<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/NCT04416126</url>
  </required_header>
  <id_info>
    <org_study_id>ARCT- 810-01</org_study_id>
    <nct_id>NCT04416126</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Pharmacokinetics of ARCT-810 in Healthy Adult Subjects</brief_title>
  <official_title>A Phase 1 Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Arcturus Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Arcturus Therapeutics, Inc.</source>
  <oversight_info>
    <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>
      Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in&#xD;
      healthy adult subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single ascending dose study of ARCT-810 in which approximately 30 subjects are&#xD;
      planned to be enrolled. The length of each study participant is approximately 8 weeks from&#xD;
      screening to last study visit.&#xD;
&#xD;
      Study participants will be allocated to one of the five different study groups (also called&#xD;
      cohorts), to test different doses of ARCT-810. There will be 6 participants in each group.&#xD;
      Within each cohort, subjects will be randomized 2:1 to receive ARCT-810 or placebo as an IV&#xD;
      infusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">December 9, 2020</completion_date>
  <primary_completion_date type="Actual">December 9, 2020</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>Double (Participant, Investigator)</masking>
    <masking_description>Double blinded, Placebo Controlled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence, severity and dose-relationship of AEs</measure>
    <time_frame>4 weeks</time_frame>
    <description>Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with changes in plasma pharmacokinetic parameters after single dose of ARCT-810</measure>
    <time_frame>Up to 15 days</time_frame>
    <description>The plasma pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with changes in urine pharmacokinetic parameters after single dose of ARCT-810</measure>
    <time_frame>Up to 24 hours</time_frame>
    <description>The urine pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Ornithine Transcarbamylase Deficiency</condition>
  <arm_group>
    <arm_group_label>ARCT-810</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ascending single doses of ARCT-810 administered intravenously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single doses of 0.9% Saline administered intravenously</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ARCT-810</intervention_name>
    <description>ARCT-810 is an investigational medicinal product comprising OTC mRNA formulated in a lipid nanoparticle (LNP) under development.</description>
    <arm_group_label>ARCT-810</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo for this study is 0.9% sterile saline.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy males or females aged 18 to 65 at the time of informed consent.&#xD;
&#xD;
          2. Body weight ≤ 100Kg and body mass index &lt;35 kg/m2&#xD;
&#xD;
          3. Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight&#xD;
             training, intense aerobics classes etc.) and alcohol for at least 72 hours prior to&#xD;
             study visits and willing to refrain from taking protein supplements for the duration&#xD;
             of the study.&#xD;
&#xD;
          4. Willing and able to comply with protocol-defined procedures and complete all study&#xD;
             visits&#xD;
&#xD;
          5. Males must be surgically sterile or, if engaged in sexual relations with a female of&#xD;
             child-bearing potential, the subject must be using an acceptable contraceptive method&#xD;
             from the time of signing the informed consent form until at least 30 days after the&#xD;
             last dose of Study Drug. Females: must be non-pregnant and non-lactating and either:&#xD;
             i. surgically sterile or ii. post-menopausal&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinically significant abnormalities in medical history&#xD;
&#xD;
          2. Screening laboratory results as follows:&#xD;
&#xD;
               -  ALT, AST, GGT, total bilirubin or alkaline phosphatase, &gt; ULN.&#xD;
&#xD;
               -  Random blood glucose and/or HbA1c &gt; ULN&#xD;
&#xD;
               -  Hemoglobin &lt; LLN&#xD;
&#xD;
               -  Platelet count &lt; 100x109/L&#xD;
&#xD;
               -  Estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73m2 calculated by&#xD;
                  Modification to Diet in Renal Disease [MDRD] study equation.&#xD;
&#xD;
               -  Urine protein:creatinine ratio (UPCR) &gt; 50 mg/mmol&#xD;
&#xD;
          3. Active infection requiring systemic antiviral or antimicrobial therapy that will not&#xD;
             be completed within 7 days prior to Study Day 1&#xD;
&#xD;
          4. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C&#xD;
             or chronic hepatitis B&#xD;
&#xD;
          5. Uncontrolled hypertension (BP &gt; 160/100 mm Hg)&#xD;
&#xD;
          6. Treatment with another investigational drug, biological agent, or device within one&#xD;
             month of screening, or 5 half-lives of investigational drug, whichever is longer&#xD;
&#xD;
          7. Recent (within 1 year) history of, or current drug or alcohol abuse&#xD;
&#xD;
          8. Have any other conditions, which, in the opinion of the Investigator or Sponsor would&#xD;
             make the subject unsuitable for inclusion, or could interfere with the subject&#xD;
             participating in or completing the Study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christian Schwabe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Auckland Clinical Studies (ACS) Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Auckland Clinical Studies (ACS) Ltd.</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>April 6, 2023</last_update_submitted>
  <last_update_submitted_qc>April 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</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>Ornithine Carbamoyltransferase Deficiency Disease</mesh_term>
  </condition_browse>
  <!-- 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/NCT04416126
org study id: ARCT- 810-01
nct id: NCT04416126
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in
      healthy adult subjects.
This is a single ascending dose study of ARCT-810 in which approximately 30 subjects are
      planned to be enrolled. The length of each study participant is approximately 8 weeks from
      screening to last study visit.

      Study participants will be allocated to one of the five different study groups (also called
      cohorts), to test different doses of ARCT-810. There will be 6 participants in each group.
      Within each cohort, subjects will be randomized 2:1 to receive ARCT-810 or placebo as an IV
      infusion.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double blinded, Placebo Controlled
measure: Incidence, severity and dose-relationship of AEs
time frame: 4 weeks
description: Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose
measure: Number of participants with changes in plasma pharmacokinetic parameters after single dose of ARCT-810
time frame: Up to 15 days
description: The plasma pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose
measure: Number of participants with changes in urine pharmacokinetic parameters after single dose of ARCT-810
time frame: Up to 24 hours
description: The urine pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose
arm group label: ARCT-810
arm group type: Experimental
description: Ascending single doses of ARCT-810 administered intravenously
arm group label: Placebo
arm group type: Placebo Comparator
description: Single doses of 0.9% Saline administered intravenously
intervention type: Biological
intervention name: ARCT-810
description: ARCT-810 is an investigational medicinal product comprising OTC mRNA formulated in a lipid nanoparticle (LNP) under development.
arm group label: ARCT-810
intervention type: Other
intervention name: Placebo
description: The placebo for this study is 0.9% sterile saline.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christian Schwabe, MD
role: Principal Investigator
affiliation: Auckland Clinical Studies (ACS) Ltd.
facility: 
country: New Zealand
responsible party type: Sponsor
mesh term: Ornithine Carbamoyltransferase Deficiency Disease