xml: <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/NCT05968846</url>
    </required_header>
    <id_info>
      <org_study_id>UTMC-AT01-163117</org_study_id>
      <nct_id>NCT05968846</nct_id>
    </id_info>
    <brief_title>Repeat PET/CT Imaging of Patients With Amyloid 124I-AT-01 to Measure Changes in Organ-specific Amyloid Load</brief_title>
    <official_title>Repeat PET/CT Imaging of Patients With Systemic Amyloidosis Using Amyloid Reactive Peptide 124I-AT-01 (124I-p5+14, Iodine-124I-evuzamitide) to Measure Changes in Organ-specific Amyloid Load</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Tennessee Graduate School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Tennessee Graduate School of Medicine</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this research study is to determine whether changes in organ-specific uptake of&#xD;
        124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate&#xD;
        with changes in a subject's disease status and thereby enable monitoring of disease response&#xD;
        over time in terms of organ-specific amyloid load.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single center, open label, prospective study using 124I-AT-01 PET/CT imaging to&#xD;
        evaluate changes in amyloid load in patients with systemic amyloidosis who had undergone&#xD;
        124I-AT-01 imaging.&#xD;
  &#xD;
        Consented eligible patients will provide 3 tablespoons of blood for the following laboratory&#xD;
        tests: CMP, CBC, CRP, Troponin, NT-proBNP, LDH, FLC and anti-drug antibody (ADA) analyses. A&#xD;
        urine sample will also be collected to assess renal function. If required, a pregnancy test&#xD;
        will be administered.&#xD;
  &#xD;
        Patients will then undergo a transthoracic echocardiographic examination and vital sign&#xD;
        assessment before receiving an intravenous injection of no more than 2 mCi 124I-AT-01&#xD;
        followed, 5 h thereafter, by repeat vital sign measurements and PET/CT imaging from crown to&#xD;
        thighs with a dynamic PET acquisition over the heart. Previously acquired 124I- AT-01 PET/CT&#xD;
        images will be used as baseline values to determine quantitative changes in uptake of the&#xD;
        radiotracer in the heart, liver, spleen, and kidney (and other organs deemed positive&#xD;
        following visual inspection of the baseline and repeat imaging) as a measure of changes in&#xD;
        amyloid load. Optionally, if the patients can return to the study site within ~30 days post&#xD;
        injection of 124I-AT-01, a second (post-injection) blood draw and ADA evaluation will be&#xD;
        performed.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">December 7, 2022</start_date>
    <completion_date type="Anticipated">June 2024</completion_date>
    <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
    <phase>Phase 2</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>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To measure visual and quantitative changes in organ-specific uptake of 124I-AT-01</measure>
      <time_frame>From enrollment to the end of the study is 8 days</time_frame>
      <description>The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load. The specific aim of this study is to measure visual and quantitative changes in organ-specific uptake of 124I-AT-01 from baseline, in patients with systemic amyloidosis, using PET/CT imaging.</description>
    </primary_outcome>
    <other_outcome>
      <measure>Measures of Interest</measure>
      <time_frame>From enrollment to the end of the study is 8 days</time_frame>
      <description>For AL, ATTR and all patients, we will correlate visual and quantitative changes in 124I- AT-01 uptake, from baseline, in the heart, liver and kidney with echocardiographic parameters (including left ventricular wall thickness (cm), intraventricular wall thickness (cm), and global logitudinal strain (%)) and serum biomarker levels (including NTproBNP, eGFR, creatinine, AST and ALT) assessed prior to imaging and from data recorded in the patients' medical record.</description>
    </other_outcome>
    <other_outcome>
      <measure>Measure of Interest</measure>
      <time_frame>From enrollment to the end of the study is 8 days</time_frame>
      <description>For AL, ATTR and all patients, we will correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in disease status (progression, response, or stable state) when this can be established from data (serum biomarkers and cardiac imaging parameters) in the patients' medical record or collected during the AMY1001 trial.</description>
    </other_outcome>
    <other_outcome>
      <measure>Measure of Interest</measure>
      <time_frame>From enrollment to the end of the study is 8 days</time_frame>
      <description>For all patients, correlate organ-specific percent change in radiotracer uptake with type of therapeutic intervention and assess qualitatively whether the patient feels that their disease is improving or worsening.</description>
    </other_outcome>
    <other_outcome>
      <measure>Measure of interest</measure>
      <time_frame>From enrollment to the end of is the study is 8 days</time_frame>
      <description>For AL patients, correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in serum free light chains over the period between imaging studies, when available in the medical record.</description>
    </other_outcome>
    <other_outcome>
      <measure>Measure of Interest</measure>
      <time_frame>From enrollment to the end of the study is 8 days</time_frame>
      <description>Compare changes, when possible, in radiotracer distribution from baseline based on analysis dynamic PET data.</description>
    </other_outcome>
    <other_outcome>
      <measure>Measure of Interest</measure>
      <time_frame>From enrollment to the end of the study is 8 days</time_frame>
      <description>Compare changes, when possible, in ejection fraction from baseline based on analysis dynamic PET data.</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Systemic Amyloidosis</condition>
    <arm_group>
      <arm_group_label>Patients will receive a single IV injection of 124I-AT-01 radiotracer and PET/CT imaging</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is an iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging. The peptide binds many forms of amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans.&#xD;
  124I-AT-01 has been evaluated previously in an open-label Phase 1/2 clinical trial, AMY1001, performed at the University of Tennessee Medical Center (IND# 132282; NCT T03678259).&#xD;
  In this repeat imaging study, patients previously enrolled in the AMY1001 study, in whom positive PET/CT imaging findings were observed will undergo repeat imaging to assess changes in radiotracer uptake in the liver, spleen, heart and kidneys.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Injection of peptide p5+14 radiolabeled with iodine-124 (124I-AT-01)</intervention_name>
      <description>124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is a a novel iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging that has been shown to bind systemic amyloid deposits of diverse types in all organs, including the heart. The peptide binds amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans.</description>
      <arm_group_label>Patients will receive a single IV injection of 124I-AT-01 radiotracer and PET/CT imaging</arm_group_label>
      <other_name>124I-p5+14</other_name>
      <other_name>iodine-124-evuzamitide</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Must have given written informed consent (signed and dated) and any authorizations&#xD;
               required by local law and be able to comply with all study requirements.&#xD;
  &#xD;
            -  Must have a diagnosis of systemic amyloidosis based on the patient's medical record.&#xD;
  &#xD;
            -  Must have undergone PET/CT imaging with 124I-AT-01 as part of the AMY1001 study (IND&#xD;
               #132282) with visually positive uptake of radiotracer in at least one abdominothoracic&#xD;
               organ.&#xD;
  &#xD;
            -  Must have been imaged with 124I-AT-01 as part of the AMY1001 study (IND #132282) more&#xD;
               than 12 months prior to repeat imaging.&#xD;
  &#xD;
            -  Females: must be non-pregnant and non-lactating and either: surgically sterile (e.g.,&#xD;
               tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy);&#xD;
               post-menopausal (defined as 12 months of spontaneous amenorrhea in females &gt; 55 years&#xD;
               of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an&#xD;
               alternative medical cause and follicle-stimulating hormone (FSH) levels in the&#xD;
               post-menopausal range for the laboratory involved).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Disabling dementia or other mental or behavioral disease.&#xD;
  &#xD;
            -  Patients on dialysis.&#xD;
  &#xD;
            -  Inability or unwillingness to comply with the study requirements.&#xD;
  &#xD;
            -  Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins)&#xD;
               for anticoagulation.&#xD;
  &#xD;
            -  Other reason that would make the subject inappropriate for entry into this study.&#xD;
  &#xD;
            -  Inability to lie still for 60 minutes on the PET/CT scanner.&#xD;
  &#xD;
            -  History of iodine (potassium iodide) allergy.&#xD;
  &#xD;
            -  Positive ADA finding defined as significantly higher than normal human serum mean&#xD;
               values AND with a mean value at least five times greater than the mean value of the&#xD;
               normal human serum control.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>University of Tennessee Graduate School of Medicine</name>
        <address>
          <city>Knoxville</city>
          <state>Tennessee</state>
          <zip>37920</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 30, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 28, 2023</last_update_submitted>
    <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>systemic amyoidosis</keyword>
    <keyword>p5+14</keyword>
    <keyword>AT-01</keyword>
    <keyword>PET/CT</keyword>
    <keyword>evuzamitide</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Amyloidosis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Iodine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05968846
  org study id: UTMC-AT01-163117
  nct id: NCT05968846
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this research study is to determine whether changes in organ-specific uptake of
        124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate
        with changes in a subject's disease status and thereby enable monitoring of disease response
        over time in terms of organ-specific amyloid load.
  This is a single center, open label, prospective study using 124I-AT-01 PET/CT imaging to
        evaluate changes in amyloid load in patients with systemic amyloidosis who had undergone
        124I-AT-01 imaging.
  
        Consented eligible patients will provide 3 tablespoons of blood for the following laboratory
        tests: CMP, CBC, CRP, Troponin, NT-proBNP, LDH, FLC and anti-drug antibody (ADA) analyses. A
        urine sample will also be collected to assess renal function. If required, a pregnancy test
        will be administered.
  
        Patients will then undergo a transthoracic echocardiographic examination and vital sign
        assessment before receiving an intravenous injection of no more than 2 mCi 124I-AT-01
        followed, 5 h thereafter, by repeat vital sign measurements and PET/CT imaging from crown to
        thighs with a dynamic PET acquisition over the heart. Previously acquired 124I- AT-01 PET/CT
        images will be used as baseline values to determine quantitative changes in uptake of the
        radiotracer in the heart, liver, spleen, and kidney (and other organs deemed positive
        following visual inspection of the baseline and repeat imaging) as a measure of changes in
        amyloid load. Optionally, if the patients can return to the study site within ~30 days post
        injection of 124I-AT-01, a second (post-injection) blood draw and ADA evaluation will be
        performed.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: To measure visual and quantitative changes in organ-specific uptake of 124I-AT-01
  time frame: From enrollment to the end of the study is 8 days
  description: The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load. The specific aim of this study is to measure visual and quantitative changes in organ-specific uptake of 124I-AT-01 from baseline, in patients with systemic amyloidosis, using PET/CT imaging.
  measure: Measures of Interest
  time frame: From enrollment to the end of the study is 8 days
  description: For AL, ATTR and all patients, we will correlate visual and quantitative changes in 124I- AT-01 uptake, from baseline, in the heart, liver and kidney with echocardiographic parameters (including left ventricular wall thickness (cm), intraventricular wall thickness (cm), and global logitudinal strain (%)) and serum biomarker levels (including NTproBNP, eGFR, creatinine, AST and ALT) assessed prior to imaging and from data recorded in the patients' medical record.
  measure: Measure of Interest
  time frame: From enrollment to the end of the study is 8 days
  description: For AL, ATTR and all patients, we will correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in disease status (progression, response, or stable state) when this can be established from data (serum biomarkers and cardiac imaging parameters) in the patients' medical record or collected during the AMY1001 trial.
  measure: Measure of Interest
  time frame: From enrollment to the end of the study is 8 days
  description: For all patients, correlate organ-specific percent change in radiotracer uptake with type of therapeutic intervention and assess qualitatively whether the patient feels that their disease is improving or worsening.
  measure: Measure of interest
  time frame: From enrollment to the end of is the study is 8 days
  description: For AL patients, correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in serum free light chains over the period between imaging studies, when available in the medical record.
  measure: Measure of Interest
  time frame: From enrollment to the end of the study is 8 days
  description: Compare changes, when possible, in radiotracer distribution from baseline based on analysis dynamic PET data.
  measure: Measure of Interest
  time frame: From enrollment to the end of the study is 8 days
  description: Compare changes, when possible, in ejection fraction from baseline based on analysis dynamic PET data.
  arm group label: Patients will receive a single IV injection of 124I-AT-01 radiotracer and PET/CT imaging
  arm group type: Experimental
  description: 124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is an iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging. The peptide binds many forms of amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans.
  124I-AT-01 has been evaluated previously in an open-label Phase 1/2 clinical trial, AMY1001, performed at the University of Tennessee Medical Center (IND# 132282; NCT T03678259).
  In this repeat imaging study, patients previously enrolled in the AMY1001 study, in whom positive PET/CT imaging findings were observed will undergo repeat imaging to assess changes in radiotracer uptake in the liver, spleen, heart and kidneys.
  intervention type: Drug
  intervention name: Injection of peptide p5+14 radiolabeled with iodine-124 (124I-AT-01)
  description: 124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is a a novel iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging that has been shown to bind systemic amyloid deposits of diverse types in all organs, including the heart. The peptide binds amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans.
  arm group label: Patients will receive a single IV injection of 124I-AT-01 radiotracer and PET/CT imaging
  other name: 124I-p5+14
  other name: iodine-124-evuzamitide
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Amyloidosis
  mesh term: Iodine
  sharing ipd: No