<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/NCT03239561</url>
  </required_header>
  <id_info>
    <org_study_id>CR108349</org_study_id>
    <secondary_id>64326067EDI0001</secondary_id>
    <nct_id>NCT03239561</nct_id>
  </id_info>
  <brief_title>Evaluation of Tau Protein in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants</brief_title>
  <official_title>Phase 0 Exploratory Study of [18F]MNI-1020 (Also Known as [18F]JNJ-64326067) as an Imaging Marker for Tau Protein in the Brain of Subjects With Alzheimer's Disease Compared to Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</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 primary objectives of this study are to characterize [18F]molecular neuroimaging&#xD;
      (MNI)-1020, a positron emission tomography (PET) radioligand for imaging tau pathology, to&#xD;
      visually and quantitatively assess and compare brain uptake and pharmacokinetics of&#xD;
      [18F]MNI-1020 in participants with probable Alzheimer's disease (AD) and compare with age&#xD;
      matched healthy participants, to evaluate the safety of a single injection of [18F]MNI-1020&#xD;
      and to compare the distribution of tau (using [18F]MNI-1020) and amyloid beta (using&#xD;
      florbetapir) in participants with probable AD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 6, 2017</start_date>
  <completion_date type="Actual">April 30, 2018</completion_date>
  <primary_completion_date type="Actual">April 30, 2018</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>Standardized Uptake Value Ratio (SUVR) of [18F]MNI-1020</measure>
    <time_frame>Up to 180 minutes after tracer injection on Day 1</time_frame>
    <description>Tracer uptake will be expressed in Standardized Uptake Value Ratio (SUVR). Regions used for tracer uptake quantitation will include cortical regions (frontal cortex, posterior cingulate, lateral temporal cortex, parietal cortex, occipital cortex, mesial temporal cortex, inferior temporal cortex, hippocampus, and anterior cingulate). Subcortical regions (basal ganglia, substantia nigra, choroid plexus) will be used for detection of possible off-target binding. Regions predicted to be free of tau pathology will be used as reference (cerebellum and pons). SUVR will be calculated as SUV target/SUV reference region (e.g., cerebellar gray).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Concentration of 18F]MNI-1020 in AD Participants Compared With age Matched Healthy Participants</measure>
    <time_frame>Pre-injection, 5, 10, 30, and 60 minutes post-injection</time_frame>
    <description>Pharmacokinetics of [18F]MNI-1020 will be assessed by using plasma concentration data and compared in participants with probable Alzheimer's disease (AD) and age matched healthy participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>Baseline up to Follow-Up (Day 4)</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Distribution of tau (Using [18F]MNI-1020) Compared to Amyloid Beta (Using Florbetapir) in Participants With Probable AD</measure>
    <time_frame>Screening for Florbetapir; Day 1 for [18F]MNI-1020</time_frame>
    <description>Within the AD participants, the distribution and binding of [18F]florbetapir will be compared to the [18F]MNI-1020 binding across multiple regions. This will be done by visual reading of scans, with amyloid signal predicted to be high in frontal cortical regions in participants with probable AD and absent from cortex in healthy participants, while tau signal is predicted to be present in hippocampus and entorhinal cortex in healthy elderly participants, and in medial and lateral temporal cortex in participants with probable AD. Semi-quantitative analysis will also be conducted comparing SUVR of the tracers in these same regions, using cerebellum as reference.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>[18F]MNI-1020</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single intravenous bolus injection of [18F]MNI-1020 at a dose of not more than 10 millicurie (mCi), with a maximum mass dose of 10 microgram (mcg) and maximum volume of 10 milliliter (mL) at imaging visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[18F]MNI-1020</intervention_name>
    <description>Participants will receive a single intravenous bolus injection of [18F]MNI-1020 at a dose of not more than 10 millicurie (mCi), with a maximum mass dose of 10 microgram (mcg) and maximum volume of 10 milliliter (mL) at imaging visit.</description>
    <arm_group_label>[18F]MNI-1020</arm_group_label>
    <other_name>[18F]JNJ-64326067</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All Participants&#xD;
&#xD;
          -  Female participants must be documented by medical records or physician's note to be&#xD;
             either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal&#xD;
             ligation) or post-menopausal for at least 1 year. Male participants and their partners&#xD;
             of childbearing potential must commit to the use of two methods of contraception, one&#xD;
             of which is a barrier method for male participants for the study duration&#xD;
&#xD;
          -  Male participants must not donate sperm during the study and for 3 months after&#xD;
             completion&#xD;
&#xD;
        Healthy Participants&#xD;
&#xD;
          -  Males and females aged greater than or equal 50 years. Healthy with no clinically&#xD;
             relevant finding on physical examination at screening and upon reporting for the&#xD;
             [18F]molecular neuroimaging (MNI)-1020 imaging visit&#xD;
&#xD;
          -  Have screening [18F]florbetapir positron emission tomography (PET) imaging&#xD;
             demonstrating no significant amyloid binding based on qualitative analysis (visual&#xD;
             read)&#xD;
&#xD;
        Alzheimer Disease - Have screening [18F]florbetapir or prior amyloid (in the last 12&#xD;
        months) PET imaging demonstrating amyloid binding based on qualitative (visual read)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All Participants&#xD;
&#xD;
          -  Prior participation in other research protocols or clinical care in the last year in&#xD;
             addition to the radiation exposure expected from participation in this clinical study,&#xD;
             such that radiation exposure exceeds the effective dose of 50 millisievert (mSv),&#xD;
             which would be above the acceptable annual limit established by the United States&#xD;
             Federal Guidelines&#xD;
&#xD;
          -  Unsuitable veins for repeated venipuncture&#xD;
&#xD;
          -  Magnetic resonance imaging exclusion criteria include: evidence of cerebrovascular&#xD;
             disease (more than two lacunar infarcts, any territorial infarct greater than 1&#xD;
             centimeter 3, or deep white matter abnormality corresponding to an overall Fazekas&#xD;
             scale of 3 with at least one confluent hyperintense lesion on the FLAIR sequence that&#xD;
             is greater than or equal to 20 millimeter (mm) in any dimension), infectious disease,&#xD;
             space-occupying lesions, normal pressure hydrocephalus or any other abnormalities&#xD;
             associated with central nervous system disease&#xD;
&#xD;
          -  Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps,&#xD;
             cochlear implants, metallic ocular foreign body, implanted neural stimulators, central&#xD;
             nervous system aneurysm clips and other medical implants that have not been certified&#xD;
             for MRI, or history of claustrophobia in Magnetic Resonance Imaging (MRI)&#xD;
&#xD;
        Alzheimer Disease&#xD;
&#xD;
        - Has received treatment that targeted amyloid beta or tau within the last 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Invicro</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>August 17, 2022</last_update_submitted>
  <last_update_submitted_qc>August 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>JNJ-64326067</mesh_term>
  </intervention_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/NCT03239561
org study id: CR108349
secondary id: 64326067EDI0001
nct id: NCT03239561
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objectives of this study are to characterize [18F]molecular neuroimaging
      (MNI)-1020, a positron emission tomography (PET) radioligand for imaging tau pathology, to
      visually and quantitatively assess and compare brain uptake and pharmacokinetics of
      [18F]MNI-1020 in participants with probable Alzheimer's disease (AD) and compare with age
      matched healthy participants, to evaluate the safety of a single injection of [18F]MNI-1020
      and to compare the distribution of tau (using [18F]MNI-1020) and amyloid beta (using
      florbetapir) in participants with probable AD.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Standardized Uptake Value Ratio (SUVR) of [18F]MNI-1020
time frame: Up to 180 minutes after tracer injection on Day 1
description: Tracer uptake will be expressed in Standardized Uptake Value Ratio (SUVR). Regions used for tracer uptake quantitation will include cortical regions (frontal cortex, posterior cingulate, lateral temporal cortex, parietal cortex, occipital cortex, mesial temporal cortex, inferior temporal cortex, hippocampus, and anterior cingulate). Subcortical regions (basal ganglia, substantia nigra, choroid plexus) will be used for detection of possible off-target binding. Regions predicted to be free of tau pathology will be used as reference (cerebellum and pons). SUVR will be calculated as SUV target/SUV reference region (e.g., cerebellar gray).
measure: Plasma Concentration of 18F]MNI-1020 in AD Participants Compared With age Matched Healthy Participants
time frame: Pre-injection, 5, 10, 30, and 60 minutes post-injection
description: Pharmacokinetics of [18F]MNI-1020 will be assessed by using plasma concentration data and compared in participants with probable Alzheimer's disease (AD) and age matched healthy participants.
measure: Number of Participants With Adverse Events
time frame: Baseline up to Follow-Up (Day 4)
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
measure: Distribution of tau (Using [18F]MNI-1020) Compared to Amyloid Beta (Using Florbetapir) in Participants With Probable AD
time frame: Screening for Florbetapir; Day 1 for [18F]MNI-1020
description: Within the AD participants, the distribution and binding of [18F]florbetapir will be compared to the [18F]MNI-1020 binding across multiple regions. This will be done by visual reading of scans, with amyloid signal predicted to be high in frontal cortical regions in participants with probable AD and absent from cortex in healthy participants, while tau signal is predicted to be present in hippocampus and entorhinal cortex in healthy elderly participants, and in medial and lateral temporal cortex in participants with probable AD. Semi-quantitative analysis will also be conducted comparing SUVR of the tracers in these same regions, using cerebellum as reference.
arm group label: [18F]MNI-1020
arm group type: Experimental
description: Participants will receive a single intravenous bolus injection of [18F]MNI-1020 at a dose of not more than 10 millicurie (mCi), with a maximum mass dose of 10 microgram (mcg) and maximum volume of 10 milliliter (mL) at imaging visit.
intervention type: Drug
intervention name: [18F]MNI-1020
description: Participants will receive a single intravenous bolus injection of [18F]MNI-1020 at a dose of not more than 10 millicurie (mCi), with a maximum mass dose of 10 microgram (mcg) and maximum volume of 10 milliliter (mL) at imaging visit.
arm group label: [18F]MNI-1020
other name: [18F]JNJ-64326067
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: JNJ-64326067