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/NCT06032026</url>
    </required_header>
    <id_info>
      <org_study_id>853636</org_study_id>
      <nct_id>NCT06032026</nct_id>
    </id_info>
    <brief_title>Phase I Pilot Study of 11C-HY-2-15</brief_title>
    <official_title>Center Without Walls for Imaging Proteinopathies With PET (CW2IP2): Phase I Pilot Study of Biodistribution, Metabolism, Excretion and Brain Uptake of 11C-HY-2-15</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Pennsylvania</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Pennsylvania</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 current protocol is to determine the biodistribution, metabolism, excretion and brain&#xD;
        uptake of 11C HY-2-15. The goal of this radiotracer is to quantify alpha-synuclein that is&#xD;
        abnormally deposited in the brain of people with Multiple System Atrophy (MSA). The&#xD;
        investigators will compare uptake in people with MSA with people with Parkinson disease (PD)&#xD;
        and progressive supranuclear palsy (PSP) as well as healthy volunteers. This multicenter&#xD;
        project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert&#xD;
        Mach) in collaboration with U Pittsburgh (Pitt) (not a clinical site), Yale U, U of&#xD;
        California at San Francisco (UCSF) and Washington University in St. Louis (WU). The&#xD;
        University of Pennsylvania will act as the sIRB for this multi-center human subjects project&#xD;
        and participants will be recruited from all sites.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The current protocol is to determine the biodistribution, metabolism, excretion and brain&#xD;
        uptake of 11C HY-2-15. The goal of this radiotracer is to quantify alpha-synuclein that is&#xD;
        abnormally deposited in the brain of people with Multiple System Atrophy (MSA). The&#xD;
        investigators will compare uptake in people with MSA with people with Parkinson disease (PD)&#xD;
        and progressive supranuclear palsy (PSP) as well as healthy volunteers. This multicenter&#xD;
        project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert&#xD;
        Mach) in collaboration with U Pittsburgh (Pitt) (not a clinical site), Yale U, U of&#xD;
        California at San Francisco (UCSF) and Washington University in St. Louis (WU). The&#xD;
        University of Pennsylvania will act as the sIRB for this multi-center human subjects project&#xD;
        and participants will be recruited from all sites.&#xD;
  &#xD;
        At all participating clinical sites will recruit 20 people with PD, 20 with MSA, 10 with PSP&#xD;
        and 20 healthy controls across sites with all participants ranging from 40-85 years old. The&#xD;
        investigators will encourage equal participation of males and females.&#xD;
  &#xD;
        This protocol will include up to 70 participants across all clinical sites (note that at&#xD;
        least 10 of these participant scans from Penn may be used to calculate whole body&#xD;
        biodistribution (BioD) and dosimetry). The investigators anticipate enrollment of up to 20-25&#xD;
        participants at each clinical site, who will undergo approximately 120 minutes of dynamic&#xD;
        brain PET scanning (with or without torso imaging, depending on the clinical site). A second&#xD;
        IV or an arterial line may be placed in the arm contralateral to the side of injection for&#xD;
        blood metabolite analysis and/or radioactive counts at various times during the scanning&#xD;
        session. These blood draw collections can be omitted at the discretion of the investigator.&#xD;
        For participants at Penn that may be part of BioD analysis urine may be collected at the end&#xD;
        of the scan session. Participants will also undergo a research brain MRI that may or may not&#xD;
        be on a separate day from the PET.&#xD;
  &#xD;
        PET imaging sessions will include an injection of ≤ 20 mCi (approximate range for most&#xD;
        studies is anticipated to be 8 - 20 mCi at sites with a standard PET scanner or 3 - 20 at&#xD;
        sites with a high sensitivity scanner) of 11C HY-2-15. Biodistribution, metabolism, excretion&#xD;
        and pilot brain uptake data will be collected and human dosimetry will be calculated from&#xD;
        participants scanned at Penn who have whole body scans. PET scans will be collected to&#xD;
        evaluate image quality and collect preliminary information on brain uptake of 11C HY-2-15 in&#xD;
        the disease cohorts and healthy controls. The safety of 11C HY-2-15 will also be evaluated in&#xD;
        all participants.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">July 20, 2023</start_date>
    <completion_date type="Anticipated">July 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2028</primary_completion_date>
    <phase>Early 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>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Organ biodistribution</measure>
      <time_frame>4 weeks</time_frame>
      <description>Determine biodistribution of the radioactive investigational drug, 11C HY-2-15</description>
    </primary_outcome>
    <primary_outcome>
      <measure>PET uptake of tracer</measure>
      <time_frame>4 weeks</time_frame>
      <description>Determine whether there is selective uptake of 11C HY-2-15 in people with MSA compared to healthy volunteers, PD and PSP participants</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>4 weeks</time_frame>
      <description>adverse events will be collected</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">70</enrollment>
    <condition>Tauopathies</condition>
    <arm_group>
      <arm_group_label>11C-HY-2-15 PET</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will undergo 11C-HY-2-15 PET scan, they may also have a brain MRI and Amyloid PET scan as well as neurological assessments</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>11C-HY-2-15 PET</intervention_name>
      <description>2 hour Positron Emission Tomography (PET) scan using new radiotracer 11C-HY-2-15</description>
      <arm_group_label>11C-HY-2-15 PET</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>brain MRI</intervention_name>
      <description>brain MRI scan</description>
      <arm_group_label>11C-HY-2-15 PET</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Amyloid PET scan</intervention_name>
      <description>PET scan with Florbetaben F18 or 11C-PiB</description>
      <arm_group_label>11C-HY-2-15 PET</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Neurological assessments</intervention_name>
      <description>Neurological assessments, including video interview</description>
      <arm_group_label>11C-HY-2-15 PET</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  The entire cohort will include men and women clinically diagnosed with MSA, PD, PSP or&#xD;
               are healthy controls. A sub-set of these participants who undergo whole body scanning&#xD;
               that will be used for analysis of biodistribution and dosimetry calculations.&#xD;
  &#xD;
            -  Patients in all cohorts will be male or female adults from 40 to 80 years of age.&#xD;
  &#xD;
            -  Participants must be informed of the investigational nature of this study and be&#xD;
               willing to provide written informed consent and participate in this study in&#xD;
               accordance with institutional and federal guidelines prior to study-specific&#xD;
               procedures or Participants who are deemed unable to provide informed consent must have&#xD;
               a designated study partner present for consent and to accompany them to study visits&#xD;
  &#xD;
            -  We will ask PD/MSA/PSP participants to agree to brain donation but this choice is not&#xD;
               mandatory for participation in this study.&#xD;
  &#xD;
            -  Diagnosis-specific inclusion criteria: Clinical diagnoses will be determined by&#xD;
               consensus committee for diagnostic agreement (PD, MSA, PSP or Healthy Control)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Females who are pregnant or breast feeding will be excluded, a urine pregnancy test&#xD;
               will be performed in women of child-bearing potential prior to injection of 11C&#xD;
               HY-2-15, 11C-PiB or Florbetaben&#xD;
  &#xD;
            -  Forms of parkinsonism other than PD, PSP and MSA as defined above&#xD;
  &#xD;
            -  Major psychiatric disorder (e.g. schizophrenia or bipolar disorder) - major depressive&#xD;
               disorder is allowed&#xD;
  &#xD;
            -  History of significant or ongoing alcohol abuse or substance abuse or dependence based&#xD;
               on medical record review or self-reported&#xD;
  &#xD;
            -  Contraindications or inability to tolerate imaging, arterial line or IV placement or&#xD;
               blood draw procedures in the opinion of an investigator or treating physician&#xD;
  &#xD;
            -  Contraindication to MRI, such as non-compatible implanted medical device&#xD;
  &#xD;
            -  History of any prior positive ß-amyloid PET scan or positive CSF AD biomarkers.&#xD;
  &#xD;
            -  Any current medical condition, illness, or disorder as assessed by medical record&#xD;
               review and/or self-reported that is considered by a physician or investigator to be a&#xD;
               condition that could compromise participant safety or successful participation in the&#xD;
               study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>University of Pennsylvania</name>
        <address>
          <city>Philadelphia</city>
          <state>Pennsylvania</state>
          <zip>19104</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Alpha synuclein</keyword>
    <keyword>Positron Emission Tomography (PET)</keyword>
    <keyword>brain MRI</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tauopathies</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>early safety assessments including whole body dosimetry studies at Penn; coordinate patient selection criteria, centrally collect and serve all imaging and demographic data, coordinate tracer kinetic methods development and validation for human imaging, and coordinate all data to efficiently enable GO-NOGO decisions for candidate radiotracers. As a final check on diagnosis and specificity of candidate radiotracers, we will request all patient participants to permit postmortem brain donation for autoradiography of relevant radiotracers on fresh frozen brain tissues. Additionally, this Core will interact with multiple ongoing studies with cohorts studying PD, MSA, PSP and FTD. Finally, a robust data sharing plan facilitates collaboration and use of support documents and imaging data.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>Data shared as participants are enrolled and then final clinical report after study is completed</ipd_time_frame>
      <ipd_access_criteria>Dosimetry data. Dosimetry data for all compounds advanced to first-in-human trials will be provided on the website link for the Clinical Core. Since it is the intent of this U19 Center to provide information to the PET community on probes that have been validated in clinical research studies, these data will be provided once the CCOC has confirmed that a probe has met the validation criteria. This will include the results of dosimetry studies (organ, whole body, and EDE data) and, as requested, the organ radioactivity uptake, clearance curves and the dosimetry images in DICOM format.&#xD;
  Imaging and Clinical Data. Links from the CCOC website will connect to XNAT and MARS to provide all de-identified clinical data, imaging data and related files including arterial blood sampling measurements. These data will be distributed upon request, as noted in the above policies for Data Sharing.</ipd_access_criteria>
    </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/NCT06032026
  org study id: 853636
  nct id: NCT06032026
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The current protocol is to determine the biodistribution, metabolism, excretion and brain
        uptake of 11C HY-2-15. The goal of this radiotracer is to quantify alpha-synuclein that is
        abnormally deposited in the brain of people with Multiple System Atrophy (MSA). The
        investigators will compare uptake in people with MSA with people with Parkinson disease (PD)
        and progressive supranuclear palsy (PSP) as well as healthy volunteers. This multicenter
        project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert
        Mach) in collaboration with U Pittsburgh (Pitt) (not a clinical site), Yale U, U of
        California at San Francisco (UCSF) and Washington University in St. Louis (WU). The
        University of Pennsylvania will act as the sIRB for this multi-center human subjects project
        and participants will be recruited from all sites.
  The current protocol is to determine the biodistribution, metabolism, excretion and brain
        uptake of 11C HY-2-15. The goal of this radiotracer is to quantify alpha-synuclein that is
        abnormally deposited in the brain of people with Multiple System Atrophy (MSA). The
        investigators will compare uptake in people with MSA with people with Parkinson disease (PD)
        and progressive supranuclear palsy (PSP) as well as healthy volunteers. This multicenter
        project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert
        Mach) in collaboration with U Pittsburgh (Pitt) (not a clinical site), Yale U, U of
        California at San Francisco (UCSF) and Washington University in St. Louis (WU). The
        University of Pennsylvania will act as the sIRB for this multi-center human subjects project
        and participants will be recruited from all sites.
  
        At all participating clinical sites will recruit 20 people with PD, 20 with MSA, 10 with PSP
        and 20 healthy controls across sites with all participants ranging from 40-85 years old. The
        investigators will encourage equal participation of males and females.
  
        This protocol will include up to 70 participants across all clinical sites (note that at
        least 10 of these participant scans from Penn may be used to calculate whole body
        biodistribution (BioD) and dosimetry). The investigators anticipate enrollment of up to 20-25
        participants at each clinical site, who will undergo approximately 120 minutes of dynamic
        brain PET scanning (with or without torso imaging, depending on the clinical site). A second
        IV or an arterial line may be placed in the arm contralateral to the side of injection for
        blood metabolite analysis and/or radioactive counts at various times during the scanning
        session. These blood draw collections can be omitted at the discretion of the investigator.
        For participants at Penn that may be part of BioD analysis urine may be collected at the end
        of the scan session. Participants will also undergo a research brain MRI that may or may not
        be on a separate day from the PET.
  
        PET imaging sessions will include an injection of ≤ 20 mCi (approximate range for most
        studies is anticipated to be 8 - 20 mCi at sites with a standard PET scanner or 3 - 20 at
        sites with a high sensitivity scanner) of 11C HY-2-15. Biodistribution, metabolism, excretion
        and pilot brain uptake data will be collected and human dosimetry will be calculated from
        participants scanned at Penn who have whole body scans. PET scans will be collected to
        evaluate image quality and collect preliminary information on brain uptake of 11C HY-2-15 in
        the disease cohorts and healthy controls. The safety of 11C HY-2-15 will also be evaluated in
        all participants.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Organ biodistribution
  time frame: 4 weeks
  description: Determine biodistribution of the radioactive investigational drug, 11C HY-2-15
  measure: PET uptake of tracer
  time frame: 4 weeks
  description: Determine whether there is selective uptake of 11C HY-2-15 in people with MSA compared to healthy volunteers, PD and PSP participants
  measure: Adverse events
  time frame: 4 weeks
  description: adverse events will be collected
  arm group label: 11C-HY-2-15 PET
  arm group type: Experimental
  description: Participants will undergo 11C-HY-2-15 PET scan, they may also have a brain MRI and Amyloid PET scan as well as neurological assessments
  intervention type: Drug
  intervention name: 11C-HY-2-15 PET
  description: 2 hour Positron Emission Tomography (PET) scan using new radiotracer 11C-HY-2-15
  arm group label: 11C-HY-2-15 PET
  intervention type: Diagnostic Test
  intervention name: brain MRI
  description: brain MRI scan
  arm group label: 11C-HY-2-15 PET
  intervention type: Diagnostic Test
  intervention name: Amyloid PET scan
  description: PET scan with Florbetaben F18 or 11C-PiB
  arm group label: 11C-HY-2-15 PET
  intervention type: Behavioral
  intervention name: Neurological assessments
  description: Neurological assessments, including video interview
  arm group label: 11C-HY-2-15 PET
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 80 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Tauopathies
  sharing ipd: Yes
  ipd description: early safety assessments including whole body dosimetry studies at Penn; coordinate patient selection criteria, centrally collect and serve all imaging and demographic data, coordinate tracer kinetic methods development and validation for human imaging, and coordinate all data to efficiently enable GO-NOGO decisions for candidate radiotracers. As a final check on diagnosis and specificity of candidate radiotracers, we will request all patient participants to permit postmortem brain donation for autoradiography of relevant radiotracers on fresh frozen brain tissues. Additionally, this Core will interact with multiple ongoing studies with cohorts studying PD, MSA, PSP and FTD. Finally, a robust data sharing plan facilitates collaboration and use of support documents and imaging data.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: Data shared as participants are enrolled and then final clinical report after study is completed
  ipd access criteria: Dosimetry data. Dosimetry data for all compounds advanced to first-in-human trials will be provided on the website link for the Clinical Core. Since it is the intent of this U19 Center to provide information to the PET community on probes that have been validated in clinical research studies, these data will be provided once the CCOC has confirmed that a probe has met the validation criteria. This will include the results of dosimetry studies (organ, whole body, and EDE data) and, as requested, the organ radioactivity uptake, clearance curves and the dosimetry images in DICOM format.
  Imaging and Clinical Data. Links from the CCOC website will connect to XNAT and MARS to provide all de-identified clinical data, imaging data and related files including arterial blood sampling measurements. These data will be distributed upon request, as noted in the above policies for Data Sharing.