<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/NCT03298672</url>
  </required_header>
  <id_info>
    <org_study_id>NDX-1017-0101-01</org_study_id>
    <nct_id>NCT03298672</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Pharmacokinetics Study of NDX-1017</brief_title>
  <official_title>A Randomized, Placebo-Controlled, Double-Blinded, First-in-Human Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (Part A) and Multiple Ascending Doses (Part B) of NDX-1017 in Healthy Young and Elderly Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Athira Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Alzheimer's Drug Discovery Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Biotrial Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Athira Pharma</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 Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will&#xD;
      evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of&#xD;
      NDX-1017 in healthy young and elderly subjects, and elderly subjects with amnestic mild&#xD;
      cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or&#xD;
      mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or&#xD;
      moderate).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      NDX-1017 is being developed for the treatment of Alzheimer's disease (AD).&#xD;
&#xD;
      This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will&#xD;
      evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of&#xD;
      NDX-1017 in healthy young and elderly subjects, and elderly subjects with mild AD. The study&#xD;
      contains the following two parts:&#xD;
&#xD;
      Part A:&#xD;
&#xD;
      A single-ascending dose (SAD) study conducted in an inpatient setting for 3 days in healthy&#xD;
      young male and healthy elderly male and female volunteers evaluated in up to 7 dose cohorts&#xD;
      to identify the maximum tolerated dose (MTD) within the single dose range studied. Up to 56&#xD;
      subjects (aged 18 to 45 years for young and 60 to 85 years for elderly) may be enrolled in&#xD;
      Part A.&#xD;
&#xD;
      Part B:&#xD;
&#xD;
      A multiple ascending dose (MAD) study conducted in an inpatient setting for 10 days in male&#xD;
      or female healthy elderly volunteers (aged 60 to 85 years) or subjects with amnestic mild&#xD;
      cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or&#xD;
      mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate)&#xD;
      (aged 40 to 85 years) in up to 6 dose cohorts that were proven tolerable in the SAD part of&#xD;
      the study to identify the MTD within the multiple dose range studied. Up to 44 subjects (aged&#xD;
      40 to 85 years) may be enrolled in Part B.&#xD;
&#xD;
      Subjects will be screened for eligibility within 28 days (or 90 days for amnestic MCI,&#xD;
      Alzheimer's Disease, or mixed dementia with Alzheimer's and vascular components) prior to&#xD;
      enrollment. Those eligible will be admitted to an inpatient facility for investigational&#xD;
      product administration, safety monitoring, and collection of blood or urine for&#xD;
      pharmacokinetic evaluations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 9, 2017</start_date>
  <completion_date type="Actual">September 5, 2019</completion_date>
  <primary_completion_date type="Actual">September 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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].</measure>
    <time_frame>Up to 20 days</time_frame>
    <description>Safety and tolerability of single or multiple ascending doses of NDX-1017 as measured by vital signs and clinical laboratory measurements.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax).</measure>
    <time_frame>Samples collected at predetermined timepoints within 48 hours post-dose.</time_frame>
    <description>Cmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed plasma concentration (Tmax).</measure>
    <time_frame>Samples collected at predetermined timepoints within 48 hours post-dose.</time_frame>
    <description>Tmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration at the end of the dosing interval (Ctrough).</measure>
    <time_frame>Samples collected at predetermined timepoints within 48 hours post-dose.</time_frame>
    <description>Ctrough will be determined from the last plasma sample prior to the following dose (MAD only).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration time curve (AUC).</measure>
    <time_frame>Samples collected at predetermined timepoints within 48 hours post-dose.</time_frame>
    <description>AUC will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (t1/2).</measure>
    <time_frame>Samples collected at predetermined timepoints within 48 hours post-dose.</time_frame>
    <description>t1/2 will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">88</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>NDX-1017</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NDX-1017 will be administered via subcutaneous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered via subcutaneous injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NDX-1017</intervention_name>
    <description>Solution of NDX-1017 for subcutaneous injection</description>
    <arm_group_label>NDX-1017</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo solution for subcutaneous injection</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
          -  Generally in good health&#xD;
&#xD;
          -  Body mass index (BMI) of ≥ 18.0 and ≤ 30.0 kg/m2 at Screening, with minimum weight of&#xD;
             60 kg. (No BMI upper limit for mild AD and amnestic MCI subjects)&#xD;
&#xD;
          -  Male subjects and their partners must be willing to comply with the contraceptive&#xD;
             requirements of the study. Only female subjects of non-childbearing potential are&#xD;
             eligible for participation.&#xD;
&#xD;
          -  [Young subjects] Male subjects must be aged 18 to 45 years (inclusive) at the time of&#xD;
             Screening.&#xD;
&#xD;
          -  [Healthy elder subjects only] Male and female subjects must be aged 60 to 85 years at&#xD;
             the time of screening&#xD;
&#xD;
          -  [Amnestic MCI and Alzheimer's Subjects] 9. Patients with Alzheimer's disease, with&#xD;
             confirmed diagnosis of amnestic mild cognitive impairment, Alzheimer's disease (mild,&#xD;
             mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular&#xD;
             components (mild, mild-to-moderate, or moderate).&#xD;
&#xD;
               1. Either newly diagnosed treatment naïve patients, OR,&#xD;
&#xD;
               2. Patients who are currently on standard Alzheimer's Disease treatment may be&#xD;
                  considered for participation if they are not tolerating treatment and/or they are&#xD;
                  willing and clinically able to tolerate a discontinuation, 14 days for dose&#xD;
                  titration + 5x half-lives for washout, or 4 weeks (whichever is longer) prior to&#xD;
                  randomization. For these patients, the screening window will be allowed for up to&#xD;
                  90 days prior to randomization to evaluate discontinuation of symptomatic&#xD;
                  treatment for Alzheimer's disease.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Any medical condition that requires chronic medication use.&#xD;
&#xD;
          -  History of drug and/or alcohol abuse within 12 months prior to Screening.&#xD;
&#xD;
          -  History of having taken another investigational drug within 30 days prior to Admission&#xD;
             (Day -1).&#xD;
&#xD;
          -  Donation of blood or plasma within 30 days prior to dosing.&#xD;
&#xD;
          -  Major surgery within 90 days prior to Admission (Day -1) or anticipated surgery during&#xD;
             the study.&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  [Healthy elderly subjects] Reported changes in cognition and reported history of&#xD;
             declines in everyday life in the last year.&#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>Xue Hua, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Athira Pharma, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Biotrial Inc.</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>September 6, 2019</last_update_submitted>
  <last_update_submitted_qc>September 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer's Disease</keyword>
  <keyword>Dementia</keyword>
  <keyword>Brain Diseases</keyword>
  <keyword>Central Nervous System Diseases</keyword>
  <keyword>Cognition</keyword>
  <keyword>Neurodegenerative Diseases</keyword>
  <keyword>Neurocognitive Disorders</keyword>
  <keyword>Mental Disorders</keyword>
  <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>No</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/NCT03298672
org study id: NDX-1017-0101-01
nct id: NCT03298672
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will
      evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of
      NDX-1017 in healthy young and elderly subjects, and elderly subjects with amnestic mild
      cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or
      mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or
      moderate).
NDX-1017 is being developed for the treatment of Alzheimer's disease (AD).

      This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will
      evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of
      NDX-1017 in healthy young and elderly subjects, and elderly subjects with mild AD. The study
      contains the following two parts:

      Part A:

      A single-ascending dose (SAD) study conducted in an inpatient setting for 3 days in healthy
      young male and healthy elderly male and female volunteers evaluated in up to 7 dose cohorts
      to identify the maximum tolerated dose (MTD) within the single dose range studied. Up to 56
      subjects (aged 18 to 45 years for young and 60 to 85 years for elderly) may be enrolled in
      Part A.

      Part B:

      A multiple ascending dose (MAD) study conducted in an inpatient setting for 10 days in male
      or female healthy elderly volunteers (aged 60 to 85 years) or subjects with amnestic mild
      cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or
      mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate)
      (aged 40 to 85 years) in up to 6 dose cohorts that were proven tolerable in the SAD part of
      the study to identify the MTD within the multiple dose range studied. Up to 44 subjects (aged
      40 to 85 years) may be enrolled in Part B.

      Subjects will be screened for eligibility within 28 days (or 90 days for amnestic MCI,
      Alzheimer's Disease, or mixed dementia with Alzheimer's and vascular components) prior to
      enrollment. Those eligible will be admitted to an inpatient facility for investigational
      product administration, safety monitoring, and collection of blood or urine for
      pharmacokinetic evaluations.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].
time frame: Up to 20 days
description: Safety and tolerability of single or multiple ascending doses of NDX-1017 as measured by vital signs and clinical laboratory measurements.
measure: Maximum observed plasma concentration (Cmax).
time frame: Samples collected at predetermined timepoints within 48 hours post-dose.
description: Cmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.
measure: Time to maximum observed plasma concentration (Tmax).
time frame: Samples collected at predetermined timepoints within 48 hours post-dose.
description: Tmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.
measure: Plasma concentration at the end of the dosing interval (Ctrough).
time frame: Samples collected at predetermined timepoints within 48 hours post-dose.
description: Ctrough will be determined from the last plasma sample prior to the following dose (MAD only).
measure: Area under the plasma concentration time curve (AUC).
time frame: Samples collected at predetermined timepoints within 48 hours post-dose.
description: AUC will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.
measure: Half-life (t1/2).
time frame: Samples collected at predetermined timepoints within 48 hours post-dose.
description: t1/2 will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.
arm group label: NDX-1017
arm group type: Experimental
description: NDX-1017 will be administered via subcutaneous injection
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered via subcutaneous injection
intervention type: Drug
intervention name: NDX-1017
description: Solution of NDX-1017 for subcutaneous injection
arm group label: NDX-1017
intervention type: Drug
intervention name: Placebo
description: Placebo solution for subcutaneous injection
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Xue Hua, PhD
role: Study Director
affiliation: Athira Pharma, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: No