<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/NCT03298061</url>
  </required_header>
  <id_info>
    <org_study_id>116841</org_study_id>
    <secondary_id>2014-003162-25</secondary_id>
    <nct_id>NCT03298061</nct_id>
  </id_info>
  <brief_title>Long-term Access Program (LAP) of Mepolizumab for Subjects Who Participated in Study MEA115921</brief_title>
  <official_title>Mepolizumab Long-term Access Programme for Subjects Who Participated in Study MEA115921 (Placebo-controlled Study of Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis in Subjects Receiving Standard-of-care Therapy)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Eosinophilic Granulomatosis with Polyangiitis (EGPA), also referred to as Churg-Strauss&#xD;
      syndrome, is a rare hyper-eosinophilic syndrome. Eosinophilia is central to the&#xD;
      pathophysiology of EGPA and interleukin-5 (IL-5) is a key cytokine regulating the life-cycle&#xD;
      of the eosinophil. Neutralization of IL-5 with mepolizumab, an anti-IL5 monoclonal antibody,&#xD;
      therefore offers a potential therapeutic option for EGPA. The objective of study MEA115921&#xD;
      was to investigate the efficacy and safety of mepolizumab compared with placebo wherein the&#xD;
      subjects were randomized to receive either: 300 milligram (mg) mepolizumab or Placebo&#xD;
      subcutaneous (SC) injection every 4 weeks in addition to their background standard-of-care&#xD;
      therapy. Subjects were treated for a period of 52 weeks and then followed up for a further 8&#xD;
      weeks to study completion at Week 60. This is a LAP to support provision of open-label&#xD;
      mepolizumab on an individual basis to eligible subjects who participated in clinical study&#xD;
      MEA115921 and who require a dose of prednisolone (or equivalent) of &gt;=5 milligrams per day&#xD;
      (mg/day) for adequate control of their EGPA. Eligible subjects can initiate mepolizumab under&#xD;
      this LAP within a 6-month period starting from completion of study MEA115921 (that is, at&#xD;
      Week 60) or, in case of premature discontinuation from study MEA115921, the subjects will&#xD;
      initiate mepolizumab at the time point that would have been Week 60 if the subject had&#xD;
      completed the study. Eligible subjects will receive subcutaneously administered mepolizumab&#xD;
      at a dose of 300 mg SC every 4 weeks. Eligible subjects will continue to receive mepolizumab&#xD;
      under this LAP until mepolizumab is commercially licensed for the treatment of EGPA in the&#xD;
      relevant country or until GlaxoSmithKline (GSK) discontinues the program or until the subject&#xD;
      meets any of the withdrawal/stopping criteria.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 14, 2015</start_date>
  <completion_date type="Anticipated">March 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2023</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>Subjects who participated in clinical study MEA115921 and require a dose of prednisolone (or equivalent) of &gt;=5 mg/day for adequate control of their EGPA will be included in this study based on the confirmation of their eligibility by GSK Medical Monitor. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with corticosteroid use</measure>
    <time_frame>Up to 3 years approximately</time_frame>
    <description>The use of corticosteroids excluding inhaled and topical steroids will be summarized.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with adverse events (AEs) and serious adverse events (SAEs)</measure>
    <time_frame>Up to 3 years approximately</time_frame>
    <description>An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is 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 disability/incapacity; is a congenital anomaly/birth defect; other important medical events based on medical or scientific judgment; and is associated with liver injury and impaired liver function. Additionally, systemic (that is, allergic/hypersensitivity and non-allergic) reactions and local injection site reactions will be recorded throughout the treatment and follow-up period.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Churg-Strauss Syndrome</condition>
  <arm_group>
    <arm_group_label>Subjects from clinical study MEA115921</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who participated in clinical study MEA115921 and who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mepolizumab</intervention_name>
    <description>Mepolizumab will be available as lyophilized powder for injection to be reconstituted with sterile water for injection, prior to use. Subjects will be dosed with mepolizumab at a dose of 300 mg which will be administered as three separate 100 mg SC injections every 4 weeks. The injections will be administered into any of the upper arm, thigh or anterior abdominal wall.</description>
    <arm_group_label>Subjects from clinical study MEA115921</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisolone</intervention_name>
    <description>Subjects who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included.</description>
    <arm_group_label>Subjects from clinical study MEA115921</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject participated in study MEA115921.&#xD;
&#xD;
          -  Subject has either: a) completed study MEA115921 to Week 60, that is, completion of&#xD;
             follow up period, or b) if the subject was withdrawn prematurely from study MEA115921,&#xD;
             the subject has reached the date of what would have been the Week 60 if the subject&#xD;
             had completed the study, that is, 60 weeks from Baseline (Visit 2).&#xD;
&#xD;
          -  At or up to 6 months after the MEA115921 Week 60 time- point the subject requires a&#xD;
             dose of prednisolone (or equivalent) of &gt;=5 mg/day for adequate control of their EGPA.&#xD;
&#xD;
          -  The treating physician requesting mepolizumab under this LAP considers the benefits of&#xD;
             treatment with mepolizumab outweigh the risks for the individual subject.&#xD;
&#xD;
          -  To be eligible for mepolizumab treatment under this LAP, females of childbearing&#xD;
             potential (FCBP) must commit to consistent and correct use of an acceptable method of&#xD;
             birth control, beginning with consent, for the duration of the treatment with&#xD;
             mepolizumab and for 4 months after the last mepolizumab administration.&#xD;
&#xD;
          -  The subject consents to receiving treatment with mepolizumab under this LAP.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A current malignancy or history of cancer in remission for less than 12 months&#xD;
             (Subjects who had localized carcinoma (that is, basal or squamous cell) of the skin&#xD;
             which was resected for cure will not be excluded).&#xD;
&#xD;
          -  Subject has other clinically significant medical conditions uncontrolled with standard&#xD;
             of care therapy not associated with EGPA, example, unstable liver disease,&#xD;
             uncontrolled cardiovascular disease, ongoing active infectious disease requiring&#xD;
             systemic treatment.&#xD;
&#xD;
          -  Subject is pregnant or breastfeeding. Subjects should not be considered for continued&#xD;
             treatment if they plan to become pregnant during the course of treatment with&#xD;
             mepolizumab.&#xD;
&#xD;
          -  Subject has a known allergy or intolerance to a monoclonal antibody or biologic&#xD;
             therapy including mepolizumab.&#xD;
&#xD;
          -  Subject had an adverse event (serious or non-serious) considered related to study&#xD;
             treatment whilst participating in study MEA115921 which resulted in permanent&#xD;
             withdrawal of study treatment.&#xD;
&#xD;
          -  Subject is receiving treatment with another biological therapy such as a monoclonal&#xD;
             antibody therapy or intravenous (IV) immunoglobulin therapy without prior agreement&#xD;
             from the GSK Medical Monitor.&#xD;
&#xD;
          -  Subjects who have received treatment with an investigational drug within the past 30&#xD;
             days or 5 terminal phase half-lives of the drug whichever is longer, prior to&#xD;
             initiation of mepolizumab treatment under this LAP (this also includes investigational&#xD;
             formulations of marketed products).&#xD;
&#xD;
          -  Subject is currently participating in any other interventional clinical study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 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>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118-2307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mempis</city>
        <state>Tennessee</state>
        <zip>38119</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>Saint George</city>
        <state>Utah</state>
        <zip>84770</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Abingdon</city>
        <state>Virginia</state>
        <zip>24210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98004</zip>
        <country>United States</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>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 4A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bron Cedex</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Marseille Cedex 20</city>
        <zip>13915</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Montpellier cedex 5</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint-Priest en Jarez</city>
        <zip>42270</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>Freiburg</city>
        <state>Baden-Wuerttemberg</state>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kirchheim -Teck</city>
        <state>Baden-Wuerttemberg</state>
        <zip>73230</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>Bad Bramstedt</city>
        <state>Schleswig-Holstein</state>
        <zip>24576</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Jena</city>
        <state>Thueringen</state>
        <zip>07740</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kanagawa</city>
        <zip>252-0392</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Miyagi</city>
        <zip>980-8574</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Portsmouth</city>
        <state>Hampshire</state>
        <zip>PO6 3LY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</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>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Japan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>November 24, 2022</last_update_submitted>
  <last_update_submitted_qc>November 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Eosinophilic Granulomatosis</keyword>
  <keyword>MEA115921</keyword>
  <keyword>Polyangiitis</keyword>
  <keyword>Long-term access program</keyword>
  <keyword>mepolizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Churg-Strauss Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisolone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03298061
org study id: 116841
secondary id: 2014-003162-25
nct id: NCT03298061
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Eosinophilic Granulomatosis with Polyangiitis (EGPA), also referred to as Churg-Strauss
      syndrome, is a rare hyper-eosinophilic syndrome. Eosinophilia is central to the
      pathophysiology of EGPA and interleukin-5 (IL-5) is a key cytokine regulating the life-cycle
      of the eosinophil. Neutralization of IL-5 with mepolizumab, an anti-IL5 monoclonal antibody,
      therefore offers a potential therapeutic option for EGPA. The objective of study MEA115921
      was to investigate the efficacy and safety of mepolizumab compared with placebo wherein the
      subjects were randomized to receive either: 300 milligram (mg) mepolizumab or Placebo
      subcutaneous (SC) injection every 4 weeks in addition to their background standard-of-care
      therapy. Subjects were treated for a period of 52 weeks and then followed up for a further 8
      weeks to study completion at Week 60. This is a LAP to support provision of open-label
      mepolizumab on an individual basis to eligible subjects who participated in clinical study
      MEA115921 and who require a dose of prednisolone (or equivalent) of >=5 milligrams per day
      (mg/day) for adequate control of their EGPA. Eligible subjects can initiate mepolizumab under
      this LAP within a 6-month period starting from completion of study MEA115921 (that is, at
      Week 60) or, in case of premature discontinuation from study MEA115921, the subjects will
      initiate mepolizumab at the time point that would have been Week 60 if the subject had
      completed the study. Eligible subjects will receive subcutaneously administered mepolizumab
      at a dose of 300 mg SC every 4 weeks. Eligible subjects will continue to receive mepolizumab
      under this LAP until mepolizumab is commercially licensed for the treatment of EGPA in the
      relevant country or until GlaxoSmithKline (GSK) discontinues the program or until the subject
      meets any of the withdrawal/stopping criteria.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Subjects who participated in clinical study MEA115921 and require a dose of prednisolone (or equivalent) of >=5 mg/day for adequate control of their EGPA will be included in this study based on the confirmation of their eligibility by GSK Medical Monitor. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects with corticosteroid use
time frame: Up to 3 years approximately
description: The use of corticosteroids excluding inhaled and topical steroids will be summarized.
measure: Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
time frame: Up to 3 years approximately
description: An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is 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 disability/incapacity; is a congenital anomaly/birth defect; other important medical events based on medical or scientific judgment; and is associated with liver injury and impaired liver function. Additionally, systemic (that is, allergic/hypersensitivity and non-allergic) reactions and local injection site reactions will be recorded throughout the treatment and follow-up period.
arm group label: Subjects from clinical study MEA115921
arm group type: Experimental
description: Subjects who participated in clinical study MEA115921 and who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks.
intervention type: Drug
intervention name: Mepolizumab
description: Mepolizumab will be available as lyophilized powder for injection to be reconstituted with sterile water for injection, prior to use. Subjects will be dosed with mepolizumab at a dose of 300 mg which will be administered as three separate 100 mg SC injections every 4 weeks. The injections will be administered into any of the upper arm, thigh or anterior abdominal wall.
arm group label: Subjects from clinical study MEA115921
intervention type: Drug
intervention name: Prednisolone
description: Subjects who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included.
arm group label: Subjects from clinical study MEA115921
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
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country: Belgium
country: Canada
country: France
country: Germany
country: Japan
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Churg-Strauss Syndrome
mesh term: Prednisolone