<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/NCT03822208</url>
  </required_header>
  <id_info>
    <org_study_id>AL003-1</org_study_id>
    <nct_id>NCT03822208</nct_id>
  </id_info>
  <brief_title>First in Human Study for Safety and Tolerability of AL003.</brief_title>
  <official_title>A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Doses of AL003 in Healthy Participants and in Participants With Mild to Moderate Alzheimer's Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alector Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alector Inc.</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>
      This is a multi-center, randomized, double-blind, placebo-controlled, dose escalation first&#xD;
      in human (FIH) study in healthy adults and in patients with mild to moderate Alzheimer's&#xD;
      disease. The study is designed to systematically assess the safety (including immunogenicity)&#xD;
      and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AL003.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted in 2 phases:&#xD;
&#xD;
      In the single ascending dose (SAD) phase, up to approximately 42 healthy adult participants&#xD;
      will be sequentially enrolled into up to approximately 7 cohorts. In the multiple-dose (MD)&#xD;
      phase, approximately 12 patients with mild to moderate Alzheimer's disease will be enrolled&#xD;
      in one cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 29, 2019</start_date>
  <completion_date type="Actual">May 6, 2021</completion_date>
  <primary_completion_date type="Actual">May 6, 2021</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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of safety and tolerability of AL003 measured by number of subjects with adverse events and dose limiting adverse events (DLAE)</measure>
    <time_frame>141 days</time_frame>
    <description>Incidence of adverse events during the treatment and follow up periods through out the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of AL003</measure>
    <time_frame>85 days</time_frame>
    <description>Serum and CSF concentration of AL003 at specific time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration (Cmax) for AL003</measure>
    <time_frame>85 days</time_frame>
    <description>Evaluate Cmax for serum and CSF concentration of AL003 at specified time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve concentration (AUC) for AL003</measure>
    <time_frame>85 days</time_frame>
    <description>Evaluate AUC for serum and CSF concentration of AL003 at specified time points</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Healthy</condition>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>AL003 by intravenous (IV) infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single-doses of AL003 in dose-escalating cohorts Multiple doses of AL003 in single cohort</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo by intravenous (IV) infusion</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching saline solution will be administered for placebo subjects</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AL003</intervention_name>
    <description>Single-doses of AL003 in dose-escalating cohorts&#xD;
Multiple doses of AL003 in a single cohort</description>
    <arm_group_label>AL003 by intravenous (IV) infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saline Solution</intervention_name>
    <description>Saline Solution will be administered as a single infusion for each dose escalation cohort in a ratio of 6 active and 2 placebo and as multiple infusions in the single cohort in a ratio of 10 active and 2 placebo</description>
    <arm_group_label>Placebo by intravenous (IV) infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Total body weight between 50 and 120 kg, inclusive&#xD;
&#xD;
          2. Clinical laboratory evaluations (including chemistry panel fasted [at least 8 hours],&#xD;
             complete blood count (CBC), and urine analysis) within the reference range for the&#xD;
             test laboratory, unless deemed not clinically significant by the Investigator. A count&#xD;
             of the segmented neutrophils and bands should be performed when results from the white&#xD;
             blood cells (WBCs) are not within the reference range.&#xD;
&#xD;
          3. Negative test for selected drugs of abuse at screening (dose not include alcohol) and&#xD;
             at admission (does include alcohol breath test). A positive result may be verified by&#xD;
             re-testing (up to one false positive result permitted) and may be followed up at the&#xD;
             discretion of the Investigator.&#xD;
&#xD;
          4. Females must be non-pregnant and non-lactating, and either surgically sterile, using&#xD;
             double barrier method or abstinence.&#xD;
&#xD;
          5. In good health, determined by no clinically significant findings from medical history,&#xD;
             physical examination, 12-lead electrocardiogram (ECG), laboratory tests, and vital&#xD;
             signs.&#xD;
&#xD;
        For MD cohort&#xD;
&#xD;
          1. Ages 50-85 years, inclusive.&#xD;
&#xD;
          2. The participant should be capable of completing assessments alone, per local&#xD;
             guidelines.&#xD;
&#xD;
          3. Availability of a person (&quot;study partner&quot;) who, in the Investigator's judgment, has&#xD;
             frequent and sufficient contact with the participant and is able to provide accurate&#xD;
             information regarding the participant's cognitive and functional abilities, agrees to&#xD;
             provide information at clinic visits, which require partner input for scale&#xD;
             completion, and signs the necessary consent form, per local guidelines.&#xD;
&#xD;
          4. Clinical diagnosis of probable Alzheimer's disease dementia based on National&#xD;
             Institute on Aging Alzheimer's Association criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating, or intending to become pregnant within 16 weeks after last dose&#xD;
             of study drug.&#xD;
&#xD;
          2. Participation in a clinical trial within 30 days before randomization; use of any&#xD;
             experimental oral therapy within 30 days or 5 half-lives prior to Day 1, whichever is&#xD;
             greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to Day&#xD;
             1, whichever is greater. Participants who have received an experimental therapy that&#xD;
             has no half-life, like a vaccine, should have completed that therapy at least 12 weeks&#xD;
             prior to Day 1. Participants who have received an experimental vaccine against a&#xD;
             central nervous system (CNS) target, such as beta-amyloid or tau, are not eligible for&#xD;
             this study.&#xD;
&#xD;
          3. Any non-experimental vaccine within 2 weeks of randomization, until 2 weeks after the&#xD;
             last dose. It is advised that prospective participants receive their annual influenza&#xD;
             vaccine as early as possible in advance of the flu season, and then wait 2 weeks prior&#xD;
             to randomization. It is permitted to receive the annual influenza vaccine during the&#xD;
             screening period.&#xD;
&#xD;
          4. Surgery or hospitalization during the 4 weeks prior to screening.&#xD;
&#xD;
          5. Planned procedure or surgery during the study.&#xD;
&#xD;
          6. Systemically, clinically significantly immunocompromised patients, owing to continuing&#xD;
             effects of immune suppressing medication.&#xD;
&#xD;
          7. Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric, human, or humanized antibodies or fusion proteins.&#xD;
&#xD;
          8. Past history of seizures, with the exception of childhood febrile seizures.&#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>Robert Paul, MD</last_name>
    <role>Study Director</role>
    <affiliation>Alector Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brain Matters Research</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33445</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charter Research</name>
      <address>
        <city>Lady Lake</city>
        <state>Florida</state>
        <zip>32159</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PPD Clinical Research Unit</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus AES</name>
      <address>
        <city>The Villages</city>
        <state>Florida</state>
        <zip>32162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nucleus Network</name>
      <address>
        <city>Melbourne</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>September 15, 2021</last_update_submitted>
  <last_update_submitted_qc>September 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2021</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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03822208
org study id: AL003-1
nct id: NCT03822208
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a multi-center, randomized, double-blind, placebo-controlled, dose escalation first
      in human (FIH) study in healthy adults and in patients with mild to moderate Alzheimer's
      disease. The study is designed to systematically assess the safety (including immunogenicity)
      and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AL003.
The study will be conducted in 2 phases:

      In the single ascending dose (SAD) phase, up to approximately 42 healthy adult participants
      will be sequentially enrolled into up to approximately 7 cohorts. In the multiple-dose (MD)
      phase, approximately 12 patients with mild to moderate Alzheimer's disease will be enrolled
      in one cohort.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Evaluation of safety and tolerability of AL003 measured by number of subjects with adverse events and dose limiting adverse events (DLAE)
time frame: 141 days
description: Incidence of adverse events during the treatment and follow up periods through out the study.
measure: Pharmacokinetics (PK) of AL003
time frame: 85 days
description: Serum and CSF concentration of AL003 at specific time points
measure: Maximum concentration (Cmax) for AL003
time frame: 85 days
description: Evaluate Cmax for serum and CSF concentration of AL003 at specified time points
measure: Area under the curve concentration (AUC) for AL003
time frame: 85 days
description: Evaluate AUC for serum and CSF concentration of AL003 at specified time points
arm group label: AL003 by intravenous (IV) infusion
arm group type: Active Comparator
description: Single-doses of AL003 in dose-escalating cohorts Multiple doses of AL003 in single cohort
arm group label: Placebo by intravenous (IV) infusion
arm group type: Placebo Comparator
description: Matching saline solution will be administered for placebo subjects
intervention type: Biological
intervention name: AL003
description: Single-doses of AL003 in dose-escalating cohorts
Multiple doses of AL003 in a single cohort
arm group label: AL003 by intravenous (IV) infusion
intervention type: Other
intervention name: Saline Solution
description: Saline Solution will be administered as a single infusion for each dose escalation cohort in a ratio of 6 active and 2 placebo and as multiple infusions in the single cohort in a ratio of 10 active and 2 placebo
arm group label: Placebo by intravenous (IV) infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert Paul, MD
role: Study Director
affiliation: Alector Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: Yes