<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/NCT04485481</url>
  </required_header>
  <id_info>
    <org_study_id>ADX-914-001</org_study_id>
    <nct_id>NCT04485481</nct_id>
  </id_info>
  <brief_title>Single and Multiple Ascending Dose Study of ADX-914 in Healthy Adult Volunteers</brief_title>
  <official_title>A Double-Blind, Phase 1, Single and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of ADX-914 in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Q32 Bio Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Q32 Bio Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A two (2) part study to evaluate the safety, tolerability and PK of ADX-914&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part 1 - SAD:&#xD;
&#xD;
      It is expected that there will be up to 6 cohorts of 8 participants per cohort. In each&#xD;
      cohort, participants will be randomly assigned in a 3:1 ratio to receive either ADX-914 or&#xD;
      matching placebo.&#xD;
&#xD;
      It is planned that for each cohort in Part 1 a staggered 'sentinel' dose design will be used.&#xD;
&#xD;
      Part 2 - MAD It is expected that there will be up to 3 cohorts of 8 participants per cohort.&#xD;
      In each cohort, participants will be randomly assigned in a 3:1 ratio to receive either&#xD;
      ADX-914 or matching placebo. Doses will occur every 2 weeks, for a total of 4 doses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 8, 2020</start_date>
  <completion_date type="Actual">January 12, 2022</completion_date>
  <primary_completion_date type="Actual">January 12, 2022</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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>Screening to end of study, up to 18 weeks</time_frame>
    <description>Listing and summary of AE incidence</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with Physical exam findings</measure>
    <time_frame>Screening to end of study, up to 18 weeks</time_frame>
    <description>Listing of clinically significant changes in PE findings</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with Clinical safety lab changes</measure>
    <time_frame>Screening to end of study, up to 18 weeks</time_frame>
    <description>Listing and change from baseline to end of study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with Systolic blood pressure changes</measure>
    <time_frame>Screening to end of study, up to 18 weeks</time_frame>
    <description>Listing and change from baseline to end of study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with Heart rate changes</measure>
    <time_frame>Screening to end of study, up to 18 weeks</time_frame>
    <description>Listing and change from baseline to end of study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with 12 Lead ECG changes</measure>
    <time_frame>Screening to end of study, up to 18 weeks</time_frame>
    <description>Change in 12-lead ECG parameters from baseline to end of study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration, Cmax</measure>
    <time_frame>Predose to Day 91 (SAD) and Day 127 (MAD)</time_frame>
    <description>Of ADX-914</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum observed plasma concentration, Tmax</measure>
    <time_frame>Predose to Day 91 (SAD) and Day 127 (MAD)</time_frame>
    <description>Of ADX-914</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the plasma concentration time curve, AUC</measure>
    <time_frame>Predose to Day 91 (SAD) and Day 127 (MAD)</time_frame>
    <description>Of ADX-914</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Safety Issues</condition>
  <arm_group>
    <arm_group_label>Experimental: Cohort 1:1 - 1:6 ADX-914</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ADX-914 single SC dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator: Cohort 1:1 - 1:6 placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo single SC dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Cohort 2:1- 2:3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ADX-914 multiple SC dose once every 2 weeks for 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator: Cohort 2:1- 2:3</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo multiple SC dose once every 2 weeks for 6 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADX-914</intervention_name>
    <description>Single dose from 0.1mg/kg to TBD</description>
    <arm_group_label>Experimental: Cohort 1:1 - 1:6 ADX-914</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching single dose placebo</description>
    <arm_group_label>Placebo Comparator: Cohort 1:1 - 1:6 placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADX-914</intervention_name>
    <description>Multiple dose from TBD to TBD</description>
    <arm_group_label>Experimental: Cohort 2:1- 2:3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching multiple dose placebo</description>
    <arm_group_label>Placebo Comparator: Cohort 2:1- 2:3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy as determined by the Investigator, based on a medical evaluation including&#xD;
             medical history, physical examination, laboratory tests and ECG recording&#xD;
&#xD;
          -  Men and women age 18-50&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin&#xD;
             levels greater than 1.5 x the upper limit of normal (ULN) at Screening or Day -1.&#xD;
&#xD;
          -  QT-interval measurements corrected according to the Fridericia rule (QTcF &gt;450 msec)&#xD;
             during controlled rest at Screening or family history of long QT syndrome.&#xD;
&#xD;
          -  Any clinically significant abnormalities in rhythm, conduction, or morphology of the&#xD;
             resting ECG and any abnormalities in the 12-lead ECG that, in the judgment of the&#xD;
             Investigator, may interfere with the interpretation of QTc-interval changes, including&#xD;
             abnormal ST-T-wave morphology or left ventricular hypertrophy.&#xD;
&#xD;
          -  A clinically significant vital signs abnormality, as judged by the Investigator, at&#xD;
             Screening, or Day -1. This includes, but is not limited to, the following, in the&#xD;
             supine position: (a) systolic blood pressure &lt;90 or &gt;140 mmHg, (b) diastolic blood&#xD;
             pressure &lt;40 or &gt;90 mmHg, or (c) heart rate &lt;40 or &gt;100 beats per minute.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Nucleus Network</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>July 27, 2022</last_update_submitted>
  <last_update_submitted_qc>July 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT04485481
org study id: ADX-914-001
nct id: NCT04485481
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A two (2) part study to evaluate the safety, tolerability and PK of ADX-914
Part 1 - SAD:

      It is expected that there will be up to 6 cohorts of 8 participants per cohort. In each
      cohort, participants will be randomly assigned in a 3:1 ratio to receive either ADX-914 or
      matching placebo.

      It is planned that for each cohort in Part 1 a staggered 'sentinel' dose design will be used.

      Part 2 - MAD It is expected that there will be up to 3 cohorts of 8 participants per cohort.
      In each cohort, participants will be randomly assigned in a 3:1 ratio to receive either
      ADX-914 or matching placebo. Doses will occur every 2 weeks, for a total of 4 doses.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of subjects with adverse events
time frame: Screening to end of study, up to 18 weeks
description: Listing and summary of AE incidence
measure: Number of subjects with Physical exam findings
time frame: Screening to end of study, up to 18 weeks
description: Listing of clinically significant changes in PE findings
measure: Number of subjects with Clinical safety lab changes
time frame: Screening to end of study, up to 18 weeks
description: Listing and change from baseline to end of study
measure: Number of subjects with Systolic blood pressure changes
time frame: Screening to end of study, up to 18 weeks
description: Listing and change from baseline to end of study
measure: Number of subjects with Heart rate changes
time frame: Screening to end of study, up to 18 weeks
description: Listing and change from baseline to end of study
measure: Number of subjects with 12 Lead ECG changes
time frame: Screening to end of study, up to 18 weeks
description: Change in 12-lead ECG parameters from baseline to end of study
measure: Maximum observed plasma concentration, Cmax
time frame: Predose to Day 91 (SAD) and Day 127 (MAD)
description: Of ADX-914
measure: Time to reach maximum observed plasma concentration, Tmax
time frame: Predose to Day 91 (SAD) and Day 127 (MAD)
description: Of ADX-914
measure: Area Under the plasma concentration time curve, AUC
time frame: Predose to Day 91 (SAD) and Day 127 (MAD)
description: Of ADX-914
arm group label: Experimental: Cohort 1:1 - 1:6 ADX-914
arm group type: Experimental
description: ADX-914 single SC dose
arm group label: Placebo Comparator: Cohort 1:1 - 1:6 placebo
arm group type: Placebo Comparator
description: Placebo single SC dose
arm group label: Experimental: Cohort 2:1- 2:3
arm group type: Experimental
description: ADX-914 multiple SC dose once every 2 weeks for 6 weeks
arm group label: Placebo Comparator: Cohort 2:1- 2:3
arm group type: Placebo Comparator
description: Placebo multiple SC dose once every 2 weeks for 6 weeks
intervention type: Drug
intervention name: ADX-914
description: Single dose from 0.1mg/kg to TBD
arm group label: Experimental: Cohort 1:1 - 1:6 ADX-914
intervention type: Drug
intervention name: Placebo
description: Matching single dose placebo
arm group label: Placebo Comparator: Cohort 1:1 - 1:6 placebo
intervention type: Drug
intervention name: ADX-914
description: Multiple dose from TBD to TBD
arm group label: Experimental: Cohort 2:1- 2:3
intervention type: Drug
intervention name: Placebo
description: Matching multiple dose placebo
arm group label: Placebo Comparator: Cohort 2:1- 2:3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Australia
responsible party type: Sponsor
sharing ipd: No