<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/NCT04483167</url>
  </required_header>
  <id_info>
    <org_study_id>38RC19.051</org_study_id>
    <nct_id>NCT04483167</nct_id>
  </id_info>
  <brief_title>Clinical Transfer of a Vulnerable Atherosclerotic Plaque Tracer : 99mTc-cAbVCAM1-5 (ATHENA)</brief_title>
  <acronym>ATHENA</acronym>
  <official_title>Phase I Study, Prospective, Monocentric, Uncontrolled, Non-randomized, Open, Interventional. First Human Administration of an Inflammation Tracer (99mTc-cAbVCAM1-5) Using the Scintigraphy in Healthy Volunteers and Asymptomatic Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Grenoble</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinical Transfer of a Tracer of the Vulnerable Atheroma Plate: 99mTc-cAbVCAM1-5. (ATHENA).&#xD;
&#xD;
      This is a phase I/IIa, prospective, monocentric, non-controlled, non-randomized, open-label,&#xD;
      interventional study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cardiovascular disease (CVD) is the leading cause of death worldwide with more than 17.6&#xD;
      million deaths. Of these 17.6 millions deaths, 15 millions (85.1%) are attributable to&#xD;
      coronary heart disease and cerebrovascular disease, and in both cases the main etiology is&#xD;
      atherosclerosis.&#xD;
&#xD;
      In the coronary arteries, while the presence of a stenosing atherosclerotic plate can be&#xD;
      detected by the coronary angiography technique that allows visualization of the lumen of the&#xD;
      vessels, the same cannot be said of a plate that is vulnerable to eccentric remodeling.&#xD;
      Indeed, this plate has little or no effect on the lumen of the artery. As a result, it is&#xD;
      undetectable on coronary angiography. These vulnerable coronary atheromatous plaques are&#xD;
      characterized by intense inflammatory phenomena leading to the formation of a large lipidic&#xD;
      and necrotic heart covered by a thin fibrous capsule. They are prone to rupture, with the&#xD;
      immediate consequence of the formation of a thrombus that can cause ischemia and necrosis of&#xD;
      the downstream myocardial territory. In practice, 68% of myocardial infarctions are caused by&#xD;
      the rupture of vulnerable plaques resulting in stenosis of less than 50% of the vascular&#xD;
      lumen. In addition, in two-thirds of cases the infarction is the inaugural clinical event of&#xD;
      coronary artery disease.&#xD;
&#xD;
      Currently, there are no validated non-invasive techniques for diagnosing vulnerable atheroma&#xD;
      plate. In this context, the Laboratory Radiopharmaceutiques Biocliniques (LRB, UMR_S1039),&#xD;
      has selected Vascular Cell Adhesion Molecule 1 (VCAM-1) as a potential target for molecular&#xD;
      imaging of vulnerable plate. Indeed, in the arterial tree, its expression is restricted to&#xD;
      atheromatous plates presenting an inflammatory phenotype which is considered a major&#xD;
      vulnerability criterion. A radiopharmaceutical targeting VCAM-1 (99mTccAbVCAM1-5) has&#xD;
      therefore been developed and validated in preclinical studies.&#xD;
&#xD;
      The final objective of this project is to evaluate in clinical practice the potential of this&#xD;
      new imaging agent for the non invasive diagnosis of the vulnerable atheroma plates.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 15, 2020</start_date>
  <completion_date type="Anticipated">May 2023</completion_date>
  <primary_completion_date type="Anticipated">May 2023</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>7 healthy volunteers (1+3+3) and 6 asymptomatic patients</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by all adverse event according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.</measure>
    <time_frame>70 days after IP injection +/- 10 days</time_frame>
    <description>All Adverse events reported according to according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients.</time_frame>
    <description>Total Cholesterol (g/L)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients.</time_frame>
    <description>Liver enzymes (ASAT - ALAT - GGT)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients.</time_frame>
    <description>Total bilirubin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by Electrocardiogram.</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group</time_frame>
    <description>ECG (P Wave, QRS Complex, QT Interval)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group</time_frame>
    <description>Blood preasure (mmHg)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group</time_frame>
    <description>Heart rate (beats/min)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of biodistribution in all subjects included in the study (healthy volunteers + patients)</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients.</time_frame>
    <description>Radioactive activity (MBq) measured in urine, blood and stool + full body images</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosimetry evaluation of 99mTc-cAbVCAM1-5 in healthy volunteers and patients.</measure>
    <time_frame>24 hours for healthy volonteers, 6 hours for patients.</time_frame>
    <description>Dosimetry mesured in healthy subjects and patients in the different organs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the feasibility of the technique using 99mTccAbVCAM1-5 as a tracer for the vulnerable atheroma plate.</measure>
    <time_frame>3 hours after injection</time_frame>
    <description>Verification of the concordance between the expression of VCAM-1 in imaging and on operative part of carotid endarterectomy in patients. Comparison between the intensity of the 99mTc-cAbVCAM1-5 signal observed at the level of the carotids and the level of expression of VCAM-1 determined on an operative endarterectomy part of the carotid concerned, by immunohistochemistry and / or ELISA assay.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <condition>Atherosclerosis</condition>
  <arm_group>
    <arm_group_label>99mTccAbVCAM1-5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy volunteers and asymptomatic patients&#xD;
Pré-screening of the volunteers by the CIC or the Vascular Surgeon and sending or handing over the newsletter&#xD;
Visit 0 Selection: Validation of IC / NIC + Consent collection + additional exams&#xD;
Visit 1 Inclusion: J0 Scintigraphic imaging following injection 99mTc-cAbVCAM1-5 (370 MBq - 550 MBq - 750 MBq depend of the SAE or AE )&#xD;
Visit 2: Follow-up visit (Day 14 +/- 7 days post injection)&#xD;
Visit 3: End of the study, follow-up visit (70 days +/- 10 days post injection)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>99mTccAbVCAM1-5 injection</intervention_name>
    <description>intravenous injection of 99mTccAbVCAM1-5 with dose increase</description>
    <arm_group_label>99mTccAbVCAM1-5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy volunteers:&#xD;
&#xD;
          -  Ages 18-55&#xD;
&#xD;
          -  No nuclear imaging or CT scans in the year prior to inclusion&#xD;
&#xD;
          -  A person not exposed to ionizing radiation according to the labour code.&#xD;
&#xD;
        Patients:&#xD;
&#xD;
          -  Ages between 18 and 80&#xD;
&#xD;
          -  Atherosclerosis with asymptomatic carotid atheroma plate.&#xD;
&#xD;
          -  Indication of carotid endarterectomy.&#xD;
&#xD;
        All:&#xD;
&#xD;
          -  Person affiliated with or benefiting from social security&#xD;
&#xD;
          -  Person who has given written informed consent&#xD;
&#xD;
        Non inclusion Criteria:&#xD;
&#xD;
          -  Woman of childbearing potential in the absence of highly effective contraception or&#xD;
             man of childbearing potential without mechanical contraception.&#xD;
&#xD;
          -  Medical history that significantly interferes with biodistribution&#xD;
&#xD;
          -  History of disease which may impair the absorption, diffusion and excretion of the&#xD;
             radiopharmaceutical: Crohn's disease, celiac disease.&#xD;
&#xD;
          -  Known allergy to one of the constituents of the product.&#xD;
&#xD;
          -  Intoxication with alcohol or drugs on purpose&#xD;
&#xD;
          -  Grade 3 haematological toxicity for the following parameters : Hemoglobin, platelets,&#xD;
             leukocytes and neutrophil polynuclear cells.&#xD;
&#xD;
          -  Grade 2 renal toxicity for the following parameters: Urea and creatinine and/or&#xD;
             Glomerular filtration rate according to the CPK-EPI formula &lt; 60mL/min/1.73m².&#xD;
&#xD;
          -  Grade 2 liver toxicity for the following parameters : AST, ALT, GGT, PAL and&#xD;
             bilirubin.&#xD;
&#xD;
          -  Grade 2 pancreatic toxicity for the following parameter: lipase.&#xD;
&#xD;
          -  Blood or urine pregnancy test (confirmed in blood) inconclusive or positive for women&#xD;
             of childbearing potential.&#xD;
&#xD;
          -  Participation in other research involving the type 1 or 2 human being at the same time&#xD;
&#xD;
          -  Person in a period of exclusion from other research involving the human person&#xD;
&#xD;
          -  Living conditions suggesting an inability to follow all the visits provided for in the&#xD;
             protocol.&#xD;
&#xD;
          -  Subject who would receive more than 4,500 euros in compensation as a result of&#xD;
             participation in other research involving the human person in the 12 months preceding&#xD;
             this study.&#xD;
&#xD;
          -  Subject not contactable in case of emergency&#xD;
&#xD;
          -  Protected person (Sections L1121-5 to L1121-8 of the CSP)&#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>Nicolas DE LEIRIS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Grenoble Alpes University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Grenoble Alpes University Hospital</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1151-1210. doi: 10.1016/S0140-6736(17)32152-9. Erratum In: Lancet. 2017 Oct 28;390(10106):e38.</citation>
    <PMID>28919116</PMID>
  </reference>
  <reference>
    <citation>Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988 Nov;78(5 Pt 1):1157-66. doi: 10.1161/01.cir.78.5.1157.</citation>
    <PMID>3180375</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>March 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>May 22, 2023</last_update_submitted>
  <last_update_submitted_qc>May 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>99mTc-cAbVCAM1-5</keyword>
  <keyword>intravenous injection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04483167
org study id: 38RC19.051
nct id: NCT04483167
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Clinical Transfer of a Tracer of the Vulnerable Atheroma Plate: 99mTc-cAbVCAM1-5. (ATHENA).

      This is a phase I/IIa, prospective, monocentric, non-controlled, non-randomized, open-label,
      interventional study.
Cardiovascular disease (CVD) is the leading cause of death worldwide with more than 17.6
      million deaths. Of these 17.6 millions deaths, 15 millions (85.1%) are attributable to
      coronary heart disease and cerebrovascular disease, and in both cases the main etiology is
      atherosclerosis.

      In the coronary arteries, while the presence of a stenosing atherosclerotic plate can be
      detected by the coronary angiography technique that allows visualization of the lumen of the
      vessels, the same cannot be said of a plate that is vulnerable to eccentric remodeling.
      Indeed, this plate has little or no effect on the lumen of the artery. As a result, it is
      undetectable on coronary angiography. These vulnerable coronary atheromatous plaques are
      characterized by intense inflammatory phenomena leading to the formation of a large lipidic
      and necrotic heart covered by a thin fibrous capsule. They are prone to rupture, with the
      immediate consequence of the formation of a thrombus that can cause ischemia and necrosis of
      the downstream myocardial territory. In practice, 68% of myocardial infarctions are caused by
      the rupture of vulnerable plaques resulting in stenosis of less than 50% of the vascular
      lumen. In addition, in two-thirds of cases the infarction is the inaugural clinical event of
      coronary artery disease.

      Currently, there are no validated non-invasive techniques for diagnosing vulnerable atheroma
      plate. In this context, the Laboratory Radiopharmaceutiques Biocliniques (LRB, UMR_S1039),
      has selected Vascular Cell Adhesion Molecule 1 (VCAM-1) as a potential target for molecular
      imaging of vulnerable plate. Indeed, in the arterial tree, its expression is restricted to
      atheromatous plates presenting an inflammatory phenotype which is considered a major
      vulnerability criterion. A radiopharmaceutical targeting VCAM-1 (99mTccAbVCAM1-5) has
      therefore been developed and validated in preclinical studies.

      The final objective of this project is to evaluate in clinical practice the potential of this
      new imaging agent for the non invasive diagnosis of the vulnerable atheroma plates.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: 7 healthy volunteers (1+3+3) and 6 asymptomatic patients
primary purpose: Diagnostic
masking: None (Open Label)
measure: Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by all adverse event according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.
time frame: 70 days after IP injection +/- 10 days
description: All Adverse events reported according to according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.
measure: Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
time frame: 24 hours for healthy volonteers, 6 hours for patients.
description: Total Cholesterol (g/L)
measure: Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
time frame: 24 hours for healthy volonteers, 6 hours for patients.
description: Liver enzymes (ASAT - ALAT - GGT)
measure: Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
time frame: 24 hours for healthy volonteers, 6 hours for patients.
description: Total bilirubin
measure: Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by Electrocardiogram.
time frame: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
description: ECG (P Wave, QRS Complex, QT Interval)
measure: Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
time frame: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
description: Blood preasure (mmHg)
measure: Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
time frame: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
description: Heart rate (beats/min)
measure: Assessment of biodistribution in all subjects included in the study (healthy volunteers + patients)
time frame: 24 hours for healthy volonteers, 6 hours for patients.
description: Radioactive activity (MBq) measured in urine, blood and stool + full body images
measure: Dosimetry evaluation of 99mTc-cAbVCAM1-5 in healthy volunteers and patients.
time frame: 24 hours for healthy volonteers, 6 hours for patients.
description: Dosimetry mesured in healthy subjects and patients in the different organs
measure: Evaluation of the feasibility of the technique using 99mTccAbVCAM1-5 as a tracer for the vulnerable atheroma plate.
time frame: 3 hours after injection
description: Verification of the concordance between the expression of VCAM-1 in imaging and on operative part of carotid endarterectomy in patients. Comparison between the intensity of the 99mTc-cAbVCAM1-5 signal observed at the level of the carotids and the level of expression of VCAM-1 determined on an operative endarterectomy part of the carotid concerned, by immunohistochemistry and / or ELISA assay.
arm group label: 99mTccAbVCAM1-5
arm group type: Experimental
description: Healthy volunteers and asymptomatic patients
Pré-screening of the volunteers by the CIC or the Vascular Surgeon and sending or handing over the newsletter
Visit 0 Selection: Validation of IC / NIC + Consent collection + additional exams
Visit 1 Inclusion: J0 Scintigraphic imaging following injection 99mTc-cAbVCAM1-5 (370 MBq - 550 MBq - 750 MBq depend of the SAE or AE )
Visit 2: Follow-up visit (Day 14 +/- 7 days post injection)
Visit 3: End of the study, follow-up visit (70 days +/- 10 days post injection)
intervention type: Drug
intervention name: 99mTccAbVCAM1-5 injection
description: intravenous injection of 99mTccAbVCAM1-5 with dose increase
arm group label: 99mTccAbVCAM1-5
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Nicolas DE LEIRIS
role: Principal Investigator
affiliation: Grenoble Alpes University Hospital
facility: 
country: France
citation: GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1151-1210. doi: 10.1016/S0140-6736(17)32152-9. Erratum In: Lancet. 2017 Oct 28;390(10106):e38.
PMID: 28919116
citation: Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988 Nov;78(5 Pt 1):1157-66. doi: 10.1161/01.cir.78.5.1157.
PMID: 3180375
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Atherosclerosis
sharing ipd: No