<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/NCT02243228</url>
  </required_header>
  <id_info>
    <org_study_id>XT 01</org_study_id>
    <nct_id>NCT02243228</nct_id>
  </id_info>
  <brief_title>Inhalation of Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Autoimmune Pulmonary Alveolar Proteinosis (PAP)</brief_title>
  <official_title>A Prospective Study of Inhaling Granulocyte-macrophage Colony Stimulating Factor in Adult Patients With Mild-to-moderate Autoimmune Pulmonary Alveolar Proteinosis in China: a Randomized Open-label Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate if inhaled granulocyte-macrophage colony stimulating&#xD;
      factor delay the increase in alveolar-arterial oxygen difference, compared to no treatment,&#xD;
      for adult patients with mild-to-moderate autoimmune pulmonary alveolar proteinosis in China&#xD;
      over a two-year period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autoimmune pulmonary alveolar proteinosis (PAP, previously known as idiopathic PAP) is a rare&#xD;
      interstitial lung disease elicited by the formation of autoantibodies which neutralize the&#xD;
      activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) which decreases&#xD;
      macrophage clearance of surfactant.&#xD;
&#xD;
      Currently, the standard treatment strategy for PAP is whole lung lavage (WLL)，which is&#xD;
      invasive and has limitations. Inhaled GM-CSF therapy became a new option for PAP patients not&#xD;
      only because of its effectiveness and safety, but it is convenient way for patients who are&#xD;
      reluctant to do operation as well. We are planning to prospectively evaluate if inhaled&#xD;
      granulocyte-macrophage colony stimulating factor would delay the increase in&#xD;
      alveolar-arterial oxygen difference (A-aDO2, which is the most sensitive factor in evaluating&#xD;
      APAP5), compared to placebo, for patients with mild-to-moderate autoimmune pulmonary alveolar&#xD;
      over a two-year period.&#xD;
&#xD;
      A total of 42 subjects with APAP who meet the inclusion criteria will be enrolled at Peking&#xD;
      Union Medical College Hospital and Nanjing Drum Tower Hospital. After observe APAP patients&#xD;
      for 3 months to rule out patients who resolved spontaneously, the participants will undergo&#xD;
      randomization (by random number table)and stratified into two different groups by their DSS.&#xD;
      Then they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week or no&#xD;
      treatment for 6 months, and will be followed on an outpatient basis at 2 weeks, and 1, 3, 6,&#xD;
      9, 12, 15, 18, 21 and 24 months after initiation of therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">August 2017</completion_date>
  <primary_completion_date type="Anticipated">August 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A-aDO2 difference</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to relapse</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The definition of relapse were as follow: 1) newly requirement for whole lung lavage (WLL); or 2) PAP associated death; or 3) a reduction in PaO2 of more than 10mmHg, or an increase in DA-aO2 of more than 10mmHg; or 4) a worsen chest HRCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FEV1 difference</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 minutes walking distance difference</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe adverse event</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Autoimmune Pulmonary Alveolar Proteinosis</condition>
  <arm_group>
    <arm_group_label>GM-CSF, nebulizer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After the patients were randomly divided into two groups, they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GM-CSF</intervention_name>
    <arm_group_label>GM-CSF, nebulizer</arm_group_label>
    <other_name>HUABEI JIMUXIN</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Accessible population:&#xD;
&#xD;
        Adult patients with mild-to-moderate autoimmune pulmonary alveolar and without spontaneous&#xD;
        remission will be enrolled at Peking Union Medical College Hospital and Nanjing Drum Tower&#xD;
        Hospital.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult autoimmune PAP subjects will be included: 1) a positive PAS stain from BALF or&#xD;
             lung biopsy; 2) high level of serum anti-GM-CSF antibody (&gt;2.39ug/ml, the cut-off&#xD;
             point in our hospital); 3) age above 18 years old; 4) exclude hereditary and secondary&#xD;
             PAP.&#xD;
&#xD;
          -  Able to give written informed consent and comply with the requirements of the study.&#xD;
&#xD;
          -  Patients are not eligible for the whole lung lavage (WLL), decided by clinicians.&#xD;
&#xD;
          -  Eligibility for GM-CSF inhalation: 1) Disease severity score (DSS) is 1-3; 2) No&#xD;
             treatment with GM-CSF therapy or WLLin the 3 months prior to enrollment. Definition of&#xD;
             DSS2: 1, no symptom and PaO2&gt;=70mmHg；2, PaO2&gt;=70mmHg with symptoms；3, PaO2&gt;=60 and&#xD;
             &lt;70mmHg; 4, PaO2&gt;=50 and &lt;60mmHg; 5, PaO2&lt;50mmHg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients will be observed for 3 months and all APAP patients who resolved&#xD;
             spontaneously will be excluded from our study.&#xD;
&#xD;
          -  PAP resulting from another condition (e.g. occupational exposure to silica, underlying&#xD;
             HIV, respiratory infections, myeloproliferative disorder or leukaemia);&#xD;
&#xD;
          -  A normal or low-titre serum anti-GM-CSF antibody (≤2.39ug/ml);&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal&#xD;
             antibodies；&#xD;
&#xD;
          -  Chronic lung disease associated with already existing respiratory failure (such as&#xD;
             pulmonary emphysema or fibrosis);&#xD;
&#xD;
          -  Other serious medical conditions which, in the opinion of the investigator, would make&#xD;
             the patient unsuitable for the study.&#xD;
&#xD;
          -  Pregnancy.&#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>Kai-Feng Xu, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hosptial</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kai-Feng Xu, M.D.</last_name>
    <phone>10-69155039</phone>
    <phone_ext>86</phone_ext>
    <email>kaifeng.xu@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xin-Lun Tian, M.D.</last_name>
    <phone>10-69155039</phone>
    <phone_ext>86</phone_ext>
    <email>xinlun_t@sina.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kai-Feng Xu, M.D.</last_name>
      <phone>10-69155039</phone>
      <phone_ext>86</phone_ext>
      <email>kaifeng.xu@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Xin-Lun Tian, M.D.</last_name>
      <phone>10-69155039</phone>
      <phone_ext>86</phone_ext>
      <email>xinlun_t@sina.com</email>
    </contact_backup>
    <investigator>
      <last_name>Xin-Lun Tian, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>September 16, 2014</last_update_submitted>
  <last_update_submitted_qc>September 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 17, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
    <investigator_full_name>Kaifeng Xu</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>granulocyte-macrophage colony stimulating factor(GM-CSF)</keyword>
  <keyword>Autoimmune pulmonary alveolar proteinosis (PAP)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Alveolar Proteinosis</mesh_term>
    <mesh_term>Autoimmune Diseases</mesh_term>
  </condition_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/NCT02243228
org study id: XT 01
nct id: NCT02243228
lead sponsor: 
collaborator: 
has dmc: No
The purpose of the study is to evaluate if inhaled granulocyte-macrophage colony stimulating
      factor delay the increase in alveolar-arterial oxygen difference, compared to no treatment,
      for adult patients with mild-to-moderate autoimmune pulmonary alveolar proteinosis in China
      over a two-year period.
Autoimmune pulmonary alveolar proteinosis (PAP, previously known as idiopathic PAP) is a rare
      interstitial lung disease elicited by the formation of autoantibodies which neutralize the
      activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) which decreases
      macrophage clearance of surfactant.

      Currently, the standard treatment strategy for PAP is whole lung lavage (WLL)，which is
      invasive and has limitations. Inhaled GM-CSF therapy became a new option for PAP patients not
      only because of its effectiveness and safety, but it is convenient way for patients who are
      reluctant to do operation as well. We are planning to prospectively evaluate if inhaled
      granulocyte-macrophage colony stimulating factor would delay the increase in
      alveolar-arterial oxygen difference (A-aDO2, which is the most sensitive factor in evaluating
      APAP5), compared to placebo, for patients with mild-to-moderate autoimmune pulmonary alveolar
      over a two-year period.

      A total of 42 subjects with APAP who meet the inclusion criteria will be enrolled at Peking
      Union Medical College Hospital and Nanjing Drum Tower Hospital. After observe APAP patients
      for 3 months to rule out patients who resolved spontaneously, the participants will undergo
      randomization (by random number table)and stratified into two different groups by their DSS.
      Then they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week or no
      treatment for 6 months, and will be followed on an outpatient basis at 2 weeks, and 1, 3, 6,
      9, 12, 15, 18, 21 and 24 months after initiation of therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: A-aDO2 difference
time frame: 2 years
measure: Time to relapse
time frame: up to 2 years
description: The definition of relapse were as follow: 1) newly requirement for whole lung lavage (WLL); or 2) PAP associated death; or 3) a reduction in PaO2 of more than 10mmHg, or an increase in DA-aO2 of more than 10mmHg; or 4) a worsen chest HRCT.
measure: FEV1 difference
time frame: 2 years
measure: 6 minutes walking distance difference
time frame: 2 years
measure: Severe adverse event
time frame: 2 years
arm group label: GM-CSF, nebulizer
arm group type: Experimental
description: After the patients were randomly divided into two groups, they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week for 6 months.
intervention type: Drug
intervention name: GM-CSF
arm group label: GM-CSF, nebulizer
other name: HUABEI JIMUXIN
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kai-Feng Xu, M.D.
role: Principal Investigator
affiliation: Peking Union Medical College Hosptial
last name: Kai-Feng Xu, M.D.
phone: 10-69155039
phone ext: 86
email: kaifeng.xu@gmail.com
last name: Xin-Lun Tian, M.D.
phone: 10-69155039
phone ext: 86
email: xinlun_t@sina.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking Union Medical College Hospital
investigator full name: Kaifeng Xu
investigator title: MD
mesh term: Pulmonary Alveolar Proteinosis
mesh term: Autoimmune Diseases