<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/NCT03783377</url>
  </required_header>
  <id_info>
    <org_study_id>AROAPOC31001</org_study_id>
    <nct_id>NCT03783377</nct_id>
  </id_info>
  <brief_title>Study of ARO-APOC3 in Healthy Volunteers, Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome (FCS)</brief_title>
  <official_title>A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Arrowhead Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Arrowhead Pharmaceuticals</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and&#xD;
      pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and&#xD;
      in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 8, 2019</start_date>
  <completion_date type="Actual">February 11, 2021</completion_date>
  <primary_completion_date type="Actual">February 11, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment</measure>
    <time_frame>Up to Day 113 (+/- 3 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of ARO-APOC3 in Normal Healthy Volunteers (NHVs): Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Single dose phase: Up to 48 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of ARO-APOC3 in NHVs: Time to Maximum Plasma Concentration (Tmax)</measure>
    <time_frame>Single dose phase: Up to 48 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of ARO-APOC3 in NHVs: Terminal Elimination Half-Life (t1/2)</measure>
    <time_frame>Single dose phase: Up to 48 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)</measure>
    <time_frame>Single dose phase: Up to 48 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)</measure>
    <time_frame>Single dose phase: Up to 48 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in Fasting Serum APOC3 from Pre-Dose Baseline</measure>
    <time_frame>Up to Day 113 (+/- 3 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">112</enrollment>
  <condition>Hypertriglyceridemia</condition>
  <condition>Familial Chylomicronemia</condition>
  <arm_group>
    <arm_group_label>ARO-APOC3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ARO-APOC3</intervention_name>
    <description>single or multiple doses of ARO-APOC3 by subcutaneous (sc) injections</description>
    <arm_group_label>ARO-APOC3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sterile normal saline (0.9% NaCl)</intervention_name>
    <description>calculated volume to match active treatment</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women of childbearing potential must have a negative pregnancy test, cannot be&#xD;
             breastfeeding and must be willing to use contraception&#xD;
&#xD;
          -  Willing to provide written informed consent and to comply with study requirements&#xD;
&#xD;
          -  Normal electrocardiogram (ECG) at screening&#xD;
&#xD;
          -  Hypertriglyceridemic patients must have a history of fasting serum triglycerides of at&#xD;
             least 300 mg/dL (3.38 mmol/L) at screening or verifiable diagnosis of FCS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant health concerns&#xD;
&#xD;
          -  Regular use of alcohol within one month prior to Screening&#xD;
&#xD;
          -  Use of an investigational agent or device within 30 days prior to dosing or current&#xD;
             participation in an investigational study&#xD;
&#xD;
          -  Recent use of illicit drugs&#xD;
&#xD;
          -  Use of more than two tobacco/nicotine containing or cannabis products per month within&#xD;
             6 months prior to drug administration (applicable only to Normal Healthy Volunteers)&#xD;
&#xD;
        Note: additional inclusion/exclusion criteria may apply, per protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of the Sunshine Coast Clinical Trial Centre</name>
      <address>
        <city>Sippy Downs</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linear Clinical Research</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robarts Research Institute</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ecogene-21</name>
      <address>
        <city>Chicoutimi</city>
        <state>Quebec</state>
        <zip>G7H 7K9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute de Recherches Cliniques de Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W 1R7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland Clinical Studies Limited</name>
      <address>
        <city>Grafton</city>
        <state>Auckland</state>
        <zip>1010</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Middlemore Hospital</name>
      <address>
        <city>Papatoetoe</city>
        <state>Auckland</state>
        <zip>2025</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lipid &amp; Diabetes Research Group</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>March 2, 2021</last_update_submitted>
  <last_update_submitted_qc>March 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 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>Hyperlipoproteinemia Type I</mesh_term>
    <mesh_term>Hypertriglyceridemia</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/NCT03783377
org study id: AROAPOC31001
nct id: NCT03783377
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and
      pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and
      in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment
time frame: Up to Day 113 (+/- 3 days)
measure: Pharmacokinetics (PK) of ARO-APOC3 in Normal Healthy Volunteers (NHVs): Maximum Observed Plasma Concentration (Cmax)
time frame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Time to Maximum Plasma Concentration (Tmax)
time frame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Terminal Elimination Half-Life (t1/2)
time frame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
time frame: Single dose phase: Up to 48 hours post-dose
measure: PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
time frame: Single dose phase: Up to 48 hours post-dose
measure: Reduction in Fasting Serum APOC3 from Pre-Dose Baseline
time frame: Up to Day 113 (+/- 3 days)
arm group label: ARO-APOC3
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: ARO-APOC3
description: single or multiple doses of ARO-APOC3 by subcutaneous (sc) injections
arm group label: ARO-APOC3
intervention type: Drug
intervention name: sterile normal saline (0.9% NaCl)
description: calculated volume to match active treatment
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Canada
country: New Zealand
responsible party type: Sponsor
mesh term: Hyperlipoproteinemia Type I
mesh term: Hypertriglyceridemia
sharing ipd: No