<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/NCT02976467</url>
  </required_header>
  <id_info>
    <org_study_id>16673</org_study_id>
    <secondary_id>2016-002167-33</secondary_id>
    <nct_id>NCT02976467</nct_id>
  </id_info>
  <brief_title>A Double-blind Study to Investigate Efficacy, Safety and Tolerability of BAY 1142524 in Patients After Acute Myocardial Infarction With Left-ventricular Dysfunction</brief_title>
  <acronym>CHIARA MIA 2</acronym>
  <official_title>A Randomized, Double-blind, Multicenter Study to Assess the Safety and Efficacy of a 6 Month Oral Treatment With the Chymase Inhibitor BAY 1142524 at a Dose of 25 mg BID in Comparison to Placebo on Top of Standard of Care in Patients With Reduced Left-ventricular Ejection Fraction (LVEF≤ 45%) After Acute Myocardial Infarction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the trial is the analysis of safety and efficacy of the chymase inhibitor&#xD;
      BAY1142524 at a dose of 25 mg BID in comparison to placebo using a 6 months treatment period&#xD;
      in patients with left-ventricular (LV) dysfunction after myocardial infarction (MI).&#xD;
      BAY1142524 or placebo will be given on top of evidence-based standard of care for&#xD;
      left-ventricular dysfunction after myocardial infarction. Primary objective is the analysis&#xD;
      of first signs of efficacy as determined by favourable changes in functional parameters of&#xD;
      adverse cardiac remodelling (i.e. endsystolic and enddiastolic volume index, ejection&#xD;
      fraction). Secondary objective is the analysis of safety and tolerability as evidenced by the&#xD;
      incidence and severity of adverse events. 30 patients have to complete treatment with verum&#xD;
      and 30 patients have to complete treatment with placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 30, 2016</start_date>
  <completion_date type="Actual">September 4, 2018</completion_date>
  <primary_completion_date type="Actual">July 31, 2018</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in left-ventricular ejection fraction (LVEF)</measure>
    <time_frame>At 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in end diastolic volume index (EDVI)</measure>
    <time_frame>At 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in end systolic volume index (ESVI)</measure>
    <time_frame>At 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 7 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with serious adverse events</measure>
    <time_frame>Up to 7 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Fulacimstat (BAY1142524)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 patients with left-ventricular dysfunction after acute myocardial infarction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>30 patients with left-ventricular dysfunction after acute myocardial infarction</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fulacimstat (BAY1142524)</intervention_name>
    <description>25 mg BAY 1142524 are given twice daily over a treatment period of 6 months</description>
    <arm_group_label>Fulacimstat (BAY1142524)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo tablets are given twice daily over a treatment period of 6 months</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with first ST elevation myocardial infarction (STEMI) treated with primary&#xD;
             percutaneous intervention (PCI) or thrombolysis within 24 hours after symptom onset&#xD;
&#xD;
          -  Diagnosis of STEMI requires the presence of the following three criteria:&#xD;
&#xD;
               -  Typical clinical symptoms such as chest pain, shortness of breath for more than&#xD;
                  20 minutes related to the myocardial infarction&#xD;
&#xD;
               -  New ST elevation indicating myocardial infarction&#xD;
&#xD;
               -  Significant elevation in troponin T or I with at least one value above the 99th&#xD;
                  percentile upper reference limit (URL) and/or elevation creatine kinase (CK) and&#xD;
                  creatine kinase MB (6-10% of total CK)&#xD;
&#xD;
          -  At the screening period, on day 5 to 9 after MI, patients have to have a LVEF ≤ 45%&#xD;
             and an infarct size &gt;10% LV mass (as measured by LGE-MRI, central-blinded evaluation)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to perform contrast-enhanced cardiac MRI&#xD;
&#xD;
          -  LVEF &lt; 20%&#xD;
&#xD;
          -  History of heart failure or LVEF &lt; 50% before occurrence of the first STEMI&#xD;
&#xD;
          -  Infarct size &gt; 45% (g/g; LV mass) between 5 and 9 days after myocardial infarction&#xD;
&#xD;
          -  NYHA (New York Heart Association) class IV at randomization&#xD;
&#xD;
          -  Any planned cardiac intervention after baseline MRI or any other planned operations&#xD;
&#xD;
          -  Non-ischemic causes for cardiomyopathy&#xD;
&#xD;
          -  Diagnosis of atrial fibrillation&#xD;
&#xD;
          -  Systolic blood pressure &lt; 100 mm Hg or &gt; 180 mm Hg; diastolic blood pressure &lt; 50 mm&#xD;
             Hg or &gt;110 mm Hg, heart rate &lt; 50 or &gt;100 beat/minute; mean of triplicate values at&#xD;
             randomization&#xD;
&#xD;
          -  Clinically relevant hepatic dysfunction&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bayer Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Bayer</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Kladno</city>
        <zip>27259</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 10</city>
        <zip>100 34</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 4</city>
        <zip>140 21</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 5</city>
        <zip>150 06</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 5</city>
        <zip>150 30</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dortmund</city>
        <state>Nordrhein-Westfalen</state>
        <zip>44137</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Erfurt</city>
        <state>Thüringen</state>
        <zip>99089</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Beer Sheva</city>
        <zip>8410101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jerusalem</city>
        <zip>9103102</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Petah Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bergamo</city>
        <state>Lombardia</state>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Brescia</city>
        <state>Lombardia</state>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Monza-Brianza</city>
        <state>Lombardia</state>
        <zip>20090</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Babio - Beade</city>
        <state>Pontevedra</state>
        <zip>36312</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>November 24, 2016</study_first_submitted>
  <study_first_submitted_qc>November 24, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>August 30, 2019</last_update_submitted>
  <last_update_submitted_qc>August 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fulacimstat</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/NCT02976467
org study id: 16673
secondary id: 2016-002167-33
nct id: NCT02976467
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of the trial is the analysis of safety and efficacy of the chymase inhibitor
      BAY1142524 at a dose of 25 mg BID in comparison to placebo using a 6 months treatment period
      in patients with left-ventricular (LV) dysfunction after myocardial infarction (MI).
      BAY1142524 or placebo will be given on top of evidence-based standard of care for
      left-ventricular dysfunction after myocardial infarction. Primary objective is the analysis
      of first signs of efficacy as determined by favourable changes in functional parameters of
      adverse cardiac remodelling (i.e. endsystolic and enddiastolic volume index, ejection
      fraction). Secondary objective is the analysis of safety and tolerability as evidenced by the
      incidence and severity of adverse events. 30 patients have to complete treatment with verum
      and 30 patients have to complete treatment with placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in left-ventricular ejection fraction (LVEF)
time frame: At 6 months
measure: Change in end diastolic volume index (EDVI)
time frame: At 6 months
measure: Change in end systolic volume index (ESVI)
time frame: At 6 months
measure: Number of patients with adverse events
time frame: Up to 7 months
measure: Number of patients with serious adverse events
time frame: Up to 7 months
arm group label: Fulacimstat (BAY1142524)
arm group type: Experimental
description: 30 patients with left-ventricular dysfunction after acute myocardial infarction
arm group label: Placebo
arm group type: Placebo Comparator
description: 30 patients with left-ventricular dysfunction after acute myocardial infarction
intervention type: Drug
intervention name: Fulacimstat (BAY1142524)
description: 25 mg BAY 1142524 are given twice daily over a treatment period of 6 months
arm group label: Fulacimstat (BAY1142524)
intervention type: Drug
intervention name: Placebo
description: Matching placebo tablets are given twice daily over a treatment period of 6 months
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 79 Years
healthy volunteers: No
last name: Bayer Study Director
role: Study Director
affiliation: Bayer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Czechia
country: Germany
country: Israel
country: Italy
country: Spain
country: Czech Republic
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: Infarction
mesh term: Fulacimstat