<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/NCT01680588</url>
  </required_header>
  <id_info>
    <org_study_id>NAV4-01</org_study_id>
    <nct_id>NCT01680588</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of the PET Imaging Agent [18F]NAV4694 in Subjects With Probable Alzheimer's Disease</brief_title>
  <official_title>A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of [18F]NAV4694 PET in the Detection of Beta Amyloid in Subjects With Probable Alzheimer's Disease, Older Healthy Volunteers, and Young Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Navidea Biopharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Navidea Biopharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2, open-label, multiple-center, non-randomized single dose study to assess&#xD;
      the safety and efficacy of [18F]NAV4694 PET imaging in detecting beta-amyloid plaque in the&#xD;
      brain in subjects with probable AD compared with healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>[18F]NAV4694 PET visual assessment by centralized readers</measure>
    <time_frame>25 minutes post injection</time_frame>
    <description>To evaluate [18F]NAV4694 PET visual assessment by centralized readers for detection of cerebral beta-amyloid plaque in subjects diagnosed with probable Alzheimer's disease compared with similarly aged and young healthy volunteers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the incidence of adverse events after a single dose of [18F]NAV4694</measure>
    <time_frame>7 Days</time_frame>
    <description>To assess the incidence of adverse events after a single dose of [18F]NAV4694 PET in individuals diagnosed with probable AD and similarly aged and young healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate [18F]NAV4694 PET quantitative assessment</measure>
    <time_frame>25 minutes post injection</time_frame>
    <description>To evaluate [18F]NAV4694 PET quantitative assessment, by assessing standard uptake value ratios (SUVR) for detection of cerebral beta-amyloid plaque in subjects diagnosed with probable Alzheimer's disease compared with similarly aged and young healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine correlation of neuro-psychiatric tests with [18F]NAV4694 imaging</measure>
    <time_frame>25 minutes post injection</time_frame>
    <description>To determine the correlation of neuro-psychiatric tests with the beta-amyloid plaque burden determined by correlating various baseline neuro-psychiatric test scores with the [18F]NAV4694 PET imaging results in subjects diagnosed with probable AD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess changes in laboratory values after a single dose of [18F]NAV4694</measure>
    <time_frame>7 days</time_frame>
    <description>To assess changes in laboratory values after a single dose of [18F]NAV4694 PET in individuals diagnosed with probable AD and similarly aged and young healthy volunteers.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>[18F]NAV4694</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single intravenous injection of 8.1 millicuries of [18F]NAV4694</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[18F]NAV4694</intervention_name>
    <arm_group_label>[18F]NAV4694</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All participants:&#xD;
&#xD;
          -  is able to provide informed consent or assent, and exhibits adequate visual, auditory,&#xD;
             and communication capabilities to enable compliance with study procedures&#xD;
&#xD;
          -  should be able to perform the psychometric testing&#xD;
&#xD;
          -  has a modified Hachinski score ((Hachinski, et al., 2012; Rosen, et al., 1980) ≤ 4 at&#xD;
             screening&#xD;
&#xD;
          -  possesses a general health that permits adequate compliance with all study procedures&#xD;
             as ascertained by a detailed review of the medical history, surgical history,&#xD;
             laboratory and physical examination findings, which must be performed within 56 days&#xD;
             prior to administration of [18F]NAV4694&#xD;
&#xD;
          -  informed consent has been signed and dated by the subject and/or the subject's legally&#xD;
             authorized representative (LAR; for probable AD subjects)&#xD;
&#xD;
        Healthy Volunteers Only&#xD;
&#xD;
          -  is male or female and is between the age of 18 and 40 years (for younger HVs) or 55 to&#xD;
             85 years of age (for older HVs)&#xD;
&#xD;
          -  if female does not have childbearing potential: must be confirmed by either:&#xD;
             post-menopausal status; or history of surgical sterilization or of hysterectomy&#xD;
&#xD;
          -  if female has childbearing potential: must demonstrate a negative serum beta-HCG level&#xD;
             at screening and a negative urine pregnancy test on the day of injection (prior to&#xD;
             injection) consistent with a non-gravid state and agree to use two acceptable forms of&#xD;
             birth control&#xD;
&#xD;
          -  has no evidence of cognitive impairment as indicated by a clinical dementia rating&#xD;
             (CDR) (Morris, 1993) score of 0 (zero) and a score of ≥ 28 in the Mini-Mental State&#xD;
             Examination (MMSE) (Folstein, et al., 1975)&#xD;
&#xD;
          -  has MRI brain scan that has been judged as &quot;normal (age-appropriate)&quot; supporting the&#xD;
             lack of cerebrovascular disease (e.g., a white matter lesion score of 0, 1, or 2 and a&#xD;
             basal ganglia score of 0 to 1 on the ARWMC scale)&#xD;
&#xD;
        Probable Alzheimer's Disease Subjects Only&#xD;
&#xD;
          -  is male or female and is ≥ 55 of age, whereby females must be without childbearing&#xD;
             potential (confirmed by either:post-menopausal status; or history of surgical&#xD;
             sterilization or of hysterectomy)&#xD;
&#xD;
          -  presents with positive assessment for dementia of Alzheimer's type in accordance with&#xD;
             the DSM-IV-TR and probable AD according to the NINCDS-ADRDA criteria and fulfills none&#xD;
             of the exclusion criteria of either&#xD;
&#xD;
          -  does not fulfill the International Consensus Criteria (ICC) for probable diffuse Lewy&#xD;
             body disease (DLBD), the NINDS-AIREN for probable vascular dementia, or the Neary&#xD;
             criteria for frontotemporal dementia (FTD) [Neary et al. 1998]&#xD;
&#xD;
          -  has a MMSE score between 16 and 23&#xD;
&#xD;
          -  has a CDR (Morris, 1993) score of 1 to 2&#xD;
&#xD;
          -  has a Cornell Scale for Depression in Dementia (CSDD; (Alexopoulos, et al., 1988))&#xD;
             score less than or equal to 18 (definite major depression)&#xD;
&#xD;
          -  MRI brain scan findings that do not reveal changes indicative of stroke and/or&#xD;
             generalized cerebrovascular disease changes (limited to: a white matter lesion score&#xD;
             of 0, 1, or 2 and a basal ganglia score of 0 or 1 on the ARWMC scale)&#xD;
&#xD;
          -  has a caregiver who is willing and able to attend study visits and perform the&#xD;
             psychometric tests requiring the presence of a caregiver&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  has any contraindication to MRI examination, e.g., metal implants or phobia&#xD;
&#xD;
          -  is not able to lie down flat in the MRI and PET scanners&#xD;
&#xD;
          -  is scheduled for surgery and/or another invasive procedure within the time period of&#xD;
             up to 10 days after [18F]NAV4694 application&#xD;
&#xD;
          -  is medically unstable and whose clinical course during the observation period is&#xD;
             unpredictable, e.g., subjects within 14 days of myocardial infarction or stroke,&#xD;
             unstable subjects with previous surgery (within 7 days), subjects with advanced heart&#xD;
             insufficiency (NYHA stage IV), or with acute renal failure&#xD;
&#xD;
          -  has a history of exposure to any radiation &gt; 30 mSv in the last year (e.g.,&#xD;
             occupational, diagnostic imaging, or radiation therapy)&#xD;
&#xD;
          -  is receiving drug therapy or other treatment that is known to lead to greatly&#xD;
             fluctuating values of the hematological or chemical laboratory parameters or to severe&#xD;
             side effects (e.g., chemotherapy)&#xD;
&#xD;
          -  has received anti-amyloid immunotherapy&#xD;
&#xD;
          -  has been previously enrolled in this study and received [18F]NAV4694 or participated&#xD;
             in a clinical study involving an investigational pharmaceutical product within 30 days&#xD;
             prior to screening, and/or any radiopharmaceutical within 10 radioactive half-lives&#xD;
             prior to [18F]NAV4694 administration&#xD;
&#xD;
          -  has a brain tumor or other intracranial lesion, a disturbance of cerebrospinal fluid&#xD;
             (CSF) circulation (e.g., normal pressure hydrocephalus) and/or a history of serious&#xD;
             head trauma or brain surgery&#xD;
&#xD;
          -  has a history, physical, laboratory, or imaging findings indicative of a significant&#xD;
             neurological or psychiatric illness (other than AD for the subjects with probable AD)&#xD;
&#xD;
          -  has another untreated disease that can cause disturbance of brain function (e.g.&#xD;
             vitamin B12 or folic acid deficiency, disturbed thyroid function, anemia)&#xD;
&#xD;
          -  has a history of alcohol abuse or drug dependency in the 3 years prior to study entry&#xD;
             or is an alcoholic or drug addict as determined by the investigator&#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>Cornelia Reininger, M.D., PhD</last_name>
    <role>Study Director</role>
    <affiliation>Navidea Biopharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Molecular NeuroImaging, LLC</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Brothers Neurosciences Institute</name>
      <address>
        <city>Elk Grove Village</city>
        <state>Illinois</state>
        <zip>60007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Medical Research</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham &amp; Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alzheimer's Disease Center, Quincy Medical Center</name>
      <address>
        <city>Quincy</city>
        <state>Massachusetts</state>
        <zip>02169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurological Associates of Albany</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>March 29, 2016</last_update_submitted>
  <last_update_submitted_qc>March 29, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 30, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer</keyword>
  <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/NCT01680588
org study id: NAV4-01
nct id: NCT01680588
lead sponsor: 
has dmc: No
This is a phase 2, open-label, multiple-center, non-randomized single dose study to assess
      the safety and efficacy of [18F]NAV4694 PET imaging in detecting beta-amyloid plaque in the
      brain in subjects with probable AD compared with healthy volunteers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: [18F]NAV4694 PET visual assessment by centralized readers
time frame: 25 minutes post injection
description: To evaluate [18F]NAV4694 PET visual assessment by centralized readers for detection of cerebral beta-amyloid plaque in subjects diagnosed with probable Alzheimer's disease compared with similarly aged and young healthy volunteers.
measure: Assess the incidence of adverse events after a single dose of [18F]NAV4694
time frame: 7 Days
description: To assess the incidence of adverse events after a single dose of [18F]NAV4694 PET in individuals diagnosed with probable AD and similarly aged and young healthy volunteers.
measure: Evaluate [18F]NAV4694 PET quantitative assessment
time frame: 25 minutes post injection
description: To evaluate [18F]NAV4694 PET quantitative assessment, by assessing standard uptake value ratios (SUVR) for detection of cerebral beta-amyloid plaque in subjects diagnosed with probable Alzheimer's disease compared with similarly aged and young healthy volunteers.
measure: Determine correlation of neuro-psychiatric tests with [18F]NAV4694 imaging
time frame: 25 minutes post injection
description: To determine the correlation of neuro-psychiatric tests with the beta-amyloid plaque burden determined by correlating various baseline neuro-psychiatric test scores with the [18F]NAV4694 PET imaging results in subjects diagnosed with probable AD
measure: Assess changes in laboratory values after a single dose of [18F]NAV4694
time frame: 7 days
description: To assess changes in laboratory values after a single dose of [18F]NAV4694 PET in individuals diagnosed with probable AD and similarly aged and young healthy volunteers.
arm group label: [18F]NAV4694
arm group type: Experimental
description: Single intravenous injection of 8.1 millicuries of [18F]NAV4694
intervention type: Drug
intervention name: [18F]NAV4694
arm group label: [18F]NAV4694
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cornelia Reininger, M.D., PhD
role: Study Director
affiliation: Navidea Biopharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease