<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/NCT03771040</url>
  </required_header>
  <id_info>
    <org_study_id>AB14001</org_study_id>
    <nct_id>NCT03771040</nct_id>
  </id_info>
  <brief_title>Masitinib in the Treatment of Patients With Severe Uncontrolled Asthma and Elevated Eosinophil Levels</brief_title>
  <official_title>A Prospective, Multicenter, Randomised, Double-blind, Placebo-controlled, Phase 3 Study to Compare the Efficacy and the Safety of Masitinib Versus Placebo in the Treatment of Patients With Severe Uncontrolled Asthma and Elevated Eosinophil Levels</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AB Science</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AB Science</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety and efficacy of masitinib (6 mg/kg/day) in&#xD;
      severe persistent asthma, uncontrolled with high dose of inhaled corticosteroid and with&#xD;
      elevated eosinophil levels.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Masitinib is a selective tyrosine kinase inhibitor. It is known that activation of&#xD;
      inflammatory cells, such as mast cells, and fibrous tissue remodeling are associated with&#xD;
      c-Kit, Lyn and PDGFR kinase signaling pathways; all key targets of masitinib. This is a&#xD;
      multicenter, double-blind, randomized, parallel-group (ascending dose titration of masitinib&#xD;
      to 6.0 mg/kg/day and matching placebo), comparative study of oral masitinib in the treatment&#xD;
      of patients with severe asthma, uncontrolled with high dose of inhaled corticosteroid and&#xD;
      with elevated eosinophil levels. Eligible patients will be treated during at least 48 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">September 2020</completion_date>
  <primary_completion_date type="Actual">September 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Severe asthma exacerbation rate</measure>
    <time_frame>Duration of patient treatment exposure, assessed until withdrawal from study, study completion date, or for a maximum of 60 months</time_frame>
    <description>The number of severe asthma exacerbations over time frame of outcome measure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Asthma exacerbation rate</measure>
    <time_frame>Duration of patient treatment exposure, assessed until withdrawal from study, study completion date, or for a maximum of 60 months</time_frame>
    <description>The number of asthma exacerbations over time frame of outcome measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asthma Control Questionnaire (ACQ)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Asthma Control Questionnaire (ACQ)&#xD;
Type of questionnaire-description: A simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment.&#xD;
Number of items: 7 items; 1 week recall (for items on symptoms and rescue inhaler use)&#xD;
Number of domains &amp; categories: ACQ has a multidimensional construct assessing symptoms (5 items--self-administred) and rescue inbronchodilator use (1 item-self-administered), and FEV1% (1 item) completed by clinic staff&#xD;
Scaling of items: 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7 categories for FEV1%). Scores range between 0 (totally controlled) and 6 (severely uncontrolled).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">347</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Masitinib (titration to 6.0 mg/kg/day)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive matched placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Masitinib</intervention_name>
    <arm_group_label>Masitinib (titration to 6.0 mg/kg/day)</arm_group_label>
    <other_name>AB1010</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo Oral Tablet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main inclusion criteria include:&#xD;
&#xD;
          -  Patients with a physician diagnosis of persistent asthma for at least 12 months based&#xD;
             on Global Initiative for Asthma (GINA) 2009 Guidelines whose asthma is partially&#xD;
             controlled or uncontrolled on inhaled corticosteroids (ICS) / long-acting&#xD;
             beta2-agonists (LABA) combination therapy.&#xD;
&#xD;
          -  Patient with elevated eosinophil level related to asthma at baseline: ≥0.15 K/uL or&#xD;
             patient with eosinophil level ≥0.15 K/uL related to asthma demonstrated in the year&#xD;
             prior to screening&#xD;
&#xD;
          -  Non-smoker patient for at least one year and with a prior tobacco consumption &lt;10&#xD;
             packs/year&#xD;
&#xD;
        Main exclusion criteria include:&#xD;
&#xD;
          -  Female patient who is pregnant or lactating&#xD;
&#xD;
          -  Asthmatic patient still exposed to allergens or to triggering factors influencing&#xD;
             asthma control&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease and/or other lung diseases impairing Pulmonary&#xD;
             Function Tests&#xD;
&#xD;
          -  Within 12 weeks prior to screening, patient who received oral corticosteroids for any&#xD;
             other reason than to treat severe asthma exacerbation (patients needing long term&#xD;
             corticosteroids intake to control basal asthma condition)&#xD;
&#xD;
          -  Patient with history of acute infectious sinusitis or respiratory tract infection&#xD;
             within 4 weeks prior to screening visit&#xD;
&#xD;
          -  Patient with active lung disease other than asthma (e.g. chronic bronchitis)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lavinia Davidescu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Medicine and Pharmacy Oradea, Oradea, Romania.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centro Respiratorio Quilmes</name>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarawak General Hospital</name>
      <address>
        <city>Kuching</city>
        <zip>93586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Universidad de los Andes</name>
      <address>
        <city>Miraflores</city>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Philippine Heart Center</name>
      <address>
        <city>Quezon City</city>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine</name>
      <address>
        <city>Kiev</city>
        <zip>03680</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Malaysia</country>
    <country>Peru</country>
    <country>Philippines</country>
    <country>Ukraine</country>
  </location_countries>
  <removed_countries>
    <country>Hungary</country>
  </removed_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <disposition_first_submitted>December 7, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>December 7, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">December 8, 2020</disposition_first_posted>
  <last_update_submitted>December 7, 2020</last_update_submitted>
  <last_update_submitted_qc>December 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Severe persistent asthma</keyword>
  <keyword>Eosinophil</keyword>
  <keyword>Tyrosine kinase inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03771040
org study id: AB14001
nct id: NCT03771040
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to assess the safety and efficacy of masitinib (6 mg/kg/day) in
      severe persistent asthma, uncontrolled with high dose of inhaled corticosteroid and with
      elevated eosinophil levels.
Masitinib is a selective tyrosine kinase inhibitor. It is known that activation of
      inflammatory cells, such as mast cells, and fibrous tissue remodeling are associated with
      c-Kit, Lyn and PDGFR kinase signaling pathways; all key targets of masitinib. This is a
      multicenter, double-blind, randomized, parallel-group (ascending dose titration of masitinib
      to 6.0 mg/kg/day and matching placebo), comparative study of oral masitinib in the treatment
      of patients with severe asthma, uncontrolled with high dose of inhaled corticosteroid and
      with elevated eosinophil levels. Eligible patients will be treated during at least 48 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Severe asthma exacerbation rate
time frame: Duration of patient treatment exposure, assessed until withdrawal from study, study completion date, or for a maximum of 60 months
description: The number of severe asthma exacerbations over time frame of outcome measure
measure: Asthma exacerbation rate
time frame: Duration of patient treatment exposure, assessed until withdrawal from study, study completion date, or for a maximum of 60 months
description: The number of asthma exacerbations over time frame of outcome measure
measure: Asthma Control Questionnaire (ACQ)
time frame: 48 weeks
description: Asthma Control Questionnaire (ACQ)
Type of questionnaire-description: A simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment.
Number of items: 7 items; 1 week recall (for items on symptoms and rescue inhaler use)
Number of domains & categories: ACQ has a multidimensional construct assessing symptoms (5 items--self-administred) and rescue inbronchodilator use (1 item-self-administered), and FEV1% (1 item) completed by clinic staff
Scaling of items: 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7 categories for FEV1%). Scores range between 0 (totally controlled) and 6 (severely uncontrolled).
arm group label: Masitinib (titration to 6.0 mg/kg/day)
arm group type: Experimental
description: Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants receive matched placebo
intervention type: Drug
intervention name: Masitinib
arm group label: Masitinib (titration to 6.0 mg/kg/day)
other name: AB1010
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
other name: Placebo Oral Tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Lavinia Davidescu, MD, PhD
role: Principal Investigator
affiliation: University of Medicine and Pharmacy Oradea, Oradea, Romania.
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
country: Malaysia
country: Peru
country: Philippines
country: Ukraine
country: Hungary
responsible party type: Sponsor
mesh term: Asthma
sharing ipd: No