Participants will be randomised 2:1 to receive either tezepelumab or placebo administered by&#xD;
        (SC) Subcutaneous injections for 52 weeks (double-blind Treatment period).&#xD;
  &#xD;
        There will then be a 12-week off-treatment Follow-up period for participants who do not&#xD;
        continue in the optional open-label Active Treatment Extension period.&#xD;
  &#xD;
        An optional open-label Active Treatment Extension will allow all eligible participants the&#xD;
        opportunity to receive active treatment with tezepelumab. The Active Treatment Extension&#xD;
        period of the study will start following the 52-week double-blind Treatment period and will&#xD;
        consist of a 24-week open-label Treatment period prior to the 12-week post-treatment&#xD;
        Follow-up period.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 24, 2023</start_date>
    <completion_date type="Anticipated">January 10, 2028</completion_date>
    <primary_completion_date type="Anticipated">May 3, 2027</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Participants will be randomized in a 2:1 ratio to either tezepelumab or matching placebo both administered subcutaneously</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>Double-Blind</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Annualized asthma exacerbation rate (AAER)</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to &lt; 12 years old with severe uncontrolled asthma compared with placebo.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN)</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>To assess the effect of tezepelumab on pulmonary function (FEV1) in children with severe uncontrolled asthma compared with placebo. Pre-bronchodilator FEV1% PN will be determined by spirometry at the clinic visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AAER associated with allergic asthma</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>AAER will be assessed in association with both allergic asthma (defined by a positive perennial allergen using serum specific IgE [FEIA]).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to first severe asthma exacerbation</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Time to first severe asthma exacerbation will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with ≥ 1 severe asthma exacerbation</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Proportion of participants with ≥ 1 severe asthma exacerbation will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AAER associated with ER visit or hospitalisation</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>AAER will be assessed in association with ER visits or hospitalisations.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative asthma exacerbation days</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>The cumulative asthma exacerbation days from baseline to week 52 will be assessed</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-IA) total score</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline of PAQLQ-IA total score will be assessed. The PAQLQ was developed to measure the functional problems (physical, emotional, and social) that are most troublesome to children with asthma. The PAQLQ-IA has 23 questions in 3 domains (symptoms, activity limitation, and emotional function). Participants are asked to think about how they have been during the previous week and respond to each question on a 7-point scale (1 = extremely bothered to 7 = not bothered at all or 1 = all of the time to 7 = none of the time). There are 2 coloured cards (green and blue), which list sets of response options appropriate to different questions. The appropriate card should be used by the participant during completion of each question and then taken back when it is no longer required. The overall PAQLQ-IA score is the mean of all 23 responses and the individual domain scores are the means of the items in those domains.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline in PASO score will be assessed. The PASO questionnaire will be completed by the caregiver each day from the evening of Treatment period. Caregivers in this study will complete 4 items from the morning assessment capturing night-time asthma symptoms, rescue medication use, night-time awakenings, and maintenance asthma medication use. The evening assessment will capture daytime asthma symptoms, rescue medication use, activity limitation and change in asthma.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline in ACQ-IA score will be assessed. The ACQ-IA will only be completed for participants ≥ 6 years old at Screening. The ACQ-IA is administered by trained individuals according to standardised instructions to help the child understand concepts like symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheezing) and use of SABA during the past week using a 7-point scale. The ACQ-IA score is calculated by taking the mean of the 6 equally weighted items and ranges from 0 (well controlled) to 6 (extremely poorly controlled). The estimated minimal clinically important difference is 0.5</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in weekly mean rescue medication use</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline in weekly mean rescue medication use will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in weekly mean number of night-time awakenings</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline in weekly mean number of night-time awakenings will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in blood eosinophil count</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline in blood eosinophil count will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in fractional exhaled nitric oxide (FeNO)</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline in FeNO will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in total serum IgE</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Change from baseline in total serum IgE will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in pre-bronchodilator (pre-BD) peak expiratory flow (PEF)</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>The effect of tezepelumab on pulmonary function compared with placebo will be assessed using spirometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of asthma--related healthcare resource utilization (HRU)</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Mean number and type of Asthma specific HRU (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participant/caregiver health-related absences</measure>
      <time_frame>From Baseline to Week 52</time_frame>
      <description>Mean number of participant/caregiver health-related absences from work/school due to asthma will be assessed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum concentrations of tezepelumab</measure>
      <time_frame>At Baseline, Week 4, Week 24, and Week 52</time_frame>
      <description>To evaluate the pharmacokinetics of tezepelumab.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of anti-drug antibodies (ADAs)</measure>
      <time_frame>At Baseline, and from time of first dose at Week 0 to end of study at week 64</time_frame>
      <description>To evaluate the immunogenicity of tezepelumab.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of neutralising antibodies (nAbs)</measure>
      <time_frame>At Baseline, and from time of first dose at Week 0 to end of study at week 64</time_frame>
      <description>To evaluate the immunogenicity of tezepelumab.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">372</enrollment>
    <condition>Asthma</condition>
    <arm_group>
      <arm_group_label>Tezepelumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will be receiving tezepelumab subcutaneous injection</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants will be receiving placebo through a subcutaneous injection</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Tezepelumab</intervention_name>
      <description>Participants will be receiving subcutaneous injection of tezepelumab</description>
      <arm_group_label>Tezepelumab</arm_group_label>
      <other_name>MEDI9929 and AMG157</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Participants will be receiving subcutaneous injection of matching placebo</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Written informed consent from (ICF) at least one parent/caregiver (as per local&#xD;
               guidelines) and accompanying informed assent from the participant (where the&#xD;
               participant is able to provide assent) prior to admission to the study.&#xD;
  &#xD;
            2. Participants must be 5 to &lt; 12 years of age, at the time of signing the assent form&#xD;
               (as applicable per local guidelines) and their caregivers signing the ICF and at Visit&#xD;
               3.&#xD;
  &#xD;
            3. Documented physician diagnosis of severe asthma for at least 6 months prior to Visit&#xD;
               1.&#xD;
  &#xD;
            4. Documented physician-prescribed treatment with a total daily dose of either medium or&#xD;
               high dose, for at least 3 months with stable dose ≥ 1 month prior to Visit 1.&#xD;
  &#xD;
            5. Documented treatment with at least one additional maintenance asthma controller&#xD;
               medication is required according to local guidelines and standard of care;&#xD;
               (long-acting beta agonist, leukotriene receptor antagonist, long-acting muscarinic&#xD;
               antagonist) for at least 3 months with stable dose ≥ 1 month prior to Visit 1.&#xD;
  &#xD;
            6. Evidence of asthma as documented by one of the following:&#xD;
  &#xD;
                 1. Documented historical BD responsiveness of FEV1 ≥ 10% in the previous 12 months&#xD;
                    prior to Visit 1 OR&#xD;
  &#xD;
                 2. Documented historical methacholine challenge result of ≤ 16 mg/mL in the previous&#xD;
                    12 months prior to Visit 1 OR&#xD;
  &#xD;
                 3. Post-BD (albuterol/salbutamol) responsiveness of FEV1 ≥ 10% during Screening (15&#xD;
                    to 30 min after administration of 4 puffs of albuterol/salbutamol) at either&#xD;
                    Visit 1 or Visit 2.&#xD;
  &#xD;
            7. History of at least 2 severe asthma exacerbation events OR 1 severe asthma&#xD;
               exacerbation event resulting in hospitalisation within 12 months prior to Visit 1.&#xD;
  &#xD;
            8. Pre-BD FEV-1 &gt;50% and ≤ 95%PN OR FEV1/forced vital capacity (FVC) ratio ≤ 0.8 at&#xD;
               either Visit 1 or Visit 2.&#xD;
  &#xD;
            9. Evidence of uncontrolled asthma, with at least 1 of the below criteria:&#xD;
  &#xD;
                 1. ACQ-IA score ≥ 1.5 at least once during Screening/Run-in, including Visit 3&#xD;
                    (prior to Randomisation) for participants ≥ 6 years old at Screening&#xD;
  &#xD;
                 2. Use of reliever medication, other than as a preventive for exercise induced&#xD;
                    bronchospasm, on 3 or more days per week for at least 1 week during the&#xD;
                    Screening/Run-in period&#xD;
  &#xD;
                 3. Sleep awakening due to asthma symptoms requiring use of reliever medication at&#xD;
                    least once during the Screening/Run-in period&#xD;
  &#xD;
                 4. Asthma symptoms 3 or more days per week in at least 1 week during the&#xD;
                    Screening/Run-in period&#xD;
  &#xD;
           10. Body weight ≥ 16 kg at Visit 1 (Screening) and Visit 3 (Randomisation).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of cystic fibrosis, primary ciliary dyskinesia, or chronic rhinosinusitis with&#xD;
               nasal polyposis.&#xD;
  &#xD;
            2. History of any clinically significant disease or disorder other than asthma which, in&#xD;
               the opinion of the investigator, may either put the participant at risk because of&#xD;
               participation in the study, or influence the results or the participant's ability to&#xD;
               participate in the study.&#xD;
  &#xD;
            3. History of a clinically significant deterioration in asthma or asthma exacerbation&#xD;
               including those requiring use of systemic corticosteroids or increase in the&#xD;
               maintenance dose of oral corticosteroids within 30 days prior to Visit 1.&#xD;
  &#xD;
            4. Change in ICS dose within 1 month prior to Visit 1.&#xD;
  &#xD;
            5. History of a life-threatening asthma exacerbation resulting in a hypoxic seizure or&#xD;
               requiring intubation or mechanical ventilation.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>5 Years</minimum_age>
      <maximum_age>11 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>AstraZeneca Clinical Study Information Center</last_name>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Montgomery</city>
          <state>Alabama</state>
          <zip>36106</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Little Rock</city>
          <state>Arkansas</state>
          <zip>72202</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Savannah</city>
          <state>Georgia</state>
          <zip>31406</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Schenectady</city>
          <state>New York</state>
          <zip>12304</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Oklahoma City</city>
          <state>Oklahoma</state>
          <zip>73120</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Buenos Aires</city>
          <zip>C1121ABE</zip>
          <country>Argentina</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Capital Federal</city>
          <zip>C1122AAK</zip>
          <country>Argentina</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Lobos</city>
          <zip>7240</zip>
          <country>Argentina</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Mendoza</city>
          <zip>M5500GIP</zip>
          <country>Argentina</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Rosario</city>
          <zip>2000</zip>
          <country>Argentina</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Burlington</city>
          <state>Ontario</state>
          <zip>L7L 6W6</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Hamilton</city>
          <state>Ontario</state>
          <zip>L8S 1G5</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Windsor</city>
          <state>Ontario</state>
          <zip>N8X 2G1</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Montreal</city>
          <state>Quebec</state>
          <zip>H4A 3J1</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Lanzhou</city>
          <zip>730000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Shenyang</city>
          <zip>110001</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Bogota</city>
          <country>Colombia</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Bogotá</city>
          <zip>110231</zip>
          <country>Colombia</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Bron</city>
          <zip>69677</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Creteil</city>
          <zip>94010</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Paris</city>
          <zip>75012</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Paris</city>
          <zip>77019</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Vandoeuvre les Nancy Cedex</city>
          <zip>54511</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Szeged</city>
          <zip>7620</zip>
          <country>Hungary</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Szigetvár</city>
          <zip>7900</zip>
          <country>Hungary</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Funabashi-shi</city>
          <zip>273-8588</zip>
          <country>Japan</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Saga-shi</city>
          <zip>840-8571</zip>
          <country>Japan</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Shimotsuga-gun</city>
          <zip>321-0293</zip>
          <country>Japan</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Yokohama-shi</city>
          <zip>223-0059</zip>
          <country>Japan</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Guadalajara</city>
          <zip>44100</zip>
          <country>Mexico</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Amsterdam</city>
          <zip>1105 AZ</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Rotterdam</city>
          <zip>3015 GD</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Las Piñas</city>
          <zip>1740</zip>
          <country>Philippines</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Santa Rosa</city>
          <zip>4026</zip>
          <country>Philippines</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Tarnow</city>
          <zip>33-100</zip>
          <country>Poland</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Tarnów</city>
          <zip>33-100</zip>
          <country>Poland</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Łódź</city>
          <zip>90-302</zip>
          <country>Poland</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Esplugues De Llobregat (Barc)</city>
          <zip>08950</zip>
          <country>Spain</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Villarreal (Castellón)</city>
          <zip>12540</zip>
          <country>Spain</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location_countries>
      <country>Argentina</country>
      <country>Canada</country>
      <country>China</country>
      <country>Colombia</country>
      <country>France</country>
      <country>Hungary</country>
      <country>Japan</country>
      <country>Mexico</country>
      <country>Netherlands</country>
      <country>Philippines</country>
      <country>Poland</country>
      <country>Spain</country>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Asthma</keyword>
    <keyword>Uncontrolled Asthma</keyword>
    <keyword>Severe Uncontrolled Asthma</keyword>
    <keyword>Human monoclonal antibody (IgG2λ) cytokine</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>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:&#xD;
  https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.&#xD;
  &quot;Yes&quot;, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
      <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.</ipd_access_criteria>
      <ipd_url>https://vivli.org/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06023589
  org study id: D5180C00016
  nct id: NCT06023589
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  To assess the efficacy and safety of tezepelumab in pediatric participants with severe
        uncontrolled asthma on medium to high-dose inhaled corticosteroids (ICS) and at least one
        additional asthma controller medication with or without oral corticosteroids.
  This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised
        study.
  
        The study will comprise of:
  
          1. Screening/Run-in period of 4 to 6 weeks,
  
          2. 52-week double-blind Treatment period,
  
          3. Post-treatment Follow-up period of 12 weeks.
  
        Participants will be randomised 2:1 to receive either tezepelumab or placebo administered by
        (SC) Subcutaneous injections for 52 weeks (double-blind Treatment period).
  
        There will then be a 12-week off-treatment Follow-up period for participants who do not
        continue in the optional open-label Active Treatment Extension period.
  
        An optional open-label Active Treatment Extension will allow all eligible participants the
        opportunity to receive active treatment with tezepelumab. The Active Treatment Extension
        period of the study will start following the 52-week double-blind Treatment period and will
        consist of a 24-week open-label Treatment period prior to the 12-week post-treatment
        Follow-up period.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants will be randomized in a 2:1 ratio to either tezepelumab or matching placebo both administered subcutaneously
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: Double-Blind
  measure: Annualized asthma exacerbation rate (AAER)
  time frame: From Baseline to Week 52
  description: To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to < 12 years old with severe uncontrolled asthma compared with placebo.
  measure: Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN)
  time frame: From Baseline to Week 52
  description: To assess the effect of tezepelumab on pulmonary function (FEV1) in children with severe uncontrolled asthma compared with placebo. Pre-bronchodilator FEV1% PN will be determined by spirometry at the clinic visit.
  measure: AAER associated with allergic asthma
  time frame: From Baseline to Week 52
  description: AAER will be assessed in association with both allergic asthma (defined by a positive perennial allergen using serum specific IgE [FEIA]).
  measure: Time to first severe asthma exacerbation
  time frame: From Baseline to Week 52
  description: Time to first severe asthma exacerbation will be assessed.
  measure: Proportion of participants with ≥ 1 severe asthma exacerbation
  time frame: From Baseline to Week 52
  description: Proportion of participants with ≥ 1 severe asthma exacerbation will be assessed.
  measure: AAER associated with ER visit or hospitalisation
  time frame: From Baseline to Week 52
  description: AAER will be assessed in association with ER visits or hospitalisations.
  measure: Cumulative asthma exacerbation days
  time frame: From Baseline to Week 52
  description: The cumulative asthma exacerbation days from baseline to week 52 will be assessed
  measure: Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-IA) total score
  time frame: From Baseline to Week 52
  description: Change from baseline of PAQLQ-IA total score will be assessed. The PAQLQ was developed to measure the functional problems (physical, emotional, and social) that are most troublesome to children with asthma. The PAQLQ-IA has 23 questions in 3 domains (symptoms, activity limitation, and emotional function). Participants are asked to think about how they have been during the previous week and respond to each question on a 7-point scale (1 = extremely bothered to 7 = not bothered at all or 1 = all of the time to 7 = none of the time). There are 2 coloured cards (green and blue), which list sets of response options appropriate to different questions. The appropriate card should be used by the participant during completion of each question and then taken back when it is no longer required. The overall PAQLQ-IA score is the mean of all 23 responses and the individual domain scores are the means of the items in those domains.
  measure: Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score
  time frame: From Baseline to Week 52
  description: Change from baseline in PASO score will be assessed. The PASO questionnaire will be completed by the caregiver each day from the evening of Treatment period. Caregivers in this study will complete 4 items from the morning assessment capturing night-time asthma symptoms, rescue medication use, night-time awakenings, and maintenance asthma medication use. The evening assessment will capture daytime asthma symptoms, rescue medication use, activity limitation and change in asthma.
  measure: Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score
  time frame: From Baseline to Week 52
  description: Change from baseline in ACQ-IA score will be assessed. The ACQ-IA will only be completed for participants ≥ 6 years old at Screening. The ACQ-IA is administered by trained individuals according to standardised instructions to help the child understand concepts like symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheezing) and use of SABA during the past week using a 7-point scale. The ACQ-IA score is calculated by taking the mean of the 6 equally weighted items and ranges from 0 (well controlled) to 6 (extremely poorly controlled). The estimated minimal clinically important difference is 0.5
  measure: Change from baseline in weekly mean rescue medication use
  time frame: From Baseline to Week 52
  description: Change from baseline in weekly mean rescue medication use will be assessed.
  measure: Change from baseline in weekly mean number of night-time awakenings
  time frame: From Baseline to Week 52
  description: Change from baseline in weekly mean number of night-time awakenings will be assessed.
  measure: Change from baseline in blood eosinophil count
  time frame: From Baseline to Week 52
  description: Change from baseline in blood eosinophil count will be assessed.
  measure: Change from baseline in fractional exhaled nitric oxide (FeNO)
  time frame: From Baseline to Week 52
  description: Change from baseline in FeNO will be assessed.
  measure: Change from baseline in total serum IgE
  time frame: From Baseline to Week 52
  description: Change from baseline in total serum IgE will be assessed.
  measure: Change from baseline in pre-bronchodilator (pre-BD) peak expiratory flow (PEF)
  time frame: From Baseline to Week 52
  description: The effect of tezepelumab on pulmonary function compared with placebo will be assessed using spirometry.
  measure: Number of asthma--related healthcare resource utilization (HRU)
  time frame: From Baseline to Week 52
  description: Mean number and type of Asthma specific HRU (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) will be assessed.
  measure: Number of participant/caregiver health-related absences
  time frame: From Baseline to Week 52
  description: Mean number of participant/caregiver health-related absences from work/school due to asthma will be assessed.
  measure: Serum concentrations of tezepelumab
  time frame: At Baseline, Week 4, Week 24, and Week 52
  description: To evaluate the pharmacokinetics of tezepelumab.
  measure: Incidence of anti-drug antibodies (ADAs)
  time frame: At Baseline, and from time of first dose at Week 0 to end of study at week 64
  description: To evaluate the immunogenicity of tezepelumab.
  measure: Incidence of neutralising antibodies (nAbs)
  time frame: At Baseline, and from time of first dose at Week 0 to end of study at week 64
  description: To evaluate the immunogenicity of tezepelumab.
  arm group label: Tezepelumab
  arm group type: Experimental
  description: Participants will be receiving tezepelumab subcutaneous injection
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Participants will be receiving placebo through a subcutaneous injection
  intervention type: Biological
  intervention name: Tezepelumab
  description: Participants will be receiving subcutaneous injection of tezepelumab
  arm group label: Tezepelumab
  other name: MEDI9929 and AMG157
  intervention type: Other
  intervention name: Placebo
  description: Participants will be receiving subcutaneous injection of matching placebo
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 5 Years
  maximum age: 11 Years
  healthy volunteers: No
  last name: AstraZeneca Clinical Study Information Center
  phone: 1-877-240-9479
  email: information.center@astrazeneca.com
  facility: 
  status: Recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Not yet recruiting
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  status: Recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
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  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
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  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  country: Argentina
  country: Canada
  country: China
  country: Colombia
  country: France
  country: Hungary
  country: Japan
  country: Mexico
  country: Netherlands
  country: Philippines
  country: Poland
  country: Spain
  country: United States
  responsible party type: Sponsor
  mesh term: Asthma
  sharing ipd: Yes
  ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:
  https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
  "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
  ipd access criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
  ipd url: https://vivli.org/