<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/NCT04442347</url>
  </required_header>
  <id_info>
    <org_study_id>ARCT-810-02</org_study_id>
    <nct_id>NCT04442347</nct_id>
  </id_info>
  <brief_title>Phase 1b Study to Assess Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With Ornithine Transcarbamylase Deficiency</brief_title>
  <official_title>A Phase 1b Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Clinically Stable Patients With Ornithine Transcarbamylase Deficiency</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in&#xD;
      clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia&#xD;
      scavengers) with ornithine transcarbamylase deficiency (OTCD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single ascending dose study of ARCT-810 in which approximately 12 (up to a maximum&#xD;
      of 20) clinically stable patients with ornithine transcarbamylase deficiency (OTCD) are&#xD;
      planned to be enrolled.&#xD;
&#xD;
      Each study subject's participation length is approximately 8 weeks, from screening through&#xD;
      last study visit. The study comprises an up to 4-week screening period, and a 4-week diet&#xD;
      run-in period, to occur concurrently, followed by a 1-day dosing period and a 28-day&#xD;
      post-treatment period.&#xD;
&#xD;
      Study participants will be allocated to one of the three single-dose treatment groups (also&#xD;
      referred to as cohorts), to test different doses of ARCT-810. Four subjects will be enrolled&#xD;
      in each group. Within each cohort, subjects will be randomized 3:1 to receive ARCT-810 or&#xD;
      placebo as an IV infusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 3, 2020</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</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 adverse events (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>Change in area under the curve after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>The maximum observed plasma concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time at which Cmax occurred after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>The time at which Cmax occurred (Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>AUC from time zero extrapolated to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCExtrap after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>The relative portion of AUC0-inf extrapolated beyond AUC0-t</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2 after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Terminal half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRT0-inf after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>The mean residence time extrapolated to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Total body clearance, calculated as dose divided by AUC0-inf</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vss after single dose of ARCT-810</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Volume of distribution</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">12</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 Ornithine Transcarbamylase (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. Adequate cognitive ability to consent and recall symptoms over a 1-week time period&#xD;
&#xD;
          2. Males and females ≥18 years of age with documented diagnosis of ornithine&#xD;
             transcarbamylase deficiency (OTCD) confirmed with genetic testing, or willing to&#xD;
             consent to OTC gene sequencing and deletion/duplication testing&#xD;
&#xD;
          3. Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by&#xD;
&#xD;
               1. no clinical symptoms of hyperammonemia AND b,&#xD;
&#xD;
               2. an ammonia level &lt;100 µmol/L (170 µg/dL) at the screening evaluation Subjects&#xD;
                  must remain free from symptoms of hyperammonemia throughout the screening period.&#xD;
&#xD;
          4. If using nitrogen ammonia scavenger therapy, must be on a stable regimen (no change in&#xD;
             dose or frequency) for ≥ 28 days prior to providing informed consent and throughout&#xD;
             the screening period&#xD;
&#xD;
          5. Must have maintained a stable protein-restricted diet (+/- amino acid supplementation)&#xD;
             for at least 28 days prior to providing informed consent and continue to maintain a&#xD;
             stable diet for the duration of the study&#xD;
&#xD;
          6. Good general health other than OTCD, in the opinion of the Investigator&#xD;
&#xD;
          7. Willing to refrain from strenuous exercise/activity and alcohol for 72 hours before&#xD;
             study visits&#xD;
&#xD;
          8. Willingness to comply with procedures and visits&#xD;
&#xD;
          9. Willingness to follow contraception guidelines&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of clinically significant disease(s), in the opinion of the Investigator&#xD;
&#xD;
          2. Clinically significant screening laboratory values&#xD;
&#xD;
          3. Uncontrolled diabetes&#xD;
&#xD;
          4. Clinically significant anemia&#xD;
&#xD;
          5. Subjects who develop infection during screening must be asymptomatic for at least 7&#xD;
             days prior to dosing&#xD;
&#xD;
          6. Unwillingness to comply with study requirements&#xD;
&#xD;
          7. History of positive HIV, hepatitis C, or chronic hepatitis B&#xD;
&#xD;
          8. Uncontrolled hypertension&#xD;
&#xD;
          9. Malignancy within 5 years prior to study&#xD;
&#xD;
         10. Treatment with another investigational drug, biological agent, or device within 30&#xD;
             days of screening, or 5 half-lives of investigational drug&#xD;
&#xD;
         11. Treatment with any oligonucleotide or mRNA within 6 months of screening, with&#xD;
             exceptions for some vaccinations and investigational treatments&#xD;
&#xD;
         12. History of gene therapy, hepatocyte or mesenchymal stem cell transplantation&#xD;
&#xD;
         13. Prior organ transplant&#xD;
&#xD;
         14. History of severe allergic reaction to a liposomal product&#xD;
&#xD;
         15. Recent history of, or current, drug or alcohol abuse&#xD;
&#xD;
         16. Dependence on inhaled (smoked or vaped) or oral cannabis products&#xD;
&#xD;
         17. Systemic corticosteroids within 6 weeks prior to screening&#xD;
&#xD;
         18. Blood donation of 50 to 499 mL within 30 days of screening or of .499 mL within 60&#xD;
             days of screening&#xD;
&#xD;
         19. Other conditions, in the opinion of the Investigator, that would make the subject&#xD;
             unsuitable for participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M Health Fairview Masonic Children's Hospital</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center at Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University</name>
      <address>
        <city>Waco</city>
        <state>Texas</state>
        <zip>76706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Wisconsin - Milwaukee Hospital</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 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/NCT04442347
org study id: ARCT-810-02
nct id: NCT04442347
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in
      clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia
      scavengers) with ornithine transcarbamylase deficiency (OTCD).
This is a single ascending dose study of ARCT-810 in which approximately 12 (up to a maximum
      of 20) clinically stable patients with ornithine transcarbamylase deficiency (OTCD) are
      planned to be enrolled.

      Each study subject's participation length is approximately 8 weeks, from screening through
      last study visit. The study comprises an up to 4-week screening period, and a 4-week diet
      run-in period, to occur concurrently, followed by a 1-day dosing period and a 28-day
      post-treatment period.

      Study participants will be allocated to one of the three single-dose treatment groups (also
      referred to as cohorts), to test different doses of ARCT-810. Four subjects will be enrolled
      in each group. Within each cohort, subjects will be randomized 3:1 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 adverse events (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: Change in area under the curve after single dose of ARCT-810
time frame: Up to 4 weeks
description: Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point
measure: Maximum observed plasma concentration (Cmax) after single dose of ARCT-810
time frame: Up to 4 weeks
description: The maximum observed plasma concentration (Cmax)
measure: Time at which Cmax occurred after single dose of ARCT-810
time frame: Up to 4 weeks
description: The time at which Cmax occurred (Tmax)
measure: AUC0-inf after single dose of ARCT-810
time frame: Up to 4 weeks
description: AUC from time zero extrapolated to infinity
measure: AUCExtrap after single dose of ARCT-810
time frame: Up to 4 weeks
description: The relative portion of AUC0-inf extrapolated beyond AUC0-t
measure: T1/2 after single dose of ARCT-810
time frame: Up to 4 weeks
description: Terminal half-life
measure: MRT0-inf after single dose of ARCT-810
time frame: Up to 4 weeks
description: The mean residence time extrapolated to infinity
measure: CL after single dose of ARCT-810
time frame: Up to 4 weeks
description: Total body clearance, calculated as dose divided by AUC0-inf
measure: Vss after single dose of ARCT-810
time frame: Up to 4 weeks
description: Volume of distribution
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 Ornithine Transcarbamylase (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: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ornithine Carbamoyltransferase Deficiency Disease