<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/NCT03306277</url>
  </required_header>
  <id_info>
    <org_study_id>AVXS-101-CL-303</org_study_id>
    <secondary_id>2020-000095-38</secondary_id>
    <secondary_id>COAV101A12302</secondary_id>
    <nct_id>NCT03306277</nct_id>
  </id_info>
  <brief_title>Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1</brief_title>
  <acronym>STR1VE</acronym>
  <official_title>Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Gene Therapies</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      Phase 3 pivotal US trial studying open-label intravenous administration of onasemnogene&#xD;
      abeparvovec-xioi in spinal muscular atrophy (SMA) Type 1 participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase 3, open-label, single-arm, single-dose, study of onasemnogene abeparvovec-xioi (gene&#xD;
      replacement therapy) in participants with spinal muscular atrophy (SMA) Type 1 who meet&#xD;
      enrollment criteria and are genetically defined by nonfunctional survival motor neuron 1 gene&#xD;
      (SMN1) with 1 or 2 copies of survival motor neuron 2 gene (SMN2). Fifteen (15) participants &lt;&#xD;
      6 months (&lt; 180 days) of age at the time of gene replacement therapy (Day 1) will be&#xD;
      enrolled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 24, 2017</start_date>
  <completion_date type="Actual">November 12, 2019</completion_date>
  <primary_completion_date type="Actual">November 12, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>One-time intravenous administration of onasemnogene abeparvovec-xioi.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Achievement of Independent Sitting for at Least 30 Seconds</measure>
    <time_frame>Up to 18 months</time_frame>
    <description>Independent sitting is defined as sitting up straight with head erect for at least 30 seconds.&#xD;
This endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance, was the endpoint of event-free survival assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-free Survival</measure>
    <time_frame>14 months</time_frame>
    <description>Survival is defined by the avoidance of combined endpoint of either death or permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation is considered a surrogate for death. An acute reversible illness is defined as any condition other than SMA that results in increased medical intervention.&#xD;
The endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance was the survival endpoint assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ability to Thrive</measure>
    <time_frame>18 months</time_frame>
    <description>Ability to thrive is defined as achieving all of the following at 18 months of age:&#xD;
does not receive nutrition through mechanical support or other non-oral method&#xD;
ability to tolerate thin liquids as demonstrated through a formal swallowing test&#xD;
maintains weight&#xD;
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Support Independence</measure>
    <time_frame>Up to 18 months</time_frame>
    <description>Ventilatory support independence is defined as requiring no daily ventilator support/usage at 18 months of age, excluding acute reversible illness and perioperative ventilation, through assessment of actual usage data captured from the device (Phillips Trilogy BiPAP device). This endpoint is derived solely from the Phillips Trilogy BiPAP device.&#xD;
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>SMA - Spinal Muscular Atrophy</condition>
  <condition>Gene Therapy</condition>
  <arm_group>
    <arm_group_label>Onasemnogene Abeparvovec-xioi</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Onasemnogene Abeparvovec-xioi</intervention_name>
    <description>Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
    <arm_group_label>Onasemnogene Abeparvovec-xioi</arm_group_label>
    <other_name>Zolgensma</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with SMA Type 1 as determined by the following features: a. Diagnosis of&#xD;
             SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point&#xD;
             mutations) and 1 or 2 copies of SMN2 (inclusive of the known SMN2 gene modifier&#xD;
             mutation (c.859G&gt;C))2&#xD;
&#xD;
          -  The first 3 participants enrolled must meet the criteria for the Intent-To-Treat&#xD;
             Population&#xD;
&#xD;
          -  Participants must be &lt; 6 months (&lt; 180 days) of age at the time of onasemnogene&#xD;
             abeparvovec-xioi infusion&#xD;
&#xD;
          -  Participants must have a swallowing evaluation test performed prior to administration&#xD;
             of gene replacement therapy&#xD;
&#xD;
          -  Up-to-date on childhood vaccinations. Seasonal vaccinations that include palivizumab&#xD;
             prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV)&#xD;
             infections are also recommended in accordance with American Academy of Pediatrics&#xD;
&#xD;
          -  Parent(s)/legal guardian(s) willing and able to complete the informed consent process&#xD;
             and comply with study procedures and visit schedule&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous, planned or expected scoliosis repair surgery/procedure during the study&#xD;
             assessment period&#xD;
&#xD;
          -  Pulse oximetry &lt; 96% saturation at screening while the participant is awake or asleep&#xD;
             without any supplemental oxygen or respiratory support, or for altitudes &gt; 1000 m,&#xD;
             oxygen saturation &lt; 92% awake or asleep without any supplemental oxygen or respiratory&#xD;
             support Pulse oximetry saturation may decrease to &lt; 96% after screening provided that&#xD;
             the saturation does not decrease by ≥ 4 percentage points&#xD;
&#xD;
          -  Tracheostomy or current use or requirement of non-invasive ventilatory support&#xD;
             averaging ≥ 6 hours daily over the 7 days prior to the screening visit; or ≥ 6&#xD;
             hours/day on average during the screening period or requiring ventilatory support&#xD;
             while awake over the 7 days prior to screening or at any point during the screening&#xD;
             period prior to dosing&#xD;
&#xD;
          -  Participants with signs of aspiration/inability to tolerate non-thickened- liquids&#xD;
             based on a formal swallowing test performed as part of screening. Participants with a&#xD;
             gastrostomy tube who pass the swallowing test will be allowed to enroll in the study&#xD;
&#xD;
          -  Participants whose weight-for-age is below the third percentile based on World Health&#xD;
             Organization (WHO) Child Growth Standards&#xD;
&#xD;
          -  Active viral infection (includes human immunodeficiency virus [HIV] or positive&#xD;
             serology for hepatitis B or C, or Zika virus)&#xD;
&#xD;
          -  Serious non-respiratory tract illness requiring systemic treatment and/or&#xD;
             hospitalization within 2 weeks prior to screening&#xD;
&#xD;
          -  Upper or lower respiratory infection requiring medical attention, medical&#xD;
             intervention, or increase in supportive care of any manner within 4 weeks prior to&#xD;
             screening&#xD;
&#xD;
          -  Severe non-pulmonary/respiratory tract infection within 4 weeks before administration&#xD;
             of gene replacement therapy or concomitant illness that creates unnecessary risks for&#xD;
             gene replacement therapy such as: a. Major renal or hepatic impairment b. Known&#xD;
             seizure disorder c. Diabetes mellitus d. Idiopathic hypocalcuria e. Symptomatic&#xD;
             cardiomyopathy&#xD;
&#xD;
          -  Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or&#xD;
             their excipients&#xD;
&#xD;
          -  Concomitant use of any of the following: drugs for treatment of myopathy or&#xD;
             neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive&#xD;
             therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive&#xD;
             therapy within 3 months prior to gene replacement therapy&#xD;
&#xD;
          -  Anti-adeno-associated virus serotype 9 (AAV9) antibody titer &gt; 1:50 as determined by&#xD;
             Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential&#xD;
             participant demonstrate Anti-AAV9 antibody titer &gt; 1:50, he or she may receive&#xD;
             retesting within 30 days of the screening period and will be eligible to participate&#xD;
             if the Anti-AAV9 antibody titer upon retesting is ≤ 1:50&#xD;
&#xD;
          -  Clinically significant abnormal laboratory values (gamma glutamyl- transpeptidase&#xD;
             [GGT], ALT, and AST &gt; 3 × ULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.0 mg/dL,&#xD;
             hemoglobin [Hgb] &lt; 8 or &gt; 18 g/dL; white blood cell [WBC] &gt; 20,000 per cmm) prior to&#xD;
             gene replacement therapy&#xD;
&#xD;
          -  Participation in recent SMA treatment clinical study (with the exception of&#xD;
             observational Cohort studies or non-interventional studies) or receipt of an&#xD;
             investigational or commercial compound, product, or therapy administered with the&#xD;
             intent to treat SMA at any time prior to screening for this study. Oral β-agonists&#xD;
             must be discontinued at least 30 days before gene therapy dosing. Inhaled albuterol&#xD;
             specifically prescribed for the purposes of respiratory (bronchodilator) management is&#xD;
             acceptable and not a contraindication at any time prior to screening for this study&#xD;
&#xD;
          -  Expectation of major surgical procedures during the study assessment period&#xD;
&#xD;
          -  Parent(s)/legal guardian(s) unable or unwilling to comply with study procedures or&#xD;
             inability to travel for repeat visits&#xD;
&#xD;
          -  Parent(s)/legal guardian(s) unwilling to keep study results/observations confidential&#xD;
             or to refrain from posting confidential study results/observations on social media&#xD;
             sites&#xD;
&#xD;
          -  Parent(s)/legal guardian(s) refuses to sign consent form&#xD;
&#xD;
          -  Gestational age at birth &lt; 35 weeks (245 days)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>180 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>David Geffen School of Medicine at UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Hospital</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann and Robert H Lurie Children's Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Pediatric Neurology</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington Unviersity School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin (Madison)</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://studysmanow.com</url>
    <description>Recruitment Website</description>
  </link>
  <link>
    <url>http://AveXis.com</url>
    <description>sponsor company website</description>
  </link>
  <link>
    <url>https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17657</url>
    <description>Novartis Results Record</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <results_first_submitted>June 25, 2020</results_first_submitted>
  <results_first_submitted_qc>June 25, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 16, 2020</results_first_posted>
  <last_update_submitted>August 12, 2022</last_update_submitted>
  <last_update_submitted_qc>August 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Atrophy</mesh_term>
    <mesh_term>Muscular Atrophy, Spinal</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.</ipd_description>
    <ipd_url>https://www.clinicalstudydatarequest.com/.</ipd_url>
  </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>October 4, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT03306277/Prot_001.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>December 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT03306277/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>22 participants were recruited across 16 study centers in the United States.</recruitment_details>
      <pre_assignment_details>A screening period of up to 30 days occurred before treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Onasemnogene Abeparvovec-xioi</title>
          <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.&#xD;
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Onasemnogene Abeparvovec-xioi</title>
          <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.&#xD;
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
          </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="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.7" spread="1.6"/>
                  </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="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Patient reported hospitalizations</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight at baseline</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.8" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height/length at baseline</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.3" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Achievement of Independent Sitting for at Least 30 Seconds</title>
        <description>Independent sitting is defined as sitting up straight with head erect for at least 30 seconds.&#xD;
This endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance, was the endpoint of event-free survival assessed.</description>
        <time_frame>Up to 18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Onasemnogene Abeparvovec-xioi</title>
            <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.&#xD;
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
          </group>
        </group_list>
        <measure>
          <title>Achievement of Independent Sitting for at Least 30 Seconds</title>
          <description>Independent sitting is defined as sitting up straight with head erect for at least 30 seconds.&#xD;
This endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance, was the endpoint of event-free survival assessed.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>This comparison is made to an assumed rate of zero 0 (or as low as 0.1%). By definition, children with spinal muscular atrophy Type 1 are never able to sit independently.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>One-sided Exact Binomial Test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Event-free Survival</title>
        <description>Survival is defined by the avoidance of combined endpoint of either death or permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation is considered a surrogate for death. An acute reversible illness is defined as any condition other than SMA that results in increased medical intervention.&#xD;
The endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance was the survival endpoint assessed.</description>
        <time_frame>14 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Onasemnogene Abeparvovec-xioi</title>
            <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.&#xD;
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival</title>
          <description>Survival is defined by the avoidance of combined endpoint of either death or permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation is considered a surrogate for death. An acute reversible illness is defined as any condition other than SMA that results in increased medical intervention.&#xD;
The endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance was the survival endpoint assessed.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>This comparison is made against the results from the age and gender-matched control participants selected from existing natural history data sets (PNCR) [Neurol. 2014; 83(9):810-817].</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Fisher Exact</method>
            <other_analysis_desc>Data for the current study were compared to historical control data (Finkel et al,2014 - PubMed 25080519) where event-free survival was 6 out of 23 participants (26.1%) at 14 months of age.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ability to Thrive</title>
        <description>Ability to thrive is defined as achieving all of the following at 18 months of age:&#xD;
does not receive nutrition through mechanical support or other non-oral method&#xD;
ability to tolerate thin liquids as demonstrated through a formal swallowing test&#xD;
maintains weight&#xD;
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.</description>
        <time_frame>18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Onasemnogene Abeparvovec-xioi</title>
            <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.&#xD;
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
          </group>
        </group_list>
        <measure>
          <title>Ability to Thrive</title>
          <description>Ability to thrive is defined as achieving all of the following at 18 months of age:&#xD;
does not receive nutrition through mechanical support or other non-oral method&#xD;
ability to tolerate thin liquids as demonstrated through a formal swallowing test&#xD;
maintains weight&#xD;
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Support Independence</title>
        <description>Ventilatory support independence is defined as requiring no daily ventilator support/usage at 18 months of age, excluding acute reversible illness and perioperative ventilation, through assessment of actual usage data captured from the device (Phillips Trilogy BiPAP device). This endpoint is derived solely from the Phillips Trilogy BiPAP device.&#xD;
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.</description>
        <time_frame>Up to 18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Onasemnogene Abeparvovec-xioi</title>
            <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.&#xD;
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Support Independence</title>
          <description>Ventilatory support independence is defined as requiring no daily ventilator support/usage at 18 months of age, excluding acute reversible illness and perioperative ventilation, through assessment of actual usage data captured from the device (Phillips Trilogy BiPAP device). This endpoint is derived solely from the Phillips Trilogy BiPAP device.&#xD;
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 18 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Onasemnogene Abeparvovec-xioi</title>
          <description>One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.&#xD;
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (20.1)</default_vocab>
        <default_assessment>Non-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="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cyanosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchiolitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus bronchiolitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Bacterial tracheitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Rhinovirus infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Human metapneumovirus test positive</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal weight gain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Feeding disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device malfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (20.1)</default_vocab>
        <default_assessment>Non-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="22" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Pectus excavatum</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Asphyxiating thoracic dystrophy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Cryptorchism</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>High arched palate</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Teething</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="26" subjects_affected="12" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="28" subjects_affected="11" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus bronchiolitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </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="4" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase MB increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Feeding disorder</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Weight gain poor</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Scoliosis</sub_title>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Deformity thorax</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Joint contracture</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Kyphosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Torticollis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle contractions involuntary</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Use of accessory respiratory muscles</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" events="10" subjects_affected="6" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Respiration abnormal</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Tachypnoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Respiratory track congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dermatitis atopic</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dermatitis diaper</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Diastolic hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </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>Sponsor can review results communications prior to public release and has right to request changes to communications regarding trial results for a period that is more or equal to 30 days but less than or equal to 150 days from the time submitted to the Sponsor for review in order to either delete references to Sponsor's Confidential Information or delay such results communications to permit Sponsor to obtain appropriate Intellectual Property protection as set forth in the agreement.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The complete results are available via this link: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17657</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>US Medical Information</name_or_title>
      <organization>AveXis, Inc</organization>
      <phone>833-828-3947</phone>
      <email>medinfo@avexis.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/NCT03306277
org study id: AVXS-101-CL-303
secondary id: 2020-000095-38
secondary id: COAV101A12302
nct id: NCT03306277
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase 3 pivotal US trial studying open-label intravenous administration of onasemnogene
      abeparvovec-xioi in spinal muscular atrophy (SMA) Type 1 participants.
Phase 3, open-label, single-arm, single-dose, study of onasemnogene abeparvovec-xioi (gene
      replacement therapy) in participants with spinal muscular atrophy (SMA) Type 1 who meet
      enrollment criteria and are genetically defined by nonfunctional survival motor neuron 1 gene
      (SMN1) with 1 or 2 copies of survival motor neuron 2 gene (SMN2). Fifteen (15) participants <
      6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be
      enrolled.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: One-time intravenous administration of onasemnogene abeparvovec-xioi.
primary purpose: Treatment
masking: None (Open Label)
measure: Achievement of Independent Sitting for at Least 30 Seconds
time frame: Up to 18 months
description: Independent sitting is defined as sitting up straight with head erect for at least 30 seconds.
This endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance, was the endpoint of event-free survival assessed.
measure: Event-free Survival
time frame: 14 months
description: Survival is defined by the avoidance of combined endpoint of either death or permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation is considered a surrogate for death. An acute reversible illness is defined as any condition other than SMA that results in increased medical intervention.
The endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance was the survival endpoint assessed.
measure: Ability to Thrive
time frame: 18 months
description: Ability to thrive is defined as achieving all of the following at 18 months of age:
does not receive nutrition through mechanical support or other non-oral method
ability to tolerate thin liquids as demonstrated through a formal swallowing test
maintains weight
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.
measure: Ventilatory Support Independence
time frame: Up to 18 months
description: Ventilatory support independence is defined as requiring no daily ventilator support/usage at 18 months of age, excluding acute reversible illness and perioperative ventilation, through assessment of actual usage data captured from the device (Phillips Trilogy BiPAP device). This endpoint is derived solely from the Phillips Trilogy BiPAP device.
This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.
arm group label: Onasemnogene Abeparvovec-xioi
arm group type: Experimental
description: One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
intervention type: Biological
intervention name: Onasemnogene Abeparvovec-xioi
description: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
arm group label: Onasemnogene Abeparvovec-xioi
other name: Zolgensma
criteria: 
gender: All
minimum age: N/A
maximum age: 180 Days
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
country: United States
url: http://studysmanow.com
description: Recruitment Website
url: http://AveXis.com
description: sponsor company website
url: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17657
description: Novartis Results Record
responsible party type: Sponsor
mesh term: Muscular Atrophy
mesh term: Muscular Atrophy, Spinal
mesh term: Atrophy
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
ipd url: https://www.clinicalstudydatarequest.com/.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The complete results are available via this link: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17657
point of contact: 