<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/NCT02991144</url>
  </required_header>
  <id_info>
    <org_study_id>301OTC01</org_study_id>
    <secondary_id>2016-001057-40</secondary_id>
    <nct_id>NCT02991144</nct_id>
  </id_info>
  <brief_title>Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset Ornithine Transcarbamylase (OTC) Deficiency</brief_title>
  <acronym>CAPtivate</acronym>
  <official_title>A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Adults With Late-Onset OTC Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ultragenyx Pharmaceutical Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ultragenyx Pharmaceutical Inc</source>
  <oversight_info>
    <has_dmc>Yes</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 is a Phase 1/2, open-label, single arm, multicenter, safety and dose finding study of&#xD;
      DTX301 in adults with late-onset OTC deficiency. The primary objective of the study is to&#xD;
      determine the safety of single intravenous (IV) doses of DTX301.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible participants will receive a single IV infusion of DTX301. Dose escalation will be&#xD;
      conducted according to a model that uses the collected data to predict the safety profile of&#xD;
      the dose in order to determine the optimal biological dose (OBD). The decision to proceed to&#xD;
      the next dose cohort will be made after the data monitoring committee (DMC) has evaluated the&#xD;
      safety data for all participants in a dosing cohort. Participants will be followed for 52&#xD;
      weeks after dosing. After completion of this study, participants will be asked to enroll in a&#xD;
      4-year extension study to evaluate the long term (a total of 5 years) safety and efficacy of&#xD;
      DTX301.&#xD;
&#xD;
      This study was previously posted by Dimension Therapeutics, which has been acquired by&#xD;
      Ultragenyx.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2017</start_date>
  <completion_date type="Actual">December 16, 2021</completion_date>
  <primary_completion_date type="Actual">December 16, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and TEAEs Leading to Discontinuation</measure>
    <time_frame>AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug up to End of Study (Week 52).</time_frame>
    <description>AE: any untoward medical occurrence regardless of its causal relationship to study product. TEAE: any event not present before exposure to study product or any event already present that worsens in either intensity or frequency after exposure to study product. SAE: any event that results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is an important medical event, according to the investigator. AE intensity was rated as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life threatening), or 5 (death) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). The relationship or association of the study product in causing or contributing to the AE was characterized as: unrelated; possible; probably; definite.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Over Time in Rate of Ureagenesis</measure>
    <time_frame>Baseline (Day 0), Weeks 6, 12, 20, 24, End of Study (Week 52). AUC was derived based on the following time points: 0.5, 1, 1.5, 2, 3, and 4 hours postdose.</time_frame>
    <description>The change from baseline in the rate of ureagenesis (as measured by the generation of [13C]urea over 4 hours) as determined by gas chromatography mass spectrometry over time to 52 weeks after the IV administration of DTX301. Sodium acetate was used as a tracer to measure the rate of ureagenesis.&#xD;
Rate of ureagenesis was derived in the following manner:&#xD;
Derive area under the curve from time zero to 240 minutes (AUC0-240min) of absolute 13C-urea (µmol/l/min) estimated by the linear trapezoidal rule&#xD;
Derive percent of normal AUC0-240min of absolute 13C-urea by dividing AUC0-240min of absolute 13C-urea (µmol*min/L) by 669.56 µmol*min/L (i.e. the AUC0-240min of absolute 13C-urea for an adult control)&#xD;
Derive rate of ureagenesis by multiplying % of normal AUC0-240min of absolute 13C-urea by 300 µmol*h/kg (i.e. the approximate rate of ureagenesis in healthy adults).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Over Time in Area Under the Curve From Time Zero to 24 Hours (AUC0-24) of Plasma Ammonia</measure>
    <time_frame>Baseline (Day 0), Weeks 6, 12, 24, End of Study (Week 52). AUC was derived based on predose (time 0) and approximately 2, 4, 8, 12, 16, 20, 24 hours (±5 minutes) postdose.</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Ornithine Transcarbamylase (OTC) Deficiency</condition>
  <arm_group>
    <arm_group_label>Cohort 1: DTX301 2.0 × 10^12 GC/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: DTX301 6.0 × 10^12 GC/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: DTX301 1.0 × 10^13 GC/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A prophylactic corticosteroid taper regimen (oral prednisone [or prednisolone], 60 mg tapered over 9 weeks) will be administered before dosing with DTX301 (scAAV8OTC) to prevent or minimize transient vector-induced hepatic effects. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>scAAV8OTC</intervention_name>
    <description>non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC)</description>
    <arm_group_label>Cohort 1: DTX301 2.0 × 10^12 GC/kg</arm_group_label>
    <arm_group_label>Cohort 2: DTX301 6.0 × 10^12 GC/kg</arm_group_label>
    <arm_group_label>Cohort 3: DTX301 1.0 × 10^13 GC/kg</arm_group_label>
    <arm_group_label>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</arm_group_label>
    <other_name>DTX301</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Reactive Corticosteroid Taper Regimen</intervention_name>
    <description>Oral prednisone [or oral prednisolone] 60 mg/day week 1, 40 mg/day Week 2, 30 mg/day Weeks 3 and 4, tapered by 5 mg/week Week 5 and beyond until liver enzymes return to baseline levels.&#xD;
Corticosteroid treatment will be considered when a participant's alanine aminotransferase (ALT) level exceeded the upper limit of normal (ULN) and the ALT increase was considered by the Investigator to be related to DTX301.</description>
    <arm_group_label>Cohort 1: DTX301 2.0 × 10^12 GC/kg</arm_group_label>
    <arm_group_label>Cohort 2: DTX301 6.0 × 10^12 GC/kg</arm_group_label>
    <arm_group_label>Cohort 3: DTX301 1.0 × 10^13 GC/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prophylactic Corticosteroid Taper Regimen</intervention_name>
    <description>Oral prednisone [or oral prednisolone] 60 mg/day at least 5 days prior to DTX301 administration, tapered over 9 weeks.&#xD;
A prophylactic corticosteroid taper regimen will be administered to prevent or minimize transient vector-induced hepatic effects.</description>
    <arm_group_label>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Males and females ≥18 years of age with documented diagnosis of late onset (defined as&#xD;
             first manifestation of signs and symptoms at ≥1 month of age) OTC deficiency,&#xD;
             confirmed via enzymatic, biochemical, or molecular testing&#xD;
&#xD;
          2. Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L.&#xD;
&#xD;
          3. Subject's OTC deficiency is stable as evidenced by either a) no clinical symptoms of&#xD;
             hyperammonemia OR b) an ammonia level &lt;100 µmol/L within the 4 week period preceding&#xD;
             the Screening visit.&#xD;
&#xD;
          4. On ongoing daily stable dose of ammonia scavenger therapy for ≥4 weeks.&#xD;
&#xD;
          5. Males and all females of childbearing potential must be willing to use effective&#xD;
             contraception at the time of administration of gene transfer and for the 52 weeks&#xD;
             following administration of DTX301&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. At Screening or Baseline (Day 0), plasma ammonia level ≥ 100 μmol/L for patients who&#xD;
             historically maintain normal ammonia levels; OR plasma ammonia level ≥ 200 μmol/L for&#xD;
             patients who historically are not able to fully control ammonia levels with baseline&#xD;
             management; OR signs and symptoms of hyperammonemia.&#xD;
&#xD;
          2. Liver transplant, including hepatocyte cell therapy/transplant.&#xD;
&#xD;
          3. History of liver disease&#xD;
&#xD;
          4. Significant hepatic inflammation or cirrhosis&#xD;
&#xD;
          5. Serum creatinine &gt;2.0 mg/dL.&#xD;
&#xD;
          6. Participation in another investigational medicine study (including another gene&#xD;
             transfer trial) within 3 months of Screening&#xD;
&#xD;
          7. Pregnant or nursing&#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>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Ultragenyx Pharmaceutical Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029-6508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Cleveland Medical Center/Case Western Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alberta's Children's Hospital</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T3B 6A8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Santiago</name>
      <address>
        <city>Santiago de Compostela</city>
        <state>A Coruna</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Cruzes</name>
      <address>
        <city>Barakaldo</city>
        <state>Vizcaya</state>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital for Neurology &amp; Neurosurgery</name>
      <address>
        <city>London</city>
        <state>London City</state>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <results_first_submitted>December 9, 2022</results_first_submitted>
  <results_first_submitted_qc>December 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 23, 2022</results_first_posted>
  <last_update_submitted>January 23, 2023</last_update_submitted>
  <last_update_submitted_qc>January 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gene Transfer</keyword>
  <keyword>OTC Deficiency</keyword>
  <keyword>Urea Cycle Disorder</keyword>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 25, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT02991144/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 25, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT02991144/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 27 subjects were screened for the study, 16 of whom were enrolled. Of the 16 participants enrolled, 5 participants discontinued the study before receiving DTX301, and were not assigned to a treatment arm.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: DTX301 2.0 × 10^12 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg administered as a single peripheral intravenous (IV) infusion.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2: DTX301 6.0 × 10^12 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 3: DTX301 1.0 × 10^13 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="P4">
          <title>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</title>
          <description>Oral prednisone (or prednisolone), 60 mg tapered over 9 weeks, initiated before dosing with DTX301 (scAAV8OTC) and administered through Week 4. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: DTX301 2.0 × 10^12 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2: DTX301 6.0 × 10^12 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="B3">
          <title>Cohort 3: DTX301 1.0 × 10^13 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="B4">
          <title>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</title>
          <description>Oral prednisone (or prednisolone), 60 mg tapered over 9 weeks, initiated before dosing with DTX301 (scAAV8OTC) and administered through Week 4. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="2"/>
            <count group_id="B5" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="2"/>
                    <count group_id="B5" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.3" spread="11.06"/>
                    <measurement group_id="B2" value="27.7" spread="1.15"/>
                    <measurement group_id="B3" value="26.7" spread="7.09"/>
                    <measurement group_id="B4" value="30.5" spread="13.44"/>
                    <measurement group_id="B5" value="29.2" spread="7.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="2"/>
                    <count group_id="B5" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="2"/>
                    <count group_id="B5" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="2"/>
                    <count group_id="B5" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Rate of Ureagenesis</title>
          <description>Rate of ureagenesis (as measured by the generation of [13C]urea over 4 hours; see outcome measure 2 for details). Baseline is defined as the average of all non-missing assessments taken before the study drug administration. If the absolute difference of results between Screening and Day 1 was ≥ 25% of normal rate of ureagenesis, then the screening value is defined as the baseline.</description>
          <units>μmol*h/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="2"/>
                    <count group_id="B5" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="166.293" spread="28.0167"/>
                    <measurement group_id="B2" value="103.329" spread="76.9798"/>
                    <measurement group_id="B3" value="115.492" spread="71.0753"/>
                    <measurement group_id="B4" value="174.678" spread="210.9140"/>
                    <measurement group_id="B5" value="136.791" spread="88.4373"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Area Under the Curve From Time Zero to 24 Hours (AUC0 24) of Plasma Ammonia</title>
          <description>Baseline is defined as the Day -1 result.</description>
          <population>participants with a baseline assessment</population>
          <units>μmol*h/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="1"/>
                    <count group_id="B4" value="2"/>
                    <count group_id="B5" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1831.78" spread="1445.240"/>
                    <measurement group_id="B2" value="2153.74" spread="1406.173"/>
                    <measurement group_id="B3" value="4444.76" spread="NA">1 participant analyzed</measurement>
                    <measurement group_id="B4" value="1834.39" spread="1091.019"/>
                    <measurement group_id="B5" value="2230.01" spread="1370.847"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and TEAEs Leading to Discontinuation</title>
        <description>AE: any untoward medical occurrence regardless of its causal relationship to study product. TEAE: any event not present before exposure to study product or any event already present that worsens in either intensity or frequency after exposure to study product. SAE: any event that results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is an important medical event, according to the investigator. AE intensity was rated as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life threatening), or 5 (death) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). The relationship or association of the study product in causing or contributing to the AE was characterized as: unrelated; possible; probably; definite.</description>
        <time_frame>AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug up to End of Study (Week 52).</time_frame>
        <population>Safety Set: all participants who received DTX301.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: DTX301 2.0 × 10^12 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: DTX301 6.0 × 10^12 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: DTX301 1.0 × 10^13 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</title>
            <description>Oral prednisone (or prednisolone), 60 mg tapered over 9 weeks, initiated before dosing with DTX301 (scAAV8OTC) and administered through Week 4. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and TEAEs Leading to Discontinuation</title>
          <description>AE: any untoward medical occurrence regardless of its causal relationship to study product. TEAE: any event not present before exposure to study product or any event already present that worsens in either intensity or frequency after exposure to study product. SAE: any event that results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is an important medical event, according to the investigator. AE intensity was rated as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life threatening), or 5 (death) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). The relationship or association of the study product in causing or contributing to the AE was characterized as: unrelated; possible; probably; definite.</description>
          <population>Safety Set: all participants who received DTX301.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any AE prior to dosing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE with grade &gt;=3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any study drug-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE related to corticosteroid regimen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any hyperammonemic crisis-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any study drug-related serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any study drug-related TEAE with grade &gt;=3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE leading to study discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any adverse event leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Over Time in Rate of Ureagenesis</title>
        <description>The change from baseline in the rate of ureagenesis (as measured by the generation of [13C]urea over 4 hours) as determined by gas chromatography mass spectrometry over time to 52 weeks after the IV administration of DTX301. Sodium acetate was used as a tracer to measure the rate of ureagenesis.&#xD;
Rate of ureagenesis was derived in the following manner:&#xD;
Derive area under the curve from time zero to 240 minutes (AUC0-240min) of absolute 13C-urea (µmol/l/min) estimated by the linear trapezoidal rule&#xD;
Derive percent of normal AUC0-240min of absolute 13C-urea by dividing AUC0-240min of absolute 13C-urea (µmol*min/L) by 669.56 µmol*min/L (i.e. the AUC0-240min of absolute 13C-urea for an adult control)&#xD;
Derive rate of ureagenesis by multiplying % of normal AUC0-240min of absolute 13C-urea by 300 µmol*h/kg (i.e. the approximate rate of ureagenesis in healthy adults).</description>
        <time_frame>Baseline (Day 0), Weeks 6, 12, 20, 24, End of Study (Week 52). AUC was derived based on the following time points: 0.5, 1, 1.5, 2, 3, and 4 hours postdose.</time_frame>
        <population>Safety Set: all participants who received DTX301.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: DTX301 2.0 × 10^12 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: DTX301 6.0 × 10^12 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: DTX301 1.0 × 10^13 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</title>
            <description>Oral prednisone (or prednisolone), 60 mg tapered over 9 weeks, initiated before dosing with DTX301 (scAAV8OTC) and administered through Week 4. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Over Time in Rate of Ureagenesis</title>
          <description>The change from baseline in the rate of ureagenesis (as measured by the generation of [13C]urea over 4 hours) as determined by gas chromatography mass spectrometry over time to 52 weeks after the IV administration of DTX301. Sodium acetate was used as a tracer to measure the rate of ureagenesis.&#xD;
Rate of ureagenesis was derived in the following manner:&#xD;
Derive area under the curve from time zero to 240 minutes (AUC0-240min) of absolute 13C-urea (µmol/l/min) estimated by the linear trapezoidal rule&#xD;
Derive percent of normal AUC0-240min of absolute 13C-urea by dividing AUC0-240min of absolute 13C-urea (µmol*min/L) by 669.56 µmol*min/L (i.e. the AUC0-240min of absolute 13C-urea for an adult control)&#xD;
Derive rate of ureagenesis by multiplying % of normal AUC0-240min of absolute 13C-urea by 300 µmol*h/kg (i.e. the approximate rate of ureagenesis in healthy adults).</description>
          <population>Safety Set: all participants who received DTX301.</population>
          <units>μmol*h/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.139" spread="83.3604"/>
                    <measurement group_id="O2" value="46.857" spread="105.9147"/>
                    <measurement group_id="O3" value="-29.017" spread="127.2471"/>
                    <measurement group_id="O4" value="14.586" spread="17.3499"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.363" spread="51.2516"/>
                    <measurement group_id="O2" value="20.897" spread="56.9733"/>
                    <measurement group_id="O3" value="7.544" spread="133.1715"/>
                    <measurement group_id="O4" value="65.781" spread="33.9137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.929" spread="71.0500"/>
                    <measurement group_id="O2" value="77.465" spread="67.1567"/>
                    <measurement group_id="O3" value="-0.194" spread="112.5922"/>
                    <measurement group_id="O4" value="67.103" spread="102.5409"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.540" spread="136.5861"/>
                    <measurement group_id="O2" value="65.513" spread="50.5169"/>
                    <measurement group_id="O3" value="45.114" spread="147.5760"/>
                    <measurement group_id="O4" value="63.854" spread="106.7694"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at End of Study (Week 52)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.611" spread="171.0689"/>
                    <measurement group_id="O2" value="114.446" spread="98.8701"/>
                    <measurement group_id="O3" value="10.016" spread="47.9128"/>
                    <measurement group_id="O4" value="128.023" spread="131.6469"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Over Time in Area Under the Curve From Time Zero to 24 Hours (AUC0-24) of Plasma Ammonia</title>
        <time_frame>Baseline (Day 0), Weeks 6, 12, 24, End of Study (Week 52). AUC was derived based on predose (time 0) and approximately 2, 4, 8, 12, 16, 20, 24 hours (±5 minutes) postdose.</time_frame>
        <population>Safety Set: all participants who received DTX301. Participants with an assessment at given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: DTX301 2.0 × 10^12 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: DTX301 6.0 × 10^12 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: DTX301 1.0 × 10^13 GC/kg</title>
            <description>DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</title>
            <description>Oral prednisone (or prednisolone), 60 mg tapered over 9 weeks, initiated before dosing with DTX301 (scAAV8OTC) and administered through Week 4. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Over Time in Area Under the Curve From Time Zero to 24 Hours (AUC0-24) of Plasma Ammonia</title>
          <population>Safety Set: all participants who received DTX301. Participants with an assessment at given time point.</population>
          <units>μmol*h/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="1"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.69" spread="104.381"/>
                    <measurement group_id="O2" value="-1334.27" spread="1271.205"/>
                    <measurement group_id="O3" value="-3790.83" spread="NA">1 participant analyzed</measurement>
                    <measurement group_id="O4" value="-1095.20" spread="785.719"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="1"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-264.07" spread="1471.172"/>
                    <measurement group_id="O2" value="-1384.95" spread="1279.839"/>
                    <measurement group_id="O3" value="-3827.36" spread="NA">1 participant analyzed</measurement>
                    <measurement group_id="O4" value="-1242.69" spread="931.242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="1"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-252.54" spread="586.131"/>
                    <measurement group_id="O2" value="-1065.48" spread="1024.167"/>
                    <measurement group_id="O3" value="-3978.51" spread="NA">1 participant analyzed</measurement>
                    <measurement group_id="O4" value="-1276.25" spread="943.999"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at End of Study (Week 52)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                    <count group_id="O3" value="1"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-381.54" spread="1116.898"/>
                    <measurement group_id="O2" value="-387.02" spread="277.086"/>
                    <measurement group_id="O3" value="-594.76" spread="NA">1 participant analyzed</measurement>
                    <measurement group_id="O4" value="-359.17" spread="1641.519"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All Cause Mortality: from screening up to End of Study (Week 52). Adverse Events and Serious Adverse Events: From first dose of study drug up to End of Study (Week 52).</time_frame>
      <desc>2 enrolled participants died before receiving DTX301, and were not assigned to a treatment arm. These participants are reflected in the 'total' column of the all-cause mortality table.</desc>
      <group_list>
        <group group_id="E1">
          <title>DTX301 2.0 × 10^12 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="E2">
          <title>DTX301 6.0 × 10^12 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="E3">
          <title>DTX301 1.0 × 10^13 GC/kg</title>
          <description>DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="E4">
          <title>DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids</title>
          <description>Oral prednisone (or prednisolone), 60 mg tapered over 9 weeks, initiated before dosing with DTX301 (scAAV8OTC) and administered through Week 4. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion.</description>
        </group>
        <group group_id="E5">
          <title>Total</title>
          <description>All Participants</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperammonaemic Crisis</sub_title>
                <description>There were 2 serious adverse events of hyperammonaemic crisis that occurred in 1 subject post-dosing.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Cushingoid</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Retching</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter Site Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Feeling Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Feeling Jittery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gait Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Gallbladder Polyp</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hepatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Exposure To Sars-Cov-2</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic Enzyme Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Liver Function Test Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Liver Function Test Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperammonaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neuropathy Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Claustrophobia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Phonophobia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper-Airway Cough Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Information</name_or_title>
      <organization>Ultragenyx Pharmaceutical Inc</organization>
      <phone>1-888-756-8657</phone>
      <email>medinfo@ultragenyx.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02991144
org study id: 301OTC01
secondary id: 2016-001057-40
nct id: NCT02991144
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1/2, open-label, single arm, multicenter, safety and dose finding study of
      DTX301 in adults with late-onset OTC deficiency. The primary objective of the study is to
      determine the safety of single intravenous (IV) doses of DTX301.
Eligible participants will receive a single IV infusion of DTX301. Dose escalation will be
      conducted according to a model that uses the collected data to predict the safety profile of
      the dose in order to determine the optimal biological dose (OBD). The decision to proceed to
      the next dose cohort will be made after the data monitoring committee (DMC) has evaluated the
      safety data for all participants in a dosing cohort. Participants will be followed for 52
      weeks after dosing. After completion of this study, participants will be asked to enroll in a
      4-year extension study to evaluate the long term (a total of 5 years) safety and efficacy of
      DTX301.

      This study was previously posted by Dimension Therapeutics, which has been acquired by
      Ultragenyx.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and TEAEs Leading to Discontinuation
time frame: AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug up to End of Study (Week 52).
description: AE: any untoward medical occurrence regardless of its causal relationship to study product. TEAE: any event not present before exposure to study product or any event already present that worsens in either intensity or frequency after exposure to study product. SAE: any event that results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is an important medical event, according to the investigator. AE intensity was rated as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life threatening), or 5 (death) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). The relationship or association of the study product in causing or contributing to the AE was characterized as: unrelated; possible; probably; definite.
measure: Change From Baseline Over Time in Rate of Ureagenesis
time frame: Baseline (Day 0), Weeks 6, 12, 20, 24, End of Study (Week 52). AUC was derived based on the following time points: 0.5, 1, 1.5, 2, 3, and 4 hours postdose.
description: The change from baseline in the rate of ureagenesis (as measured by the generation of [13C]urea over 4 hours) as determined by gas chromatography mass spectrometry over time to 52 weeks after the IV administration of DTX301. Sodium acetate was used as a tracer to measure the rate of ureagenesis.
Rate of ureagenesis was derived in the following manner:
Derive area under the curve from time zero to 240 minutes (AUC0-240min) of absolute 13C-urea (µmol/l/min) estimated by the linear trapezoidal rule
Derive percent of normal AUC0-240min of absolute 13C-urea by dividing AUC0-240min of absolute 13C-urea (µmol*min/L) by 669.56 µmol*min/L (i.e. the AUC0-240min of absolute 13C-urea for an adult control)
Derive rate of ureagenesis by multiplying % of normal AUC0-240min of absolute 13C-urea by 300 µmol*h/kg (i.e. the approximate rate of ureagenesis in healthy adults).
measure: Change From Baseline Over Time in Area Under the Curve From Time Zero to 24 Hours (AUC0-24) of Plasma Ammonia
time frame: Baseline (Day 0), Weeks 6, 12, 24, End of Study (Week 52). AUC was derived based on predose (time 0) and approximately 2, 4, 8, 12, 16, 20, 24 hours (±5 minutes) postdose.
arm group label: Cohort 1: DTX301 2.0 × 10^12 GC/kg
arm group type: Experimental
description: DTX301 (scAAV8OTC) 2.0 × 10^12 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.
arm group label: Cohort 2: DTX301 6.0 × 10^12 GC/kg
arm group type: Experimental
description: DTX301 (scAAV8OTC) 6.0 × 10^12 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.
arm group label: Cohort 3: DTX301 1.0 × 10^13 GC/kg
arm group type: Experimental
description: DTX301 (scAAV8OTC) 1.0 × 10^13 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.
arm group label: Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids
arm group type: Experimental
description: A prophylactic corticosteroid taper regimen (oral prednisone [or prednisolone], 60 mg tapered over 9 weeks) will be administered before dosing with DTX301 (scAAV8OTC) to prevent or minimize transient vector-induced hepatic effects. DTX301 (scAAV8OTC) 1.0x10^13 GC/kg administered as a single peripheral IV infusion. Sodium acetate will be used as a tracer to measure the rate of ureagenesis.
intervention type: Genetic
intervention name: scAAV8OTC
description: non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC)
arm group label: Cohort 1: DTX301 2.0 × 10^12 GC/kg
arm group label: Cohort 2: DTX301 6.0 × 10^12 GC/kg
arm group label: Cohort 3: DTX301 1.0 × 10^13 GC/kg
arm group label: Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids
other name: DTX301
intervention type: Drug
intervention name: Reactive Corticosteroid Taper Regimen
description: Oral prednisone [or oral prednisolone] 60 mg/day week 1, 40 mg/day Week 2, 30 mg/day Weeks 3 and 4, tapered by 5 mg/week Week 5 and beyond until liver enzymes return to baseline levels.
Corticosteroid treatment will be considered when a participant's alanine aminotransferase (ALT) level exceeded the upper limit of normal (ULN) and the ALT increase was considered by the Investigator to be related to DTX301.
arm group label: Cohort 1: DTX301 2.0 × 10^12 GC/kg
arm group label: Cohort 2: DTX301 6.0 × 10^12 GC/kg
arm group label: Cohort 3: DTX301 1.0 × 10^13 GC/kg
intervention type: Drug
intervention name: Prophylactic Corticosteroid Taper Regimen
description: Oral prednisone [or oral prednisolone] 60 mg/day at least 5 days prior to DTX301 administration, tapered over 9 weeks.
A prophylactic corticosteroid taper regimen will be administered to prevent or minimize transient vector-induced hepatic effects.
arm group label: Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Ultragenyx Pharmaceutical Inc
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 