<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/NCT03019536</url>
  </required_header>
  <id_info>
    <org_study_id>16452</org_study_id>
    <secondary_id>I8G-MC-LMDD</secondary_id>
    <secondary_id>2016-002102-39</secondary_id>
    <nct_id>NCT03019536</nct_id>
  </id_info>
  <brief_title>A Study of LY3303560 in Participants With Mild Cognitive Impairment or Alzheimer's Disease</brief_title>
  <official_title>Multiple-Dose, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY3303560 in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild to Moderate Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eli Lilly and Company</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 study involves repeated doses of LY3303560 given by injection for 25 weeks. The study&#xD;
      will examine how safe repeated doses of LY3303560 are, whether they cause side effects in&#xD;
      participants with mild cognitive impairment or Alzheimer's Disease, and how LY3303560 is&#xD;
      handled by the body and acts in the body. This study will last up to 64 weeks, not including&#xD;
      screening. Screening is required within 90 days prior to the start of the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Actual">June 5, 2019</completion_date>
  <primary_completion_date type="Actual">June 5, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration</measure>
    <time_frame>Baseline up to 16 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3303560</measure>
    <time_frame>Post first dose through 64 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUC) of LY3303560</measure>
    <time_frame>Post first dose through 64 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>LY3303560 IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of LY3303560 administered intravenously (IV) for up to 48 weeks, followed by a 16 week follow-up period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of placebo administered IV for up to 48 weeks, followed by a 16 week follow-up period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY3303560 - IV</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>LY3303560 IV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - IV</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>Placebo IV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Florbetapir F 18</intervention_name>
    <description>Administered IV during the Positron Emission Tomography (PET) scan performed during screening.</description>
    <arm_group_label>LY3303560 IV</arm_group_label>
    <arm_group_label>Placebo IV</arm_group_label>
    <other_name>Florbetaben F 18</other_name>
    <other_name>Flutemetamol F 18</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Flortaucipir F18</intervention_name>
    <description>Administered IV during the PET scan performed during the study.</description>
    <arm_group_label>LY3303560 IV</arm_group_label>
    <arm_group_label>Placebo IV</arm_group_label>
    <other_name>AV-1451</other_name>
    <other_name>[F-18]T807</other_name>
    <other_name>LY3191748</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild-to-moderate AD&#xD;
             based on National Institute of Aging and Alzheimer's Association diagnostic criteria&#xD;
&#xD;
          -  Female participants: women not of child-bearing potential may participate, and include&#xD;
             those who are:&#xD;
&#xD;
               -  Infertile due to surgical sterilisation (hysterectomy, bilateral oophorectomy, or&#xD;
                  for countries outside of Japan, tubal ligation), congenital anomaly such as&#xD;
                  mullerian agenesis; or&#xD;
&#xD;
               -  Postmenopausal defined as women at least 50 years of age with an intact uterus&#xD;
                  who have not taken hormones or oral contraceptives within 1 year, who have had&#xD;
                  either cessation of menses for at least 1 year, or 6 to 12 months of spontaneous&#xD;
                  amenorrhea with follicle-stimulating greater than (&gt;) 40 milli-international&#xD;
                  units per millilitre (mIU/mL)&#xD;
&#xD;
          -  Have a body weight of at least 50 kilogram (kg) (except for Japanese sites) and have a&#xD;
             body mass index (BMI) of 18.0 to 35.0 kilogram per meter square (kg/m²) (for all&#xD;
             sites), inclusive, at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are currently enrolled in a clinical trial involving an investigational product (IP)&#xD;
             or any other type of medical research judged not to be scientifically or medically&#xD;
             compatible with this study&#xD;
&#xD;
          -  Have participated, within the last 30 days (3 months and 4 months for sites in the&#xD;
             European Union [EU] and Japan, respectively) in a clinical trial involving an IP. If&#xD;
             the previous IP has a long half-life, 3 months (4 months for sites in Japan) or 5&#xD;
             half-lives (whichever is longer) should have passed&#xD;
&#xD;
          -  Have known allergies to LY3303560, related compounds or any components of the&#xD;
             formulation, or history of significant atopy&#xD;
&#xD;
          -  Have significant allergies to humanised monoclonal antibodies, diphenhydramine,&#xD;
             adrenaline, or methylprednisolone; or have a history of clinically significant&#xD;
             multiple or severe drug allergies, or intolerance to topical corticosteroids, or&#xD;
             severe post treatment hypersensitivity reactions (including, but not limited to,&#xD;
             erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal&#xD;
             necrolysis, or exfoliative dermatitis)&#xD;
&#xD;
          -  Have an increased risk of seizures as evidenced by a history of head trauma with loss&#xD;
             of consciousness within the last 5 years or any seizure; prior electroencephalogram&#xD;
             with epileptiform activity; surgery to the cerebral cortex; or history within the last&#xD;
             5 years of a serious infectious disease affecting the brain&#xD;
&#xD;
          -  Have any contraindications for Magnetic Resonance Imaging (MRI) studies, including&#xD;
             claustrophobia, or the presence of metal (ferromagnetic) implants or a cardiac&#xD;
             pacemaker&#xD;
&#xD;
          -  Have a history of intracranial haemorrhage, cerebrovascular aneurysm, or arteriovenous&#xD;
             malformation, carotid artery occlusion, or epilepsy&#xD;
&#xD;
          -  Have received acetylcholinesterase inhibitors (AChEIs), memantine, and/or other AD&#xD;
             therapy for less than 4 weeks, or have less than 4 weeks of stable therapy on these&#xD;
             treatments by time of randomisation (including less than 4 weeks since stopping AChEIs&#xD;
             and/or memantine); or have received medications that affect the central nervous&#xD;
             system, except treatments for AD, for less than 4 weeks at a stable dose&#xD;
&#xD;
          -  Have used stable medical therapy for less than 2 months by time of randomization for&#xD;
             any concurrent medical condition that is not exclusionary&#xD;
&#xD;
          -  Are currently using or intend to use drugs known to significantly prolong the QT&#xD;
             interval, or who have a known risk factor for Torsades de Pointes. A participant will&#xD;
             not be excluded if they have been using stable medication that is known to potentially&#xD;
             cause significant prolongation of the QT interval, but does not present with any&#xD;
             clinically significant prolongation of the QT interval at screening, in the opinion of&#xD;
             the investigator&#xD;
&#xD;
          -  History of cancer within the last 5 years, with the exception of non-metastatic basal&#xD;
             and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive&#xD;
             prostate cancer, or other cancers with low risk of recurrence or spread.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bioclinica</name>
      <address>
        <city>Melbourne</city>
        <state>Florida</state>
        <zip>32940</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bioclinica</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Progressive Medical Research</name>
      <address>
        <city>Port Orange</city>
        <state>Florida</state>
        <zip>32127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bioclinica</name>
      <address>
        <city>The Villages</city>
        <state>Florida</state>
        <zip>32162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princeton Medical Institute</name>
      <address>
        <city>Princeton</city>
        <state>New Jersey</state>
        <zip>08540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.</name>
      <address>
        <city>Bunkyo-ku</city>
        <zip>113-8655</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>Hyogo</city>
        <zip>650-0047</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.</name>
      <address>
        <city>Kurume</city>
        <zip>830-0011</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>Tokyo</city>
        <zip>192-0071</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.</name>
      <address>
        <city>Bath</city>
        <zip>BA1 3NG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.lillytrialguide.com/en-US/studies/alzheimer-s/LMDD#?postal=</url>
    <description>Click here for more information about this study: A Study of LY3303560 in Participants with Mild Cognitive Impairment or Alzheimer's Disease</description>
  </link>
  <verification_date>July 1, 2019</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>July 2, 2019</last_update_submitted>
  <last_update_submitted_qc>July 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 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>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Flutemetamol</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>November 11, 2022</submitted>
  </pending_results>
  <!-- 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/NCT03019536
org study id: 16452
secondary id: I8G-MC-LMDD
secondary id: 2016-002102-39
nct id: NCT03019536
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study involves repeated doses of LY3303560 given by injection for 25 weeks. The study
      will examine how safe repeated doses of LY3303560 are, whether they cause side effects in
      participants with mild cognitive impairment or Alzheimer's Disease, and how LY3303560 is
      handled by the body and acts in the body. This study will last up to 64 weeks, not including
      screening. Screening is required within 90 days prior to the start of the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
time frame: Baseline up to 16 weeks
measure: Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3303560
time frame: Post first dose through 64 weeks
measure: Pharmacokinetics: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUC) of LY3303560
time frame: Post first dose through 64 weeks
arm group label: LY3303560 IV
arm group type: Experimental
description: Multiple doses of LY3303560 administered intravenously (IV) for up to 48 weeks, followed by a 16 week follow-up period
arm group label: Placebo IV
arm group type: Experimental
description: Multiple doses of placebo administered IV for up to 48 weeks, followed by a 16 week follow-up period
intervention type: Drug
intervention name: LY3303560 - IV
description: Administered IV
arm group label: LY3303560 IV
intervention type: Drug
intervention name: Placebo - IV
description: Administered IV
arm group label: Placebo IV
intervention type: Drug
intervention name: Florbetapir F 18
description: Administered IV during the Positron Emission Tomography (PET) scan performed during screening.
arm group label: LY3303560 IV
arm group label: Placebo IV
other name: Florbetaben F 18
other name: Flutemetamol F 18
intervention type: Drug
intervention name: Flortaucipir F18
description: Administered IV during the PET scan performed during the study.
arm group label: LY3303560 IV
arm group label: Placebo IV
other name: AV-1451
other name: [F-18]T807
other name: LY3191748
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
country: United Kingdom
country: United States
url: https://www.lillytrialguide.com/en-US/studies/alzheimer-s/LMDD#?postal=
description: Click here for more information about this study: A Study of LY3303560 in Participants with Mild Cognitive Impairment or Alzheimer's Disease
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
mesh term: Flutemetamol
submitted: November 11, 2022