<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/NCT03306043</url>
  </required_header>
  <id_info>
    <org_study_id>205203</org_study_id>
    <secondary_id>2017-000184-32</secondary_id>
    <nct_id>NCT03306043</nct_id>
  </id_info>
  <brief_title>A Multi-center, Open-label Extension, Safety Study of Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES) From Study 200622</brief_title>
  <official_title>A Multi-centre, Open-label Extension, Safety Study to Describe the Long-term Clinical Experience of Mepolizumab in Participants With Hypereosinophilic Syndrome (HES) From Study 200622</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label extension study to Study 200622.In this study subjects from Study&#xD;
      200622 will be continued on 4-weekly dosing with open-label mepolizumab 300 milligram (mg)&#xD;
      subcutaneously (SC) for an additional 20 Weeks after completing the 32 Week study assessments&#xD;
      post-randomization, while they continue with their background HES therapy per standard of&#xD;
      care (SoC). Subjects from study 200622 will participate in this extension study if they had&#xD;
      completed the 32-Week treatment period in study 200622 or if they were withdrawn from the&#xD;
      study pre-maturely, but were continued in the study per protocol until 32 Weeks from&#xD;
      randomization. Data from this study (205203) and 200622 will be combined to provide up to&#xD;
      52-Week exposure data to further characterize the long-term safety profile of mepolizumab and&#xD;
      provide additional data on the clinical benefit in HES subjects beyond 32 Weeks. The duration&#xD;
      of the study participation will be 20 Weeks for subjects who continue with mepolizumab&#xD;
      treatment via MHE104317/MHE112562 after this open-label extension study; and 28 Weeks for&#xD;
      subjects who do not continue with MHE104317/MHE112562.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 13, 2017</start_date>
  <completion_date type="Actual">December 30, 2019</completion_date>
  <primary_completion_date type="Actual">December 30, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Common (&gt;=3%) Non-serious Adverse Events (AEs)</measure>
    <time_frame>Up to Week 20</time_frame>
    <description>An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-serious AEs from start of study treatment until 28 days after last dose (up to Week 20) are reported. Number of participants with common (&gt;=3% incidence) non-serious AEs are presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Serious AEs</measure>
    <time_frame>Up to Week 28</time_frame>
    <description>An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with serious AEs are presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With the Presence of Anti-drug Antibody</measure>
    <time_frame>Baseline (Day 1), Week 20 and Week 28</time_frame>
    <description>Blood samples were analyzed for the presence of anti-mepolizumab antibodies by binding anti-drug antibody (ADA) assay. The binding ADA assay results at each visit were summarized as negative or positive. The binding ADA assay was performed in three steps; screening, confirmation and titration. The screening assay produced a result of positive or negative relative to a screening cut point. Positive samples continued with the confirmation assay, which also produced a result of positive or negative relative to a confirmation cut point. For positive confirmation samples, a titre value was obtained to quantify the degree of binding in a titration assay. Participants were considered 'Positive' if they had a positive confirmation ADA assay result.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">102</enrollment>
  <condition>Hypereosinophilic Syndrome</condition>
  <arm_group>
    <arm_group_label>Subjects who received mepolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who were part of study 200622 and were randomized to receive either placebo or mepolizumab will be enrolled in this study as per study eligibility criteria. In this study, subjects will receive 300 mg of mepolizumab SC (three 100 mg SC injections) every 4 Weeks for a total of 5 doses during 20-Week treatment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mepolizumab</intervention_name>
    <description>Mepolizumab will be available as 100 mg vial for injection. Subjects will receive three 100 mg SC injections for every 4 Weeks for a total of 5 doses during 20 Week treatment period.</description>
    <arm_group_label>Subjects who received mepolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 12 years and older subjects who were enrolled in Study 200622.&#xD;
&#xD;
          -  To be considered for Study 205203, subjects from study 200622 must have completed&#xD;
             32-Week treatment period in the study or if the subject was withdrawn from study&#xD;
             treatment prematurely during the 200622 study, but continued in the study per protocol&#xD;
             (including HES flare-related assessments) until 32 Weeks from randomization.&#xD;
&#xD;
          -  Male or female subjects. Female subjects must be either not a woman of childbearing&#xD;
             potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance at least 30&#xD;
             days prior to the first dose of study treatment and until 16 weeks after the last dose&#xD;
             of study treatment.&#xD;
&#xD;
          -  The treating physician must confirm a positive benefit/risk ratio. The anticipated&#xD;
             clinical benefit from mepolizumab must outweigh any potential safety or tolerability&#xD;
             risk in Study 205203.&#xD;
&#xD;
          -  Capable of giving signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with any history of hypersensitivity to any monoclonal antibody (including&#xD;
             mepolizumab).&#xD;
&#xD;
          -  Subjects with current malignancy or malignancy that developed during Study 200622.&#xD;
&#xD;
          -  Subjects who is pregnant or breastfeeding.&#xD;
&#xD;
          -  Subjects who has other clinically significant medical conditions uncontrolled with SoC&#xD;
             therapy not associated with HES, example (e. g.), unstable liver disease, uncontrolled&#xD;
             cardiovascular disease, ongoing active infectious disease.&#xD;
&#xD;
          -  Subjects with QT interval corrected (QTc) greater than 450 millisecond (msec) or QTc&#xD;
             greater than 480 msec in subjects with bundle branch block based on local&#xD;
             Electrocardiogram (EGC) reading.&#xD;
&#xD;
          -  Subjects who discontinue study treatment based on liver chemistry stopping criteria&#xD;
             during Study 200622.&#xD;
&#xD;
          -  Current active liver or biliary disease (with the exception of Gilbert's syndrome or&#xD;
             asymptomatic gallstones or otherwise stable chronic liver disease per investigator&#xD;
             assessment).&#xD;
&#xD;
          -  Subjects who have received treatment with an investigational agent (biologic or&#xD;
             non-biologic) within the past 30 days or 5 drug half-lives whichever is longer, prior&#xD;
             to the first dose, other than Study 200622 study treatment. The term &quot;investigational&quot;&#xD;
             applies to any drug not approved for sale for the disease/indication to treat in the&#xD;
             country in which it is being used or investigational formulations of marketed&#xD;
             products.&#xD;
&#xD;
          -  Subjects who are currently participating in any other interventional clinical study.&#xD;
&#xD;
          -  Subjects had an AE (serious or non-serious) considered related to study treatment&#xD;
             while participating in Study 200622 which resulted in permanent withdrawal of study&#xD;
             treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mayfield Heights</city>
        <state>Ohio</state>
        <zip>44124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autonoma de Buenos Aires</city>
        <state>Buenos Aires</state>
        <zip>C1028AAP</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>La Plata</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mar del Plata</city>
        <state>Buenos Aires</state>
        <zip>7600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>40110-160</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santo André - SP</city>
        <state>São Paulo</state>
        <zip>09080-110</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Sorocaba</city>
        <state>São Paulo</state>
        <zip>18040-425</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lille Cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nantes Cedex 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Suresnes</city>
        <zip>92151</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Toulouse Cedex 9</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mannheim</city>
        <state>Baden-Wuerttemberg</state>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fulda</city>
        <state>Hessen</state>
        <zip>36043</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kirchheim unter Teck</city>
        <zip>73230</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Firenze</city>
        <state>Toscana</state>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44100</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo León</state>
        <zip>64060</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Villahermosa</city>
        <state>Tabasco</state>
        <zip>86035</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Krakow</city>
        <zip>31-066</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lodz</city>
        <zip>90-153</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>010306</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Targu Mures</city>
        <zip>540327</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>125167</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197341</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leicester</city>
        <zip>LE3 9QP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Mexico</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>October 5, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 10, 2017</study_first_posted>
  <results_first_submitted>June 4, 2020</results_first_submitted>
  <results_first_submitted_qc>June 4, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2020</results_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hypereosinophilic syndrome</keyword>
  <keyword>hypereosinophilic syndrome flare</keyword>
  <keyword>open-label extension study</keyword>
  <keyword>Mepolizumab</keyword>
  <keyword>SB240563</keyword>
  <keyword>Long-term safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypereosinophilic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>http://clinicalstudydatarequest.com</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 16, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT03306043/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT03306043/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a multi-center, open-label extension study to evaluate the long-term safety profile of mepolizumab in participants with Hypereosinophilic Syndrome (HES). In this study, participants received open-label mepolizumab 300 milligram (mg) subcutaneously (SC).</recruitment_details>
      <pre_assignment_details>A total of 102 participants who completed the parent study (200622 [NCT02836496]) and met the eligibility criteria were enrolled in this open-label extension study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Mepolizumab 300 mg SC</title>
          <description>Participants were administered 300 mg SC mepolizumab every 4 weeks (starting approximately 32 weeks after the first dose of study treatment in Study 200622). The final dose of mepolizumab was administered at Visit 5 (Week 16).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="102"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="98"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Mepolizumab 300 mg SC</title>
          <description>Participants were administered 300 mg SC mepolizumab every 4 weeks (starting approximately 32 weeks after the first dose of study treatment in Study 200622). The final dose of mepolizumab was administered at Visit 5 (Week 16).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="102"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.0" spread="15.54"/>
                  </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="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Asian-East Asian Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White-White/Caucasian/European Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaskan Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Common (&gt;=3%) Non-serious Adverse Events (AEs)</title>
        <description>An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-serious AEs from start of study treatment until 28 days after last dose (up to Week 20) are reported. Number of participants with common (&gt;=3% incidence) non-serious AEs are presented.</description>
        <time_frame>Up to Week 20</time_frame>
        <population>Safety Population comprised of all participants who received at least one dose of open-label mepolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab 300 mg SC</title>
            <description>Participants were administered 300 mg SC mepolizumab every 4 weeks (starting approximately 32 weeks after the first dose of study treatment in Study 200622). The final dose of mepolizumab was administered at Visit 5 (Week 16).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Common (&gt;=3%) Non-serious Adverse Events (AEs)</title>
          <description>An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-serious AEs from start of study treatment until 28 days after last dose (up to Week 20) are reported. Number of participants with common (&gt;=3% incidence) non-serious AEs are presented.</description>
          <population>Safety Population comprised of all participants who received at least one dose of open-label mepolizumab.</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="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Serious AEs</title>
        <description>An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with serious AEs are presented.</description>
        <time_frame>Up to Week 28</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab 300 mg SC</title>
            <description>Participants were administered 300 mg SC mepolizumab every 4 weeks (starting approximately 32 weeks after the first dose of study treatment in Study 200622). The final dose of mepolizumab was administered at Visit 5 (Week 16).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious AEs</title>
          <description>An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with serious AEs are presented.</description>
          <population>Safety Population</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="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With the Presence of Anti-drug Antibody</title>
        <description>Blood samples were analyzed for the presence of anti-mepolizumab antibodies by binding anti-drug antibody (ADA) assay. The binding ADA assay results at each visit were summarized as negative or positive. The binding ADA assay was performed in three steps; screening, confirmation and titration. The screening assay produced a result of positive or negative relative to a screening cut point. Positive samples continued with the confirmation assay, which also produced a result of positive or negative relative to a confirmation cut point. For positive confirmation samples, a titre value was obtained to quantify the degree of binding in a titration assay. Participants were considered 'Positive' if they had a positive confirmation ADA assay result.</description>
        <time_frame>Baseline (Day 1), Week 20 and Week 28</time_frame>
        <population>Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Mepolizumab 300 mg SC</title>
            <description>Participants were administered 300 mg SC mepolizumab every 4 weeks (starting approximately 32 weeks after the first dose of study treatment in Study 200622). The final dose of mepolizumab was administered at Visit 5 (Week 16).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With the Presence of Anti-drug Antibody</title>
          <description>Blood samples were analyzed for the presence of anti-mepolizumab antibodies by binding anti-drug antibody (ADA) assay. The binding ADA assay results at each visit were summarized as negative or positive. The binding ADA assay was performed in three steps; screening, confirmation and titration. The screening assay produced a result of positive or negative relative to a screening cut point. Positive samples continued with the confirmation assay, which also produced a result of positive or negative relative to a confirmation cut point. For positive confirmation samples, a titre value was obtained to quantify the degree of binding in a titration assay. Participants were considered 'Positive' if they had a positive confirmation ADA assay result.</description>
          <population>Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).</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="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline, Negative, n=102</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline, Positive, n=102</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20, Negative, n=101</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20, Positive, n=101</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 28, Negative, n=14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 28, Positive, n=14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Serious AEs were reported from start of study (Week 0) up to end of study (up to Week 28) and non-serious AEs were reported from start of study treatment until 28 days after last dose (up to Week 20)</time_frame>
      <desc>Non-serious AEs and serious AEs were reported for Safety Population.</desc>
      <group_list>
        <group group_id="E1">
          <title>Mepolizumab 300 mg SC</title>
          <description>Participants were administered 300 mg SC mepolizumab every 4 weeks (starting approximately 32 weeks after the first dose of study treatment in Study 200622). The final dose of mepolizumab was administered at Visit 5 (Week 16).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.1</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="0" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypereosinophilic syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis eosinophilic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Gastrointestinal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of bronchiectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Mycobacterium abscessus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Perihepatic abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Joint dislocation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Peripheral T-cell lymphoma unspecified</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA 22.1</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="34" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="11" subjects_affected="4" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
      <email>GSKClinicalSupportHD@gsk.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03306043
org study id: 205203
secondary id: 2017-000184-32
nct id: NCT03306043
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label extension study to Study 200622.In this study subjects from Study
      200622 will be continued on 4-weekly dosing with open-label mepolizumab 300 milligram (mg)
      subcutaneously (SC) for an additional 20 Weeks after completing the 32 Week study assessments
      post-randomization, while they continue with their background HES therapy per standard of
      care (SoC). Subjects from study 200622 will participate in this extension study if they had
      completed the 32-Week treatment period in study 200622 or if they were withdrawn from the
      study pre-maturely, but were continued in the study per protocol until 32 Weeks from
      randomization. Data from this study (205203) and 200622 will be combined to provide up to
      52-Week exposure data to further characterize the long-term safety profile of mepolizumab and
      provide additional data on the clinical benefit in HES subjects beyond 32 Weeks. The duration
      of the study participation will be 20 Weeks for subjects who continue with mepolizumab
      treatment via MHE104317/MHE112562 after this open-label extension study; and 28 Weeks for
      subjects who do not continue with MHE104317/MHE112562.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Common (>=3%) Non-serious Adverse Events (AEs)
time frame: Up to Week 20
description: An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-serious AEs from start of study treatment until 28 days after last dose (up to Week 20) are reported. Number of participants with common (>=3% incidence) non-serious AEs are presented.
measure: Number of Participants With Serious AEs
time frame: Up to Week 28
description: An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with serious AEs are presented.
measure: Number of Participants With the Presence of Anti-drug Antibody
time frame: Baseline (Day 1), Week 20 and Week 28
description: Blood samples were analyzed for the presence of anti-mepolizumab antibodies by binding anti-drug antibody (ADA) assay. The binding ADA assay results at each visit were summarized as negative or positive. The binding ADA assay was performed in three steps; screening, confirmation and titration. The screening assay produced a result of positive or negative relative to a screening cut point. Positive samples continued with the confirmation assay, which also produced a result of positive or negative relative to a confirmation cut point. For positive confirmation samples, a titre value was obtained to quantify the degree of binding in a titration assay. Participants were considered 'Positive' if they had a positive confirmation ADA assay result.
arm group label: Subjects who received mepolizumab
arm group type: Experimental
description: Subjects who were part of study 200622 and were randomized to receive either placebo or mepolizumab will be enrolled in this study as per study eligibility criteria. In this study, subjects will receive 300 mg of mepolizumab SC (three 100 mg SC injections) every 4 Weeks for a total of 5 doses during 20-Week treatment period.
intervention type: Drug
intervention name: Mepolizumab
description: Mepolizumab will be available as 100 mg vial for injection. Subjects will receive three 100 mg SC injections for every 4 Weeks for a total of 5 doses during 20 Week treatment period.
arm group label: Subjects who received mepolizumab
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
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country: Argentina
country: Belgium
country: Brazil
country: France
country: Germany
country: Italy
country: Mexico
country: Poland
country: Romania
country: Russian Federation
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Hypereosinophilic Syndrome
mesh term: Syndrome
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: http://clinicalstudydatarequest.com
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