<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/NCT03830320</url>
  </required_header>
  <id_info>
    <org_study_id>2015P002385</org_study_id>
    <nct_id>NCT03830320</nct_id>
  </id_info>
  <brief_title>Positron Emission Tomography (PET) Imaging of Thrombosis</brief_title>
  <official_title>Preliminary Evaluation of [64Cu]FBP8 in Healthy Individuals and Subjects With Known or at Risk of Developing Thrombosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate a new radiotracer called 64Cu-FBP8 for PET-MR imaging&#xD;
      of thrombosis. The tracer has the potential of detecting thrombosis anywhere in the body, for&#xD;
      instance in the left atrial appendage of patients with atrial fibrillation, and thereby may&#xD;
      provide a non-invasive alternative to the current standard-of-care methods.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objectives of this study are:&#xD;
&#xD;
        1. To evaluate the safety of [64Cu]FBP8 and its whole body distribution, metabolism,&#xD;
           pharmacokinetics, and radiation burden in healthy volunteers.&#xD;
&#xD;
        2. To establish the accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in&#xD;
           patients with atrial fibrillation.&#xD;
&#xD;
        3. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with&#xD;
           COVID-19.&#xD;
&#xD;
        4. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with&#xD;
           cancer.&#xD;
&#xD;
        5. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with&#xD;
           known or suspicion of thrombus outside of the left atrial appendage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2016</start_date>
  <completion_date type="Anticipated">January 30, 2026</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2025</primary_completion_date>
  <phase>Phase 1</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>Complete blood count</measure>
    <time_frame>36 hours</time_frame>
    <description>To model pharmacokinetics of [64Cu]FBP8 metabolism in healthy volunteers.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Target to Background Ratio LAA</measure>
    <time_frame>4 hours</time_frame>
    <description>To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in patients with atrial fibrillation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Target to Background Ratio</measure>
    <time_frame>4 hours</time_frame>
    <description>To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect thrombosis in patients with known thrombus or suspicion of thrombus.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time activity curve</measure>
    <time_frame>48 hours</time_frame>
    <description>To evaluate human dosimetry and radiation burden in healthy volunteers.</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">240</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>COVID-19</condition>
  <condition>Cancer</condition>
  <condition>Thrombosis</condition>
  <arm_group>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Twenty (20) healthy adult subjects will be injected with [64Cu]FBP8 to establish the safety, whole body distribution, metabolism, pharmacokinetics, and radiation burden of the probe. All subjects will be imaged using PET/MR. Healthy subjects will undergo blood collection before, during, and after the scan. Healthy subjects will also undergo electrocardiogram before and after the scan. An interim review of the data will be conducted after the first six subjects receive the study agent and complete all safety assessments.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atrial Fibrillation Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thirty-five (35) patients with LAA thrombus documented by TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus with MR-PET. The TEE studies in these patients will be part of their routine clinical care. Thirty-five (35) patients with atrial fibrillation and negative TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus. Forty (40) patients with atrial fibrillation who are scheduled for TEE in the upcoming 14 days will be injected with [64Cu]FBP8 and imaged for LAA thrombus.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COVID-19 Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thirty (30) COVID-19 patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cancer Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thirty (30) cancer patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Other Thrombotic Condition Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fifty (50) patients with other thrombotic conditions will be injected with [64Cu]FBP8 and imaged for thrombi in the body.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[64Cu]FBP8</intervention_name>
    <description>Injection of Copper-64 radiopeptide to detect thrombosis</description>
    <arm_group_label>Atrial Fibrillation Patients</arm_group_label>
    <arm_group_label>COVID-19 Patients</arm_group_label>
    <arm_group_label>Cancer Patients</arm_group_label>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_label>Other Thrombotic Condition Patients</arm_group_label>
    <other_name>64Cu-FBP8</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PET/MR</intervention_name>
    <description>Whole body imaging using Siemens mMR PET/MR scanner</description>
    <arm_group_label>Atrial Fibrillation Patients</arm_group_label>
    <arm_group_label>COVID-19 Patients</arm_group_label>
    <arm_group_label>Cancer Patients</arm_group_label>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_label>Other Thrombotic Condition Patients</arm_group_label>
    <other_name>PET-MR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood Collection</intervention_name>
    <description>A total of 9 cc of blood sampled before, during, and after imaging for clinical chemistry</description>
    <arm_group_label>Healthy Volunteers</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Electrocardiogram</intervention_name>
    <description>A standard 12-lead ECG will be obtained pre-and-post injection with radiotracer</description>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <other_name>ECG</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For Atrial Fibrillation Patient subjects:&#xD;
&#xD;
          -  History of atrial fibrillation or paroxysmal atrial fibrillation;&#xD;
&#xD;
          -  Retrospective enrollment: TEE to evaluate LAA within the last 14 days, provided the&#xD;
             anticoagulation regimen the patient is on is not changed after the TEE. If a patient&#xD;
             has a negative TEE and continues the same stable anti-coagulation regimen he/she is&#xD;
             on, then it is extremely unlikely that a new thrombus will develop in the left atrial&#xD;
             appendage within the next two weeks. Likewise, if a patient not taking any&#xD;
             anti-coagulation has a thrombus in the left atrial appendage, then it is extremely&#xD;
             unlikely that this thrombus will resolve spontaneously in the next 14 days if the&#xD;
             patient continues not to take any anticoagulation. If the TEE leads to a change being&#xD;
             made in the anticoagulation regimen (started/stopped/dose modified), then a time&#xD;
             window of 72 hours from the TEE to PET imaging will be used. This scheme will ensure&#xD;
             that the TEE can serve as an accurate gold standard;&#xD;
&#xD;
          -  Prospective enrollment: TEE to evaluate LAA scheduled in upcoming 14 days;&#xD;
&#xD;
        For COVID-19 Patient subjects:&#xD;
&#xD;
          -  Positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper or lower&#xD;
             respiratory tract analyzed by a certified lab with an FDA approved assay within the&#xD;
             last month;&#xD;
&#xD;
          -  Patient not requiring mechanical ventilation;&#xD;
&#xD;
        For Cancer Patient subjects:&#xD;
&#xD;
        • Patient is diagnosed with cancer;&#xD;
&#xD;
        For Other Patient subjects:&#xD;
&#xD;
          -  Ultrasound- or CT-confirmed or high likelihood of thrombus (e.g., elevated D-dimer)&#xD;
&#xD;
          -  Has not received thrombolytics&#xD;
&#xD;
        Exclusion criteria: A subject will not be eligible for inclusion in this study if any of&#xD;
        the following criteria apply:&#xD;
&#xD;
          -  Subjects less than 18 years of age;&#xD;
&#xD;
          -  Electrical implants such as cardiac pacemaker or perfusion pump;&#xD;
&#xD;
          -  Pregnant or breastfeeding (a negative STAT quantitative serum hCG pregnancy test is&#xD;
             required for females having child-bearing potential before the subject can&#xD;
             participate);&#xD;
&#xD;
          -  Claustrophobic reactions;&#xD;
&#xD;
          -  Subjects will be excluded if research-related radiation exposure exceeds current&#xD;
             Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);&#xD;
&#xD;
          -  Unable to lie comfortably on a bed inside the PET scanner;&#xD;
&#xD;
          -  Subjects under direct or indirect (i.e. same department as PIs) supervision of the&#xD;
             principal investigator;&#xD;
&#xD;
          -  Body weight over the weight limit for the moving table (&gt; 300 lbs for the MRI table&#xD;
             and &gt;441 lbs for the CT table);&#xD;
&#xD;
          -  Metallic or electric implants contraindicated for MR-PET scanning when applicable;&#xD;
&#xD;
          -  Does not have the ability to give written informed consent.&#xD;
&#xD;
          -  Determined by the investigator(s) to be clinically unsuitable for the study (e.g.&#xD;
             based on screening visit and/or during study procedures);&#xD;
&#xD;
        Additional exclusion criteria for Atrial Fibrillation Patient subjects:&#xD;
&#xD;
          -  Stroke within the last 3 months;&#xD;
&#xD;
          -  Myocardial infarction within the last 3 months;&#xD;
&#xD;
          -  Cardiac or major surgery within the last 3 months;&#xD;
&#xD;
          -  History of chest pain within the last 6 weeks unless followed by a subsequent stress&#xD;
             test or coronary angiography;&#xD;
&#xD;
          -  History of syncope within the last 6 weeks;&#xD;
&#xD;
          -  Heart rate persistently &gt;120 bpm or persistently &lt; 50 bpm;&#xD;
&#xD;
          -  Presence of daytime pauses &gt; 3s&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ciprian Catana, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David E Sosnovik, MD</last_name>
    <phone>617-724-3407</phone>
    <email>sosnovik@nmr.mgh.harvard.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anne L Philip, MPH</last_name>
    <phone>617-726-0431</phone>
    <email>alphilip@mgh.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David E Sosnovik, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>December 20, 2022</last_update_submitted>
  <last_update_submitted_qc>December 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Peter Caravan</investigator_full_name>
    <investigator_title>Professor of Radiology</investigator_title>
  </responsible_party>
  <keyword>PET-MRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Thrombosis</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/NCT03830320
org study id: 2015P002385
nct id: NCT03830320
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
The purpose of the study is to evaluate a new radiotracer called 64Cu-FBP8 for PET-MR imaging
      of thrombosis. The tracer has the potential of detecting thrombosis anywhere in the body, for
      instance in the left atrial appendage of patients with atrial fibrillation, and thereby may
      provide a non-invasive alternative to the current standard-of-care methods.
The primary objectives of this study are:

        1. To evaluate the safety of [64Cu]FBP8 and its whole body distribution, metabolism,
           pharmacokinetics, and radiation burden in healthy volunteers.

        2. To establish the accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in
           patients with atrial fibrillation.

        3. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with
           COVID-19.

        4. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with
           cancer.

        5. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with
           known or suspicion of thrombus outside of the left atrial appendage.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Complete blood count
time frame: 36 hours
description: To model pharmacokinetics of [64Cu]FBP8 metabolism in healthy volunteers.
measure: Target to Background Ratio LAA
time frame: 4 hours
description: To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in patients with atrial fibrillation.
measure: Target to Background Ratio
time frame: 4 hours
description: To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect thrombosis in patients with known thrombus or suspicion of thrombus.
measure: Time activity curve
time frame: 48 hours
description: To evaluate human dosimetry and radiation burden in healthy volunteers.
arm group label: Healthy Volunteers
arm group type: Active Comparator
description: Twenty (20) healthy adult subjects will be injected with [64Cu]FBP8 to establish the safety, whole body distribution, metabolism, pharmacokinetics, and radiation burden of the probe. All subjects will be imaged using PET/MR. Healthy subjects will undergo blood collection before, during, and after the scan. Healthy subjects will also undergo electrocardiogram before and after the scan. An interim review of the data will be conducted after the first six subjects receive the study agent and complete all safety assessments.
arm group label: Atrial Fibrillation Patients
arm group type: Experimental
description: Thirty-five (35) patients with LAA thrombus documented by TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus with MR-PET. The TEE studies in these patients will be part of their routine clinical care. Thirty-five (35) patients with atrial fibrillation and negative TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus. Forty (40) patients with atrial fibrillation who are scheduled for TEE in the upcoming 14 days will be injected with [64Cu]FBP8 and imaged for LAA thrombus.
arm group label: COVID-19 Patients
arm group type: Experimental
description: Thirty (30) COVID-19 patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.
arm group label: Cancer Patients
arm group type: Experimental
description: Thirty (30) cancer patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.
arm group label: Other Thrombotic Condition Patients
arm group type: Experimental
description: Fifty (50) patients with other thrombotic conditions will be injected with [64Cu]FBP8 and imaged for thrombi in the body.
intervention type: Drug
intervention name: [64Cu]FBP8
description: Injection of Copper-64 radiopeptide to detect thrombosis
arm group label: Atrial Fibrillation Patients
arm group label: COVID-19 Patients
arm group label: Cancer Patients
arm group label: Healthy Volunteers
arm group label: Other Thrombotic Condition Patients
other name: 64Cu-FBP8
intervention type: Device
intervention name: PET/MR
description: Whole body imaging using Siemens mMR PET/MR scanner
arm group label: Atrial Fibrillation Patients
arm group label: COVID-19 Patients
arm group label: Cancer Patients
arm group label: Healthy Volunteers
arm group label: Other Thrombotic Condition Patients
other name: PET-MR
intervention type: Procedure
intervention name: Blood Collection
description: A total of 9 cc of blood sampled before, during, and after imaging for clinical chemistry
arm group label: Healthy Volunteers
intervention type: Procedure
intervention name: Electrocardiogram
description: A standard 12-lead ECG will be obtained pre-and-post injection with radiotracer
arm group label: Healthy Volunteers
other name: ECG
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ciprian Catana, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: David E Sosnovik, MD
phone: 617-724-3407
email: sosnovik@nmr.mgh.harvard.edu
last name: Anne L Philip, MPH
phone: 617-726-0431
email: alphilip@mgh.harvard.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Peter Caravan
investigator title: Professor of Radiology
mesh term: Atrial Fibrillation
mesh term: Thrombosis