<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/NCT02187627</url>
  </required_header>
  <id_info>
    <org_study_id>BP29409</org_study_id>
    <nct_id>NCT02187627</nct_id>
  </id_info>
  <brief_title>Evaluation of [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948 as Tracers for Positron Emission Tomography (PET) Imaging of Tau in Healthy and Alzheimer's Disease (AD) Participants</brief_title>
  <official_title>Evaluation of [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948 as Tracers for Tau Imaging With Positron Emission Tomography in Healthy Control Subjects and Subjects With Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This study is designed to obtain basic information on three PET imaging tracers developed to&#xD;
      detect tau pathology in the brain. In this study, healthy control participants and&#xD;
      participants with AD will be studied. Information collected will include brain and plasma&#xD;
      kinetics, tissue distribution (in the brain), radiation dosimetry, and test-retest&#xD;
      variability of the signal in the brain. The study will consist of Part 1, Part 2A, and Part&#xD;
      2B. During Part 1, imaging data will be assessed on an ongoing basis and based on data, one&#xD;
      tracer will be prioritized over the other two tracers. The tracer selected will be further&#xD;
      investigated in Part 2A and Part 2B.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2014</start_date>
  <completion_date type="Actual">February 29, 2016</completion_date>
  <primary_completion_date type="Actual">February 29, 2016</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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Standard Uptake Value (SUV), as Assessed by Tau PET Brain Scan</measure>
    <time_frame>Day 1 up to Day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Standard Uptake Value Ratio (SUVR), as Assessed by Tau PET Brain Scan</measure>
    <time_frame>Day 1 up to Day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: SUV, as Assessed by Tau PET Scan of Whole Body</measure>
    <time_frame>Day 1 up to Day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: SUVR, as Assessed by Tau PET Scan of Whole Body</measure>
    <time_frame>Day 1 up to Day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Residence Times for Each Organ, as Assessed by Tau PET Scan of Whole Body</measure>
    <time_frame>Day 1 up to Day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Distribution Volume (VT), as Assessed by Tau PET Brain Scan</measure>
    <time_frame>Day 1 up to Day 14</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 2A: Absolute Percentage Difference Between Test and Retest of SUVR</measure>
    <time_frame>Days 1, 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2A: Absolute Percentage Difference Between Test and Retest of VT</measure>
    <time_frame>Days 1, 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2B: Effective dose (ED), as Assessed by Whole Body PET Scan</measure>
    <time_frame>From the time of tracer injection on Day 1 up to 120 minutes post injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2A: Absolute Percentage Difference Between Test and Retest of SUV</measure>
    <time_frame>Days 1, 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs)</measure>
    <time_frame>Part 1: Day 1 up to Day 28, Part 2a: Day 1 up to Day 42, Part 2b: Day 1 up to Day 15</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Alzheimer's Disease, Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>Part 1: Tracer Selection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single dose of one tracer on one occasion and a single dose of a different tracer after 7 to 14 days and will be followed for 7 to 14 days for safety. At the end of Part 1, one tracer with the best performance will be selected for further study in Part 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2A: Test-Retest</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single dose of selected tracer from Part 1 on one occasion and then same tracer will be administered after 6 weeks. Participants will be followed for 7 to 14 days after last PET tracer administration for safety.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2B: Dosimetry</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single dose of selected tracer from Part 1 and will be followed for 7 to 14 days for evaluation of radiation dosimetry.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[11C]RO6924963</intervention_name>
    <description>Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6924963 injected will be &lt;/=10 micrograms (mcg), injection volume &lt;/=20 milliliters (mL). Target injected activity for [11C]RO6924963 will be 370-740 megabecquerel (MBq) [10-20 millicurie (mCi)].</description>
    <arm_group_label>Part 1: Tracer Selection</arm_group_label>
    <arm_group_label>Part 2A: Test-Retest</arm_group_label>
    <arm_group_label>Part 2B: Dosimetry</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[11C]RO6931643</intervention_name>
    <description>Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6931643 injected will be &lt;/=10 mcg, injection volume &lt;/=20 mL. Target injected activity for [11C]RO6931643 will be 370-740 MBq (10-20 mCi).</description>
    <arm_group_label>Part 1: Tracer Selection</arm_group_label>
    <arm_group_label>Part 2A: Test-Retest</arm_group_label>
    <arm_group_label>Part 2B: Dosimetry</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[18F]RO6958948</intervention_name>
    <description>Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [18F]RO6958948 injected will be &lt;/=10 mcg, injection volume &lt;/=20 mL. Target injected activity for [18F]RO6958948 will be 185-370 MBq (5-10 mCi). The final activity of [18F] RO6958948 will be adjusted up to 10 mCi per scan to allow sufficient counts by end of 200 minutes post radiotracer injection.</description>
    <arm_group_label>Part 1: Tracer Selection</arm_group_label>
    <arm_group_label>Part 2A: Test-Retest</arm_group_label>
    <arm_group_label>Part 2B: Dosimetry</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria for All Participants&#xD;
&#xD;
          -  Agreement to use highly effective contraception measures&#xD;
&#xD;
          -  If participants are on any concomitant medication, the indication and dosage of these&#xD;
             medicines should be stable for at least 4 weeks prior to study start with the&#xD;
             expectation that no relevant changes in use or dose will occur throughout the study&#xD;
&#xD;
          -  Body mass index (BMI) between 18 and 32 kilograms per square meter (kg/m^2)&#xD;
&#xD;
          -  Weight less than or equal to (&lt;/=) 300 pounds (lb)&#xD;
&#xD;
        Inclusion Criteria for Healthy Control Participants&#xD;
&#xD;
          -  Healthy &quot;young&quot; control participants aged 25-40 years or healthy &quot;elderly&quot; control&#xD;
             participants aged greater than or equal to (&gt;/=) 50 years&#xD;
&#xD;
          -  Normal cognitive function, including a normal Mini Mental State Examination (MMSE)&#xD;
             score as judged by the investigator&#xD;
&#xD;
          -  Healthy control participants who participate in Part 2B: must be less than (&lt;) 195&#xD;
             centimeter (cm) (6 feet, 5 inches) tall in order to accommodate the whole body&#xD;
             scanning&#xD;
&#xD;
        Inclusion Criteria for Participants with a Diagnosis of Probable AD&#xD;
&#xD;
          -  Diagnosis of probable AD, according to the National Institute of Neurological and&#xD;
             Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders&#xD;
             Association criteria&#xD;
&#xD;
          -  Participants aged &gt;/= 50 years&#xD;
&#xD;
          -  A study partner able to accompany the participant to all visits and answer questions&#xD;
             about the participant&#xD;
&#xD;
          -  MMSE score between 16 and 26, inclusive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion Criteria for All Participants&#xD;
&#xD;
          -  History or presence of a neurological diagnosis other than AD that may influence the&#xD;
             outcome or analysis of the scan results; examples include but are not limited to&#xD;
             stroke, traumatic brain injury, space occupying lesions, non-Alzheimer's tauopathies,&#xD;
             and Parkinson's disease&#xD;
&#xD;
          -  Participants with a medical history that includes known autosomal dominant AD&#xD;
             mutations in amyloid precursor protein (APP) or presenilin (PS1, PS2) or mutations in&#xD;
             genes that cause other types of autosomal dominant familial dementia&#xD;
&#xD;
          -  History or presence of any clinically relevant hematological, hepatic, respiratory,&#xD;
             cardiovascular, renal, metabolic, endocrine, or central nervous system disease or&#xD;
             other medical conditions that are not well controlled, may put the participant at&#xD;
             risk, could interfere with the objectives of the study, or make the participant&#xD;
             unsuitable for participation in the study for any other reason in the opinion of the&#xD;
             principal investigator&#xD;
&#xD;
          -  Clinically relevant pathological findings in physical examination, electrocardiogram,&#xD;
             or laboratory values at the screening assessment that could interfere with the&#xD;
             objectives of the study&#xD;
&#xD;
          -  Known history of clinically significant infectious disease including acquired&#xD;
             immunodeficiency syndrome (AIDS) or serological indication of acute/chronic hepatitis&#xD;
             B or C or human immunodeficiency virus infection&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Unsuitable veins for repeated venipuncture&#xD;
&#xD;
          -  Current symptoms of allergy and/or severe allergy to drugs in medical history&#xD;
&#xD;
          -  Alcohol consumption that averages &gt;3 drinks daily or regular smoker (&gt;10 cigarettes,&#xD;
             &gt;3 pipefuls, or &gt;3 cigars per day)&#xD;
&#xD;
          -  Coffee (or tea) consumption &gt;10 cups per day or methylxanthine-containing drinks &gt;1.5&#xD;
             liters per day (L/day)&#xD;
&#xD;
          -  Have received an investigational medication within the last 3 months or 5 times (x)&#xD;
             the elimination half-life, whichever is longer, prior to Day 1 (i.e., enrollment)&#xD;
&#xD;
        Exclusion Criteria Related to Trial Procedures&#xD;
&#xD;
          -  Presence of pacemakers; aneurysm clips; artificial heart valves; ear implants; foreign&#xD;
             metal objects in the eyes, skin, or body, or any other circumstance (e.g.&#xD;
             claustrophobia) that would contraindicate a magnetic resonance imaging (MRI) scan&#xD;
&#xD;
          -  For participants of Part 1 and Part 2A, any contraindications to arterial cannulation&#xD;
&#xD;
        Exclusion Criterion for Participants with Probable Alzheimer's Disease&#xD;
&#xD;
          -  Has received treatment that targeted amyloid-beta or tau within the last 24 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Parexel International; Harbor Hospital Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Universtiy; Radiology Dept</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>June 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>December 28, 2018</last_update_submitted>
  <last_update_submitted_qc>December 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2019</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>
  <!-- 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/NCT02187627
org study id: BP29409
nct id: NCT02187627
lead sponsor: 
This study is designed to obtain basic information on three PET imaging tracers developed to
      detect tau pathology in the brain. In this study, healthy control participants and
      participants with AD will be studied. Information collected will include brain and plasma
      kinetics, tissue distribution (in the brain), radiation dosimetry, and test-retest
      variability of the signal in the brain. The study will consist of Part 1, Part 2A, and Part
      2B. During Part 1, imaging data will be assessed on an ongoing basis and based on data, one
      tracer will be prioritized over the other two tracers. The tracer selected will be further
      investigated in Part 2A and Part 2B.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Part 1: Standard Uptake Value (SUV), as Assessed by Tau PET Brain Scan
time frame: Day 1 up to Day 14
measure: Part 1: Standard Uptake Value Ratio (SUVR), as Assessed by Tau PET Brain Scan
time frame: Day 1 up to Day 14
measure: Part 1: SUV, as Assessed by Tau PET Scan of Whole Body
time frame: Day 1 up to Day 14
measure: Part 1: SUVR, as Assessed by Tau PET Scan of Whole Body
time frame: Day 1 up to Day 14
measure: Mean Residence Times for Each Organ, as Assessed by Tau PET Scan of Whole Body
time frame: Day 1 up to Day 14
measure: Part 1: Distribution Volume (VT), as Assessed by Tau PET Brain Scan
time frame: Day 1 up to Day 14
measure: Part 2A: Absolute Percentage Difference Between Test and Retest of SUVR
time frame: Days 1, 28
measure: Part 2A: Absolute Percentage Difference Between Test and Retest of VT
time frame: Days 1, 28
measure: Part 2B: Effective dose (ED), as Assessed by Whole Body PET Scan
time frame: From the time of tracer injection on Day 1 up to 120 minutes post injection
measure: Part 2A: Absolute Percentage Difference Between Test and Retest of SUV
time frame: Days 1, 28
measure: Percentage of Participants With Adverse Events (AEs)
time frame: Part 1: Day 1 up to Day 28, Part 2a: Day 1 up to Day 42, Part 2b: Day 1 up to Day 15
arm group label: Part 1: Tracer Selection
arm group type: Experimental
description: Participants will receive a single dose of one tracer on one occasion and a single dose of a different tracer after 7 to 14 days and will be followed for 7 to 14 days for safety. At the end of Part 1, one tracer with the best performance will be selected for further study in Part 2.
arm group label: Part 2A: Test-Retest
arm group type: Experimental
description: Participants will receive a single dose of selected tracer from Part 1 on one occasion and then same tracer will be administered after 6 weeks. Participants will be followed for 7 to 14 days after last PET tracer administration for safety.
arm group label: Part 2B: Dosimetry
arm group type: Experimental
description: Participants will receive a single dose of selected tracer from Part 1 and will be followed for 7 to 14 days for evaluation of radiation dosimetry.
intervention type: Drug
intervention name: [11C]RO6924963
description: Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6924963 injected will be </=10 micrograms (mcg), injection volume </=20 milliliters (mL). Target injected activity for [11C]RO6924963 will be 370-740 megabecquerel (MBq) [10-20 millicurie (mCi)].
arm group label: Part 1: Tracer Selection
arm group label: Part 2A: Test-Retest
arm group label: Part 2B: Dosimetry
intervention type: Drug
intervention name: [11C]RO6931643
description: Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6931643 injected will be </=10 mcg, injection volume </=20 mL. Target injected activity for [11C]RO6931643 will be 370-740 MBq (10-20 mCi).
arm group label: Part 1: Tracer Selection
arm group label: Part 2A: Test-Retest
arm group label: Part 2B: Dosimetry
intervention type: Drug
intervention name: [18F]RO6958948
description: Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [18F]RO6958948 injected will be </=10 mcg, injection volume </=20 mL. Target injected activity for [18F]RO6958948 will be 185-370 MBq (5-10 mCi). The final activity of [18F] RO6958948 will be adjusted up to 10 mCi per scan to allow sufficient counts by end of 200 minutes post radiotracer injection.
arm group label: Part 1: Tracer Selection
arm group label: Part 2A: Test-Retest
arm group label: Part 2B: Dosimetry
criteria: 
gender: All
minimum age: 25 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease