<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/NCT03041324</url>
  </required_header>
  <id_info>
    <org_study_id>SB-913-1602</org_study_id>
    <nct_id>NCT03041324</nct_id>
  </id_info>
  <brief_title>Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II</brief_title>
  <official_title>A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-913, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis II (MPS II)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sangamo Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sangamo Therapeutics</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>
      The purpose of the study is to evaluate the safety, tolerability and effect on leukocyte and&#xD;
      plasma Iduronate 2-Sulfatase (IDS) enzyme activity of ascending doses of SB-913. SB-913 is an&#xD;
      intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts&#xD;
      a correct copy of the IDS gene into the Albumin locus in hepatocytes with the goal of&#xD;
      lifelong therapeutic production of the IDS enzyme.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objectives of the study are to provide long term expression of IDS and improve the&#xD;
      current clinical outcome of enzyme replacement therapy (ERT) in subjects with MPS II, a&#xD;
      recessive lysosomal storage disorder that results from mutations in the gene encoding IDS.&#xD;
      SB-913 is a therapeutic for ZFN-mediated genome editing which will be delivered by&#xD;
      adeno-associated virus (AAV)-derived vectors. SB-913 is intended to function by placement of&#xD;
      the corrective copy of IDS transgene into the genome of the subject's own hepatocytes, under&#xD;
      the control of the highly expressed endogenous albumin locus, and is expected to provide&#xD;
      permanent, liver-specific expression of Iduronate 2-Sulfatase for the lifetime of an MPS II&#xD;
      patient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    All nine subjects dosed in the study have rolled over to the Long-Term Follow-up Study&#xD;
    IVPRP-LT01 [NCT04628871]&#xD;
  </why_stopped>
  <start_date type="Actual">May 11, 2017</start_date>
  <completion_date type="Actual">May 7, 2021</completion_date>
  <primary_completion_date type="Actual">May 7, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 Months After the SB-913 Infusion</measure>
    <time_frame>Up to 36 months after the SB-913 infusion</time_frame>
    <description>Number of participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive SB-913 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of SB-913 on IDS Activity</measure>
    <time_frame>Baseline and Month 33 after the SB-913 infusion</time_frame>
    <description>Change from baseline in clinical laboratory measurement of IDS activity measured in blood, at Month 33.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels</measure>
    <time_frame>Baseline and 36 months after the SB-913 infusion</time_frame>
    <description>Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 36</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized Frequency of Idursulfase (or Equivalent ERT) Administration.</measure>
    <time_frame>Up to 36 months after the SB-913 infusion</time_frame>
    <description>Change from baseline in annualized frequency of idursulfase (or equivalent ERT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen</measure>
    <time_frame>Up to 36 months after the SB-913 infusion</time_frame>
    <description>Subjects with AAV2/6 clearance in plasma, saliva, urine, stool, and semen by PCR by Week 24.&#xD;
All the subjects had AAV2/6 clearance in all the samples assessed (i.e., plasma, saliva, urine, stool, and semen) by week 24.&#xD;
Subjects were only tested until Week 24 because, by that time, they all had 3 consecutive negative tests in all body fluids.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Mucopolysaccharidosis II</condition>
  <condition>MPS II</condition>
  <arm_group>
    <arm_group_label>Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SB-913</intervention_name>
    <description>Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor</description>
    <arm_group_label>Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</arm_group_label>
    <arm_group_label>Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</arm_group_label>
    <arm_group_label>Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female 5 years to 65 years of age.&#xD;
&#xD;
          -  Clinical diagnosis of MPS II (based on evidence of hepatosplenomegaly, dysostosis&#xD;
             multiplex by X-ray, valvular heart disease, or obstructive airway disease) IDS&#xD;
             deficiency confirmed by gene sequencing.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known to be unresponsive to ERT&#xD;
&#xD;
          -  Neutralizing antibodies to AAV 2/6&#xD;
&#xD;
          -  Serious intercurrent illness or clinically significant organic disease (unless&#xD;
             secondary to MPS II)&#xD;
&#xD;
          -  Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or&#xD;
             hepatitis C or HIV 1/2&#xD;
&#xD;
          -  Lack of tolerance to idursulfase treatment with significant IARs or occurrence of&#xD;
             anaphylaxis&#xD;
&#xD;
          -  Markers of hepatic dysfunction&#xD;
&#xD;
          -  Creatinine ≥ 1.5 mg/dL&#xD;
&#xD;
          -  Contraindication to the use of corticosteroids for immunosuppression&#xD;
&#xD;
          -  Current treatment with systemic (IV or oral) immunomodulatory agent or steroid use&#xD;
             (topical treatment allowed)&#xD;
&#xD;
          -  Participation in prior investigational drug or medical device study within the&#xD;
             previous 3 months&#xD;
&#xD;
          -  Prior treatment with a gene therapy product&#xD;
&#xD;
          -  Elevated or abnormal circulating α-fetoprotein (AFP)&#xD;
&#xD;
          -  Weight &lt; 20 kg at Screening Visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor</last_name>
    <role>Study Director</role>
    <affiliation>Sangamo Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU School of Medicine, Neurogenetics Division</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <results_first_submitted>May 7, 2022</results_first_submitted>
  <results_first_submitted_qc>August 30, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 27, 2022</results_first_posted>
  <last_update_submitted>October 21, 2022</last_update_submitted>
  <last_update_submitted_qc>October 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MPS ll</keyword>
  <keyword>Mucopolysaccharidosis II</keyword>
  <keyword>Hunter syndrome</keyword>
  <keyword>Gene Editing</keyword>
  <keyword>Gene therapy</keyword>
  <keyword>Zinc Finger</keyword>
  <keyword>ZFN</keyword>
  <keyword>SB-913</keyword>
  <keyword>Rare</keyword>
  <keyword>Genetic</keyword>
  <keyword>DNA</keyword>
  <keyword>Sangamo</keyword>
  <keyword>Genome editing</keyword>
  <keyword>Champions</keyword>
  <keyword>Hunter</keyword>
  <keyword>Gene Specific Targeted Insertion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucopolysaccharidosis II</mesh_term>
    <mesh_term>Mucopolysaccharidoses</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>December 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT03041324/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>October 30, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT03041324/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The original enrollment goal was 32 subjects: Subjects with MPS II disease sequentially enrolled in age cohorts:&#xD;
age &gt;18 (adult cohorts 1 through 4), age 12-17 (pediatric cohorts 5 and 6), and age 5-11 (pediatric cohorts 7 and 8).&#xD;
Due to the lack of observed clinical benefit, Sangamo Therapeutics, Inc. decided to stop enrollment in this study at 9 subjects, all adults in 3 cohorts. We continue to monitor the subjects in a 10-year, long-term follow-up study ST-IVPRP-LT01 (NCT04628871).</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
        <group group_id="P2">
          <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
        <group group_id="P3">
          <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (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="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="5"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
        <group group_id="B2">
          <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
        <group group_id="B3">
          <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
        <group group_id="B4">
          <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="2"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_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>
              <category_list>
                <category>
                  <title>Female</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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="9"/>
                  </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>
              <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_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="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_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_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="8"/>
                  </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_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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Iduronate 2 Sulfatase (IDS) Results</title>
          <units>nmol/mL/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.93" spread="1.79605"/>
                    <measurement group_id="B2" value="1.21" spread="0.55154"/>
                    <measurement group_id="B3" value="7.054" spread="3.74949"/>
                    <measurement group_id="B4" value="5.2833" spread="3.68909"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Urine Glycosaminoglycans (GAG) Levels</title>
          <units>(g/mol creatinine)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Dermatan Sulfate, Urine (g/mol creatinine)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.255" spread="1.70413"/>
                    <measurement group_id="B2" value="5.165" spread="1.83141"/>
                    <measurement group_id="B3" value="4.094" spread="0.79563"/>
                    <measurement group_id="B4" value="4.3678" spread="1.14354"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heparan Sulfate, Urine (g/mol creatinine)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.955" spread="0.24749"/>
                    <measurement group_id="B2" value="9.795" spread="4.16486"/>
                    <measurement group_id="B3" value="5.074" spread="0.76843"/>
                    <measurement group_id="B4" value="6.0967" spread="2.62108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total GAG (g/mol creatinine)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.785" spread="1.44957"/>
                    <measurement group_id="B2" value="6.88" spread="0.9051"/>
                    <measurement group_id="B3" value="4.816" spread="2.96001"/>
                    <measurement group_id="B4" value="5.2678" spread="2.36252"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 Months After the SB-913 Infusion</title>
        <description>Number of participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive SB-913 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)</description>
        <time_frame>Up to 36 months after the SB-913 infusion</time_frame>
        <population>All subjects in this study who received any portion of the SB-913 infusion</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.&#xD;
SB-913: Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor</description>
          </group>
          <group group_id="O2">
            <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.&#xD;
SB-913: Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor</description>
          </group>
          <group group_id="O3">
            <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.&#xD;
SB-913: Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 Months After the SB-913 Infusion</title>
          <description>Number of participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive SB-913 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)</description>
          <population>All subjects in this study who received any portion of the SB-913 infusion</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect of SB-913 on IDS Activity</title>
        <description>Change from baseline in clinical laboratory measurement of IDS activity measured in blood, at Month 33.</description>
        <time_frame>Baseline and Month 33 after the SB-913 infusion</time_frame>
        <population>All subjects in this study who received any dose of the SB-913 infusion</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
          <group group_id="O2">
            <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
          <group group_id="O3">
            <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of SB-913 on IDS Activity</title>
          <description>Change from baseline in clinical laboratory measurement of IDS activity measured in blood, at Month 33.</description>
          <population>All subjects in this study who received any dose of the SB-913 infusion</population>
          <units>nmol/mL/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6600" spread="3.5213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels</title>
        <description>Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 36</description>
        <time_frame>Baseline and 36 months after the SB-913 infusion</time_frame>
        <population>All subjects in this study who received any dose of the SB-913 infusion</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
          <group group_id="O2">
            <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
          <group group_id="O3">
            <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels</title>
          <description>Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 36</description>
          <population>All subjects in this study who received any dose of the SB-913 infusion</population>
          <units>g/mol creatinine</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total GAG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.035" spread="0.03536"/>
                    <measurement group_id="O2" value="-2.6" spread="NA">For total GAG, at month 36, only one patient in cohort 2 had a sample tested for total GAG, so no standard deviation was available.</measurement>
                    <measurement group_id="O3" value="1.734" spread="1.58357"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermatan Sulfate Urine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.025" spread="1.18087"/>
                    <measurement group_id="O2" value="-3.39" spread="NA">For DS GAG, at month 36, only one patient in cohort 2 had a sample tested for DS GAG, so no standard deviation was available.</measurement>
                    <measurement group_id="O3" value="0.262" spread="0.6985"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heparan Sulfate Urine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.895" spread="2.39709"/>
                    <measurement group_id="O2" value="-7.6" spread="NA">For HS GAG, at month 36, only one patient in cohort 2 had a sample tested for HS GAG, so no standard deviation was available.</measurement>
                    <measurement group_id="O3" value="2.880" spread="2.91261"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Frequency of Idursulfase (or Equivalent ERT) Administration.</title>
        <description>Change from baseline in annualized frequency of idursulfase (or equivalent ERT)</description>
        <time_frame>Up to 36 months after the SB-913 infusion</time_frame>
        <population>All subjects in this study who received any dose of the SB-913 infusion</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
          <group group_id="O2">
            <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
          <group group_id="O3">
            <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Frequency of Idursulfase (or Equivalent ERT) Administration.</title>
          <description>Change from baseline in annualized frequency of idursulfase (or equivalent ERT)</description>
          <population>All subjects in this study who received any dose of the SB-913 infusion</population>
          <units>Number of Infusions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.8" spread="NA">Only one subject in this cohort had ERT withdrawal, so no standard deviation is available.</measurement>
                    <measurement group_id="O2" value="9.9" spread="25.5"/>
                    <measurement group_id="O3" value="-0.5" spread="6.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen</title>
        <description>Subjects with AAV2/6 clearance in plasma, saliva, urine, stool, and semen by PCR by Week 24.&#xD;
All the subjects had AAV2/6 clearance in all the samples assessed (i.e., plasma, saliva, urine, stool, and semen) by week 24.&#xD;
Subjects were only tested until Week 24 because, by that time, they all had 3 consecutive negative tests in all body fluids.</description>
        <time_frame>Up to 36 months after the SB-913 infusion</time_frame>
        <population>All subjects in this study who received any portion of the SB-913 infusion</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.&#xD;
SB-913: Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor</description>
          </group>
          <group group_id="O2">
            <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.&#xD;
SB-913: Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor</description>
          </group>
          <group group_id="O3">
            <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
            <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.&#xD;
SB-913: Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor</description>
          </group>
        </group_list>
        <measure>
          <title>AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen</title>
          <description>Subjects with AAV2/6 clearance in plasma, saliva, urine, stool, and semen by PCR by Week 24.&#xD;
All the subjects had AAV2/6 clearance in all the samples assessed (i.e., plasma, saliva, urine, stool, and semen) by week 24.&#xD;
Subjects were only tested until Week 24 because, by that time, they all had 3 consecutive negative tests in all body fluids.</description>
          <population>All subjects in this study who received any portion of the SB-913 infusion</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="2"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected from the subject's date of screening until their end of study visit which ranged from 24 to 36 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
        <group group_id="E2">
          <title>Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
        <group group_id="E3">
          <title>Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg</title>
          <description>A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.</description>
        </group>
      </group_list>
      <serious_events>
        <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="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Incarcerated Umbilical Hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Intestinal Obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <description>fever</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Spinal Stenosis</sub_title>
                <description>worsening</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Lacunar Stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device Dislocation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="2" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Splenomegaly</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiomegaly</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Left Atrial Dilatation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Mitral Spinal Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Palpatations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Tachypnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Visual Impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdomen Pain, Upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Abdominal Pain, Lower</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Food Poisoning</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Gastroesophageal Reflux Disease</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Jejunal Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Oesophageal Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pancreatic Cyst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Incarcerated Umbilical Hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Impaired Healing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Influenza like Illness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Prosthetic Cardiac Valve Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Application Site Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Infusion Site Extravasation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hepatocellular Injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hepatomegaly</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Mild Fibrosis in few portal tracts</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Portal Fibrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal Allergy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis Viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Bacterial Test Positive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Ear Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Skin Candida</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="8" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Bacteriuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Incision Site Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Infusion Related Reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Post Procedural Discharge</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Post Procedural Hematoma</sub_title>
                <description>following liver biosy</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Post Procedural Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Procedural Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Skin Abrasion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Sunburn</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Cervical Vertebral Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Muscle Strain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Foreign Body Aspiration</sub_title>
                <description>aspiration from c-pap machine</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Skin Irritation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood Urine Present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <description>elevated liver function test</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <description>elevated liver function test</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Blood Phosphorus Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Blood Pressure Systolic Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Blood Thyroid Stimulating Hormone Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>CSF Glucose Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Crystals Urine Present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Decreased Phosphorous</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Lmphocyte Count Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Neutrophils Count Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Prothrombin Time Prolonged</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Red Cell Distribution Width Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Urinary Glycosaminoglycans Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Weight Decreased.</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Blood Lactate Dehydrogenase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Obesity</sub_title>
                <description>worsening</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Lumbar Spinal Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Cervical Spinal Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Intervertebral Disc Degeneration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Intervertebral Disc Protrusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Mobility Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Muscle Spasms Musculoskeletal Stiffness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Muscular Weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Spinal Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal Cell Carcinoma</sub_title>
                <description>left mid scalp (superficial and nodular patterns)</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral Atrophy</sub_title>
                <description>thinning and atrophy (noted on ct)</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <description>transient slurred speech</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>White Matter Lesion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Devise Dislocation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Device Loosening</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hepatic Lesion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Renal Cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Scrotal Swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Tract Congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <description>worsening</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <description>bloody nose</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Sore Throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Tracheal Disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Lower Respiratory Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Cold Sweat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Rash on wrists, bilaterally</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Skin Abrasion</sub_title>
                <description>arm</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Loss Of Personal Independence In Daily Activities</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic Stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Aortic Dilatation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Deep Vein Thrombosis</sub_title>
                <description>lower left extremity</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <description>during and post ert infusion</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Lymphoedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to the limited sample size of 9 subjects, the primary and secondary endpoints could not be analyzed, and this study could not report any conclusions.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Monitor</name_or_title>
      <organization>Sangamo Therapeutics, Inc.</organization>
      <phone>(510) 307-7266</phone>
      <email>clinicaltrials@sangamo.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/NCT03041324
org study id: SB-913-1602
nct id: NCT03041324
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to evaluate the safety, tolerability and effect on leukocyte and
      plasma Iduronate 2-Sulfatase (IDS) enzyme activity of ascending doses of SB-913. SB-913 is an
      intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts
      a correct copy of the IDS gene into the Albumin locus in hepatocytes with the goal of
      lifelong therapeutic production of the IDS enzyme.
The objectives of the study are to provide long term expression of IDS and improve the
      current clinical outcome of enzyme replacement therapy (ERT) in subjects with MPS II, a
      recessive lysosomal storage disorder that results from mutations in the gene encoding IDS.
      SB-913 is a therapeutic for ZFN-mediated genome editing which will be delivered by
      adeno-associated virus (AAV)-derived vectors. SB-913 is intended to function by placement of
      the corrective copy of IDS transgene into the genome of the subject's own hepatocytes, under
      the control of the highly expressed endogenous albumin locus, and is expected to provide
      permanent, liver-specific expression of Iduronate 2-Sulfatase for the lifetime of an MPS II
      patient.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 Months After the SB-913 Infusion
time frame: Up to 36 months after the SB-913 infusion
description: Number of participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive SB-913 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
measure: Effect of SB-913 on IDS Activity
time frame: Baseline and Month 33 after the SB-913 infusion
description: Change from baseline in clinical laboratory measurement of IDS activity measured in blood, at Month 33.
measure: Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels
time frame: Baseline and 36 months after the SB-913 infusion
description: Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 36
measure: Annualized Frequency of Idursulfase (or Equivalent ERT) Administration.
time frame: Up to 36 months after the SB-913 infusion
description: Change from baseline in annualized frequency of idursulfase (or equivalent ERT)
measure: AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen
time frame: Up to 36 months after the SB-913 infusion
description: Subjects with AAV2/6 clearance in plasma, saliva, urine, stool, and semen by PCR by Week 24.
All the subjects had AAV2/6 clearance in all the samples assessed (i.e., plasma, saliva, urine, stool, and semen) by week 24.
Subjects were only tested until Week 24 because, by that time, they all had 3 consecutive negative tests in all body fluids.
arm group label: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg
arm group type: Experimental
description: A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.
arm group label: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg
arm group type: Experimental
description: A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.
arm group label: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg
arm group type: Experimental
description: A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.
intervention type: Biological
intervention name: SB-913
description: Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor
arm group label: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg
arm group label: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg
arm group label: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg
criteria: 
gender: All
minimum age: 5 Years
maximum age: 65 Years
healthy volunteers: No
last name: Medical Monitor
role: Study Director
affiliation: Sangamo Therapeutics
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mucopolysaccharidosis II
mesh term: Mucopolysaccharidoses
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to the limited sample size of 9 subjects, the primary and secondary endpoints could not be analyzed, and this study could not report any conclusions.
point of contact: 