<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/NCT02216279</url>
  </required_header>
  <id_info>
    <org_study_id>PulmoBind II safety Trial</org_study_id>
    <nct_id>NCT02216279</nct_id>
  </id_info>
  <brief_title>Phase-II Study of the Use of PulmoBind for Molecular Imaging of Pulmonary Hypertension</brief_title>
  <acronym>PB-02</acronym>
  <official_title>Phase-II Study of the Use of PulmoBind for Molecular Imaging of Pulmonary Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Montreal Heart Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Montreal Heart Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pulmonary hypertension or elevation of the pressure in the pulmonary vessels, results from&#xD;
      various clinical conditions. It may be idiopathic (of unknown cause) or associated with&#xD;
      numerous diseases including cardiovascular and lung disorders. Affected individuals suffer&#xD;
      from progressive shortness of breath and, in its most sever forms; pulmonary hypertension&#xD;
      carries a worse prognosis than many types of cancer. There is no test currently that can&#xD;
      easily and non-invasively detect abnormalities of the pulmonary circulation. Presently there&#xD;
      is no cure for pulmonary hypertension and substantial research efforts are dedicated to the&#xD;
      development of new drugs that will stop progression or better yet, reverse the disease&#xD;
      process. The investigators do not know if any of the drugs currently commercialized for&#xD;
      pulmonary hypertension directly improve the status of the pulmonary vessels since no test&#xD;
      currently provides this information. Direct earlier detection of lung vessel abnormalities&#xD;
      associated with pulmonary hypertension using a sensitive and non-invasive test would allow&#xD;
      not only earlier testing of these and of new drugs, but would provide a much better surrogate&#xD;
      of disease severity allowing more efficient pre-clinical drug testing. The aim of this phase&#xD;
      II study is to evaluate the safety of PulmoBind in participants with pulmonary hypertension&#xD;
      and its potential to detect abnormal pulmonary circulation associated within pulmonary&#xD;
      hypertension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently there is only one radiopharmaceutical agent approved in Canada (and the world) for&#xD;
      clinical imaging of the pulmonary circulation, metastable isotope 99 of technetium. This&#xD;
      agent is exclusively used for the diagnosis of physical defects of the circulation due to&#xD;
      pulmonary embolus. There is imperative need for new lung tracers that will provide a greater&#xD;
      safety profile while enabling functional as well as anatomical imaging of the pulmonary&#xD;
      circulation. A novel adrenomedullin derivative has been developed, for molecular imaging of&#xD;
      the pulmonary circulation. PulmoBind is labelled with metastable isotope 99 of technetium,&#xD;
      the most commonly used imaging isotope in clinical nuclear medicine. PulmoBind is a&#xD;
      adrenomedullin derivative specifically designed to bind to the adrenomedullin receptor while&#xD;
      avoiding any hemodynamic effects. This novel tracer has the potential to help in the&#xD;
      diagnosis and follow-up of various disorders of the pulmonary circulation for which there is&#xD;
      currently no alternative. In PulmoBind I three escalating doses were administered and safety&#xD;
      was assessed. The product was well tolerated and there were no safety concerns. Imaging&#xD;
      revealed predominant lung uptake.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine the absence of allergic reaction after repeated exposures to PulmoBind in healthy participants</measure>
    <time_frame>Static lung uptake 10 minutes duration post injection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the safety of PulmoBind in participants diagnosed with pulmonary hypertension.</measure>
    <time_frame>Static lung uptake 10 minutes duration post injection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the capacity of PulmoBind lung scan for the detection of abnormal pulmonary circulation associated with pulmonary hypertension.</measure>
    <time_frame>Status lung uptake 10 minutes duration post injection</time_frame>
    <description>This is an efficacy outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine the intra-subject variability for quantification of PulmoBind lung uptake in control participants</measure>
    <time_frame>Status lung uptake 10 minutes duration post injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the capacity of PulmoBind lung scan to diagnose pulmonary perfusion defects in participants with chronic thromboembolic pulmonary hypertension.</measure>
    <time_frame>Status lung uptake 10 minutes duration post injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To correlate lung PulmoBind scan results with parameters of the severity of pulmonary hypertension: 6 minutes walking distance, New York Heart Association functional class, pulmonary artery pressure measured by echo, pulmonary artery pressure measured by</measure>
    <time_frame>Status lung uptake 10 minutes duration post injection</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Pulmonary Hypertension</condition>
  <arm_group>
    <arm_group_label>Pulmonary Hypertension Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Non-Smoking Participants</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PulmoBind</intervention_name>
    <description>PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine).</description>
    <arm_group_label>Control Non-Smoking Participants</arm_group_label>
    <arm_group_label>Pulmonary Hypertension Patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        HEALTHY VOLUNTEERS:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Male of female participants greater than 18 years of age,&#xD;
&#xD;
          -  Female participants must be post-menopausal (defined as two year after last menstrual&#xD;
             cycle) or surgically sterilized or use 1 form of contraception with a urine negative&#xD;
             pregnancy test (commercial brand: first response kit) within 2 hours of study drug&#xD;
             injection,&#xD;
&#xD;
          -  Baseline measurements must be within limits of normal or judged non-clinically&#xD;
             significant by the investigator:&#xD;
&#xD;
               -  Blood pressure systolic 90 mmHg to 140 mmHg,and diastolic 50 mmHg to 90 mmHg;&#xD;
&#xD;
               -  Heart rate: 50 to 100 beats per minute;&#xD;
&#xD;
               -  Oral temperature: less than 37.6C;&#xD;
&#xD;
               -  Respiratory rate: 12 to 20 breaths per minute;&#xD;
&#xD;
               -  Lung function testing within 6 months;&#xD;
&#xD;
               -  Electrocardiogram in the past three years;&#xD;
&#xD;
               -  Chest X-Ray in the past three years;&#xD;
&#xD;
               -  Electrocardiogram.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any known chronic or acute medical condition with or without the need for chronic&#xD;
             pharmacologic therapy or any condition that may interfere with normal biodistribution&#xD;
             of PulmoBind. This includes but is not restricted to: lung parenchymal or lung&#xD;
             vascular diseases such as chronic obstructive pulmonary disease, bronchitis, lung&#xD;
             cancer, pleural effusion, emphysema, asthma, pulmonary fibrosis, occupational lung&#xD;
             disease,pulmonary hypertension (primary or secondary), systemic hypertension,&#xD;
             diabetes, cancer, kidney disease, liver disease, heart failure or previous myocardial&#xD;
             infarction, coronary artery disease, peripheral vascular disease or inflammatory&#xD;
             disease,&#xD;
&#xD;
          -  Participants requiring chronic administration of any substance for a medical&#xD;
             condition,&#xD;
&#xD;
          -  Active smoking or history of smoking within 6 months,&#xD;
&#xD;
          -  Alcoholism or known substance abuse,&#xD;
&#xD;
          -  Psychotic,addictive or other disorder limiting the ability to provide informed consent&#xD;
             or to comply with study requirements,&#xD;
&#xD;
          -  Unable to tolerate study procedures (e.g. venipuncture, movement restrictions during&#xD;
             imaging),&#xD;
&#xD;
          -  Previous nuclear medicine study within one week (to avoid cross-contamination).&#xD;
&#xD;
        PULMONARY HYPERTENSION PARTICIPANTS:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Male of female participants greater than 18 years of age and upper age 70,&#xD;
&#xD;
          -  Female participants must be post-menopausal (defined as two year after last menstrual&#xD;
             cycle) or surgically sterilized or use 1 form of contraception with a urine negative&#xD;
             pregnancy test (commercial brand: first response kit) within 2 hours of study drug&#xD;
             injection,&#xD;
&#xD;
          -  Diagnosis of pulmonary hypertension (PH) according to the Dana Point PH classification&#xD;
             of the following types:&#xD;
&#xD;
               -  Type I: idiopathic, heritable or scleroderma spectrum of disease,&#xD;
&#xD;
               -  Type IV: unoperated chronic thromboembolic PH.&#xD;
&#xD;
          -  Participants with chronic thromboembolic pulmonary hypertension (CTEPH) must have a&#xD;
             previous positive V/Q scan and multiple chronic/organised occlusive thrombi/emboli in&#xD;
             the pulmonary arteries (main, lobar, segmental, subsegmental) on CT angiogram or&#xD;
             conventional pulmonary angiography,&#xD;
&#xD;
          -  Documented hemodynamic diagnosis of significant PH by right heart catheterization -&#xD;
             performed at any time prior to Screening showing:&#xD;
&#xD;
               -  Resting mean pulmonary arterial pressure (mPAP) &gt; 25 mmHg and&#xD;
&#xD;
               -  Resting pulmonary vascular resistance (PVR) &gt; 240 dyn/s.cm5 and&#xD;
&#xD;
               -  Resting capillary wedge pressure (PCWP) or left ventricular end diastolic&#xD;
                  pressure (LVDEP) ≤ 15 mmHg (if available),&#xD;
&#xD;
          -  New York Heart Association (NYHA) functional class II-III,&#xD;
&#xD;
          -  Six minutes walking distance test of ≥ 250 meters, and ≤ 450 meters within 6 months,&#xD;
&#xD;
          -  Echocardiogram documented in the participants medical history (including an agitated&#xD;
             saline study),&#xD;
&#xD;
          -  Computed tomography of the chest documented in the participants medical history.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with impaired renal function defined as estimated creatinine clearance ≤&#xD;
             30 ml/min (eGFR with modification of diet in renal disease (MDRD) calculator formula),&#xD;
&#xD;
          -  Significant liver impairment:&#xD;
&#xD;
               -  Aspartate alanine transferase ( ALT) and/or Aspartate transaminase (AST) ≥ 3 x&#xD;
                  upper limit of normal (ULN)&#xD;
&#xD;
               -  Bilirubin ≥ 1.5x ULN ( &gt; 35% direct bilirubin)&#xD;
&#xD;
          -  Unstable pulmonary arterial hypertension defined as recent syncope or World Health&#xD;
             Organization (WHO) functional class IV,&#xD;
&#xD;
          -  Participants with CTEPH not on anticoagulant therapy,&#xD;
&#xD;
          -  Echocardiographic restrictive lung disease (total lung capacity &lt; 70% of predicted) or&#xD;
             obstructive (FEC1/Forced Vital Capacity &lt; 70%),&#xD;
&#xD;
          -  Systemic blood pressure &lt; 90 mmHG systolic or less than 50 mmHG diastolic,&#xD;
&#xD;
          -  Patient foramen ovale with significant right to left shunting with hypoxia (room air&#xD;
             saturation &lt; 88%),&#xD;
&#xD;
          -  Active smoking within six months,&#xD;
&#xD;
          -  More than minimal pulmonary fibrosis on high resolution computed tomography of the&#xD;
             chest,&#xD;
&#xD;
          -  The subject's clinical condition is such that they are not expected to remain&#xD;
             clinically stable for the duration of the study,&#xD;
&#xD;
          -  Active coronary artery disease or stable coronary artery disease that has required an&#xD;
             intervention or any change of therapy within 6 months,&#xD;
&#xD;
          -  Alcoholism or known substance abuse,&#xD;
&#xD;
          -  Psychotic,addictive or other disorder limiting the ability to provide informed consent&#xD;
             or to comply with study requirements,&#xD;
&#xD;
          -  Participants who have participated in a clinical study involving another&#xD;
             investigational drug or devise within four weeks before screening,&#xD;
&#xD;
          -  Female participants who are pregnant or breastfeeding,&#xD;
&#xD;
          -  Previous nuclear medicine study within one week,&#xD;
&#xD;
          -  Unable to tolerate study procedures (e.g. venipuncture, movement restrictions during&#xD;
             imaging).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jocelyn Dupuis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Montreal Heart Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Montreal Heart Institute</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H1T 1C8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Mortimer B.Davis Jewish General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de Cardiologie et de Pneumologie de Quebec</name>
      <address>
        <city>Quebec city</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>June 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>September 28, 2015</last_update_submitted>
  <last_update_submitted_qc>September 28, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 30, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pulmonary</keyword>
  <keyword>Hypertension</keyword>
  <keyword>PH</keyword>
  <keyword>PulmoBind</keyword>
  <keyword>Imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>April 29, 2022</submitted>
    <returned>January 30, 2023</returned>
  </pending_results>
  <!-- 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/NCT02216279
org study id: PulmoBind II safety Trial
nct id: NCT02216279
lead sponsor: 
has dmc: Yes
Pulmonary hypertension or elevation of the pressure in the pulmonary vessels, results from
      various clinical conditions. It may be idiopathic (of unknown cause) or associated with
      numerous diseases including cardiovascular and lung disorders. Affected individuals suffer
      from progressive shortness of breath and, in its most sever forms; pulmonary hypertension
      carries a worse prognosis than many types of cancer. There is no test currently that can
      easily and non-invasively detect abnormalities of the pulmonary circulation. Presently there
      is no cure for pulmonary hypertension and substantial research efforts are dedicated to the
      development of new drugs that will stop progression or better yet, reverse the disease
      process. The investigators do not know if any of the drugs currently commercialized for
      pulmonary hypertension directly improve the status of the pulmonary vessels since no test
      currently provides this information. Direct earlier detection of lung vessel abnormalities
      associated with pulmonary hypertension using a sensitive and non-invasive test would allow
      not only earlier testing of these and of new drugs, but would provide a much better surrogate
      of disease severity allowing more efficient pre-clinical drug testing. The aim of this phase
      II study is to evaluate the safety of PulmoBind in participants with pulmonary hypertension
      and its potential to detect abnormal pulmonary circulation associated within pulmonary
      hypertension.
Currently there is only one radiopharmaceutical agent approved in Canada (and the world) for
      clinical imaging of the pulmonary circulation, metastable isotope 99 of technetium. This
      agent is exclusively used for the diagnosis of physical defects of the circulation due to
      pulmonary embolus. There is imperative need for new lung tracers that will provide a greater
      safety profile while enabling functional as well as anatomical imaging of the pulmonary
      circulation. A novel adrenomedullin derivative has been developed, for molecular imaging of
      the pulmonary circulation. PulmoBind is labelled with metastable isotope 99 of technetium,
      the most commonly used imaging isotope in clinical nuclear medicine. PulmoBind is a
      adrenomedullin derivative specifically designed to bind to the adrenomedullin receptor while
      avoiding any hemodynamic effects. This novel tracer has the potential to help in the
      diagnosis and follow-up of various disorders of the pulmonary circulation for which there is
      currently no alternative. In PulmoBind I three escalating doses were administered and safety
      was assessed. The product was well tolerated and there were no safety concerns. Imaging
      revealed predominant lung uptake.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: To determine the absence of allergic reaction after repeated exposures to PulmoBind in healthy participants
time frame: Static lung uptake 10 minutes duration post injection
measure: To determine the safety of PulmoBind in participants diagnosed with pulmonary hypertension.
time frame: Static lung uptake 10 minutes duration post injection
measure: To determine the capacity of PulmoBind lung scan for the detection of abnormal pulmonary circulation associated with pulmonary hypertension.
time frame: Status lung uptake 10 minutes duration post injection
description: This is an efficacy outcome
measure: To determine the intra-subject variability for quantification of PulmoBind lung uptake in control participants
time frame: Status lung uptake 10 minutes duration post injection
measure: Determine the capacity of PulmoBind lung scan to diagnose pulmonary perfusion defects in participants with chronic thromboembolic pulmonary hypertension.
time frame: Status lung uptake 10 minutes duration post injection
measure: To correlate lung PulmoBind scan results with parameters of the severity of pulmonary hypertension: 6 minutes walking distance, New York Heart Association functional class, pulmonary artery pressure measured by echo, pulmonary artery pressure measured by
time frame: Status lung uptake 10 minutes duration post injection
arm group label: Pulmonary Hypertension Patients
arm group type: Experimental
description: PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine).
arm group label: Control Non-Smoking Participants
arm group type: Active Comparator
description: PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine).
intervention type: Drug
intervention name: PulmoBind
description: PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine).
arm group label: Control Non-Smoking Participants
arm group label: Pulmonary Hypertension Patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jocelyn Dupuis, MD
role: Principal Investigator
affiliation: Montreal Heart Institute
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
submitted: April 29, 2022
returned: January 30, 2023